Flavopiridol in Treating Children With Relapsed or Refractory Solid Tumors or Lymphomas

ClinicalTrials.gov

2013-07-01

Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

ClinicalTrials.gov

2015-04-14

Childhood Desmoplastic Small Round Cell Tumor; Childhood Synovial Sarcoma; Gastrointestinal Stromal Tumor; Lung Metastases; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

ClinicalTrials.gov

2018-03-21

Childhood Alveolar Soft Part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Gliosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Rhabdomyosarcoma

Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

ClinicalTrials.gov

2017-05-15

Childhood Acute Lymphoblastic Leukemia; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Ewing Sarcoma; Ewing Sarcoma of Bone; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Unspecified Childhood Solid Tumor, Protocol Specific; Wilms Tumor and Other Childhood Kidney Tumors

Peripheral primitive neuroectodermal tumor of the vulva: report of a case with imprint cytology.

PubMed

Takeshima, N; Tabata, T; Nishida, H; Furuta, N; Tsuzuku, M; Hirai, Y; Hasumi, K

2001-01-01

Peripheral primitive neuroectodermal tumor (PNET) of the vulva is an extremely rare disease, and, to our knowledge, only two cases have been previously reported. A 45-year-old woman presented with a mass in the right labium major. Three years after removal of the tumor, she noticed a new lesion in the same place and underwent a partial vulvectomy. The imprint cytology of the recurrent tumor showed a monomorphic appearance, composed of small round cells with scant cytoplasm against a hemorrhagic background. These tumor cells were loosely connective, but rosettelike structures were observed focally. On pathologic examination, the neoplasm was composed of small round tumor cells showing sinusoidal, diffuse or micropapillary growth. Immunohistochemically, the neoplastic cells stained positively for neuron-specific enolase, vimentin and HBA 71 and negatively for cytokeratin, HBA 45 and muscle-specific actin. The morphologic characteristics of the disease were well expressed in the imprint cytology, and this influenced the selection of immunohistochemical studies. Cytologic examination for vulvar tumors, even imprint cytology, can be a useful tool in obtaining an accurate pathologic diagnosis of a rare disease, such as peripheral PNET.

Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies

ClinicalTrials.gov

2018-03-02

Adult Solid Neoplasm; Childhood Solid Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Malignant Solid Neoplasm; Refractory Central Nervous System Neoplasm

Stereotactic Radiosurgery in Treating Patients With Brain Tumors

ClinicalTrials.gov

2012-03-21

Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

ClinicalTrials.gov

2017-09-21

Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

ClinicalTrials.gov

2013-06-04

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Melanoma; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

ClinicalTrials.gov

2015-03-18

Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Childhood Hepatoblastoma; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adrenocortical Carcinoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive; Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

High grade primitive neuroectodermal tumor of the uterus: A case report.

PubMed

Dizon, A Mitch; Kilgore, Larry C; Grindstaff, Alan; Winkler, Marcus; Kimball, Kristopher J

2014-01-01

•Primitive neuroectodermal tumor of the uterus is extremely rare.•Diagnosis requires timely evaluation with molecular analysis.•Different combinations of adjuvant chemotherapy have been reported.

Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

ClinicalTrials.gov

2013-10-07

Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Endometrial endometrioid adenocarcinoma associated with primitive neuroectodermal tumour of the uterus: a poor prognostic subtype of uterine tumours.

PubMed

Bartosch, Carla; Vieira, Joana; Teixeira, Manuel R; Lopes, José Manuel

2011-12-01

Uterine primitive neuroectodermal tumours are extremely rare tumours. They can occur in pure form or combined with another component including endometrioid adenocarcinoma. We aimed to review the clinical impact of neuroectodermal phenotype in uterine tumours, after we recently diagnosed one such case. A 58-year-old female presented with irregular vaginal bleeding. Ultrasonography and CT showed the presence of a large uterine mass with irregular contours. At laparotomy it was found to extend to the right ureter, sigmoid colon and some small intestinal loops. Microscopic examination revealed that the tumour consisted of an endometrioid adenocarcinoma component merging with an extensive neuroectodermal component. No EWSR1 or FUS rearrangement was found in the two tumour components. The patient received two courses of chemotherapy but died 11 months after the initial diagnosis. We reviewed the morphological and molecular criteria for the diagnosis of uterine primitive neuroectodermal tumours published in the literature. We conclude that regardless of the detection of an EWSR1 rearrangement, the presence of a neuroectodermal differentiation component in these rare uterine tumours is a marker of aggressive behaviour, and its presence should be highlighted in the diagnosis.

Congenital extraskeletal Ewing's sarcoma of chest wall--a rare case report.

PubMed

Atla, Bhagyalakshmi; Prasad, B Satya Vara; Sri, K Satya; Vandana, Geeta

2011-01-01

Congenital extraskeletal Ewing's sarcoma or peripheral primitive neuroectodermal tumor is an extremely uncommon and invariably fatal tumor. We report a case of extraskeletal congenital Ewing's sarcoma in a female fetus delivered at 34 weeks of gestation who died immediately after birth. In English literature, majority of cases of Ewing's sarcoma in neonates reported were skeletal. To the best of our knowledge, very few cases of extra-skeletal Ewing's sarcoma in neonates are reported in the literature.

Primitive neuroectodermal tumour of the kidney: radiologic-pathological correlations.

PubMed

Chea, Y W; Agrawal, Rashi; Poh, Angeline C C

2008-06-01

A primitive neuroectodermal tumour of the kidney is a rare malignancy. We report the computed tomographic features and the histopathological correlation of such a tumour occurring in a middle-aged man. Although the radiological appearance has significant overlap with other renal tumours, this tumour should be included in the differential diagnosis of a large renal mass in younger patients.

Irinotecan in Treating Children With Refractory Solid Tumors

ClinicalTrials.gov

2013-06-13

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

ClinicalTrials.gov

2018-06-25

Metastatic Melanoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Rhabdomyosarcoma; Refractory Hodgkin Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Non-Hodgkin Lymphoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

PubMed

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

ClinicalTrials.gov

2013-02-06

AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Stage IV Uterine Sarcoma; Unspecified Adult Solid Tumor, Protocol Specific

Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

PubMed

Chiang, Sarah; Snuderl, Matija; Kojiro-Sanada, Sakiko; Quer Pi-Sunyer, Ariadna; Daya, Dean; Hayashi, Tohru; Bosincu, Luisanna; Ogawa, Fumihiro; Rosenberg, Andrew E; Horn, Lars-Christian; Wang, Lu; Iafrate, A John; Oliva, Esther

2017-06-01

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

Fine-Needle Aspiration of Metastatic Central Type Primitive Neuroectodermal Tumors in Patients with a Germ Cell Tumor.

PubMed

Chen, Shaoxiong; Idrees, Muhammad; Lin, Jingmei; Wu, Howard H

2017-01-01

Central type primitive neuroectodermal tumors (PNET) are some of the most frequent somatic type tumors derived from germ cell tumors and can metastasize. We studied the cytomorphological features of metastatic central type PNET by fine-needle aspiration (FNA). A computerized search of our laboratory information system was performed for the 9-year period from 2005 through 2014 to identify all cytology cases in which a diagnosis of metastatic central type PNET had been rendered. A total of 5 FNA cases were collected and direct smears were reexamined. All patients had a history of testicular or ovarian germ cell tumors. Direct smears displayed single and clusters of atypical round to oval cells with scant to moderate cytoplasm. Abundant naked nuclei were present in Diff-Quik-stained smears with mild to marked crushed artifacts and nuclear molding. Tumor cells showed fine granular chromatin, nuclear size variation (up to 1:3), and one or more small nucleoli. Pseudorosettes (Homer Wright-like rosette) were noticed in 1 case. Tumor cells were commonly positive for synaptophysin. Metastatic PNET can be reliably diagnosed by FNA. Differential diagnoses include Ewing sarcoma/peripheral PNET, alveolar rhabdomyosarcoma, neuroblastoma, etc. It is important to be familiar with this entity to avoid diagnostic pitfalls. © 2017 S. Karger AG, Basel.

Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.

PubMed

Gardner, L J; Polski, J M; Fallon, R; Dunphy, C H

1998-07-01

CD56 and CD57 are commonly considered as natural killer and neuroectodermal markers, but their expression has been identified in a wide spectrum of neoplasms including some cases of Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET). We report two cases of small, round blue cell tumor (SRBCT), in which flow cytometry immunophenotyping (FCI) detected strong expression of CD56 and CD57 (one case). Immunohistochemical staining with Leu-19 and Leu-7 confirmed the FI results. Although CD56 and CD57 expression is consistent with ES/PNET, it can be potentially misleading if results of FCI are interpreted in the absence of other findings. These cases suggest the utility of FCI in undifferentiated SRBCT. The literature on CD56 and CD57 expression in ES/PNET is reviewed and discussed.

Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF NP_004324.2:p.V600X; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Histiocytosis; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor

Primary primitive neuroectodermal tumor of the cervix

PubMed Central

Li, Bo; Ouyang, Ling; Han, Xue; Zhou, Yang; Tong, Xin; Zhang, Shulang; Zhang, Qingfu

2013-01-01

Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy. PMID:23836982

Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

ClinicalTrials.gov

2013-06-04

Childhood Central Nervous System Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Hepatoblastoma; Childhood Hepatocellular Carcinoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Colon Cancer; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Nasopharyngeal Cancer; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer

High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

ClinicalTrials.gov

2018-04-05

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Neuroblastoma; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Regional Neuroblastoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

TCRαβ+/CD19+ Depleted Haploidentical HSCT + Zoledronate

ClinicalTrials.gov

2018-05-09

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Syndrome; Rhabdomyosarcoma; Ewing Sarcoma; Primitive Neuroectodermal Tumor; Osteosarcoma; Neuroblastoma

Ewing sarcoma

MedlinePlus

Bone cancer - Ewing sarcoma; Ewing family of tumors; Primitive neuroectodermal tumors (PNET); Bone neoplasm - Ewing sarcoma ... adulthood. But it usually develops during puberty, when bones are growing rapidly. It is more common in ...

p28 in Treating Younger Patients With Recurrent or Progressive Central Nervous System Tumors

ClinicalTrials.gov

2017-08-03

Teratoid Tumor, Atypical; Choroid Plexus Neoplasms; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Brainstem Tumors; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Medulloblastoma; Neuroectodermal Tumor, Primitive

[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature].

PubMed

Schmid, I; Stachel, D; Graubner, U B; Elsner, R; Schulze, S; Pöllinger, B; Goetz, C; Haas, R J

2005-01-01

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System

ClinicalTrials.gov

2018-05-16

Medulloblastoma; Pineoblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified; Untreated Childhood Medulloblastoma; Untreated Childhood Pineoblastoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

[Primitive neuroectodermal tumor/Ewing's sarcoma of the penis in children: a case report and review of the literature].

PubMed

Zhang, Da-Wei; Jin, Mei; Zhou, Chun-Ju; Song, Hong-Cheng; Ma, Xiao-Li

2012-12-01

To investigate the clinical manifestations, pathological characteristics and treatment of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) of the penis in children. We analyzed the clinical data of a case of PNET/EWS and reviewed relevant literature. The patient was a 5-year-old boy, admitted for penis swelling with pain for 11 months. Biopsy showed a small round cell tumor, CD99 positive by immunohistochemical staining, with EWS translocation by fluorescence in situ hybridization on molecular biological examination. The tumor was confirmed to be PNET/EWS of the penis, and disappeared after 45 weeks of chemotherapy and local radiotherapy. PNET/EWS of the penis is an extremely rare disease, with no specific clinical symptoms except penis enlargement with pain. Immunohistochemistry and molecular biological examination contribute to its diagnosis.

Primitive Neuroectodermal Tumor Presenting with Diffuse Leptomeningeal Involvement in a 55-Year-Old Woman: A Case Report and Brief Summary of Current Diagnostic Tests and Treatment

PubMed Central

Kalidindi, Navya; Torres, Carlos H.; Michaud, Jean; Zwicker, Jocelyn Christine

2014-01-01

Primitive neuroectodermal tumors (PNETs) are typically present as masses in children and adolescents, but rarely in adults. Diagnoses, management strategies, and prognostication factors are not well established in adult cases of PNETs. We describe the case of a central nervous system PNET diagnosed in a 55-year-old woman presenting with a sudden onset of symptoms consisting of increased intracranial pressure and findings of diffuse leptomeningeal enhancement and a small medullary lesion seen on MRI. Amongst the small database of PNETs diagnosed in adults, our case report stands out as one of few cases describing a primarily leptomeningeal PNET diagnosed on biopsy. We also review the literature on PNETs presenting with diffuse leptomeningeal disease and the treatment of PNETs in the adult population. PMID:25202261

Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)

ClinicalTrials.gov

2017-06-20

Lymphoma; Childhood Lymphoma; Solid Tumor; Childhood Solid Tumor; Neuroblastoma; Ewing Sarcoma; Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Medulloblastoma; Germ Cell Tumor; Wilms Tumor; Brain Neoplasms; Medulloblastoma, Childhood; Neuroectodermal Tumors, Primitive

Molecular-Guided Therapy for Childhood Cancer

ClinicalTrials.gov

2017-07-07

Neuroblastoma; Medulloblastoma; Glioma; Ependymoma; Choroid Plexus Neoplasms; Craniopharyngioma; Dysembryoplastic Neuroepithelial Tumor; Meningioma; Primitive Neuroectodermal Tumors (PNETs); Germ Cell Tumors; Rhabdomyosarcoma; Non-rhabdomyosarcoma; Ewings Sarcoma; Osteosarcoma; Wilms Tumor; Renal Cell Carcinoma; Malignant Rhabdoid Tumor; Clear Cell Sarcoma; Liver Tumors

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

PubMed Central

Lin, Patrick P.; Wang, Yongxing; Lozano, Guillermina

2011-01-01

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further. PMID:20953407

Epidemiology, management and treatment outcome of medulloblastoma in singapore.

PubMed

Chan, Mei-Yoke; Teo, Wan-Yee; Seow, Wan-Tew; Tan, Ah-Moy

2007-05-01

Medulloblastoma/primitive neuroectodermal tumour is the most common type of malignant brain tumour in children. Long-term survival rates have improved over the years with a combination of surgical, radiotherapeutic and chemotherapeutic treatment modalities in the developed world. This paper aims to analyse the epidemiology and outcome of medulloblastoma in Singapore and compare our results with those reported in the literature. A 9-year retrospective study was done using data reported to the Singapore Children's Cancer Registry from June 1997 to June 2005. Only 39 children up to the age of 15 years diagnosed histologically with medulloblastoma or primitive neuroectodermal tumour arising from the cerebellum were included in the study. Follow-up data were collected up to June 2006 and analysed using SPSS v 13.0 software. Medulloblastoma/primitive neuroectodermal tumour was the most common type of brain tumour, accounting for 40.7% of all brain tumours diagnosed in children in Singapore. The 5-year event-free survival rate was 44.5%, while the 5- year overall survival rate was 51.5%. Nearly half (41%) of our patients had spinal metastasis at presentation and this was associated with a worse event-free survival (6.3% vs 71.9%, P = 0). Children under 36 months of age had a significantly poorer overall survival (28.8% vs 52.2%, P = 0.041). The outcome of medulloblastoma in Singapore was inferior to reported figures in the literature. We need to close identified gaps in care, like standardising assessment and treatment protocols, in order to improve our results. Research into molecular and genetic characteristics may also throw light on whether the disease is inherently more aggressive in our population.

The role of immunohistochemistry in medullomyoblastoma--a case series highlighting divergent differentiation.

PubMed

Sachdeva, Man Updesh S; Vankalakunti, Mahesha; Rangan, Aruna; Radotra, Bishan D; Chhabra, Rajesh; Vasishta, Rakesh K

2008-04-25

To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation. A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructural analysis was done on tissue obtained from paraffin blocks in 2 cases. Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search. Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.

Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract.

PubMed

Xiao, Changji; Zhao, Jing; Guo, Peng; Wang, Dan; Zhao, Dachun; Ren, Tong; Yang, Jiaxin; Shen, Keng; Lang, Jinghe; Xiang, Yang; Cui, Quancai

2014-03-01

The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.

Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Deleterious ATM Gene Mutation; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious RAD51D Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Wilms Tumor

Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; FGFR1 Gene Mutation; FGFR2 Gene Mutation; FGFR3 Gene Mutation; FGFR4 Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Relapsed or Refractory Brain Tumors

ClinicalTrials.gov

2018-03-16

Childhood Astrocytoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Glioblastoma; Recurrent Childhood Medulloblastoma; Recurrent Primitive Neuroectodermal Tumor; Refractory Brain Neoplasm

Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer

ClinicalTrials.gov

2017-03-28

Childhood Choroid Plexus Tumor; Childhood Medulloblastoma; Childhood Pineoblastoma; Childhood Soft Tissue Sarcoma; Childhood Supratentorial Primitive Neuroectodermal Tumor; Neuroblastoma; Osteosarcoma; Retinoblastoma; Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

PubMed

Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

2007-08-01

Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

Primary Pulmonary Ewing's Sarcoma/Primitive Neuroectodermal Tumor in a 67-year-old Man

PubMed Central

Lee, Yoon Young; Kim, Do Hoon; Lee, Ji Hye; Choi, Jong Sang; In, Kwang Ho; Oh, Yu Whan; Cho, Kyung Hwan

2007-01-01

Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy. PMID:17923745

Thyroid-Stimulating Hormone Suppression for Protection Against Hypothyroidism Due to Craniospinal Irradiation for Childhood Medulloblastoma/Primitive Neuroectodermal Tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massimino, Maura; Gandola, Lorenza; Collini, Paola

Purpose: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. Patients and Methods: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginningmore » and end of CSI. From 14 days before and up to the end of CSI, patients were administered L-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 {mu}M/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Results: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the 'adequately TSH-suppressed' group and 20% for the 'inadequately TSH-suppressed' group (p = 0.02). Conclusions: Thyroid-stimulating hormone suppression with L-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.« less

Ewing’s Sarcoma Family Tumors in the Jaws: Case Report, Immunohistochemical Analysis and Literature Review

PubMed Central

CASAROTO, ANA REGINA; SAMPIERI, MARCELO BONIFACIO DA SILVA; SOARES, CLEVERSON TEIXEIRA; SANTOS, PAULO SERGIO DA SILVA; YAEDU, RENATO YASSUTAKA FARIA; DAMANTE, JOSÉ HUMBERTO; LARA, VANESSA SOARES

2017-01-01

Due to the low incidence of the Ewing’s Sarcoma (ES) family tumors, the available epidemiology is likely to be unreliable, and at present, there are no standard diagnostic or clinical guidelines outlining their management. This report describes a case of peripheral primitive neuroectodermal tumor (ES/pPNET) which initially mimicked cystic lesions, and describes a comparison between ES and ES/pPNET in the jaws by the World Health Organization classification. This review addressed 63 cases published in the English literature between 1950 and 2016. The majority of cases were ES. Both ES and ES/pPNET mimicked other benign entities such as traumatic, cystic and inflammatory lesions. The patients who died of their disease had a history of metastatic tumors, and primary tumor located in the mandible and maxilla for ES and ES/pPNET, respectively. The differentiation of the ES family tumors from other small blue-cell tumors may be difficult and requires familiarity with histological and immunohistochemical features. PMID:28438883

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Childhood Langerhans Cell Histiocytosis; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Malignant Glioma; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-18

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; TSC1 Gene Mutation; TSC2 Gene Mutation; Wilms Tumor

Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

ClinicalTrials.gov

2017-04-27

Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilocytic Astrocytoma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Pleomorphic Xanthoastrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood Medulloblastoma; Untreated Childhood Oligoastrocytoma; Untreated Childhood Oligodendroglioma; Untreated Childhood Pilocytic Astrocytoma; Untreated Childhood Pilomyxoid Astrocytoma; Untreated Childhood Pineoblastoma; Untreated Childhood Pleomorphic Xanthoastrocytoma; Untreated Childhood Protoplasmic Astrocytoma; Untreated Childhood Subependymal Giant Cell Astrocytoma; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor; Untreated Childhood Visual Pathway and Hypothalamic Glioma; Untreated Childhood Visual Pathway Glioma

Yoga Therapy in Treating Patients With Malignant Brain Tumors

ClinicalTrials.gov

2017-07-27

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

Intraventricular mass lesions at magnetic resonance imaging: iconographic essay - part 1*

PubMed Central

de Castro, Felipe Damásio; Reis, Fabiano; Guerra, José Guilherme Giocondo

2014-01-01

The present essay is illustrated with magnetic resonance images obtained at the authors' institution over the past 15 years and discusses the main imaging findings of intraventricular tumor-like lesions (ependymoma, pilocytic astrocytoma, central neurocytoma, ganglioglioma, choroid plexus papilloma, primitive neuroectodermal tumors, meningioma, epidermoid tumor). Such lesions represent a subgroup of intracranial lesions with unique characteristics and some image patterns that may facilitate the differential diagnosis. PMID:25741075

Conservative Treatment of Ewing's Sarcoma of the Uterus in Young Women.

PubMed

Loverro, Giuseppe; Resta, Leonardo; Di Naro, Edoardo; Caringella, Anna Maria; Mastrolia, Salvatore Andrea; Vicino, Mario; Tartagni, Massimo; Schonauer, Luca Maria

2015-01-01

Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women.

Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors.

PubMed

Fukuda, Takahiro; Akiyama, Nobutake; Ikegami, Masahiro; Takahashi, Hitoshi; Sasaki, Atsushi; Oka, Hidehiro; Komori, Takashi; Tanaka, Yuko; Nakazato, Youichi; Akimoto, Jiro; Tanaka, Masahiko; Okada, Yoshikazu; Saito, Saburo

2010-05-01

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Cytogenetically confirmed primary Ewing's sarcoma of the pancreas.

PubMed

Golhar, Ankush; Ray, Samrat; Haugk, Beate; Singhvi, Suresh Kumar

2017-05-04

Ewing's sarcoma is a highly aggressive malignant tumour most commonly affecting long bones in children and adolescents. It is part of the Ewing's sarcoma family of tumours (ESFTs) that also include peripheral primitive neuroectodermal tumour and Askin's tumours. ESFTs share common cytogenetic aberrations, antigenic profiles and proto-oncogene expression with an overall similar clinical course. In 99% of ESFTs, genetic translocation with molecular fusion involves the EWSR1 gene on 22q12. Approximately 30% of ESFTs are extraosseous, most commonly occurring in the soft tissues of extremities, pelvis, retroperitoneum and chest wall. Primary presentation in solid organs is very rare but has been described in multiple sites including the pancreas. Accurate diagnosis of a Ewing's sarcoma in a solid organ is critical in facilitating correct treatment. We report the case of a 17-year-old girl with cytogenetically confirmed primary pancreatic Ewing's sarcoma and provide a brief review of the published literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

PubMed

Marinova, L; Hristozova, I; Mihaylova, I; Perenovska, P

2015-07-01

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Primary Ewing's sarcoma of vulva: a case report and a review of the literature.

PubMed

Che, Shao-Min; Cao, Pei-Long; Chen, Hong-Wei; Liu, Zi; Meng, Du

2013-03-01

Ewing sarcomas/peripheral primitive neuroectodermal tumors (ES/pPNET) are extremely rare in the vulva. A review of the literature reveals only 14 previously reported possible cases. Here we reported a case of primary extraskeletal Ewing's sarcoma (EES) of the vulva in a 37-year-old woman. Characteristic histologic features of ES/pPNET were present in this case, including a monomorphic population of small round blue cells with cytoplasmic glycogen confirmed by periodic acid-Schiff, membrane staining with CD99 and nuclear staining with FLI-1. After surgery, the patient was found to have pulmonary metastasis and then received six cycles of polychemotherapy. She is still alive with stable disease after 1 year of follow up. Our findings underline the crucial role of immunohistochemical techniques in the differential diagnosis of small round cell tumors in these unusual locations. We also give a summary about the clinical and pathological features of the primary ES/pPNET in the vulva reported previously in the literature. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors in children and adolescents.

PubMed

Magro, Gaetano; Salvatorelli, Lucia; Alaggio, Rita; D'Agata, Velia; Nicoletti, Ferdinando; Di Cataldo, Andrea; Parenti, Rosalba

2017-02-01

Small round blue cell tumors (SRBCTs) of children and adolescents are often diagnostically challenging lesions. With the increasing diagnostic approach based on small biopsies, there is the need of specific immunomarkers that can help in the differential diagnosis among the different tumor histotypes to assure the patient a correct diagnosis for proper treatment. Based on our recent studies showing cyclin D1 overexpression in both Ewing sarcoma/primitive peripheral neuroectodermal tumor (EWS/pPNET) and peripheral neuroblastic tumors (neuroblastoma and ganglioneuroblastoma), we immunohistochemically assessed cyclin D1 immunoreactivity in 128 cases of SRBCTs in children and adolescents to establish its potential utility in the differential diagnosis. All cases of EWS/pPNET and the undifferentiated/poorly differentiated neuroblastomatous component of all peripheral neuroblastic tumors exhibited strong and diffuse nuclear staining (>50% of neoplastic cells) for cyclin D1. In contrast, this marker was absent from rhabdomyosarcoma (regardless of subtype) and lymphoblastic lymphoma (either B- or T-cell precursors), whereas it was only focally detected (<5% of neoplastic cells) in some cases of Wilms tumor (blastemal component) and desmoplastic small round cell tumor. Our findings suggest that cyclin D1 can be exploitable as a diagnostic adjunct to conventional markers in confirming the diagnosis of EWS/pPNET or neuroblastoma/ganglioneuroblastoma. Its use in routine practice may also be helpful for those cases of SRBCT with undifferentiated morphology that are difficult to diagnose after application of the conventional markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review.

PubMed

Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-02-01

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum

PubMed Central

Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-01-01

Abstract Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID:26886614

Primitive neuroectodermal tumor of the cervix uteri. A case report.

PubMed

Horn, L C; Fischer, U; Bilek, K

1997-02-01

Primitive neuroectodermal tumors (PNET) of the female genital tract are rare and more common in the ovary, but uncommon in the cervix uteri. A 26-year-old woman presented with suspect cervical smears. The conization specimen showed a small cell non-keratinised squamous cell carcinoma with involved margins. The patient underwent radical abdominal hysterectomy and pelvic lymphonodectomy. The microscopic examination showed a densely cellular tumor of small neuroendocrine cells with scanty cytoplasm and rosettes. Immunohistochemically, the cells were slightly positive for NSE and negative for S 100, GFAP, neurofilaments, squamous cell cytokeratin 1, vimentin, desmin and leukocyte common antigen. The diagnosis of PNET, stage pT1b1,N0, M0 was made. The patient underwent adjuvant pelvic radiation. Three years later, pulmonary metastases occured. Radiation therapy of the thorax and six courses of combination chemotherapy (5-FU and cis-platinium) could not prevent tumor progression. The patient died 4.2 years after diagnosis. The autopsy showed widespread lymphatic metastases and hepatic, pulmonal and skeletal metastases and a peritoneal carcinosis. The tumors are resistent to radio- and chemotherapy, and the prognosis is generally poor. Up to 15% foci of squamous or glandular differentiation occur in or adjacent to these tumors. So the authors favor the histogenesis from a pluripotent endocervical stem cell. The neuroendocrine component of mixed tumors improve the prognosis. Therefore, it is necessary to recognize this component.

Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

ClinicalTrials.gov

2017-09-27

Childhood Choroid Plexus Tumor; Childhood Ependymoblastoma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Identification of Two Candidate Tumor Suppressor Genes on Chromosome 17p13.3: Assessment of Their Roles in Breast and Ovarian Carcinogenesis.

DTIC Science & Technology

1998-08-01

has also been reported in primitive neuroectodermal tumors (19), carcinoma of the cervix uteri (20), medulloblastoma, osteosarcoma (21), astrocytoma...Knudson, A. G., Jr. Oncogenes and tumor-suppressor genes. In: W. J. Hoskins, C. A. Perez, and R. C. Young (eds.), Principles and Practice of... Young , B. D., Nakayama, K., and Steiner, D. F. Processing of wild-type and mutant proinsulin-like growth factor-IA by subtilisin-related proprotein

PDGF-C is an EWS/FLI induced transforming growth factor in Ewing Family Tumors

PubMed Central

Zwerner, Jeffrey P.; May, William A.

2013-01-01

The aberrant transcription factors associated with many human malignancies function by deregulation of tumorigenic pathways. However, identification of these pathways has come slowly. Virtually all cases of Ewing’s Sarcoma and peripheral Primitive Neuroectodermal Tumor (PNET) are associated with aberrant transcription factors which fuse amino-terminal EWS with the DNA binding moiety of an ETS transcription factor (FLI-1 in 90% of cases). Attempts to identify the downstream targets of these chimeras in the Ewing Family Tumors (EFT) on the basis of differential gene regulation have produced little association with tumor biology. As an alternative approach, we have used highly efficient retroviral systems to biologically screen cDNA derived from cells transformed by EWS/FLI-1. We have identified the recently described PDGF-C as target of EWS/ETS transcriptional deregulation. This transcriptional deregulation is specific to EWS/FLI. PDGF-C possesses substantial biologic activity in vitro and in vivo. It is expressed in EFT cell lines and in primary tumors. Within these EFT cell lines, PDGF-C expression is dependent upon EWS/FLI activity. These results suggest that PDGF-C may be a significant mediator of EWS/FLI driven oncogenesis. PMID:11313995

Extraosseous Primary Intracranial Ewing Sarcoma/peripheral Primitive Neuroectodermal Tumor: Series of Seven Cases and Review of Literature

PubMed Central

Singh, Amit Kumar; Srivastava, Arun Kumar; Pal, Lily; Sardhara, Jayesh; Yadav, Rajan; Singh, Shalini; Bhaisora, Kamlesh Singh; Das, Kuntal Kanti; Mehrotra, Anant; Sahu, Rabi Narayan; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2018-01-01

Background: The Ewing sarcoma peripheral PNET (ES-pPNET) is very rare small round cell tumour that involves the CNS as either a primary dural neoplasm or by direct extension from contiguous bone or soft tissue. Materials and Methods: Biopsy proven cases of intracranial ES/pPNET with orbital involvement operated during Jan 2010-Jan 2014 were retrospectively included and their clinical data, operative and histological findings were reviewed from institutional oncology register. Results: seven patients (4 males; 3 female) were studied with mean age at presentation of 13 years. Six patients had orbital involvement in one or other form. Surgical excision was gross total in five, near total in one, and subtotal in one patient. All patients received adjuvant therapy, only chemotherapy in 2, only Radiotherapy in four, both in one. MRI characteristics were studied in six patients. Four patients died with average survival of 33.2 months and three patients are having Progression free survival of average 23.3 months. Conclusions: The EWS-pPNET is very rare tumour and very poorly described in literature. These tumours are showing special predilection for the frontotemporal dura and erode through the flat bone of cranium like orbital roof and lateral wall of the orbit. These tumours are aggressive, multi compartmental, vascular and very rapidly growing, so missing or overlooking the primary symptoms of dural stretching/bony involvement leads to delay in management and poor outcome. PMID:29682023

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

PubMed

Jiang, Tao; Wang, Junmei; Wang, Ying; Li, Chunde

2016-08-12

Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

Primary Ewing's sarcoma/primitive neuroectodermal tumor of the ileum: case report of a 16-year-old Chinese female and literature review.

PubMed

Li, Teng; Zhang, Fang; Cao, Yarui; Ning, Shoubin; Bi, Yongmin; Xue, Weicheng; Ren, Li

2017-05-04

Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) are closely related tumors. Although soft tissue ES/PNET are common in clinical practice, they are rare in the small intestine. Because of the absence of characteristic clinical symptoms, they are easily misdiagnosed as other benign or malignant diseases. Here, we present the case of a 16-year-old female who complained of anemia and interval hematochezia. Her serum test results showed only a slight elevation of CA-125 and a low level of hemoglobin. Computer tomography and magnetic resonance imaging revealed a cystic and solid mass in the lower abdominal quadrant and pelvic region, which prompted suspicion of a malignant gastrointestinal stromal tumor of the small intestine. After resection, the tumor's histology and immunohistochemistry (positive for CD99, vimentin and synaptophysin) results suggested ES/PNET. Fluorescent in situ hybridization tests proved the breakpoint rearrangement of the EWSR1 gene in chr 22.Ultrastructural analysis revealed neurosecretory and glycogen granules in the tumor cell cytoplasm. Together, these data supported the diagnosis of a rare case of localized ES/PNET in the small intestine without adjuvant chemo- or radiotherapy. To our knowledge, this is the first report from China of a primary small bowel ES/PNET in the English-language literature. In addition, on the basis of findings from previous publications and the current case, the optimal treatment for localized gastrointestinal ES/PNET is discussed.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial.

PubMed

Cefalo, Graziella; Massimino, Maura; Ruggiero, Antonio; Barone, Giuseppe; Ridola, Vita; Spreafico, Filippo; Potepan, Paolo; Abate, Massimo E; Mascarin, Maurizio; Garrè, Maria Luisa; Perilongo, Giorgio; Madon, Enrico; Colosimo, Cesare; Riccardi, Riccardo

2014-05-01

The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days. Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m(2)/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment. Median age was 10 years (range, 2-21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%). TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile.

Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI.

PubMed

Perreault, Sébastien; Lober, Robert M; Carret, Anne-Sophie; Zhang, Guohua; Hershon, Linda; Décarie, Jean-Claude; Vogel, Hannes; Yeom, Kristen W; Fisher, Paul G; Partap, Sonia

2014-02-01

Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97% of all relapses occurred in the brain and 3% were isolated to the spine. Relapse was identified in 226 (8%) brain and 48 (4%) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care.

AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

ClinicalTrials.gov

2016-03-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Cerebral Anaplastic Astrocytoma; Childhood Cerebral Astrocytoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway Glioma

Collecting and Storing Blood and Brain Tumor Tissue Samples From Children With Brain Tumors

ClinicalTrials.gov

2017-12-11

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Newly Diagnosed Childhood Ependymoma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma

Embryonal tumor with abundant neuropil and true rosettes: a systematic literature review and report of 2 new cases.

PubMed

Alexiou, George A; Stefanaki, Kalliopi; Vartholomatos, George; Sfakianos, George; Prodromou, Neofytos; Moschovi, Maria

2013-12-01

Embryonal tumor with abundant neuropil and true rosettes has been recently defined as a distinct central nervous system embryonal neoplasm, although it was initially regarded as a subtype of central nervous system primitive neuroectodermal tumor. To date 70 cases have been reported. We have performed a literature review and we present 2 new cases. Analysis of the reported data revealed that radiotherapy, tumor excision and high-dose adjuvant chemotherapy with sequential autologous hematopoietic stem cell rescue have a prognostic significance.

Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial

PubMed Central

Cefalo, Graziella; Massimino, Maura; Ruggiero, Antonio; Barone, Giuseppe; Ridola, Vita; Spreafico, Filippo; Potepan, Paolo; Abate, Massimo E.; Mascarin, Maurizio; Garrè, Maria Luisa; Perilongo, Giorgio; Madon, Enrico; Colosimo, Cesare; Riccardi, Riccardo

2014-01-01

Background The aim of this study was to assess the objective response rate (ORR) of children and young adults with recurrent medulloblastoma/primitive neuroectodermal tumor (MB/PNET) treated with temozolomide (TMZ). The secondary purpose was to analyze the toxicity profile of TMZ when administered orally for 5 days in 3 divided daily doses every 28 days. Methods Forty-two patients with recurrent MB/PNET, aged 21 years and younger, were recruited. Patients were treated with oral TMZ. Starting doses ranged from 120 to 200 mg/m2/day based on previous treatments. A craniospinal MRI was performed prior to the first cycle of TMZ and following every 2 cycles of treatment. Results Median age was 10 years (range, 2–21 years). Forty of 42 patients were assessed for response and toxicity. The objective response rate was 42.5%: 6 patients achieved a complete response, 11 had a partial response, and 10 had stable disease. Progression-free survival rates for all patients at 6 and 12 months were 30% and 7.5%, respectively. Their median overall survival rates at 6 and 12 months were 42.5% and 17.5%, respectively. No major extrahematological effects or life-threatening events were reported. The most common grade 3/4 toxicity included thrombocytopenia (17.5%), neutropenia (7.5%), and anemia (2.5%). Conclusions TMZ proved to be an effective agent in children and young adults with MB/PNET, heavily pre-treated, with a tolerable toxicity profile. PMID:24482446

Ultrasound-guided core needle biopsy in diagnosis of abdominal and pelvic neoplasm in pediatric patients.

PubMed

Wang, Hailing; Li, Fangxuan; Liu, Juntian; Zhang, Sheng

2014-01-01

Ultrasound-guided core needle biopsy of abdominal and pelvic masses in adults has gained tremendous popularity. However, the application of the same treatment in children is not as popular because of apprehensions regarding inadequate tissues for the biopsy and accidental puncture of vital organs. Data of the application of ultrasound-guided core needle biopsy in 105 pediatric patients with clinically or ultrasound-diagnosed abdominopelvic masses were reviewed. Diagnostic procedures were conducted in our institution from May 2011 to May 2013. The biopsies were conducted on 86 malignant lesions and 19 benign lesions. 86 malignant tumors comprised neuroblastomas (30 cases), hepatoblastomas (15 cases), nephroblastomas (11 cases), and primitive neuroectodermal tumors/malignant small round cells (6 cases). Among malignant tumor cases, only a pelvic primitive neuroectodermal tumor did not receive a pathological diagnosis. Therefore, the biopsy accuracy was 98.8 % in malignant tumor. However, the biopsies for one neuroblastomas and one malignant small round cell tumor were inadequate for cytogenetic analysis. Therefore, 96.5 % of the malignant tumor patients received complete diagnosis via biopsy. 19 benign tumors comprised mature teratoma (10 cases), hemangioendothelioma (3 cases), paraganglioma (2 cases), and infection (2 cases). The diagnostic accuracy for benign neoplasm was 100 %. Five patients experienced postoperative complications, including pain (2 patients), bleeding from the biopsy site (2 patients), and wound infection (1 patient). Ultrasound-guided core needle biopsy is an efficient, minimally invasive, accurate, and safe diagnostic method that can be applied in the management of abdominal or pelvic mass of pediatric patients.

A practical approach to the clinical diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue.

PubMed

Yamaguchi, U; Hasegawa, T; Morimoto, Y; Tateishi, U; Endo, M; Nakatani, F; Kawai, A; Chuman, H; Beppu, Y; Endo, M; Kurotaki, H; Furuta, K

2005-10-01

Over 90% of Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis. To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS. Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe. One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls. Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.

A well-known lesion in an unusual location: infantile myofibroma of the eyelid: a case report and review of literature.

PubMed

Asadi Amoli, Fahimeh; Sina, Amir Hossein; Kasai, Aboulfazl; Ayan, Zahra

2010-01-01

Myofibroma is a neoplasia of myofibroblasts that can be solitary or multiple and it is found most commonly in the head & neck region including scalp, forehead, parotid region and oral cavity. In the eyelid it is rarely reported. It has a benign course in the solitary form and fatal in its multiple form. A 4 month male infant referred to Farabi hospital -the referral center for eye diseases- with a 2 month history of a mass in his eyelid with gradual enlargement with no other complaints. The only abnormal physical finding was a 2.5 cm mass in the eyelid. This mass was excised and sent to the hospital pathology laboratory. When confronting a spindle cell lesion with a nodular or multinodular growth pattern which appears biphasic due to alteration of light and dark staining areas, the surgical pathologist should think to the possibility of myofibroma. Its pattern of growth and architecture rules out the other differential diagnoses like nodular fasciitis, fibrous histiocytoma, infantile fibromatosis, and peripheral primitive neuroectodermal tumor, mesenchymal chondrosarcoma, malignant hemangiopericytoma, juvenile fibrosarcoma and poorly differentiated synovial sarcoma. In difficult cases immunohistochemical staining is helpful that is Vimentin & Actin positivity & Desmin, CK, EMA & S100 negativity.

Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum.

PubMed

Weiss, William A; Israel, Mark; Cobbs, Charles; Holland, Eric; James, C David; Louis, David N; Marks, Cheryl; McClatchey, Andrea I; Roberts, Tim; Van Dyke, Terry; Wetmore, Cynthia; Chiu, Ing-Ming; Giovannini, Marco; Guha, Abhijit; Higgins, Robert J; Marino, Silvia; Radovanovic, Ivan; Reilly, Karlyne; Aldape, Ken

2002-10-24

The Mouse Models of Cancer Consortium of the NCI sponsored a meeting of neuropathologists and veterinary pathologists in New York City in November of 2000. A rapidly growing number of genetically engineered mice (GEM) predisposed to tumors of the nervous system have led to a concomitant need for neuropathological evaluation and validation of these models. A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve. The GEM tumors were found to have many similarities and some distinct differences with respect to human disease. After review of the biology and pathology for all models presented, participants were split into groups reflective of clinical expertise in human pathology, tumor biology, neuroimaging, or treatment/intervention. Recommendations were made detailing an extensive and complete neuropathological characterization of animals. Importance was placed on including information on strains, tumor clonality, and examination for genetic mutation or altered gene expression characteristics of the corresponding human malignancy. Specific proposals were made to incorporate GEM models in emerging neuroradiological modalities. Recommendations were also made for preclinical validation of these models in cancer therapeutics, and for incorporation of surrogate markers of tumor burden to facilitate preclinical evaluation of new therapies.

RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

ClinicalTrials.gov

2015-09-28

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

ClinicalTrials.gov

2017-03-22

Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

Positron Emission Tomography Using Fluorine F 18 EF5 to Find Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Newly Diagnosed Brain Tumors

ClinicalTrials.gov

2013-01-15

Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Central Nervous System Germ Cell Tumor; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Meningeal Melanocytoma

Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

ClinicalTrials.gov

2014-06-16

Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

Radiation Is an Important Component of Multimodality Therapy for Pediatric Non-Pineal Supratentorial Primitive Neuroectodermal Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

McBride, Sean M.; Daganzo, Sally M.; Banerjee, Anuradha

Purpose: To review a historical cohort of pediatric patients with supratentorial primitive neuroectodermal tumors (sPNET), to clarify the role of radiation in the treatment of these tumors. Patients and Methods: Fifteen children aged <18 years with non-pineal sPNETs diagnosed between 1992 and 2006 were identified. Initial therapy consisted of surgical resection and chemotherapy in all patients and up-front radiotherapy (RT) in 5 patients. Five patients had RT at the time of progression, and 5 received no RT whatever. Kaplan-Meier estimates of overall survival were then calculated. Results: The median follow-up from diagnosis for all patients was 31 months (range, 0.5-165more » months) and for surviving patients was 49 months (range, 10-165). Of the 5 patients who received up-front RT, all were alive without evidence of disease at a median follow-up of 50 months (range, 25-165 months). Only 5 of the 10 patients who did not receive up-front RT were alive at last follow-up. There was a statistically significant difference in overall survival between the patient group that received up-front RT and the group that did not (p = 0.048). In addition, we found a trend toward a statistically significant improvement in overall survival for those patients who received gross total resections (p = 0.10). Conclusions: Up-front RT and gross total resection may confer a survival benefit in patients with sPNET. Local failure was the dominant pattern of recurrence. Efforts should be made to determine patients most likely to have local failure exclusively or as a first recurrence, in order to delay or eliminate craniospinal irradiation.« less

Radiological features of primitive neuroectodermal tumors in intra-abdominal and retroperitoneal regions: A series of 18 cases

PubMed Central

Zhang, Youming; Xiao, Desheng; Yin, Hongling; Long, Xueying; Li, Li; Zai, Hongyan; Chen, Minfeng; Li, Wenzheng; Sun, Lunquan

2017-01-01

Objectives To characterize the imaging and clinicopathological features of primitive neuroectodermal tumors (PNETs) arising in intra-abdominal and retroperitoneal regions. Methods Eighteen patients with histopathologically proven intra-abdominal and retroperitoneal PNET were enrolled; computed tomography was performed for all cases, and magnetic resonance imaging was performed for a single case. Typical computed tomography and magnetic resonance imaging findings, including morphology, texture and enhancement features, as well as clinicopathological characteristics and prognosis data were retrospectively analyzed. Results Of eighteen PNET patients, fifteen were male and three were female, with a median age of 36 years (range, 2–65 years). The onset of symptoms was most often nonspecific and insidious. The mean tumor diameter was 7.2 cm (range, 3.0–12.1 cm), with necrosis in fifteen cases, cystic changes in eight, partition structure in five, calcification in five, hemorrhage in two, and mural nodules in one. Contrast enhanced computed tomography showed multiple tiny feeding arteries within the masses in six cases, resulting in a crab-like appearance, and mild ring enhancement pattern in five cases. Eleven cases showed surrounding invasion and metastasis. Of the eighteen PNET cases, nine cases showed smooth, well-defined margins, and nine cases had irregular, ill-defined margins. A median survival was 10.0±1.6 months. However, chemotherapy had efficacy on patients even those with advanced disease. Conclusions Primary intra-abdominal and retroperitoneal PNETs are rare, and imaging features documented here may help the diagnosis of this severe disease. Notably, two signs present in retroperitoneal PNET tumors, including a mild ring enhancement pattern and a crab-like appearance of the tiny feeding arteries, may have the potential to help us improve the ability to make a relatively reliable diagnosis. PMID:28319177

A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh

2009-07-15

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm{sup 2} postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) withmore » a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% {+-} 5% and 52% {+-} 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.« less

Proton Radiation Therapy for Pediatric Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumors: Outcomes for Very Young Children Treated With Upfront Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez, Rachel B., E-mail: rbjimenez@partners.org; Sethi, Roshan; Depauw, Nicolas

Purpose: To report the early outcomes for very young children with medulloblastoma or supratentorial primitive neuroectodermal tumor (SPNET) treated with upfront chemotherapy followed by 3-dimensional proton radiation therapy (3D-CPT). Methods and Materials: All patients aged <60 months with medulloblastoma or SPNET treated with chemotherapy before 3D-CPT from 2002 to 2010 at our institution were included. All patients underwent maximal surgical resection, chemotherapy, and adjuvant 3D-CPT with either craniospinal irradiation followed by involved-field radiation therapy or involved-field radiation therapy alone. Results: Fifteen patients (median age at diagnosis, 35 months) were treated with high-dose chemotherapy and 3D-CPT. Twelve of 15 patients hadmore » medulloblastoma; 3 of 15 patients had SPNET. Median time from surgery to initiation of radiation was 219 days. Median craniospinal irradiation dose was 21.6 Gy (relative biologic effectiveness); median boost dose was 54.0 Gy (relative biologic effectiveness). At a median of 39 months from completion of radiation, 1 of 15 was deceased after a local failure, 1 of 15 had died from a non-disease-related cause, and the remaining 13 of 15 patients were alive without evidence of disease recurrence. Ototoxicity and endocrinopathies were the most common long-term toxicities, with 2 of 15 children requiring hearing aids and 3 of 15 requiring exogenous hormones. Conclusions: Proton radiation after chemotherapy resulted in good disease outcomes for a small cohort of very young patients with medulloblastoma and SPNET. Longer follow-up and larger numbers of patients are needed to assess long-term outcomes and late toxicity.« less

Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

PubMed Central

Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

2013-01-01

Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

131-I coupled to monoclonal antibodies as therapeutic agents for neuroectodermally derived tumors: fact or fiction?

PubMed

Kemshead, J T; Jones, D H; Lashford, L; Prichard, J; Gordon, I; Breatnach, F; Coakham, H B

1986-01-01

It has been suggested that monoclonal antibodies may be useful in targeting cytotoxic compounds to tumor cells. We have explored their use in targeting 131-I to highly radiosensitive primitive neural tumors such as neuroblastoma and pineoblastomas. Two routes of administration have been employed, intravenous and intrathecal. Our current experience in using radiolabelled antibodies is described, indicating toxicities seen and any therapeutic benefit observed. The results of the study suggest that if targeted radiation has a role in the treatment of these malignancies, it will be restricted to the eradication of small tumor masses from the body.

Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

PubMed

Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

2016-05-01

We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury. © 2016 Wiley Periodicals, Inc.

Cilengitide in Treating Children With Refractory Primary Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Lenalidomide in Treating Young Patients With Recurrent, Progressive, or Refractory CNS Tumors

ClinicalTrials.gov

2013-09-27

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Episome-generated N-myc antisense RNA restricts the differentiation potential of primitive neuroectodermal cell lines.

PubMed Central

Whitesell, L; Rosolen, A; Neckers, L M

1991-01-01

Neuroectodermal tumors of childhood provide a unique opportunity to examine the role of genes potentially regulating neuronal growth and differentiation because many cell lines derived from these tumors are composed of at least two distinct morphologic cell types. These types display variant phenotypic characteristics and spontaneously interconvert, or transdifferentiate, in vitro. The factors that regulate transdifferentiation are unknown. Application of antisense approaches to the transdifferentiation process has allowed us to explore the precise role that N-myc may play in regulating developing systems. We now report construction of an episomally replicating expression vector designed to generate RNA antisense to part of the human N-myc gene. Such a vector is able to specifically inhibit N-myc expression in cell lines carrying both normal and amplified N-myc alleles. Inhibition of N-myc expression blocks transdifferentiation in these lines, with accumulation of cells of an intermediate phenotype. A concomitant decrease in growth rate but not loss of tumorigenicity was observed in the N-myc nonamplified cell line CHP-100. Vector-generated antisense RNA should allow identification of genes specifically regulated by the proto-oncogene N-myc. Images PMID:1996098

Primary soft tissue Ewing's sarcoma of the maxillary sinus in elderly patients: presentation, management and prognosis.

PubMed

Dutta, M; Ghatak, S; Biswas, G; Sen, A

2014-06-01

Nonosseous or soft tissue Ewing's sarcoma is a rare form of Ewing's sarcoma/primitive neuroectodermal tumour that seldom affects the head and neck region. Involvement of the nose and paranasal sinuses is extremely uncommon, with only eight of such patients being reported to date, mostly affecting adolescents and young adults. To our knowledge, this study is the first comprehensive report of primary soft tissue Ewing's sarcoma involving the paranasal sinuses in an elderly patient who successfully completed treatment. We herein discuss the pathogenesis, management and factors affecting the prognosis of this rare group of tumours involving the nose and paranasal sinuses, in relation to the available literature.

Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma

ClinicalTrials.gov

2013-01-15

Childhood Burkitt Lymphoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Unspecified Childhood Solid Tumor, Protocol Specific

FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

ClinicalTrials.gov

2013-01-15

Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

"Pre-emptive strike"-the case for early treatment of hepatic sinusoidal obstruction syndrome with defibrotide.

PubMed

Rajagopal, Revathi; Phillips, Marianne B; Gottardo, Nicholas G

2018-07-01

The initial signs of hepatic sinusoidal obstruction syndrome (HSOS) can be challenging to recognize in children, especially outside the hematopoietic stem cell transplantation setting. To assist clinicians to promptly identify HSOS, the European Society for Blood and Marrow Transplantation has proposed pediatric HSOS diagnostic criteria which emphasize unexplained consumptive and transfusion-refractory thrombocytopenia. To highlight the importance of these "bellwether" early signs of HSOS and the efficacy of pre-emptive treatment with defibrotide, we describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo

Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere inmore » 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.« less

Treatment outcome and patterns of failure in patients of non-pineal supratentorial primitive neuroectodermal tumor: review of literature and clinical experience form a regional cancer center in north India.

PubMed

Biswas, Ahitagni; Mallick, Supriya; Purkait, Suvendu; Roy, Soumyajit; Sarkar, Chitra; Bakhshi, Sameer; Singh, Manmohan; Julka, Pramod Kumar; Rath, Goura Kishor

2015-07-01

Supra-tentorial primitive neuroectodermal tumors (SPNET) are high-grade, hemispheric tumors, which account for around 2-3 % of pediatric brain tumors. We herein intend to report the clinical features and treatment outcome of patients with nonpineal SPNET treated at our institute. Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed, and relevant immunohistochemistry stains were done. Overall survival (OS), recurrence-free survival (RFS) and event-free survival (EFS) were analyzed by the Kaplan-Meier product-limit method. Fifteen patients met the study criterion (male: female = 2:1). Median age at presentation was 11 years (range 3-49 years). Surgical resection was gross total in 6 (40%) and subtotal in 8 (53.33%) patients. At presentation, two patients had leptomeningeal dissemination. Radiation therapy was delivered in 11 (73.33%) patients: craniospinal irradiation in 8 (36 Gy/20 fractions/4 weeks to the craniospinal axis followed by a local boost of 20 Gy/10 fractions/2 weeks) and focal RT in 3 patients. Systemic chemotherapy (median 6 cycles; range 1-16 cycles), given in 13 (86.67%) patients, included the VAC regimen (vincristine, adriamycin, cyclophosphamide) alternating with IE (ifosfamide,etoposide). After a median follow-up of 22.6 months (mean, 24.47 months), complete response and progressive disease were noted in 8 (53.33%) and 7 (46.67%) patients, respectively. Median OS was not reached, and estimated median EFS was noted to be 4.12 years (actuarial rate of EFS at 2 years, 55.2%). Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with 6-12 cycles of an alternating regimen of VAC and IE is a reasonable treatment strategy in patients with nonpineal SPNET.

Ruptured profunda femoris aneurysm secondary to neurofibromatosis: vascular involvement in an unusual location.

PubMed

Emrecan, Bilgin; Onem, Gokhan; Susam, Ibrahim

2010-01-01

Neurofibromatosis is an autosomal dominant genetic disease characterized by abnormal growth that involves tissues of mesodermal and neuroectodermal origin. Aneurysms are rarely seen in peripheral arteries. This report presents a case of ruptured arterial aneurysm secondary to neurofibromatosis; the lesion occurred in the profunda femoris artery, a highly unusual location. Treatment of patients with ruptured arterial aneurysm secondary to neurofibromatosis may be interventional or surgical. In this case, a surgical approach was successful.

Engineered Herpes Simplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2015-11-01

lines). This is an entry receptor usually limited to lymphoid cells has not been previously identified in neuroectodermal tissue. Year 3: As a... innate and adaptive immune 327 response. However, resistance is common in vitro and therefore, to the extent that tumor cell lines 328 maintain the...Handgretinger R, et al. Innate immune 461 defense defines susceptibility of sarcoma cells to measles vaccine virus-based oncolysis. J Virol. 462 2013;87

Multimodality Treatment in Ewing's Sarcoma Family Tumors of the Maxilla and Maxillary Sinus: Review of the Literature

PubMed Central

Mamot, Christoph; Krasniqi, Fatime; Metternich, Frank

2016-01-01

The Ewing sarcoma family of tumors (ESFT) encompasses a group of highly aggressive, morphologically similar, malignant neoplasms sharing a common spontaneous genetic translocation that affect mostly children and young adults. These predominantly characteristic, small round-cell tumors include Ewing's sarcoma of the bone and soft tissue, as well as primitive neuroectodermal tumors (PNETs) involving the bone, soft tissue, and thoracopulmonary region (Askin's tumor). Extraosseous ESFTs are extremely rare, especially in the head and neck region, where literature to date consists of sporadic case reports and very small series. We hereby present a review of the literature published on ESFTs reported in the maxilla and maxillary sinus region from 1968 to 2016. PMID:27413360

Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

PubMed

Ding, Yinghui; Huang, Zhenlin; Ding, Yafei; Jia, Zhankui; Gu, Chaohui; Xue, Rui; Yang, Jinjian

2016-01-01

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible. © 2016 S. Karger AG, Basel.

ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

ClinicalTrials.gov

2014-07-07

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

A Case of Desmoplastic Small Round Cell Tumor.

PubMed

Reisner, David; Brahee, Deborah; Patel, Shweta; Hartman, Matthew

2015-08-01

Desmoplastic small round cell tumor is a rare, aggressive tumor primarily affecting young males. It is considered a childhood cancer, and is characterized by a unique chromosomal translocation which leads to failure to suppress tumor growth. It is classified as a soft tissue sarcoma, sharing some features with other small round cell tumors such as Ewing's Sarcoma and primitive neuroectodermal tumor. Typical imaging findings include multiple heterogeneous, lobular abdominal masses, which can grow very large. Often there is a dominant mass with additional peritoneal, omental, retroperitoneal and retrovesical masses. Prognosis is relatively poor with a 3 year survival rate of 50% in those treated aggressively with surgical resection, chemotherapy, and radiation therapy. The clinical presentation, imaging characteristics and pathology are discussed in regards to a recent case.

Round Cell Tumors: Classification and Immunohistochemistry.

PubMed

Sharma, Shweta; Kamala, R; Nair, Divya; Ragavendra, T Raju; Mhatre, Swapnil; Sabharwal, Robin; Choudhury, Basanta Kumar; Rana, Vivek

2017-01-01

Round cell tumors as the name suggest are comprised round cells with increased nuclear-cytoplasmic ratio. This group of tumor includes entities such as peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, neuroblastoma, hepatoblastoma, Wilms' tumor, and desmoplastic small round cell tumor. These round cells tumors are characterized by typical histological pattern, immunohistochemical, and electron microscopic features that can help in differential diagnosis. The present article describes the classification and explains the histopathology and immunohistochemistry of some important round cell tumors.

Ultrastructural findings in transplanted experimental brain tumors and their significance for the cytogenesis of such tumors.

PubMed

Mennel, H D

1988-01-01

Tumors induced by transplacental action in the spinal cord of rats were transplanted into the brains of the same rat strain. They were followed up by electron microscopy during the first ten passages. Three architectural features were detected: First pure tumor parts, second myelin breakdown and phagocytosis, and third the resulting accumulation of resting macrophages. Architecture two and three were interpreted as result of considerable phagocytotic activity of tumor cells localized within the white substance of the brain and spinal cord. Only architecture one was considered to represent proper tumor. Since this was low differentiated and partial astrocytic differentiation only occurred around vessels to remarkable extent, the thesis is put forward that these transplacentally induced tumors correspond to human primitive neuroectodermal tumors.

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serizawa, Itsuko, E-mail: s_itsuko@nirs.go.j; Kagei, Kenji; Kamada, Tadashi

2009-11-15

Purpose: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. Methods and Materials: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologicmore » grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm{sup 3} and 1,194 cm{sup 3} (median 525 cm{sup 3}). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. Results: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. Conclusions: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.« less

Tissue Elasticity Regulated Tumor Gene Expression: Implication for Diagnostic Biomarkers of Primitive Neuroectodermal Tumor

PubMed Central

Vu, Long T.; Keschrumrus, Vic; Zhang, Xi; Zhong, Jiang F.; Su, Qingning; Kabeer, Mustafa H.; Loudon, William G.; Li, Shengwen Calvin

2015-01-01

Background The tumor microenvironment consists of both physical and chemical factors. Tissue elasticity is one physical factor contributing to the microenvironment of tumor cells. To test the importance of tissue elasticity in cell culture, primitive neuroectodermal tumor (PNET) stem cells were cultured on soft polyacrylamide (PAA) hydrogel plates that mimics the elasticity of brain tissue compared with PNET on standard polystyrene (PS) plates. We report the molecular profiles of PNET grown on either PAA or PS. Methodology/Principal Findings A whole-genome microarray profile of transcriptional expression between the two culture conditions was performed as a way to probe effects of substrate on cell behavior in culture. The results showed more genes downregulated on PAA compared to PS. This led us to propose microRNA (miRNA) silencing as a potential mechanism for downregulation. Bioinformatic analysis predicted a greater number of miRNA binding sites from the 3' UTR of downregulated genes and identified as specific miRNA binding sites that were enriched when cells were grown on PAA—this supports the hypothesis that tissue elasticity plays a role in influencing miRNA expression. Thus, Dicer was examined to determine if miRNA processing was affected by tissue elasticity. Dicer genes were downregulated on PAA and had multiple predicted miRNA binding sites in its 3' UTR that matched the miRNA binding sites found enriched on PAA. Many differentially regulated genes were found to be present on PS but downregulated on PAA were mapped onto intron sequences. This suggests expression of alternative polyadenylation sites within intron regions that provide alternative 3' UTRs and alternative miRNA binding sites. This results in tissue specific transcriptional downregulation of mRNA in humans by miRNA. We propose a mechanism, driven by the physical characteristics of the microenvironment by which downregulation of genes occur. We found that tissue elasticity-mediated cytokines (TGFβ2 and TNFα) signaling affect expression of ECM proteins. Conclusions Our results suggest that tissue elasticity plays important roles in miRNA expression, which, in turn, regulate tumor growth or tumorigenicity. PMID:25774514

Clinical management of a unique case of PNET of the uterus during pregnancy, and review of the literature.

PubMed

De Nola, Rosalba; Di Naro, Edoardo; Schonauer, Luca Maria; Lucarelli, Giuseppe; Battaglia, Michele; Fiore, Maria Grazia; Mastrolia, Salvatore Andrea; Loverro, Giuseppe

2018-01-01

PNETs (primitive neuroectodermal tumors) are a family of highly malignant neoplasms characterized by small round cells of neuroepithelial origin. They usually involve bone and soft tissues, and have a higher incidence in childhood. In this case report, we describe the obstetric and oncological outcome of a huge mass diagnosed as a leiomyoma in a 39-year-old pregnant woman who complained of low back pain, dysuria, and urinary frequency at 22 weeks of gestation. During the 25th week of pregnancy, the patient was referred to our hospital at night with severe anemia and suspected hemoperitoneum. She underwent an emergency caesarean section, delivering a female fetus weighing 400 g, with an Apgar score of 7 at 1 minute and 9 at 5 minutes. During surgery, we found a huge uterine sarcoma-like metastatic tumor, invading the pelvic peritoneum and parametria bilaterally; the adnexae seemed disease-free. We performed a type B radical hysterectomy, bilateral salpingo-oophorectomy, pelvic peritonectomy, omentectomy, appendectomy, and excision of a bulky lymph node. Seven days after delivery, staging computed tomography (CT) scan demonstrated a large lombo-aortic lymph node compressing the left renal vein and we completed debulking with a second surgery, including diaphragmatic peritonectomy and excision of a huge lymph node by lombo-aortic lymphadenectomy, requiring partial reconstruction of an infiltrated renal vein. Ten days after the second surgery, echo-color Doppler showed a regular microcirculation in the left kidney. The patient was discharged after 10 days, and the baby after 1 month, both in good health.Histological examination revealed a uterine body cPNET (central primitive neuroectodermal tumor) orienting the clinical management toward chemotherapy with cisplatin and etoposide. PNETs are aggressive neoplasms, usually diagnosed at an advanced stage. Due to their low incidence, universally accepted guidelines are still unavailable. Radical surgery leaving no macroscopic residual disease is mandatory in advanced stages. A good fertility-sparing procedure can be performed only in young women at early stages of disease, when the wish for childbearing is not yet fulfilled. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Treatment of Children With Central Nervous System Primitive Neuroectodermal Tumors/Pinealoblastomas in the Prospective Multicentric Trial HIT 2000 Using Hyperfractionated Radiation Therapy Followed by Maintenance Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerber, Nicolas U., E-mail: nicolas.gerber@kispi.uzh.ch; Hoff, Katja von; Resch, Anika

Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4. Methods and Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, andmore » vincristine). Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (±standard error [SE]) were each 58% (±10%) for the entire cohort: CNS-PNET was 53% (±13); pinealoblastoma was 64% (±15%; P=.524 and P=.627, respectively). Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.« less

A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.

PubMed

Leacock, Stefanie W; Basse, Audrey N; Chandler, Garvin L; Kirk, Anne M; Rakheja, Dinesh; Amatruda, James F

2012-01-01

Ewing's sarcoma, a malignant bone tumor of children and young adults, is a member of the small-round-blue-cell tumor family. Ewing's sarcoma family tumors (ESFTs), which include peripheral primitive neuroectodermal tumors (PNETs), are characterized by chromosomal translocations that generate fusions between the EWS gene and ETS-family transcription factors, most commonly FLI1. The EWS-FLI1 fusion oncoprotein represents an attractive therapeutic target for treatment of Ewing's sarcoma. The cell of origin of ESFT and the molecular mechanisms by which EWS-FLI1 mediates tumorigenesis remain unknown, and few animal models of Ewing's sarcoma exist. Here, we report the use of zebrafish as a vertebrate model of EWS-FLI1 function and tumorigenesis. Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewing's sarcoma. The incidence of tumors increased in a p53 mutant background, suggesting that the p53 pathway suppresses EWS-FLI1-driven tumorigenesis. Gene expression profiling of the zebrafish tumors defined a set of genes that might be regulated by EWS-FLI1, including the zebrafish ortholog of a crucial EWS-FLI1 target gene in humans. Stable zebrafish transgenic lines expressing EWS-FLI1 under the control of the heat-shock promoter exhibit altered embryonic development and defective convergence and extension, suggesting that EWS-FLI1 interacts with conserved developmental pathways. These results indicate that functional targets of EWS-FLI1 that mediate tumorigenesis are conserved from zebrafish to human and provide a novel context in which to study the function of this fusion oncogene.

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma].

PubMed

Delaplace, M; Mélard, P; Perrinaud, A; Goré, C; Vergier, B; Machet, L

2011-05-01

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Renal cell carcinoma and a constitutional t(11;22)(q23;q11.2): case report and review of the potential link between the constitutional t(11;22) and cancer.

PubMed

Doyen, Jérôme; Carpentier, Xavier; Haudebourg, Juliette; Hoch, Benjamin; Karmous-Benailly, Houda; Ambrosetti, Damien; Fabas, Thibault; Amiel, Jean; Lambert, Jean-Claude; Pedeutour, Florence

2012-11-01

We observed a t(11;22)(q23-24;q11.2-12) and monosomy 3 in renal tumor cells from a 72-year-old man. The hypothesis of a primitive peripheral neuroectodermal tumor (PPNET) located in the kidney was promptly excluded: Histologically, the tumor was a clear cell renal cell carcinoma (RCC) and we did not observe an EWSR1 gene rearrangement. The constitutional origin of this alteration was established. We report on the second case of RCC in a patient with a constitutional t(11;22). The t(11;22)(q23;q11.2) is the main recurrent germline translocation in humans. Unbalanced translocation can be transmitted to the progeny and can cause Emanuel syndrome. Our observation alerts cancer cytogeneticists to the fortuitous discovery of the constitutional t(11;22) in tumor cells. This translocation appears grossly similar to the t(11;22)(q24;q12) of PPNET and should be evoked if present in all cells of a tumor other than PPNET. This is important when providing appropriate genetic counseling. Moreover, the potential oncogenic role of the t(11;22) and its predisposing risk of cancer are under debate. The family history of the patient revealed a disabled brother who died at an early age from colon cancer and a sister with breast cancer. This observation reopens the issue of a link between the constitutional t(11;22) and cancer, and the utility of cancer prevention workups for t(11;22) carriers. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical features and outcomes in patients with extraskeletal Ewing sarcoma

PubMed Central

Applebaum, Mark A.; Worch, Jennifer; Matthay, Katherine K.; Goldsby, Robert; Neuhaus, John; West, Daniel C.; DuBois, Steven G.

2010-01-01

Background Ewing sarcoma can arise in either bone or soft tissue locations. We sought to investigate if patient characteristics, treatment strategies, and outcomes differ between skeletal Ewing sarcoma and extraskeletal Ewing sarcoma (EES). Procedure Patients < 40 years of age with Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) reported to the US SEER database from 1973 to 2007 were evaluated based on skeletal (n=1519) vs. extraskeletal (n=683) site of origin. Patient characteristics were compared using Fisher exact tests. Overall survival was estimated by Kaplan-Meier methods and compared using log-rank tests and Cox models. Results Patients with EES had a higher mean age (19.5 vs. 16.3 years; p < 0.001) and were less likely to be male (53.4% vs. 63.3%; p < 0.001) or white (84.8% vs. 92.5%; p < 0.001) compared to patients with skeletal tumors. Extraskeletal tumors were more likely to arise in axial locations (72.9% vs. 54.2%; p = 0.001), though less likely to arise specifically in the pelvis (19.8% vs. 26.6%; p < 0.001). Metastatic status or tumor size did not differ by group. Five-year overall survival was superior for localized EES compared to localized skeletal tumors (69.7% vs. 62.6%; p = 0.02). The hazard ratio for death in patients with localized skeletal tumors compared to localized EES was 2.36 (95% CI 1.61-3.44) beyond 24 months from initial diagnosis. Conclusions Patient characteristics and outcomes differ among patients with EES compared to patients with skeletal Ewing sarcoma. These findings may have important implications for patient care. PMID:21692057

High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

PubMed

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

2011-03-01

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

Guidelines for imaging retinoblastoma: imaging principles and MRI standardization.

PubMed

de Graaf, Pim; Göricke, Sophia; Rodjan, Firazia; Galluzzi, Paolo; Maeder, Philippe; Castelijns, Jonas A; Brisse, Hervé J

2012-01-01

Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation.

Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC

PubMed Central

Swartling, Fredrik J.; Savov, Vasil; Persson, Anders I.; Chen, Justin; Hackett, Christopher S.; Northcott, Paul A.; Grimmer, Matthew R.; Lau, Jasmine; Chesler, Louis; Perry, Arie; Phillips, Joanna J.; Taylor, Michael D.; Weiss, William A.

2012-01-01

SUMMARY The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally-stabilized murine N-mycT58A into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem and forebrain. Transplantation of N-mycWT NSCs was insufficient for tumor formation. N-mycT58A cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating SHH-dependence and SHH-independence, respectively. These differences were regulated in-part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal. PMID:22624711

Vertebrate homologues of Frodo are dynamically expressed during embryonic development in tissues undergoing extensive morphogenetic movements.

PubMed

Hunter, Nina L; Hikasa, Hiroki; Dymecki, Susan M; Sokol, Sergei Y

2006-01-01

Frodo has been identified as a protein interacting with Dishevelled, an essential mediator of the Wnt signaling pathway, critical for the determination of cell fate and polarity in embryonic development. In this study, we use specific gene probes to characterize stage- and tissue-specific expression patterns of the mouse Frodo homologue and compare them with Frodo expression patterns in Xenopus embryos. In situ hybridization analysis of mouse Frodo transcripts demonstrates that, similar to Xenopus Frodo, mouse Frodo is expressed in primitive streak mesoderm, neuroectoderm, neural crest, presomitic mesoderm, and somites. In many cases, Frodo expression is confined to tissues undergoing extensive morphogenesis, suggesting that Frodo may be involved in the regulation of cell shape and motility. Highly conserved dynamic expression patterns of Frodo homologues indicate a similar function for these proteins in different vertebrates. 2005 Wiley-Liss, Inc.

Embryonal tumors with abundant neuropil and true rosettes: 2 illustrative cases and a review of the literature.

PubMed

Manjila, Sunil; Ray, Abhishek; Hu, Yin; Cai, Dan X; Cohen, Mark L; Cohen, Alan R

2011-01-01

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently identified variant of primitive neuroectodermal tumor, with fewer than 50 cases reported in the literature to date. Histologically, this tumor has features of ependymoblastoma and neuroblastoma, demonstrating areas of fine fibrillary neuropil intermingled with ependymoblastic rosettes and zones of undifferentiated neuroepithelial cells. However, ETANTR is distinguished pathologically from other embryonal tumors by the striking abundance of neuropil. Clinically, ETANTRs have shown high malignant potential and poor clinical outcome despite aggressive treatment. The authors describe 2 illustrative surgical cases of ETANTR, one involving the longest reported survival in the literature to date. The other had a poor outcome despite high-dose adjuvant chemotherapy with sequential autologous hematopoietic stem cell rescue. The authors review the natural history and treatment strategies available for this unusual malignant pediatric brain tumor.

Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor.

PubMed

Folpe, A L; Hill, C E; Parham, D M; O'Shea, P A; Weiss, S W

2000-12-01

The histologic and immunohistochemical differentiation of Ewing' s sarcoma/primitive neuroectodermal tumor (ES/PNET) from other small, blue, round cell tumors may be difficult. Despite initial promise, CD99 (MIC2) has not proven to be a specific marker. Approximately 90% of ES/PNET have a specific t(11; 22)(q24;q12) that results in fusion of the EWS and FLI-1 genes, and overexpression of FLI-1 protein. A recent study has shown immunohistochemical FLI-1 expression in five of seven of the ES/PNET cases tested. We evaluated FLI-1 expression in 132 well-characterized small, blue, round cell tumors. All tumors were immunostained for FLI-1 (1:40, Sc 356 polyclonal, Santa Cruz Biotechnology) using steam heat for epitope retrieval. Only nuclear staining was accepted as positive. Endothelial cells were strongly positive in all cases and served as an internal control. In many cases, a subset of lymphocytes also stained positive. No staining was seen in any other normal tissue. FLI-1 expression was seen in 29 of 41 (71%) ES/PNET, 7 of 8 (88%) lymphoblastic lymphomas, 0 of 8 poorly differentiated synovial sarcomas (PDSS), 0 of 32 rhabdomyosarcoma (RMS), 0 of 30 neuroblastomas, 0 of 8 esthesioneuroblastomas, 0 of 3 Wilms' tumors, 0 of 1 mesenchymal chondrosarcoma, and in 1 of 1 desmoplastic round cell tumor. This last case was known to have an EWS/WT-1 fusion. Although the EWS/FLI-1 fusion gene is specific for ES/PNET, FLI-1 protein expression is not. Significantly, the great majority of lymphoblastic lymphomas (also CD99-positive) are strongly FLI-1-positive. Immunohistochemical detection of FLI-1 may be valuable in confirming the diagnosis of ES/ PNET in cases in which molecular genetic evaluation is not feasible. FLI-1 protein expression is also helpful in distinguishing ES/PNET from other tumors that may be CD99-positive, such as PDSS and RMS. It is not surprising that some ES/ PNET are FLI-1-negative, because not all ES/PNET have the classic EWS/FLI-1, and some cases of ES/PNET may produce either low levels of protein or idiotypically different protein.

Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost

PubMed Central

Kurokawa, Daisuke; Sakurai, Yusuke; Inoue, Ai; Nakayama, Rika; Takasaki, Nobuyoshi; Suda, Yoko; Miyake, Tsutomu; Amemiya, Chris T.; Aizawa, Shinichi

2006-01-01

Otx2 is a paired type homeobox gene that plays essential roles in each step and site of head development in vertebrates. In the mouse, Otx2 expression in the anterior neuroectoderm is regulated primarily by two distinct enhancers: anterior neuroectoderm (AN) and forebrain/midbrain (FM) enhancers at 92 kb and 75 kb 5′of the Otx2 locus, respectively. The AN enhancer has activity in the entire anterior neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm. In tetrapods, both AN and FM enhancers are conserved, whereas the AN region is missing in teleosts, despite overt Otx2 expression in the anterior neuroectoderm. Here, we show that zebrafish and fugu FM regions drive expression not only in the forebrain and midbrain but also in the anterior neuroectoderm at headfold stage. The analysis of coelacanth and skate genomic Otx2 orthologues suggests that the utilization of the two enhancers, AN and FM, is an ancestral condition. In contrast, the AN enhancer has been specifically lost in the teleost lineage with a compensatory establishment of AN activity within the FM enhancer. Furthermore, the AN activity in the fish FM enhancer was established by recruiting upstream factors different from those that direct the tetrapod AN enhancer, yet zebrafish FM enhancer is active in both mouse and zebrafish anterior neuroectoderm at the headfold stage. PMID:17159156

Hanging drop culture enhances differentiation of human adipose-derived stem cells into anterior neuroectodermal cells using small molecules.

PubMed

Amirpour, Noushin; Razavi, Shahnaz; Esfandiari, Ebrahim; Hashemibeni, Batoul; Kazemi, Mohammad; Salehi, Hossein

2017-06-01

Inspired by in vivo developmental process, several studies were conducted to design a protocol for differentiating of mesenchymal stem cells into neural cells in vitro. Human adipose-derived stem cells (hADSCs) as mesenchymal stem cells are a promising source for this purpose. At current study, we applied a defined neural induction medium by using small molecules for direct differentiation of hADSCs into anterior neuroectodermal cells. Anterior neuroectodermal differentiation of hADSCs was performed by hanging drop and monolayer protocols. At these methods, three small molecules were used to suppress the BMP, Nodal, and Wnt signaling pathways in order to obtain anterior neuroectodermal (eye field) cells from hADSCs. After two and three weeks of induction, the differentiated cells with neural morphology expressed anterior neuroectodermal markers such as OTX2, SIX3, β-TUB III and PAX6. The protein expression of such markers was confirmed by real time, RT-PCR and immunocytochemistry methods According to our data, it seems that the hanging drop method is a proper approach for neuroectodermal induction of hADSCs. Considering wide availability and immunosuppressive properties of hADSCs, these cells may open a way for autologous cell therapy of neurodegenerative disorders. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

PubMed

Vallat, J-M

2014-10-01

In most dysimmune neuropathies, historically the microscopical lesions were described prior to immunological studies. The latter along with neuropathological studies have found some immune, albeit incomplete, explanations of the mechanisms of these lesions which we will describe in two main syndromes: the primitive auto-immune inflammatory peripheral polyneuropathies (GBS and CIDP) and polyneuropathies induced by a monoclonal dysglobulinemia. In some patients who have to be discussed case by case pathology (nerve biopsy) will confirm the diagnosis, may help to delineate the molecular anomalies and identify lesional mechanisms. We will review the high variability of nerve lesions which is characteristic of dysimmune neuropathies. Pathological studies confirm that both humoral and cellular immune reactions against Schwann cell and/or axonal antigens are implicated in primitive dysimmune neuropathies due to a dysfunction or failure of immune tolerance mechanisms. In case of a polyneuropathy associated to a monoclonal dysglobulinemia, pathological and immunological studies have shown that in many patients, the dysglobulinemia did harm the peripheral nerve; knowledge of the pathological lesions and their mechanisms is of major interest for orienting specific treatments. Copyright © 2014. Published by Elsevier Masson SAS.

Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

PubMed

Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

2013-09-15

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

ClinicalTrials.gov

2013-05-01

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

PubMed

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary Ewing Sarcoma of the Thyroid—Eight Cases in a Decade: A Case Report and Literature Review

PubMed Central

Kabata, Paweł; Kaniuka-Jakubowska, Sonia; Kabata, Wanda; Lakomy, Joanna; Biernat, Wojciech; Sworczak, Krzysztof; Jaśkiewicz, Janusz; Świerblewski, Maciej

2017-01-01

Sarcomas represent less than 1% of all malignant tumors found in the thyroid. Of these, primary extraosseoussarcoma has been reported only a few times in the past decade. We present the case of a 34-year-old male who had a fast-growing hard mass in the lower left neck. FNA was inconclusive. Core needle biopsy revealed the diagnosis of an Ewing sarcoma/primitive neuroectodermal tumor. Mutation of EWSR1 was confirmed using the FISH method. Following treatment by neoadjuvant chemotherapy, we observed clinical, radiological, and finally histopathological remission. This was followed by a left-sided isthmolobectomy with unilateral cervical lymph node dissection by lateral lymphadenectomy, which revealed no residual disease. Posttreatment radiotherapy was administered but discontinued upon the patient’s request. After 18 months of observation, the patient had no recurrence or metastasis and required l-thyroxine supplementation. We discuss our case using a comparative literature review to the few other known case reports. PMID:29163353

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

Skull base bony lesions: Management nuances; a retrospective analysis from a Tertiary Care Centre

PubMed Central

Singh, Amit Kumar; Srivastava, Arun Kumar; Sardhara, Jayesh; Bhaisora, Kamlesh Singh; Das, Kuntal Kanti; Mehrotra, Anant; Sahu, Rabi Narayan; Jaiswal, Awadhesh Kumar; Behari, Sanjay

2017-01-01

Background: Skull base lesions are not uncommon, but their management has been challenging for surgeons. There is large no of bony tumors at the skull base which has not been studied in detail as a group. These tumors are difficult not only because of their location but also due to their variability in the involvement of important local structure. Through this retrospective analysis from a Tertiary Care Centre, we are summarizing the details of skull base bony lesions and its management nuances. Materials and Methods: The histopathologically, radiologically, and surgically proven cases of skull base bony tumors or lesions involving bone were analyzed from the neurosurgery, neuropathology record of our Tertiary Care Institute from January 2009 to January 2014. All available preoperative and postoperative details were noted from their case files. The extent of excision was ascertained from operation records and postoperative magnetic resonance imaging if available. Results: We have surgically managed 41 cases of skull base bony tumors. It includes 11 patients of anterior skull base, 13 middle skull base, and 17 posterior skull base bony tumors. The most common bony tumor was chordoma 15 (36.6%), followed by fibrous dysplasia 5 (12.2%), chondrosarcoma (12.2%), and ewings sarcoma-peripheral primitive neuroectodermal tumor (EWS-pPNET) five cases (12.2%) each. There were more malignant lesions (n = 29, 70.7%) at skull base than benign (n = 12, 29.3%) lesions. The surgical approach employed depended on location of tumor and pathology. Total mortality was 8 (20%) of whom 5 patients were of histological proven EWS-pPNET. Conclusions: Bony skull base lesion consists of wide variety of lesions, and requires multispecialty management. The complex lesions required tailored approaches surgery of these lesions. With the advent of microsurgical and endoscopic techniques, and use of navigation better outcomes are being seen, but these lesions require further study for development of proper management plan. PMID:28761532

Evidence of Mobilization of Pluripotent Stem Cells into Peripheral Blood of Patients with Myocardial Ischemia

PubMed Central

Abdel-Latif, Ahmed; Zuba-Surma, Ewa K.; Ziada, Khaled M.; Kucia, Magdalena; Cohen, Donald A.; Kaplan, Alan M.; Zant, Gary Van; Selim, Samy; Smyth, Susan S.; Ratajczak, Mariusz Z.

2010-01-01

Objective The ischemic myocardium releases multiple chemotactic factors responsible for the mobilization and recruitment of bone marrow-derived cells to injured myocardium. However, the mobilization of primitive pluripotent stem cells (PSCs) enriched in Very Small Embryonic-Like stem cells (VSELs) in various cardiac ischemic scenarios is not well understood. Methods Fifty four ischemic heart disease patients, including subjects with stable angina, non-ST elevation (NSTME) myocardial infarction (MI) and ST elevation myocardial infarction (STEMI), and twelve matched controls were enrolled. The absolute numbers of circulating stem/primitive cells in samples of peripheral blood (PB) were quantitated by Image Stream Analysis and conventional flow cytometry. Gene expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4), and endothelial (vWF) markers was analyzed by real-time PCR. Results The absolute numbers of PSCs, stem cell populations enriched in VSELs and hematopoietic stem cells (HSCs) present in PB were significantly higher in STEMI patients at presentation and declined over time. There was a corresponding increase in pluripotent, cardiac and endothelial gene expression in unfractionated PB cells and sorted PB-derived primitive CD34+ cells. The absolute numbers of circulating VSELs and HSCs in STEMI correlated negatively with patients' age. Conclusions Myocardial ischemia mobilizes primitive PSCs including pluripotent VSELs into the circulation. The peak of mobilization occurs within 12 hours in patients presenting with STEMI, which may represent a therapeutic window for future clinical applications. Reduced stem cell mobilization with advancing age could explain, in part, the observation that age is associated with poor prognosis in patients with MI. PMID:20800644

Nucleosome eviction along with H3K9ac deposition enhances Sox2 binding during human neuroectodermal commitment

PubMed Central

Du, Yanhua; Liu, Zhenping; Cao, Xinkai; Chen, Xiaolong; Chen, Zhenyu; Zhang, Xiaobai; Zhang, Xiaoqing; Jiang, Cizhong

2017-01-01

Neuroectoderm is an important neural precursor. However, chromatin remodeling and its epigenetic regulatory roles during the differentiation of human neuroectodermal cells (hNECs) from human embryonic stem cells (hESCs) remain largely unexplored. Here, we obtained hNECs through directed differentiation from hESCs, and determined chromatin states in the two cell types. Upon differentiation, H2A.Z-mediated nucleosome depletion leads to an open chromatin structure in promoters and upregulates expression of neuroectodermal genes. Increase in H3K9ac signals and decrease in H3K27me3 signals in promoters result in an active chromatin state and activate neuroectodermal genes. Conversely, decrease in H3K9ac signals and increase in H3K27me3 signals in promoters repress pluripotency genes. Moreover, H3K9ac signals facilitate the pluripotency factor Sox2 binding to target sites unique to hNECs. Knockdown of the acetyltransferase Kat2b erases H3K9ac signals, disrupts Sox2 binding, and fails the differentiation. Our results demonstrate a hierarchy of epigenetic regulation of gene expression during the differentiation of hNECs from hESCs through chromatin remodeling. PMID:28475175

[Neurofibromatosis type 2 in childhood: a clinical characterization].

PubMed

Hinojosa-Mateo, C M; Reche-Sainz, J A; Hernandez-Nunez, A; Ramos-Lopez, M; Arpa-Fernandez, A; Natera-de Benito, D

2017-02-01

Neurofibromatosis type 2 (NF2) is a dominantly inherited neuroectodermal syndrome that predispose to the development of tumors of the central and peripheral nervous system. Additional features include eye and skin abnormalities. A 12-year old male with diagnosis of MF2 according to Baser et al and presentation in childhood was included. A comprehensive bibliographic review of evolution of the diagnostic criteria for NF2 in children was performed. The pattern of presentation of NF2 in childhood differs from adulthood in many aspects. Ophthalmologic and skin manifestations, and not an auditory dysfunction, are the most common initial symptoms in prepuberal-onset NF2. The most frequent symptoms and signs at presentation are posterior subcapsular cataract, skin manifestations as NF2 plaques and/or peripheral nerve tumors, and neurological dysfunction related to isolated or multiple cranial nerve deficits (other than nerve VIII), brainstem masses or spinal masses. As sensitivity of diagnostic criteria in children is low, those prepuberal patients with congenital or early-onset cataracts and typical skin manifestations of NF2 should be systematically assessed.

Antigen tissue distribution of Avian bornavirus (ABV) in psittacine birds with natural spontaneous proventricular dilatation disease and ABV genotype 1 infection.

PubMed

Wünschmann, Arno; Honkavuori, Kirsi; Briese, Thomas; Lipkin, W Ian; Shivers, Jan; Armien, Aníbal G

2011-07-01

Tissues of 10 psittacines from aviary 1 ("case birds") and 5 psittacines from different aviaries were investigated for the presence of Avian bornavirus (ABV) antigen by immunohistochemistry using a polyclonal serum specific for the viral nucleocapsid (N) protein. Seven of 10 case birds had clinical signs, and necropsy findings consistent with proventricular dilatation disease (PDD) while 3 case birds and the 5 birds from other aviaries did not exhibit signs and lesions of this disease. In birds with clinical signs of PDD, ABV antigen was largely limited to neuroectodermal cells including neurons, astroglia, and ependymal cells of the central nervous system, neurons of the peripheral nervous system, and adrenal cells. ABV antigen was present in the nuclei and cytoplasm of infected cells. In 2 case birds that lacked signs and lesions of PDD, viral antigen had a more widespread distribution and was present in nuclei and cytoplasm of epithelial cells of the alimentary and urogenital tract, retina, heart, skeletal muscle, and skin in addition to the mentioned neuroectodermal cells. ABV RNA was identified by reverse transcription polymerase chain reaction (RT-PCR) in tissues of all 7 case birds available for testing from aviary 1, including 4 birds with PDD lesions and the 3 birds without PDD lesions. Sequencing and phylogenetic analysis indicated the presence of ABV genotype 1 in all cases. Findings further substantiate a role of ABV in PDD of psittacine bird species.

Antigen tissue distribution of Avian bornavirus (ABV) in psittacine birds with natural spontaneous proventricular dilatation disease and ABV genotype 1 infection

PubMed Central

Wünschmann, Arno; Honkavuori, Kirsi; Briese, Thomas; Lipkin, W. Ian; Shivers, Jan; Armien, Aníbal G.

2014-01-01

Tissues of 10 psittacines from aviary 1 (“case birds”) and 5 psittacines from different aviaries were investigated for the presence of Avian bornavirus (ABV) antigen by immunohistochemistry using a polyclonal serum specific for the viral nucleocapsid (N) protein. Seven of 10 case birds had clinical signs, and necropsy findings consistent with proventricular dilatation disease (PDD) while 3 case birds and the 5 birds from other aviaries did not exhibit signs and lesions of this disease. In birds with clinical signs of PDD, ABV antigen was largely limited to neuroectodermal cells including neurons, astroglia, and ependymal cells of the central nervous system, neurons of the peripheral nervous system, and adrenal cells. ABV antigen was present in the nuclei and cytoplasm of infected cells. In 2 case birds that lacked signs and lesions of PDD, viral antigen had a more widespread distribution and was present in nuclei and cytoplasm of epithelial cells of the alimentary and urogenital tract, retina, heart, skeletal muscle, and skin in addition to the mentioned neuroectodermal cells. ABV RNA was identified by reverse transcription polymerase chain reaction (RT-PCR) in tissues of all 7 case birds available for testing from aviary 1, including 4 birds with PDD lesions and the 3 birds without PDD lesions. Sequencing and phylogenetic analysis indicated the presence of ABV genotype 1 in all cases. Findings further substantiate a role of ABV in PDD of psittacine bird species. PMID:21908314

Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

ClinicalTrials.gov

2013-07-01

Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

Embryonal tumor with abundant neuropil and true rosettes: an autopsy case-based update and review of the literature.

PubMed

Adamek, Dariusz; Sofowora, Kolawole D; Cwiklinska, Magdalena; Herman-Sucharska, Izabela; Kwiatkowski, Stanislaw

2013-05-01

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare subtype of primitive neuroectodermal tumors first reported in 2000. It is rare among the group of embryonal central nervous system tumors with approximately 50 reported cases. ETANTR has been suggested to be a separate entity among this group of tumors. Herein, we present only the second autopsy case of ETANTR, which occurred in a 17-month-old boy, and was located in the brainstem. The tumor was inoperable, and despite chemotherapy, the child died 3 months after initial hospitalization. A brain only autopsy was performed. Neuropathological and neuroimaging examinations suggest ETANTR grew by expansion rather than invasion distorting anatomical structures of the posterior fossa. We suggest that the characteristic histopathological picture of the tumor is the result of multifocal and dispersed germinative activity surrounded by mature neuropil-like areas. ETANTR is a pediatric tumor occurring in children under 4 with a significantly poor prognosis with more cases and research required to characterize this rare embryonal tumor.

Differential expression of two scribble isoforms during Drosophila embryogenesis.

PubMed

Li, M; Marhold, J; Gatos, A; Török, I; Mechler, B M

2001-10-01

The tumour suppressor gene scribble (scrib) is required for epithelial polarity and growth control in Drosophila. Here, we report the identification and embryonic expression pattern of two Scrib protein isoforms resulting from alternative splicing during scrib transcription. Both proteins are first ubiquitously expressed during early embryogenesis. Then, during morphogenesis each Scrib protein displays a specific pattern of expression in the central and peripheral nervous systems, CNS and PNS, respectively. During germ band extension, the expression of the longer form Scrib1 occurs predominantly in the neuroblasts derived from the neuro-ectoderm and becomes later restricted to CNS neurones as well as to the pole cells in the gonads. By contrast, the shorter form Scrib2 is strongly expressed in the PNS and a subset of CNS neurones.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis.

PubMed

Lamming, Christopher E D; Augustin, Lance; Blackstad, Mark; Lund, Troy C; Hebbel, Robert P; Verfaillie, Catherine M

2003-03-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.

Incidence and survival of children with central nervous system primitive tumors in the French National Registry of Childhood Solid Tumors.

PubMed

Desandes, Emmanuel; Guissou, Sandra; Chastagner, Pascal; Lacour, Brigitte

2014-07-01

Central nervous system (CNS) tumors are the second most common childhood malignancy. The French National Registry of Childhood Solid Tumors (NRCST) makes it possible to describe this variety of distinct tumor types and to provide incidence and survival data in France on a nationwide basis. All children aged 0-14 years, who were registered with a primary CNS tumor in the NRCST of France between 2000 and 2008, were identified. Tumors were classified according to the International Classification of Childhood Cancer, third edition. Approximately 57% of pediatric CNS tumors were gliomas, with astrocytomas of the pilocytic type predominating. Distributions of subtypes by age showed that primitive neuroectodermal tumors and ependymomas mainly occurred in children aged <5 years. The mean annual incidence rate of CNS tumors was 39 per million. No statistically significant change in time trends of incidence rate was observed during 2000-2008. For all tumors combined, overall survival was 84.8% (95% CI, 83.7%-85.9%) at 1 year and 72.9% (95% CI, 71.5%-74.3%) at 5 years. Survival time trends were studied in a multivariate analysis observing a reduction in the risk of death in periods of diagnosis 2003-2005 (HR = 0.8; 95% CI, 0.7–0.9) and 2006-2008 (HR = 0.7; 95% CI, 0.6-0.9) compared with 2000-2002. The stable incidence rates during the last 10 years could indicate that major changes in environmental risk factors are unlikely, but the ongoing need for population-based surveillance remains relevant. Results indicate a positive trend in the survival probability still persistent in the 2000s.

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

PubMed

Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

2003-01-01

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we strongly suggest that the final interpretation of the results from this assay be viewed in light of the other features of the case, including clinical history, histology, and immunohistochemistry, by the diagnostic pathologist. Additional studies such as FISH may be useful in clarifying the nature of equivocal or unexpected results.

PAX3-FOXO1 transgenic zebrafish models identify HES3 as a mediator of rhabdomyosarcoma tumorigenesis.

PubMed

Kendall, Genevieve C; Watson, Sarah; Xu, Lin; LaVigne, Collette A; Murchison, Whitney; Rakheja, Dinesh; Skapek, Stephen X; Tirode, Franck; Delattre, Olivier; Amatruda, James F

2018-06-05

Alveolar rhabdomyosarcoma is a pediatric soft-tissue sarcoma caused by PAX3/7-FOXO1 fusion oncogenes and is characterized by impaired skeletal muscle development. We developed human PAX3-FOXO1 -driven zebrafish models of tumorigenesis and found that PAX3-FOXO1 exhibits discrete cell lineage susceptibility and transformation. Tumors developed by 1.6-19 months and were primitive neuroectodermal tumors or rhabdomyosarcoma. We applied this PAX3-FOXO1 transgenic zebrafish model to study how PAX3-FOXO1 leverages early developmental pathways for oncogenesis and found that her3 is a unique target. Ectopic expression of the her3 human ortholog, HES3 , inhibits myogenesis in zebrafish and mammalian cells, recapitulating the arrested muscle development characteristic of rhabdomyosarcoma. In patients, HES3 is overexpressed in fusion-positive versus fusion-negative tumors. Finally, HES3 overexpression is associated with reduced survival in patients in the context of the fusion. Our novel zebrafish rhabdomyosarcoma model identifies a new PAX3-FOXO1 target, her3 / HES3 , that contributes to impaired myogenic differentiation and has prognostic significance in human disease. © 2018, Kendall et al.

MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons

PubMed Central

Shalaby, Tarek; Fiaschetti, Giulio; Baumgartner, Martin; Grotzer, Michael A.

2014-01-01

Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets. PMID:25421247

TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

PubMed

Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

2017-09-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

A case-control study of childhood brain tumors and fathers' hobbies: a Children's Oncology Group study.

PubMed

Rosso, Andrea L; Hovinga, Mary E; Rorke-Adams, Lucy B; Spector, Logan G; Bunin, Greta R

2008-12-01

A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers' hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Cases were 318 subjects under six years of age at diagnosis between 1991 and 1997 and registered with the Children's Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures.

A CASE-CONTROL STUDY OF CHILDHOOD BRAIN TUMORS AND FATHERS’ HOBBIES — A CHILDREN’S ONCOLOGY GROUP STUDY

PubMed Central

Rosso, Andrea L.; Hovinga, Mary E.; Rorke-Adams, Lucy B.; Spector, Logan G.; Bunin, Greta R.

2009-01-01

Objective A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers’ hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Methods Cases were 318 subjects under 6 years of age at diagnosis between 1991-1997 and registered with the Children’s Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. Results In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. Conclusions This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures. PMID:18560982

Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis

PubMed Central

Lamming, Christopher E.D.; Augustin, Lance; Blackstad, Mark; Lund, Troy C.; Hebbel, Robert P.; Verfaillie, Catherine M.

2003-01-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid–initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture–initiating cells, consistent with the notion that SRCs are more primitive than long-term culture–initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation. PMID:12639987

[The value of immunohistochemistry using SMARCA4/BRG1 in the diagnosis of small cell ovarian carcinoma hypercalcemic type. A report of two cases].

PubMed

Ruiz-García, Gema; Torroba-Carón, M Amparo; Ferri-Ñíguez, Belén; Lencina-Guardiola, Miriam; García-Molina, Francisco; Martínez-Barba, Enrique

Small cell carcinoma of ovary-hypercalcemic type is an undifferentiated carcinoma. We describe two cases in women aged 32 and 29. Both presented with large masses and complete surgical extirpation was impossible. Histologically, the images were similar, with diffuse cell proliferation, accompanied by the presence of follicle-like spaces. In both cases it was necessary to make a differential diagnosis with entities such as adult or juvenile granulosa cell tumour, small cell carcinoma of pulmonary type, dysgerminoma and even peripheral neuroectodermal tumour. The absence of SMARCA4/BRG1 immunostaining proved very useful in the diagnosis of hypercalcemic small cell ovarian carcinoma. Copyright © 2017 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Elicitation and abrupt termination of behaviorally significant catchlike tension in a primitive insect.

PubMed

Hoyle, G; Field, L H

1983-07-01

Sustained steady contractural or catchlike tension (CT) occurs in the metathoracic extensor tibiae muscle of the primitive insect the weta (Orthoptera: Stenopelmatidae) during its characteristic leg-extension defense behavior or following leg-position conditioning. Similar action occurs occasionally in semi-intact preparations and is abruptly turned off by a single peripheral inhibitory impulse. These phenomena were reproduced routinely by first infusing saline containing 10(-8) M (or stronger) octopamine into the muscle for 12 min, and then stimulating the slow excitatory motor neuron SETi with a brief burst. Direct stimulation of the dorsal unpaired median neuron, innervating the extensor tibiae (DUMETi) prior to SETi stimulation, also led to CT. Both octopamine and DUMETi markedly enhanced the tension developed in response to a burst of impulses in SETi.

Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

PubMed Central

Tsujimura, Tohru; Makiishi-Shimobayashi, Chiaki; Lundkvist, Johan; Lendahl, Urban; Nakasho, Keiji; Sugihara, Ayako; Iwasaki, Teruo; Mano, Masayuki; Yamada, Naoko; Yamashita, Kunihiro; Toyosaka, Akihiro; Terada, Nobuyuki

2001-01-01

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. PMID:11238030

Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

PubMed Central

Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

2014-01-01

Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the conventional treatment. PMID:25478446

Commissioning of the upgraded CSC Endcap Muon Port Cards at CMS

NASA Astrophysics Data System (ADS)

Ecklund, K.; Liu, J.; Madorsky, A.; Matveev, M.; Michlin, B.; Padley, P.; Rorie, J.

2016-01-01

There are 180 1.6 Gbps optical links from 60 Muon Port Cards (MPC) to the Cathode Strip Chamber Track Finder (CSCTF) in the original system. Before the upgrade each MPC was able to provide up to three trigger primitives from a cluster of nine CSC chambers to the Level 1 CSCTF. With an LHC luminosity increase to 1035 cm-2s-1 at full energy of 7 TeV/beam, the simulation studies suggest that we can expect two or three times more trigger primitives per bunch crossing from the front-end electronics. To comply with this requirement, the MPC, CSCTF, and optical cables need to be upgraded. The upgraded MPC allows transmission of up to 18 trigger primitives from the peripheral crate. This feature would allow searches for physics signatures of muon jets that require more trigger primitives per trigger sector. At the same time, it is very desirable to preserve all the old optical links for compatibility with the older Track Finder during transition period at the beginning of Run 2. Installation of the upgraded MPC boards and the new optical cables has been completed at the CMS detector in the summer of 2014. We describe the final design of the new MPC mezzanine FPGA, its firmware, and results of tests in laboratory and in situ with the old and new CSCTF boards.

Melanotic neuroectodermal tumour of infancy at the anterior fontanelle.

PubMed

Nishio, S; Morioka, T; Murakami, N; Fukui, M; Inamitsu, T; Ishihara, S

1999-03-01

We describe a 4-month-old girl presenting with a melanotic neuroectodermal tumour of infancy at the anterior fontanelle. According to the neuroimaging findings, this tumour was found to lie epidurally, adherent to the dura mater, with thickening of the adjacent frontal bone. The tumour was dense on CT, while MRI showed a major part of the tumour to be isointense with cerebral cortex on both T1- and T2-weighted images. The neuroimaging and clinical features are briefly discussed.

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

ClinicalTrials.gov

2018-04-09

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Ganglioglioma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Pleomorphic Xanthoastrocytoma, Anaplastic; Atypical Teratoid/Rhabdoid Tumor; Brain Cancer; Brain Tumor; Central Nervous System Neoplasms; Choroid Plexus Carcinoma; CNS Embryonal Tumor With Rhabdoid Features; Ganglioneuroblastoma of Central Nervous System; CNS Tumor; Embryonal Tumor of CNS; Ependymoma; Glioblastoma; Glioma; Glioma, Malignant; Medulloblastoma; Medulloblastoma; Unspecified Site; Medulloepithelioma; Neuroepithelial Tumor; Neoplasms; Neoplasms, Neuroepithelial; Papillary Tumor of the Pineal Region (High-grade Only); Pediatric Brain Tumor; Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only); Pineoblastoma; Primitive Neuroectodermal Tumor; Recurrent Medulloblastoma; Refractory Brain Tumor; Neuroblastoma. CNS; Glioblastoma, IDH-mutant; Glioblastoma, IDH-wildtype; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Glioma, High Grade; Neuroepithelial Tumor, High Grade; Medulloblastoma, SHH-activated and TP53 Mutant; Medulloblastoma, SHH-activated and TP53 Wildtype; Medulloblastoma, Chromosome 9q Loss; Medulloblastoma, Non-WNT Non-SHH, NOS; Medulloblastoma, Non-WNT/Non-SHH; Medulloblastoma, PTCH1 Mutation; Medulloblastoma, WNT-activated; Ependymoma, Recurrent; Glioma, Recurrent High Grade; Glioma, Recurrent Malignant; Embryonal Tumor, NOS; Glioma, Diffuse Midline, H3K27M-mutant; Embryonal Tumor With Multilayered Rosettes (ETMR); Ependymoma, NOS, WHO Grade III; Ependymoma, NOS, WHO Grade II; Medulloblastoma, G3/G4; Ependymoma, RELA Fusion Positive

Blue Cell Tumour at Unusual Site: Retropritoneal Ewings Sarcoma.

PubMed

Javalgi, Anita P; Karigoudar, Mahesh H; Palur, Katyayani

2016-04-01

Ewing's sarcoma is a highly malignant tumour of osseous or non-osseous origin, tremed as extra-skeletal Ewings sarcoma if arising from soft tissue. It is rare occurrence tumor most commonly occurring in paravertebral area, chest wall, head & neck and retroperitoneum. Reporting an interesting case of retroperitoneal Ewing's sarcoma in 39 years old female. Patient had complains of abdominal discomfort & vague pain since 2 months, following weakness in lower limb and loss of weight. On detail history and examination she was further referred to detail pathological and radiological investigations. Haematological profile, renal function test and liver function test were in normal limits. USG abdomen was normal, MRI showed a mass in pelvis retroperitoneum measuring 10x10cms, bilateral ovaries and tubes were normal. Because of retroperitoneal nature of tumor and suspicion of uterine sarcoma, laparotomy was performed. The large retroperitoneal mass adherent to posterior of uterus was excised and send for histopathological diagnosis. On gross and microscopy examination the diagnosis of blue cell tumor with PAS positivity, possibility of extraskeletal Ewing's sarcoma/primitive neuro-ectodermal tumor was made which was further confirmed by immunohistochemistry, positive for S100, Vementin and CD99 and negative for desmin and CK. Confirmed diagnosis help in accurate management and improves survival rate.

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach.

PubMed

Thompson, Lester Dr

2017-01-01

One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached. Discrimination between neoplasms is critical as there are significant differences in therapy and overall outcome. It is important to have a well developed differential diagnosis for this category of tumors, where each of the diagnoses is considered, evaluated, and either confirmed or excluded from further consideration. In an undifferentiated tumor, showing a small round blue cell morphology, using the mnemonic 'MR SLEEP' helps to highlight tumors to consider: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), Ewing sarcoma/primitive neuroectodermal tumor, pituitary adenoma, and plasmacytoma. A panel of pertinent immunohistochemistry studies, histochemistries and/or molecular tests should aid in reaching a diagnosis, especially when taking the pattern and intensity of reactions into consideration.

Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

ClinicalTrials.gov

2014-11-04

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

[Pineal anlage tumor in a 8-month-old boy. The first case reported in Spanish language].

PubMed

Rodríguez-Velasco, Alicia; Ramírez-Reyes, Alma Griselda

2014-01-01

The pineal anlage tumor is a very infrequent malign neoplasm. Even though it has been documented in literature, it is not listed yet in the World Health Organization's last nervous system classification (2007). It is a primitive pineal tumor with neuroepithelial and ectomesenchyme differentiation. Due to its low frequency, the understanding of its biological behavior and a suitable treatment are incomplete. In a search performed in PubMed with the term pineal anlage tumor, only seven informed cases were identified between 1989 and 2011. An 8-month-old infant was brought to medical attention because he had a progressive enlargement of the cephalic perimeter, and convergent strabismus of two months of evolution. A pineal tumor was identified. The histology showed glial tissue, ganglia cells, pigmented neuroepithelium and striate muscle cells. A ventriculoperitoneal derivation was done to diminish hydrocephalic pressure and also to led the complete surgical resection. The patient was treated with two courses of chemotherapy with carboplatine, ifosfamide and mesna. One year after the treatment, the patient is asymptomatic. This is the first case reported in Spanish language. Given that it is a really infrequent tumor, it could be misdiagnosed as teratome, melanotic or mesoblastic medulloblastoma, or a melanotic neuroectodermal tumor of childhood (melanotic prognoma).

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

PubMed

Trancău, I O; Huică, R; Surcel, M; Munteanu, A; Ursaciuc, C

2015-01-01

EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors.

PubMed

Barnoud, R; Sabourin, J C; Pasquier, D; Ranchère, D; Bailly, C; Terrier-Lacombe, M J; Pasquier, B

2000-06-01

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.

Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

PubMed

Bagher, Zohreh; Kamrava, Seyed Kamran; Alizadeh, Rafieh; Farhadi, Mohammad; Absalan, Moloud; Falah, Masoumeh; Faghihi, Faezeh; Zare-Sadeghi, Arash; Komeili, Ali

2018-05-25

Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

Common tree shrews and primates share leukocyte membrane antigens.

PubMed

Palley, L S; Schlossman, S F; Letvin, N L

1984-01-01

Monoclonal antibodies reactive with human peripheral blood lymphocyte and myeloid cell surface antigens were utilized to study the phylogeny of the common tree shrew. Blood cells from the common tree shrew, but not the bat or short-tailed shrew, react with certain of these antibodies. These data strengthen the argument that the Tupaiidae are primitive primates rather than insectivores. They also indicate that this approach should be useful for further work in taxonomic systemization.

[Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid tumor). Report of a congenital case associated with medulloblastoma in a brother].

PubMed

Costes, V; Medioni, D; Durand, L; Sarran, N; Marguerite, G; Baldet, P

1997-03-01

We report a case of congenital cervical rhabdoid tumor with association of a medulloblastoma in a brother. The immunohistochemical features of this tumor are compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal rhabdoid tumors share a common morphology but do not represent a single entity with only one histogenesis. Most of them are now considered to be of neuroectodermal origin. In our case, the association with a medulloblastoma in a brother seems to confirm this concept.

Cyclin D1 and Ewing's sarcoma/PNET: A microarray analysis.

PubMed

Fagone, Paolo; Nicoletti, Ferdinando; Salvatorelli, Lucia; Musumeci, Giuseppe; Magro, Gaetano

2015-10-01

Recent immunohistochemical analyses have showed that cyclin D1 is expressed in soft tissue Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) of childhood and adolescents, while it is undetectable in both embryonal and alveolar rhabdomyosarcoma. In the present paper, microarray analysis provided evidence of a significant upregulation of cyclin D1 in Ewing's sarcoma as compared to normal tissues. In addition, we confirmed our previous findings of a significant over-expression of cyclin D1 in Ewing sarcoma as compared to rhabdomyosarcoma. Bioinformatic analysis also allowed to identify some other genes, strongly correlated to cyclin D1, which, although not previously studied in pediatric tumors, could represent novel markers for the diagnosis and prognosis of Ewing's sarcoma/PNET. The data herein provided support not only the use of cyclin D1 as a diagnostic marker of Ewing sarcoma/PNET but also the possibility of using drugs targeting cyclin D1 as potential therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Spemann organizer meets the anterior-most neuroectoderm at the equator of early gastrulae in amphibian species

PubMed Central

Yanagi, Takanori; Ito, Kenta; Nishihara, Akiha; Minamino, Reika; Mori, Shoko; Sumida, Masayuki; Hashimoto, Chikara

2015-01-01

The dorsal blastopore lip (known as the Spemann organizer) is important for making the body plan in amphibian gastrulation. The organizer is believed to involute inward and migrate animally to make physical contact with the prospective head neuroectoderm at the blastocoel roof of mid- to late-gastrula. However, we found that this physical contact was already established at the equatorial region of very early gastrula in a wide variety of amphibian species. Here we propose a unified model of amphibian gastrulation movement. In the model, the organizer is present at the blastocoel roof of blastulae, moves vegetally to locate at the region that lies from the blastocoel floor to the dorsal lip at the onset of gastrulation. The organizer located at the blastocoel floor contributes to the anterior axial mesoderm including the prechordal plate, and the organizer at the dorsal lip ends up as the posterior axial mesoderm. During the early step of gastrulation, the anterior organizer moves to establish the physical contact with the prospective neuroectoderm through the “subduction and zippering” movements. Subduction makes a trench between the anterior organizer and the prospective neuroectoderm, and the tissues face each other via the trench. Zippering movement, with forming Brachet's cleft, gradually closes the gap to establish the contact between them. The contact is completed at the equator of early gastrulae and it continues throughout the gastrulation. After the contact is established, the dorsal axis is formed posteriorly, but not anteriorly. The model also implies the possibility of constructing a common model of gastrulation among chordate species. PMID:25754292

Melanotic neuroectodermal tumor of the neurocranium in infancy.

PubMed

Walsh, J W; Strand, R D

1982-01-01

Melanotic neuroectodermal tumors of the neurocranium are a rare but life-threatening disorder of infancy. 11 previously reported cases are reviewed in terms of clinical presentation, radiological diagnosis, and management. A twelfth case, a 4-month-old infant who developed three discrete sites of tumor unilaterally in the neurocranium is presented. Several hypotheses for the mechanism of formation of these tumors are reviewed. The authors propose that the mechanism of formation involves a dysontogenesis of neural crest tissue and that these tumors form, at least in part, from fragments of melanin-containing arachnoid villi which are displaced during embryonic development.

Childhood cancer incidence trends in association with US folic acid fortification (1986-2008).

PubMed

Linabery, Amy M; Johnson, Kimberly J; Ross, Julie A

2012-06-01

Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996-1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification. Using Surveillance, Epidemiology, and End Results program data (1986-2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models. From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns. These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification.

Formation and Rupture of the Internal Carotid Artery Aneurysm after Multiple Courses of Intensity-Modulated Radiation Therapy for Management of the Skull Base Ewing Sarcoma/PNET: Case Report.

PubMed

Tamura, Manabu; Kogo, Kasei; Masuo, Osamu; Oura, Yoshinori; Matsumoto, Hiroyuki; Fujita, Koji; Nakao, Naoyuki; Uematsu, Yuji; Itakura, Toru; Chernov, Mikhail; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi

2013-12-01

Background Aneurysm formation after stereotactic irradiation of skull base tumors is rare. The formation and rupture of an internal carotid artery (ICA) aneurysm in a patient with skull base Ewing sarcoma/primitive neuroectodermal tumor (PNET), who underwent surgery followed by multiple courses of intensity-modulated radiation therapy (IMRT) and chemotherapy, is described. Case Description A 25-year-old man presented with a sinonasal tumor with intraorbital and intracranial growth. At that time cerebral angiography did not reveal any vascular abnormalities. The lesion was resected subtotally. Histopathologic diagnosis was Ewing sarcoma/PNET. The patient underwent multiple courses of chemotherapy and three courses of IMRT at 3, 28, and 42 months after initial surgery. The total biologically effective dose delivered to the right ICA was 220.2 Gy. Seven months after the third IMRT, the patient experienced profound nasal bleeding that resulted in hypovolemic shock. Angiography revealed a ruptured right C4-C5 aneurysm and irregular stenotic changes of the ICA. Lifesaving endovascular trapping of the right ICA was done. The patient recovered well after surgery but died due to tumor recurrence 6 months later. Conclusion Excessive irradiation of the ICA may occasionally result in aneurysm formation, which should be borne in mind during stereotactic irradiation of malignant skull base tumors.

Survival of patients with Ewing's sarcoma in Yazd-Iran.

PubMed

Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

2014-01-01

The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

Clinicopathological findings of primary esophageal malignant melanoma: report of six cases and review of literature.

PubMed

Zheng, Jinfeng; Mo, Haiying; Ma, Shufang; Wang, Zhenzheng

2014-01-01

We studied images and histopathological features of primary esophageal malignant melanoma to explore the clinical pathological features, diagnosis, differential diagnoses, and treatment. Immunolabelling was conducted on six cases of esophageal malignant melanoma using histological and immunohistochemical techniques. Combined with the related literature, the clinical manifestations, imaging, histopathological and immunohistochemical features, treatment, and prognosis of primary esophageal malignant melanoma were observed and analyzed. The six patients with primary esophageal malignant melanoma were all male with an average age of 63.4 years. Poor food intake was observed in all patients, and the symptoms showed progressive aggravation. Endoscopic feed tube revealed dark brown and black nodular and polypoid lesions, 1/4-1/2 loop cavity. Tumor histopathology revealed the following characteristics: tumor cells arranged in nests, sheets and cords, round or polygonal, abundant and red-stained cytoplasm, melanin granules in the cytoplasm, heterogeneous nucleus sizes, centered or deviated nuclei, clearly identifiable nucleoli, and apparent pathological mitosis. The immune phenotype was as follows: tumor cells had diffuse expression of HMB45, Melan A, and S100. The cells were CK negative, and the Ki67-positive cell number was 40%-45%. Primary esophageal malignant melanoma is rare with high malignancy and poor prognosis. Immunohistochemical staining is helpful for diagnosing this tumor. The differential diagnosis includes low differentiated carcinoma, primitive neuroectodermal tumor, esophageal sarcomatoid carcinoma, esophageal lymphoma, and other tumors.

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

PubMed Central

Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

2005-01-01

Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein. PMID:15717928

Metabolic brain imaging correlated with clinical features of brain tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alavi, J.; Alavi, A.; Dann, R.

1985-05-01

Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1more » enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.« less

p53 Restoration in Induction and Maintenance of Senescence: Differential Effects in Premalignant and Malignant Tumor Cells

PubMed Central

Harajly, Mohamad; Zalzali, Hasan; Nawaz, Zafar; Ghayad, Sandra E.; Ghamloush, Farah; Basma, Hussein; Zainedin, Samiha; Rabeh, Wissam; Jabbour, Mark; Tawil, Ayman; Badro, Danielle A.; Evan, Gerard I.

2015-01-01

The restoration of p53 has been suggested as a therapeutic approach in tumors. However, the timing of p53 restoration in relation to its efficacy during tumor progression still is unclear. We now show that the restoration of p53 in murine premalignant proliferating pineal lesions resulted in cellular senescence, while p53 restoration in invasive pineal tumors did not. The effectiveness of p53 restoration was not dependent on p19Arf expression but showed an inverse correlation with Mdm2 expression. In tumor cells, p53 restoration became effective when paired with either DNA-damaging therapy or with nutlin, an inhibitor of p53-Mdm2 interaction. Interestingly, the inactivation of p53 after senescence resulted in reentry into the cell cycle and rapid tumor progression. The evaluation of a panel of human supratentorial primitive neuroectodermal tumors (sPNET) showed low activity of the p53 pathway. Together, these data suggest that the restoration of the p53 pathway has different effects in premalignant versus invasive pineal tumors, and that p53 activation needs to be continually sustained, as reversion from senescence occurs rapidly with aggressive tumor growth when p53 is lost again. Finally, p53 restoration approaches may be worth exploring in sPNET, where the p53 gene is intact but the pathway is inactive in the majority of examined tumors. PMID:26598601

MYCN induces neuroblastoma in primary neural crest cells.

PubMed

Olsen, R R; Otero, J H; García-López, J; Wallace, K; Finkelstein, D; Rehg, J E; Yin, Z; Wang, Y-D; Freeman, K W

2017-08-31

Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc, to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived NBL tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified NBL including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc, we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human NBL and establishes a new system with potential to study early stages of NBL oncogenesis, to functionally assess NBL oncogenic drivers and to characterize NBL metastasis.

Pineal tumors: analysis of treatment results in 20 patients.

PubMed

Amendola, Beatriz E; Wolf, Aizik; Coy, Sammie R; Amendola, Marco A; Eber, Daryl

2005-01-01

The authors evaluate their results when using gamma knife surgery (GKS) in the management of patients with tumors in the pineal region. This is a retrospective clinical evaluation of 20 patients with primary tumors of the pineal region treated with GKS from November 1994 through August 2003. There were 13 germ cell tumors, two pineoblastomas, two low-grade gliomas, one primitive neuroectodermal tumor, one teratoma, and one pineocytoma. There were 10 male and 10 female patients. Their median age was 15.5 years (range 5-71 years). The median margin dose was 11 Gy (range 8-20 Gy). The median target volume was 3.1 cm3 (range 0.1-49.9 cm3). Five patients received sequential systemic chemotherapy and four underwent adjuvant conventional radiation therapy. Seventeen (85%) of 20 patients are alive with a median survival of 30.4 months (range 0-85.7 months). Two patients required retreatment. Three patients died: one of unrelated causes, one who presented with extensive local disease, and the other of meningeal carcinomatosis with local control of the primary tumor. No complications from GKS were noted. This initial experience suggests that GKS is a valuable treatment modality for the management of pineal region tumors. This technique offers excellent local tumor control and minimal patient morbidity, allowing for immediate use of systemic chemotherapy and/or conventional radiation if indicated.

[A new entity in WHO classification of tumors of the central nervous system--embryonic tumor with abundant neuropil and true rosettes: case report and review of literature].

PubMed

Ryzhova, M V; Zheludkova, O G; Ozerov, S S; Shishkina, L V; Panina, T N; Gorelyshev, S K; Novikov, A I; Melikian, A G; Kushel', Iu V; Korshunov, A E

2011-01-01

Embryonic tumor with abundant neuropil and true rosettes (ETANTR) is a very aggressive rare tumor with unique histologic and molecular features occurring in very young children. At present approximately 80 cases of ETANTR have been documented in the literature since first description in 2000. We report seven patients with ETANTR below 4 years of age who underwent surgical resection in the Burdenko Neurosurgery Institute between 2005 and 2010. Four children have received different modality chemotherapy and radiotherapy and two patients were treated by chemotherapy alone. One child did not receive any adjuvant treatment. All children had local relapses, two of them were operated twice. A 2 year old girl underwent subtotal resection thrice. Histological examination showed that all tumors were composed of true multilayered rosettes admixed with large areas of paucicellular neuropil. By analysis of recurrences we have found that large areas of neuropil and number of true rosettes were lost and tumors acquired a resemblance to central nervous system primitive neuroectodermal tumors. In four cases frozen tumor material was available for array-based comparative genomic hybridization, which discovered trisomy of chromosome 2 and amplification at the 19q13.42 chromosome locus. Fluorescence in situ hybridization revealed amplification at the 19q13.42 chromosome locus in all cases.

PMS2 mutations in childhood cancer.

PubMed

De Vos, Michel; Hayward, Bruce E; Charlton, Ruth; Taylor, Graham R; Glaser, Adam W; Picton, Susan; Cole, Trevor R; Maher, Eamonn R; McKeown, Carole M E; Mann, Jill R; Yates, John R; Baralle, Diana; Rankin, Julia; Bonthron, David T; Sheridan, Eamonn

2006-03-01

Until recently, the PMS2 DNA mismatch repair gene has only rarely been implicated as a cancer susceptibility locus. New studies have shown, however, that earlier analyses of this gene have had technical limitations and also that the genetic behavior of mutant PMS2 alleles is unusual, in that, unlike MLH1 or MSH2 mutations, PMS2 mutations show low heterozygote penetrance. As a result, a dominantly inherited cancer predisposition has not been a feature reported in families with PMS2 mutations. Such families have instead been ascertained through childhood-onset cancers in homozygotes or through apparently sporadic colorectal cancer in heterozygotes. We present further information on the phenotype associated with homozygous PMS2 deficiency in 13 patients from six families of Pakistani origin living in the United Kingdom. This syndrome is characterized by café-au-lait skin pigmentation and a characteristic tumor spectrum, including leukemias, lymphomas, cerebral malignancies (such as supratentorial primitive neuroectodermal tumors, astrocytomas, and glioblastomas), and colorectal neoplasia with an onset in early adult life. We present evidence for a founder effect in five families, all of which carried the same R802-->X mutation (i.e., arginine-802 to stop) in PMS2. This cancer syndrome can be mistaken for neurofibromatosis type 1, with important management implications including the risk of the disorder occurring in siblings and the likelihood of tumor development in affected individuals.

The evolution of nervous system patterning: insights from sea urchin development

PubMed Central

Angerer, Lynne M.; Yaguchi, Shunsuke; Angerer, Robert C.; Burke, Robert D.

2011-01-01

Recent studies of the sea urchin embryo have elucidated the mechanisms that localize and pattern its nervous system. These studies have revealed the presence of two overlapping regions of neurogenic potential at the beginning of embryogenesis, each of which becomes progressively restricted by separate, yet linked, signals, including Wnt and subsequently Nodal and BMP. These signals act to specify and localize the embryonic neural fields – the anterior neuroectoderm and the more posterior ciliary band neuroectoderm – during development. Here, we review these conserved nervous system patterning signals and consider how the relationships between them might have changed during deuterostome evolution. PMID:21828090

Transient myeloproliferative disease of the newborn: case report with placental, cytogenetic, and flow cytometric findings.

PubMed

de Tar, M W; Dittman, W; Gilbert, J

2000-03-01

Transient myeloproliferative disease (TMD) of the newborn is a rare hematologic abnormality associated with trisomy 21. It is frequently difficult to distinguish the disorder from true congenital leukemia (TCL). Unlike leukemia, which has a clinically aggressive course, TMD generally resolves within weeks to months. We present a case of TMD of the newborn diagnosed on the basis of peripheral blood studies and describe the pertinent pathological findings within the placenta. Flow cytometric analysis of the blasts in the peripheral blood showed phenotypic heterogeneity with features consistent with megakaryocytic differentiation. Cytogenetic studies showed trisomy 21 within the blastic cells. The placenta showed villous dysmaturity with associated chorangiosis and prominent intravascular aggregates of primitive-appearing cells with focal, early vascular wall invasion. The neonate recovered fully and shows no evidence of disease at 2 years of age.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doi, Keiko; Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka; Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka

Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in themore » immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.« less

Restenosis after hot-tip laser-balloon angioplasty: histologic evaluation of the samples removed by Simpson atherectomy

NASA Astrophysics Data System (ADS)

Barbieri, Enrico; Tanganelli, Pietro; Taddei, Giuseppe; Perbellini, Antonio; Attino, Vito; Destro, Gianni; Zardini, Piero

1991-05-01

Laser balloon angioplasty has been used in recent years to treat peripheral artery disease. Despite a primary success the technique is plagued by a high restenosis rate. Directional atherectomy was performed in a small group of patients affected by primitive stenosis or restenosis after an invasive procedure. Light microscopy, immunohistochemistry, and transmission electron microscopy have identified the cellular component of intimal hyperplasia as smooth muscle cells in an active synthetic phenotype. The arterial healing process after invasive procedures seems to develop similarly independently of the device employed.

Transduction of Human Primitive Repopulating Hematopoietic Cells With Lentiviral Vectors Pseudotyped With Various Envelope Proteins

PubMed Central

Kim, Yoon-Sang; Wielgosz, Matthew M; Hargrove, Phillip; Kepes, Steven; Gray, John; Persons, Derek A; Nienhuis, Arthur W

2010-01-01

Lentiviral vectors are useful for transducing primitive hematopoietic cells. We examined four envelope proteins for their ability to mediate lentiviral transduction of mobilized human CD34+ peripheral blood cells. Lentiviral particles encoding green fluorescent protein (GFP) were pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G), the amphotropic (AMPHO) murine leukemia virus envelope protein, the endogenous feline leukemia viral envelope protein or the feline leukemia virus type C envelope protein. Because the relative amount of genome RNA per ml was similar for each pseudotype, we transduced CD34+ cells with a fixed volume of each vector preparation. Following an overnight transduction, CD34+ cells were transplanted into immunodeficient mice which were sacrificed 12 weeks later. The average percentages of engrafted human CD45+ cells in total bone marrow were comparable to that of the control, mock-transduced group (37–45%). Lenti-particles pseudotyped with the VSV-G envelope protein transduced engrafting cells two- to tenfold better than particles pseudotyped with any of the γ-retroviral envelope proteins. There was no correlation between receptor mRNA levels for the γ-retroviral vectors and transduction efficiency of primitive hematopoietic cells. These results support the use of the VSV-G envelope protein for the development of lentiviral producer cell lines for manufacture of clinical-grade vector. PMID:20372106

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

PubMed

Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once specified in the neuroectoderm, exhibit a higher degree of autonomy regarding generation of their lineages compared to mesectodermal midline progenitors.

Childhood Cancer Incidence Trends in Association With US Folic Acid Fortification (1986–2008)

PubMed Central

Johnson, Kimberly J.; Ross, Julie A.

2012-01-01

OBJECTIVE: Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996–1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification. METHODS: Using Surveillance, Epidemiology, and End Results program data (1986–2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models. RESULTS: From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns. CONCLUSIONS: These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification. PMID:22614769

Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group.

PubMed

Geyer, J Russell; Sposto, Richard; Jennings, Mark; Boyett, James M; Axtell, Richard A; Breiger, David; Broxson, Emmett; Donahue, Bernadine; Finlay, Jonathan L; Goldwein, Joel W; Heier, Linda A; Johnson, Dennis; Mazewski, Claire; Miller, Douglas C; Packer, Roger; Puccetti, Diane; Radcliffe, Jerilynn; Tao, May Lin; Shiminski-Maher, Tania

2005-10-20

To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

MYCN induces neuroblastoma in primary neural crest cells

PubMed Central

Olsen, R R; Otero, J H; García-López, J; Wallace, K; Finkelstein, D; Rehg, J E; Yin, Z; Wang, Y-D; Freeman, K W

2017-01-01

Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc, to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived NBL tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified NBL including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc, we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human NBL and establishes a new system with potential to study early stages of NBL oncogenesis, to functionally assess NBL oncogenic drivers and to characterize NBL metastasis. PMID:28459463

Effusion cytomorphology of small round cell tumors.

PubMed

Ikeda, Katsuhide; Tsuta, Koji

2016-01-01

Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT neoplastic cells in the effusion fluid is very rare. We reported the cytomorphological findings of SRCTs in effusion cytology, and performed statistical and mathematical analyses for a purpose to distinguish SRCTs. We analyzed the cytologic findings of effusion samples from 40 SRCT cases and measured the lengths of the nuclei, cytoplasms, and the cell cluster areas. The SRCT cases included 14 Ewing sarcoma (EWS)/primitive neuroectodermal tumor cases, 5 synovial sarcoma cases, 6 rhabdomyosarcoma cases, 9 small cell lung carcinoma (SCLC) cases, and 6 diffuse large B-cell lymphoma (DLBL) cases. Morphologically, there were no significant differences in the nuclear and cytoplasmic lengths in cases of EWS, synovial sarcoma, and rhabdomyosarcoma. The cytoplasmic lengths in cases of SCLC and DLBL were smaller than those of EWS, synovial sarcoma, and rhabdomyosarcoma. The nuclear density of the cluster in SCLC was higher than that in other SRCTs, and cases of DLBL showed a lack of anisokaryosis and anisocytosis. We believe that it might be possible to diagnose DLBL and SCLC from cytologic analysis of effusion samples but it is very difficult to use this method to distinguish EWS, synovial sarcoma, and rhabdomyosarcoma. Statistical and mathematical analyses indicated that nuclear density and dispersion of nuclear and cytoplasmic sizes are useful adjuncts to conventional cytologic diagnostic criteria, which are acquired from experience.

Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

ClinicalTrials.gov

2018-06-20

Brain Cancer; Brain Neoplasm; Glioma; Glioblastoma; Gliosarcoma; Malignant Brain Tumor; Neoplasm, Neuroepithelial; Neuroectodermal Tumors; Neoplasm by Histologic Type; Neoplasm, Nerve Tissue; Nervous System Diseases

Retinoic acid influences anteroposterior positioning of epidermal sensory neurons and their gene expression in a developing chordate (amphioxus)

PubMed Central

Schubert, Michael; Holland, Nicholas D.; Escriva, Hector; Holland, Linda Z.; Laudet, Vincent

2004-01-01

In developing chordates, retinoic acid (RA) signaling patterns the rostrocaudal body axis globally and affects gene expression locally in some differentiating cell populations. Here we focus on development of epidermal sensory neurons in an invertebrate chordate (amphioxus) to determine how RA signaling influences their rostrocaudal distribution and gene expression (for AmphiCoe, a neural precursor gene; for amphioxus islet and AmphiERR, two neural differentiation genes; and for AmphiHox1, -3, -4, and -6). Treatments with RA or an RA antagonist (BMS009) shift the distribution of developing epidermal neurons anteriorly or posteriorly, respectively. These treatments also affect gene expression patterns in the epidermal neurons, suggesting that RA levels may influence specification of neuronal subtypes. Although colinear expression of Hox genes is well known for the amphioxus central nervous system, we find an unexpected comparable colinearity for AmphiHox1, -3, -4, and -6 in the developing epidermis; moreover, RA levels affect the anteroposterior extent of these Hox expression domains, suggesting that RA signaling controls a colinear Hox code for anteroposterior patterning of the amphioxus epidermis. Thus, in amphioxus, the developing peripheral nervous system appears to be structured by mechanisms parallel to those that structure the central nervous system. One can speculate that, during evolution, an ancestral deuterostome that structured its panepidermal nervous system with an RA-influenced Hox code gave rise to chordates in which this patterning mechanism persisted within the epidermal elements of the peripheral nervous system and was transferred to the neuroectoderm as the central nervous system condensed dorsally. PMID:15226493

The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age.

PubMed

Parsons, M A; Curtis, D; Blank, C E; Hughes, H N; McCartney, A C

1992-01-01

The ocular pathology of Norrie disease was studied for the first time in a fetus of 11 weeks' gestation, following prenatal diagnosis using genetic markers for Norrie disease and elective abortion. The eyes were histologically normal, with no evidence of primary neuroectodermal maldevelopment of the retina, previously postulated to be the cause of the ocular changes. We believe that the retinal and other manifestations of Norrie disease are the result of a primary abnormality of vascular proliferation, probably in relation to persistent hyperplastic primary vitreous after approximately 14 weeks' gestation. We postulate that the ocular and otological effects of Norrie disease may be due to a genetically mediated abnormality of secretion of, or sensitivity to, angiogenic growth factors at endodermal-neuroectodermal interfaces during fetal and postnatal development.

Clinical, Pathological, and Surgical Outcomes for Adult Pineoblastomas.

PubMed

Gener, Melissa A; Conger, Andrew R; Van Gompel, Jamie; Ariai, Mohammad S; Jentoft, Mark; Meyer, Fredric B; Cardinal, Jeremy S; Bonnin, José M; Cohen-Gadol, Aaron A

2015-12-01

Pineoblastomas are uncommon primitive neuroectodermal tumors that occur mostly in children; they are exceedingly rare in adults. Few published reports have compared the various aspects of these tumors between adults and children. The authors report a series of 12 pineoblastomas in adults from 2 institutions over 24 years. The clinical, radiologic, and pathologic features and clinical outcomes were compared with previously reported cases in children and adults. Patient age ranged from 24 to 81 years, and all but 1 patient exhibited symptoms of obstructive hydrocephalus. Three patients underwent gross total resection, and subtotal resection was performed in 3 patients. Diagnostic biopsy specimens were obtained in an additional 6 patients. Pathologically, the tumors had the classical morphologic and immunohistochemical features of pineoblastomas. Postoperatively, 10 patients received radiotherapy, and 5 patients received chemotherapy. Compared with previously reported cases, several differences were noted in clinical outcomes. Of the 12 patients, only 5 (42%) died of their disease (average length of survival, 118 months); 5 patients (42%) are alive with no evidence of disease (average length of follow-up, 92 months). One patient died of unrelated causes, and one was lost to follow-up. Patients with subtotal resections or diagnostic biopsies did not suffer a worse prognosis. Of the 9 patients with biopsy or subtotal resection, 4 are alive, 4 died of their disease, and 1 died of an unrelated hemorrhagic cerebral infarction. Although this series is small, the data suggest that pineoblastomas in adults have a less aggressive clinical course than in children. Copyright © 2015 Elsevier Inc. All rights reserved.

Apparent diffusion coefficient in glioblastoma with PNET-like components, a GBM variant.

PubMed

Ali, Saad; Joseph, Nancy M; Perry, Arie; Barajas, Ramon F; Cha, Soonmee

2014-09-01

Glioblastoma (GBM) with primitive neuroectodermal tumor (PNET)-like (GBM-PNET) components is a rare variant of GBM. Recent studies describe PNET-like clinical behavior in these patients-with significantly increased propensity for CSF dissemination and a benefit of "PNET-like" chemotherapy. The imaging appearance of GBM-PNET is not well-described and given areas of marked cellularity in the PNET components one might expect significantly reduced diffusion on MRI. The purpose of this study is to quantitatively evaluate the diffusion characteristics in GBM-PNET and compare them with conventional GBMs. Nine patients with surgical specimens yielding GBM-PNET were identified from the UCSF Pathology files. MR images of these patients were reviewed retrospectively. DWI (diffusion-weighted imaging) sequences were analyzed with multiple regions of interests placed within the tumor, and ADC (apparent diffusion coefficient) values were measured. Results were compared to previously published ADC values in pathology-proven conventional GBM cases from our institution. Reduced ADC was seen in GBM-PNET (mean 581 × 10(-6) mm(2)/s, range 338-817) compared to previously published mean of 1,030 × 10(-6) mm(2)/s in the enhancing components of conventional GBMs. We report substantially reduced ADC values in GBM-PNETs compared to conventional GBMs. If demonstrated in a larger sample, when areas of marked reduced diffusion are seen in a suspected GBM, MRI may appropriately direct tissue sampling and can advocate a thorough search for PNET-like components on histopathology. These patients may have a higher chance of developing CSF dissemination and may benefit from "PNET-like" platinum-based chemotherapy.

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion

PubMed Central

Hussein, Deema; Punjaruk, Wiyada; Storer, Lisa C.D.; Shaw, Lucy; Ottoman, Ramadan; Peet, Andrew; Miller, Suzanne; Bandopadhyay, Gagori; Heath, Rachel; Kumari, Rajendra; Bowman, Karen J.; Braker, Paul; Rahman, Ruman; Jones, George D.D.; Watson, Susan; Lowe, James; Kerr, Ian D.; Grundy, Richard G.; Coyle, Beth

2011-01-01

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3–4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents. PMID:20978004

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion.

PubMed

Hussein, Deema; Punjaruk, Wiyada; Storer, Lisa C D; Shaw, Lucy; Othman, Ramadhan; Ottoman, Ramadan; Peet, Andrew; Miller, Suzanne; Bandopadhyay, Gagori; Heath, Rachel; Kumari, Rajendra; Bowman, Karen J; Braker, Paul; Rahman, Ruman; Jones, George D D; Watson, Susan; Lowe, James; Kerr, Ian D; Grundy, Richard G; Coyle, Beth

2011-01-01

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3-4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents.

Seaweed floating in the pericardium: a rare case of primary dedifferentiated liposarcoma.

PubMed

Zanini, Gregoriana; Gorga, Elio; Pasini, Federica; Salemme, Marianna; Petrilli, Giulia; Bercich, Luisa; Lorusso, Roberto; Pasini, Gian Franco

2016-01-01

Primary cardiac tumors are uncommon and primary liposarcoma of the pericardium is extremely rare. We describe the case of a 55-year-old Caucasian woman without significant medical history, who presented with 3weeks complain of dyspnea, peripheral edema, and gain weight. Echocardiography revealed a huge pericardial mass confirmed by computed tomography and by magnetic resonance. The lesion was primitive of the pericardium but the surgery was not able to cut it off because of the absence of cleavage planes. Histopathologic analysis detected a dedifferentiated liposarcoma. Mediastinum compression syndrome brought the patient to the exitus in a few days. Copyright © 2015 Elsevier Inc. All rights reserved.

Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

ClinicalTrials.gov

2018-04-24

Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

18F-FDG PET/CT in a cardiac metastasis in a patient with history of malignant neuroectodermal tumour of the chest wall: Case report and review of the literature.

PubMed

Marroquín, J A; Hernández, A C; Pilkington, J P; Saviatto, A; Tabuenca, M J; Estenoz, J M

The case presented is a 25-year-old male with a malignant neuroectodermal tumour on the left chest wall (Askin tumour), treated with surgery after neoadyuvant chemotherapy and followed by consolidation chemotherapy. After 9 years of disease free survival, the patient developed an acute pulmonary embolism. The echocardiogram, thoracic CT, and cardiac MRI scans revealed a mass in the right atrium. Recurrence of an Askin tumour versus an atrium myxoma was suspected. 18 F-FDG PET/CT showed an intense hypermetabolic right atrium mass with extension to the right ventricle highly suggestive of malignancy. The result of the histopathology examination after biopsy and subsequently exeresis of the right atrium mass was consistent with a metastasis of the primary tumour. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

YKL-40 is differentially expressed in human embryonic stem cells and in cell progeny of the three germ layers.

PubMed

Brøchner, Christian B; Johansen, Julia S; Larsen, Lars A; Bak, Mads; Mikkelsen, Hanne B; Byskov, Anne Grete; Andersen, Claus Yding; Møllgård, Kjeld

2012-03-01

The secreted glycoprotein YKL-40 participates in cell differentiation, inflammation, and cancer progression. High YKL-40 expression is reported during early human development, but its functions are unknown. Six human embryonic stem cell (hESC) lines were cultured in an atmosphere of low or high oxygen tension, in culture medium with or without basic fibroblast growth factor, and on feeder layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL-40 expression during differentiation. Secreted YKL-40 protein and YKL-40 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3β, PDX1, CD34, p63, nestin, PAX6) markers. Double-labeling showed YKL-40 expression in OCT4-positive hESCs, PAX6-positive neuroectodermal cells, and HNF-3β-positive endodermal cells. The differentiating progeny showed strong YKL-40 expression. Abrupt transition between YKL-40 and OCT4-positive hESCs and YKL-40-positive ecto- and neuroectodermal lineages was observed within the same epithelial-like layer. YKL-40-positive cells within deeper layers lacked contact with OCT4-positive cells. YKL-40 may be important in initial cell differentiation from hESCs toward ectoderm and neuroectoderm, with retained epithelial morphology, whereas later differentiation into endoderm and mesoderm involves a transition into the deeper layers of the colony.

BMPs regulate msx gene expression in the dorsal neuroectoderm of Drosophila and vertebrates by distinct mechanisms.

PubMed

Esteves, Francisco F; Springhorn, Alexander; Kague, Erika; Taylor, Erika; Pyrowolakis, George; Fisher, Shannon; Bier, Ethan

2014-09-01

In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.

BMPs Regulate msx Gene Expression in the Dorsal Neuroectoderm of Drosophila and Vertebrates by Distinct Mechanisms

PubMed Central

Esteves, Francisco F.; Taylor, Erika; Pyrowolakis, George; Fisher, Shannon; Bier, Ethan

2014-01-01

In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of “neural identity” gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages. PMID:25210771

[Bilateral anophthalmia and left-sided orbital tumor : case of an eight-month-old infant].

PubMed

Hundertmark, P; Dierks, P; Gottschalk, J; Kreusch, T; Wiegand, W

2011-08-01

An 8-month-old infant from Russia with bilateral anophthalmia presented with an expanding orbital tumor. The tumor was extirpated and the histological examination revealed a non-malignant pseudocystic process with residual neuro-ectodermal structures.

Otoconial formation in the fetal rat

NASA Technical Reports Server (NTRS)

Salamat, M. S.; Ross, M. D.; Peacor, D. R.

1980-01-01

Otoconial formation in the fetal rat is examined by scanning and transmission electron microscopy, and by X-ray elemental analysis. The primitive otoconia appear highly organic, but are trigonal in cross section, indicating that they already possess a three-fold axis of symmetry and a complement of calcite. These otoconia develop into spindle-shaped and, subsequently, dumbbell-shaped units. Transmission electron microscopy of dumbbell-shaped otoconia not exposed to fluids during embedment showed that calcite deposits mimicked the arrangement of the organic material. X-ray elemental analysis demonstrated that calcium was present in lower quantities in the central core than peripherally. It is concluded that organic material is essential to otoconial seeding and directs otoconial growth.

In vivo transduction of primitive mobilized hematopoietic stem cells after intravenous injection of integrating adenovirus vectors

PubMed Central

Richter, Maximilian; Saydaminova, Kamola; Yumul, Roma; Krishnan, Rohini; Liu, Jing; Nagy, Eniko-Eva; Singh, Manvendra; Izsvák, Zsuzsanna; Cattaneo, Roberto; Uckert, Wolfgang; Palmer, Donna; Ng, Philip; Haworth, Kevin G.; Kiem, Hans-Peter; Ehrhardt, Anja; Papayannopoulou, Thalia

2016-01-01

Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34+ cells that HSPCs transduced in the periphery home back to the BM where they stably express the transgene. In hCD46 transgenic mice, we showed that our in vivo HSPC transduction approach allows for the stable transduction of primitive HSPCs. Twenty weeks after in vivo transduction, green fluorescent protein (GFP) marking in BM HSPCs (Lin−Sca1+Kit− cells) in most of the mice was in the range of 5% to 10%. The percentage of GFP-expressing primitive HSPCs capable of forming multilineage progenitor colonies (colony-forming units [CFUs]) increased from 4% of all CFUs at week 4 to 16% at week 12, indicating transduction and expansion of long-term surviving HSPCs. Our approach was well tolerated, did not result in significant transduction of nonhematopoietic tissues, and was not associated with genotoxicty. The ability to stably genetically modify HSPCs without the need of myeloablative conditioning is relevant for a broader clinical application of gene therapy. PMID:27554082

Involvement of mTOR-autophagy in the selection of primitive mesenchymal stem cells in chitosan film 3-dimensional culture.

PubMed

Chiu, Hsiao-Ying; Tsay, Yeou-Guang; Hung, Shih-Chieh

2017-08-31

Mesenchymal stem cells (MSCs) in conventional monolayer culture are heterogeneous and contain a significant portion of senescent cells. MSCs cultured on chitosan film form 3-dimenional spheres, increase in stemness and differentiation capability; however, the underlying mechanisms remain elusive. We first demonstrate chitosan film culture induces apoptosis at 2 days, with specificity in late senescent cells. Especially in senescent cells, chitosan film culture activates mTOR, which activates S6K/S6/4E-BP1 to enhance fibronection synthesis and peripheral dead cell attachment, and phosphorylates ULK1 at S757 to further inactivate ULK1, LC3A and autophagy, thereby inducing apoptosis. Combination of chitosan film culture with mTOR inhibition prevents peripheral dead cell attachment, thereby further increasing pluripotent gene expression, in vitro osteogenesis and in vivo bone formation. These data successfully figure out the role of mTOR signaling in chitosan film culture and develop a method by combination of rapamycin treatment for promoting stemness and differentiation capability in MSCs.

Ontogenetic development of the nervus terminalis in toothed whales. Evidence for its non-olfactory nature.

PubMed

Buhl, E H; Oelschläger, H A

1986-01-01

For the first time in cetaceans, the development of the terminalis system and its continuity between the olfactory placode and the telencephalon has been demonstrated by light microscopy. In the early development of toothed whales (Odontoceti) this system is partially incorporated within the fila olfactoria which grow out from the olfactory placode. As the peripheral olfactory system is reduced in later stages, a strongly developed ganglionlike structure (terminalis ganglion) remains within the primitive meninx. Peripherally it is connected via the cribriform plate with ganglionic cell clusters near the septal mucosa. Centrally it is attached to the telencephalon (olfactory tubercle, septal region) by several nerve fibre bundles. In contrast to all other mammalian groups, toothed whales and dolphins are anosmatic while being totally adapted to aquatic life. Therefore the remaining ganglion and plexus must have non-olfactory properties. They may be responsible for the autonomic innervation of intracranial arteries and of the large mucous epithelia in the accessory nasal air sacs. The morphology, evolution and functional implications of the terminalis system in odontocetes and other mammals are discussed.

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo.

PubMed

Fossat, Nicolas; Ip, Chi Kin; Jones, Vanessa J; Studdert, Joshua B; Khoo, Poh-Lynn; Lewis, Samara L; Power, Melinda; Tourle, Karin; Loebel, David A F; Kwan, Kin Ming; Behringer, Richard R; Tam, Patrick P L

2015-06-01

Lhx1 encodes a LIM homeobox transcription factor that is expressed in the primitive streak, mesoderm and anterior mesendoderm of the mouse embryo. Using a conditional Lhx1 flox mutation and three different Cre deleters, we demonstrated that LHX1 is required in the anterior mesendoderm, but not in the mesoderm, for formation of the head. LHX1 enables the morphogenetic movement of cells that accompanies the formation of the anterior mesendoderm, in part through regulation of Pcdh7 expression. LHX1 also regulates, in the anterior mesendoderm, the transcription of genes encoding negative regulators of WNT signalling, such as Dkk1, Hesx1, Cer1 and Gsc. Embryos carrying mutations in Pcdh7, generated using CRISPR-Cas9 technology, and embryos without Lhx1 function specifically in the anterior mesendoderm displayed head defects that partially phenocopied the truncation defects of Lhx1-null mutants. Therefore, disruption of Lhx1-dependent movement of the anterior mesendoderm cells and failure to modulate WNT signalling both resulted in the truncation of head structures. Compound mutants of Lhx1, Dkk1 and Ctnnb1 show an enhanced head truncation phenotype, pointing to a functional link between LHX1 transcriptional activity and the regulation of WNT signalling. Collectively, these results provide comprehensive insight into the context-specific function of LHX1 in head formation: LHX1 enables the formation of the anterior mesendoderm that is instrumental for mediating the inductive interaction with the anterior neuroectoderm and LHX1 also regulates the expression of factors in the signalling cascade that modulate the level of WNT activity. © 2015. Published by The Company of Biologists Ltd.

Epidemiological data and case load spectrum of patients presenting to bone and soft tissue disease management group at a tertiary cancer center.

PubMed

Gulia, A; Puri, A; Chorge, S; Panda, P K

2016-01-01

This study was conducted to know the spectrum and number of bone and soft tissue (BST) tumors presenting to our institute. We needed to assess the gap between the number of patients seen and infrastructure available, and based on this information, help formulate guidelines for optimum utilization of resources and to provide best possible evidence-based cancer care. This is a prospective observational study (epidemiological). This study included all new patients seen in BST-disease management group (DMG) in the year 2010. An audit form was devised to capture all the relevant information. A comparison of our data with other national and international studies was also done. Out of total 31,951 new patients registered at our institute, 2007 patients availed BST-DMG services. Sixty percent were bone tumors and 36% were soft tissue tumors. In bone tumor, 66% were malignant, 15% were benign, and 19% were non-neoplastic. Osteosarcoma (43%) was the most common malignant tumor followed by primitive neuroectodermal tumor/Ewing's (27%) and chondrosarcoma (11%). Giant cell tumor was the most common benign bone tumor. Eighty-one percent of all soft tissue lesions were malignant, of which 75% were of mesenchymal origin and 25% were of cutaneous origin. This is an attempt to document the epidemiology of musculoskeletal tumors presenting to our institution while guiding the institute to frame and implement disease-specific protocols and generate further research questions. Continued data collection and follow-up can provide valuable information on long-term survival and treatment-related toxicities. This data (within limitations) may be extrapolated to national level to identify the need for infrastructure and human resources.

Comparison of endoscope- versus microscope-assisted resection of deep-seated intracranial lesions using a minimally invasive port retractor system.

PubMed

Hong, Christopher S; Prevedello, Daniel M; Elder, J Bradley

2016-03-01

Tubular brain retractors may improve access to deep-seated brain lesions while potentially reducing the risks of collateral neurological injury associated with standard microsurgical approaches. Here, microscope-assisted resection of lesions using tubular retractors is assessed to determine if it is superior to endoscope-assisted surgery due to the technological advancements associated with modern tubular ports and surgical microscopes. Following institutional approval of the tubular port, data obtained from the initial 20 patients to undergo transportal resection of deep-seated brain lesions were analyzed in this study. The pathological entities of the resected tissues included metastatic tumors (8 patients), glioma (7), meningioma (1), neurocytoma (1), radiation necrosis (1), primitive neuroectodermal tumor (1), and hemangioblastoma (1). Surgery incorporated endoscopic (5 patients) or microscopic (15) assistance. The locations included the basal ganglia (11 patients), cerebellum (4), frontal lobe (2), temporal lobe (2), and parietal lobe (1). Cases were reviewed for neurological outcomes, extent of resection (EOR), and complications. Technical data for the port, surgical microscope, and endoscope were analyzed. EOR was considered total in 14 (70%), near total (> 95%) in 4 (20%), and subtotal (< 90%) in 2 (10%) of 20 patients. Incomplete resection was associated with the basal ganglia location (p < 0.05) and use of the endoscope (p < 0.002). Four of 5 (80%) endoscope-assisted cases were near-total (2) or subtotal (2) resection. Histopathological diagnosis, presenting neurological symptoms, and demographics were not associated with EOR. Complication rates were low and similar between groups. Initial experience with tubular retractors favors use of the microscope rather than the endoscope due to a wider and 3D field of view. Improved microscope optics and tubular retractor design allows for binocular vision with improved lighting for the resection of deep-seated brain lesions.

Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.

PubMed

Bautista, Francisco; Fioravantti, Victoria; de Rojas, Teresa; Carceller, Fernando; Madero, Luis; Lassaletta, Alvaro; Moreno, Lucas

2017-11-01

Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0-100) and 6.5% (0-50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0-100). Smoothened inhibitors trials had a median ORR of 8% (3-8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells

PubMed Central

Rossi, Alessandra; Russo, Giuseppe; Puca, Andrew; La Montagna, Raffaele; Caputo, Mariella; Mattioli, Eliseo; Lopez, Massimo; Giordano, Antonio; Pentimalli, Francesca

2009-01-01

Abacavir is one of the most efficacious nucleoside analogues, with a well-characterized inhibitory activity on reverse transcriptase enzymes of retroviral origin, and has been clinically approved for the treatment of AIDS. Recently, Abacavir has been shown to inhibit also the human telomerase activity. Telomerase activity seems to be required in essentially all tumours for the immortalization of a subset of cells, including cancer stem cells. In fact, many cancer cells are dependent on telomerase for their continued replication and therefore telomerase is an attractive target for cancer therapy. Telomerase expression is upregulated in primary primitive neuroectodermal tumours and in the majority of medulloblastomas suggesting that its activation is associated with the development of these diseases. Therefore, we decided to test Abacavir activity on human medulloblastoma cell lines with high telomerase activity. We report that exposure to Abacavir induces a dose-dependent decrease in the proliferation rate of medulloblastoma cells. This is associated with a cell accumulation in the G2/M phase of the cell cycle in the Daoy cell line, and with increased cell death in the D283-MED cell line, and is likely to be dependent on the inhibition of telomerase activity. Interestingly, both cell lines showed features of senescence after Abacavir treatment. Moreover, following Abacavir exposure we detected, by immunofluorescence staining, increased protein expression of the glial marker glial fibrillary acidic protein (GFAP) and the neuronal marker synaptophysin (SYN) in both medulloblastoma cell lines. In conclusion, our results suggest that Abacavir reduces proliferation and induces differentiation of human medulloblastoma cells through the downregulation of telomerase activity. Thus, using Abacavir, alone or in combination with current therapies, might be an effective therapeutic strategy for the treatment of medulloblastoma. PMID:19358275

Outcome of Children With Metastatic Medulloblastoma Treated With Carboplatin During Craniospinal Radiotherapy: A Children's Oncology Group Phase I/II Study

PubMed Central

Jakacki, Regina I.; Burger, Peter C.; Zhou, Tianni; Holmes, Emiko J.; Kocak, Mehmet; Onar, Arzu; Goldwein, Joel; Mehta, Minesh; Packer, Roger J.; Tarbell, Nancy; Fitz, Charles; Vezina, Gilbert; Hilden, Joanne; Pollack, Ian F.

2012-01-01

Purpose We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB. Patients and Methods After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m2/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B). Results In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m2/dose × 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome. Conclusion The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy. PMID:22665539

Proton Therapy in Children: A Systematic Review of Clinical Effectiveness in 15 Pediatric Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leroy, Roos, E-mail: Roos.leroy@kce.fgov.be; Benahmed, Nadia; Hulstaert, Frank

Because it spares many normal tissues and reduces the integral dose, proton therapy (PT) is the preferred tumor irradiation technique for treating childhood cancer. However, to the best of our knowledge, no systematic review of the clinical effectiveness of PT in children has been reported in the scientific literature. A systematic search for clinical outcome studies on PT published between 2007 and 2015 was performed in Medline (through OVID), EMBASE, and the Cochrane Library. Twenty-three primary studies were identified, including approximately 650 patients overall. The median/mean follow-up times were limited (range, 19-91 months). None of the studies were randomized, 2 weremore » comparative, and 20 were retrospective. Most suffered from serious methodologic limitations, yielding a very low level of clinical evidence for the outcomes in all indications. For example, for retinoblastoma, very low-level evidence was found that PT might decrease the incidence of second malignancies. For chondrosarcoma, chordoma, craniopharyngioma, ependymoma, esthesioneuroblastoma, Ewing sarcoma, central nervous system germinoma, glioma, medulloblastoma, osteosarcoma, and rhabdomyosarcoma, there was insufficient evidence to either support or refute PT in children. For pelvic sarcoma (ie, nonrhabdomyosarcoma and non-Ewing sarcoma), pineal parenchymal tumor, primitive neuroectodermal tumor, and “adult-type” soft tissue sarcoma, no studies were identified that fulfilled the inclusion criteria. Although there is no doubt that PT reduces the radiation dose to normal tissues and organs, to date the critical clinical data on the long-term effectiveness and harm associated with the use of PT in the 15 pediatric cancers under investigation are lacking. High-quality clinical research in this area is needed.« less

The case for DNA methylation based molecular profiling to improve diagnostic accuracy for central nervous system embryonal tumors (not otherwise specified) in adults.

PubMed

Halliday, Gail C; Junckerstorff, Reimar C; Bentel, Jacqueline M; Miles, Andrew; Jones, David T W; Hovestadt, Volker; Capper, David; Endersby, Raelene; Cole, Catherine H; van Hagen, Tom; Gottardo, Nicholas G

2018-01-01

Central nervous system primitive neuro-ectodermal tumors (CNS-PNETs), have recently been re-classified in the most recent 2016 WHO Classification into a standby catch all category, "CNS Embryonal Tumor, not otherwise specified" (CNS embryonal tumor, NOS) based on epigenetic, biologic and histopathologic criteria. CNS embryonal tumors (NOS) are a rare, histologically and molecularly heterogeneous group of tumors that predominantly affect children, and occasionally adults. Diagnosis of this entity continues to be challenging and the ramifications of misdiagnosis of this aggressive class of brain tumors are significant. We report the case of a 45-year-old woman who was diagnosed with a central nervous system embryonal tumor (NOS) based on immunohistochemical analysis of the patient's tumor at diagnosis. However, later genome-wide methylation profiling of the diagnostic tumor undertaken to guide treatment, revealed characteristics most consistent with IDH-mutant astrocytoma. DNA sequencing and immunohistochemistry confirmed the presence of IDH1 and ATRX mutations resulting in a revised diagnosis of high-grade small cell astrocytoma, and the implementation of a less aggressive treatment regime tailored more appropriately to the patient's tumor type. This case highlights the inadequacy of histology alone for the diagnosis of brain tumours and the utility of methylation profiling and integrated genomic analysis for the diagnostic verification of adults with suspected CNS embryonal tumor (NOS), and is consistent with the increasing realization in the field that a combined diagnostic approach based on clinical, histopathological and molecular data is required to more accurately distinguish brain tumor subtypes and inform more effective therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML).

PubMed

Guan, Y; Hogge, D E

2000-12-01

One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard chemotherapeutic regimens.

Multipotent progenitor cells are present in human peripheral blood.

PubMed

Cesselli, Daniela; Beltrami, Antonio Paolo; Rigo, Silvia; Bergamin, Natascha; D'Aurizio, Federica; Verardo, Roberto; Piazza, Silvano; Klaric, Enio; Fanin, Renato; Toffoletto, Barbara; Marzinotto, Stefania; Mariuzzi, Laura; Finato, Nicoletta; Pandolfi, Maura; Leri, Annarosa; Schneider, Claudio; Beltrami, Carlo Alberto; Anversa, Piero

2009-05-22

To determine whether the peripheral blood in humans contains a population of multipotent progenitor cells (MPCs), products of leukapheresis were obtained from healthy donor volunteers following the administration of granulocyte colony-stimulating factor. Small clusters of adherent proliferating cells were collected, and these cells continued to divide up to 40 population doublings without reaching replicative senescence and growth arrest. MPCs were positive for the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed several antigens characteristic of mesenchymal stem cells. However, they were negative for markers of hematopoietic stem/progenitor cells and bone marrow cell lineages. MPCs had a cloning efficiency of approximately 3%, and following their expansion, retained a highly immature phenotype. Under permissive culture conditions, MPCs differentiated into neurons, glial cells, hepatocytes, cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression profile of MPCs partially overlapped with that of neural and embryonic stem cells, further demonstrating their primitive, uncommitted phenotype. Following subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to distant organs and integrated structurally and functionally within the new tissue, acquiring the identity of resident parenchymal cells. In conclusion, undifferentiated cells with properties of embryonic stem cells can be isolated and expanded from human peripheral blood after granulocyte colony-stimulating factor administration. This cell pool may constitute a unique source of autologous cells with critical clinical import.

The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content.

PubMed

Almeida, Inês; van Asselen, Marieke; Castelo-Branco, Miguel

2013-09-01

In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central processing engaged mainly the caudate nucleus. We conclude that the human amygdala has a central bias for face stimuli, and that visual processing recruits different striatal regions, putaminal or caudate based, depending on the task and on whether peripheral or central visual processing is involved. © 2013 Elsevier Ltd. All rights reserved.

Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1

PubMed Central

Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.

2000-01-01

Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866

On Synchronization Primitive Systems.

DTIC Science & Technology

The report studies the question: what synchronization primitive should be used to handle inter-process communication. A formal model is presented...between these synchronization primitives. Although only four synchronization primitives are compared, the general methods can be used to compare other... synchronization primitives. Moreover, in the definitions of these synchronization primitives, conditional branches are explicitly allowed. In addition

Microfluidic assay of the deformability of primitive erythroblasts.

PubMed

Zhou, Sitong; Huang, Yu-Shan; Kingsley, Paul D; Cyr, Kathryn H; Palis, James; Wan, Jiandi

2017-09-01

Primitive erythroblasts (precursors of red blood cells) enter vascular circulation during the embryonic period and mature while circulating. As a result, primitive erythroblasts constantly experience significant hemodynamic shear stress. Shear-induced deformation of primitive erythroblasts however, is poorly studied. In this work, we examined the deformability of primitive erythroblasts at physiologically relevant flow conditions in microfluidic channels and identified the regulatory roles of the maturation stage of primitive erythroblasts and cytoskeletal protein 4.1 R in shear-induced cell deformation. The results showed that the maturation stage affected the deformability of primitive erythroblasts significantly and that primitive erythroblasts at later maturational stages exhibited a better deformability due to a matured cytoskeletal structure in the cell membrane.

Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus

PubMed Central

Xu, Suhong; Cheng, Feng; Liang, Juan; Wu, Wei; Zhang, Jian

2012-01-01

Dorsal–ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin) promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification. PMID:22448144

Secure Heterogeneous Multicore Platform Through Diversity and Redundancy

DTIC Science & Technology

2012-03-31

implementation detects synchronization in this way. If a programmer uses custom synchronization primitives , our approach assumes that such primitives ... synchronization primitives . Primitives such as barriers and spinlocks explicitly enforce a pre- determined ordering among threads. Therefore, the outcome of...these synchronization operations are deterministic. In the discussion, we will refer to these primitives as ordering synchronization operations. On the

Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

PubMed

Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

2002-11-01

Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P < or = 0.0001) increased WBC counts, CFC frequencies, and CFC absolute numbers by 2-, 13-, and 27-fold, respectively. As compared with control mice, the combined administration of Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P < or = 0.0001) increased WBC counts, frequencies and absolute numbers of CFCs by 4-, 38-, and 119-fold, respectively. As compared with rhG-CSF alone, administration of Defibrotide plus rhG-CSF resulted in a significant increase (P < or = 0.001) of the frequency of circulating long-term culture-initiating cells. In addition, transplantation of 2 x 10(5) rhG-CSF- or Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P < or = 0.001), suggesting that the mobilizing effect of Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

Dynamic Primitives of Motor Behavior

PubMed Central

Hogan, Neville; Sternad, Dagmar

2013-01-01

We present in outline a theory of sensorimotor control based on dynamic primitives, which we define as attractors. To account for the broad class of human interactive behaviors—especially tool use—we propose three distinct primitives: submovements, oscillations and mechanical impedances, the latter necessary for interaction with objects. Due to fundamental features of the neuromuscular system, most notably its slow response, we argue that encoding in terms of parameterized primitives may be an essential simplification required for learning, performance, and retention of complex skills. Primitives may simultaneously and sequentially be combined to produce observable forces and motions. This may be achieved by defining a virtual trajectory composed of submovements and/or oscillations interacting with impedances. Identifying primitives requires care: in principle, overlapping submovements would be sufficient to compose all observed movements but biological evidence shows that oscillations are a distinct primitive. Conversely, we suggest that kinematic synergies, frequently discussed as primitives of complex actions, may be an emergent consequence of neuromuscular impedance. To illustrate how these dynamic primitives may account for complex actions, we briefly review three types of interactive behaviors: constrained motion, impact tasks, and manipulation of dynamic objects. PMID:23124919

Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.

PubMed

Bourdieu, Antonin; Avalon, Maryse; Lapostolle, Véronique; Ismail, Sadek; Mombled, Margaux; Debeissat, Christelle; Guérinet, Marianne; Duchez, Pascale; Chevaleyre, Jean; Vlaski-Lafarge, Marija; Villacreces, Arnaud; Praloran, Vincent; Ivanovic, Zoran; Brunet de la Grange, Philippe

2018-01-01

Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O 2 concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy. © 2017 Wiley Periodicals, Inc.

Endometrial stromal sarcoma involving the urinary bladder: a study of 6 cases.

PubMed

Tian, Wei; Latour, Mathieu; Epstein, Jonathan I

2014-07-01

Endometrial stromal sarcoma (ESS) involving the urinary bladder is very rare, with no prior series reported. We identified 6 cases of low-grade ESS involving the bladder at our institution (1998 to 2013), 5 of them consults. The median age at bladder involvement was 60 years (range, 44 to 77 y). One patient presented with bladder involvement at initial diagnosis of ESS. The remaining 5 cases with bladder involvement presented 7 to 30 years (mean 18 y) after a known diagnosis of ESS (n=2) or after a remote history of hysterectomy with an uncertain diagnosis (n=3). The location of bladder involvement included dome (n=1), trigone (n=2), diffuse (n=1), and unknown (n=2). Two cases demonstrated worm-like infiltrating tumor nests classic of low-grade ESS with little stromal reaction with retraction artifact mimicking vascular invasion. One case originating from the ovary showed focal glandular differentiation in the bladder, resembling endometriosis. Two cases had abundant keloidal collagen formation, arranged haphazardly or in a sunburst pattern. One case showed primitive cells infiltrating entirely hyalinized stroma, after chemotherapy given for a misdiagnosis of urothelial carcinoma. CD31 was negative in all cases, except for 1 case with obvious large vessel invasion. The differential diagnosis included a large nested variant of urothelial carcinoma, carcinoid tumor, synovial sarcoma, solitary fibrous tumor, Ewing sarcoma/primitive neuroectodermal tumors, and endometriosis. CD10 was strongly positive in 5 cases, and 1 case had very focal, moderate staining. Estrogen receptor showed strong and diffuse staining in all 6 cases. Progesterone receptor showed moderate to strong staining in 5 cases and focal staining in 1 case. One case showed PAX8 expression, and 2 cases showed p16 nuclear and cytoplasmic expression. CD56 showed weak to strong staining in 4 cases. Two cases had diffuse synaptophysin, and 1 case had focal p63 positivity. GATA-3, CD34, and CD99 were negative in all cases. The Ki-67 index was 1% to 10% (mean 4%). The mitotic count was 0 to 3/10 HPF (mean <1/10 HPF). Two patients had metastases to pelvic lymph nodes, and 1 had possible lung metastasis. Three patients were treated with Megace and 1 with Arimidex after surgery. Follow-up averaged 19 years (0 to 33 y) after the initial diagnosis of ESS or hysterectomy and 3.5 years (0 to 11 y) after bladder surgery. ESS involving the bladder is extremely rare with a very long interval from onset to bladder involvement. In female patients, low-grade spindle cell lesions involving the bladder should include ESS in the differential diagnosis.

Connected components of irreducible maps and 1D quantum phases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szehr, Oleg, E-mail: oleg.szehr@posteo.de; Wolf, Michael M., E-mail: wolf@ma.tum.de

We investigate elementary topological properties of sets of completely positive (CP) maps that arise in quantum Perron-Frobenius theory. We prove that the set of primitive CP maps of fixed Kraus rank is path-connected and we provide a complete classification of the connected components of irreducible CP maps at given Kraus rank and fixed peripheral spectrum in terms of a multiplicity index. These findings are then applied to analyse 1D quantum phases by studying equivalence classes of translational invariant matrix product states that correspond to the connected components of the respective CP maps. Our results extend the previously obtained picture inmore » that they do not require blocking of physical sites, they lead to analytic paths, and they allow us to decompose into ergodic components and to study the breaking of translational symmetry.« less

Breaking the rules? X-ray examination of hematopoietic stem cell grafts at international airports.

PubMed

Petzer, Andreas L; Speth, Hans-Georg; Hoflehner, Elisabeth; Clausen, Johannes; Nachbaur, David; Gastl, Günther; Gunsilius, Eberhard

2002-06-15

Hematopoietic stem cell grafts from unrelated donors are commonly transported by aircraft. They must not be subjected to x-rays during security checks, which may cause inconvenient discussions between the courier and the airport security staff. We exposed hematopoietic stem cells from mobilized peripheral blood to a widely used x-ray hand-luggage control system. Cell viability as well as growth in vitro of mature progenitor cells (colony-forming cells), primitive progenitor cells (long-term culture-initiating cells), and lymphocytes were not altered even after 10 passages through the hand-luggage control system. Thus, repeated exposure to the low radiation dose of hand-luggage control systems (1.5 +/- 0.6 microSv per exposure) seems to be harmless for hematopoietic stem cells, which should simplify the international transport of stem cell grafts.

Self-organization of neural patterns and structures in 3D culture of stem cells

NASA Astrophysics Data System (ADS)

Sasai, Yoshiki

2013-05-01

Over the last several years, much progress has been made for in vitro culture of mouse and human ES cells. Our laboratory focuses on the molecular and cellular mechanisms of neural differentiation from pluripotent cells. Pluripotent cells first become committed to the ectodermal fate and subsequently differentiate into uncommitted neuroectodermal cells. Both previous mammalian and amphibian studies on pluripotent cells have indicated that the neural fate is a sort of the basal direction of the differentiation of these cells while mesoendodermal differentiation requires extrinsic inductive signals. ES cells differentiate into neuroectodermal cells with a rostral-most character (telencephalon and hypothalamus) when they are cultured in the absence of strong patterning signals. In this talk, I first discuss this issue by referring to our recent data on the mechanism of spontaneous neural differentiation in serum-free culture of mouse ES cells. Then, I will talk about self-organization phenomena observed in 3D culture of ES cells, which lead to tissue-autonomous formation of regional structures such as layered cortical tissues. I also discuss our new attempt to monitor these in vitro morphogenetic processes by live imaging, in particular, self-organizing morphogenesis of the optic cup in three-dimensional cultures.

ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sulman, E.P.; Brodeur, G.M.; Ikegaki, N.

1997-03-01

Mouse eck, a member of the EPH gene family, has been mapped to mouse chromosome 4. The syntenic relationship between this chromosome and human chromosome 1 suggests that the human ECK gene maps to the distal short arm of human chromosome 1 (1p). Since this region is frequently deleted or altered in certain tumors of neuroectodermal origin, it is important to define the specific chromosomal localization of the human ECK gene. PCR screening of a rodent-human somatic cell hybrid panel by ECK-specific primers showed that ECK is indeed localized to human chromosome 1. Additional PCR screening of a regional screeningmore » panel for chromosome 1p indicated that ECK is localized to 1p36, distal to FUCA1. Furthermore, fluorescence in situ hybridization analysis with an ECK-specific P1 clone showed that ECK maps proximal to genetic marker D1S228. Taken together, the data suggest that ECK maps to 1p36.1, a region that is frequently deleted in neuroblastoma, melanoma, and other neuroectodermal tumors. 23 refs., 3 figs.« less

The mevalonate pathway regulates primitive streak formation via protein farnesylation

PubMed Central

Okamoto-Uchida, Yoshimi; Yu, Ruoxing; Miyamura, Norio; Arima, Norie; Ishigami-Yuasa, Mari; Kagechika, Hiroyuki; Yoshida, Suguru; Hosoya, Takamitsu; Nawa, Makiko; Kasama, Takeshi; Asaoka, Yoichi; Alois, Reiner Wimmer; Elling, Ulrich; Penninger, Josef M.; Nishina, Sachiko; Azuma, Noriyuki; Nishina, Hiroshi

2016-01-01

The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis. A tagging-via-substrate approach revealed that nuclear lamin B1 and small G proteins were farnesylated in embryoid bodies and important for primitive streak gene expression. In conclusion, protein farnesylation driven by the mevalonate pathway is a metabolic cue essential for primitive streak formation. PMID:27883036

Meningoceles, meningomyeloceles, and encephaloceles: a neuro-dermatopathologic study of 132 cases.

PubMed

Berry, A D; Patterson, J W

1991-06-01

Because there have been few comprehensive histopathologic studies of meningomyeloceles and related malformations, we undertook a systematic study of these lesions. One hundred and thirty two cases were obtained from our surgical pathology files; these included 38 meningoceles, 71 meningomyeloceles, and 23 encephaloceles. Tissue sections were stained with hematoxylin and eosin; special stains included trichrome, alcian blue, Fontana-Masson, Nissl, Holzer, and immunoperoxidase for glial fibrillary acidic protein. Epithelial changes included ulceration, atrophy, or nevoid hyperplasia of the epidermis, and loss of appendages. Mesodermal features included fibrous zones resembling dura, subarachnoid tissue or scar (99% of cases), increased numbers of blood vessels (83%), hypertrophy of arrector pili muscle (42%), lipoma formation (38%), and immature skeletal muscle fibers (5%) that rarely intermingled with neuropil-like matrix. The latter tissue was identified in 71% of cases and included neurons, astrocytes, oligodendroglia, and ependyma. Forty-eight percent of cases included peripheral nerve fibers or roots, and some fibers formed onion bulb or Pacinian corpuscle-like structures. Meningothelial cells were observed in 26% of cases and sometimes formed recognizable whorls. Choroid plexus was noted in 3 cases, one example showing an unusual dystrophic calcification that formed long parallel spicules. Pigmented dendritic cells were observed within zones of fibrous tissue in 10% of cases. These malformations involve complex arrangements of cutaneous, neuroectodermal, and mesodermal elements. Because they may be encountered by dermatopathologists, familiarity with the microscopic features of dysraphic lesions is essential.

Conserved gene regulatory module specifies lateral neural borders across bilaterians

PubMed Central

Li, Yongbin; Zhao, Di; Horie, Takeo; Chen, Geng; Bao, Hongcun; Chen, Siyu; Liu, Weihong; Horie, Ryoko; Liang, Tao; Dong, Biyu; Feng, Qianqian; Tao, Qinghua

2017-01-01

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans. Second, orthologs of the vertebrate NPB specification module (Msx/vab-15, Pax3/7/pax-3, and Zic/ref-2) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref-2 in C. elegans. Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans, Drosophila melanogaster, and Ciona intestinalis. We also identify a novel lateral neural border specifier, ZNF703/tlp-1, which functions synergistically with Msx/vab-15 in both C. elegans and Xenopus laevis. These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians. PMID:28716930

Conserved gene regulatory module specifies lateral neural borders across bilaterians.

PubMed

Li, Yongbin; Zhao, Di; Horie, Takeo; Chen, Geng; Bao, Hongcun; Chen, Siyu; Liu, Weihong; Horie, Ryoko; Liang, Tao; Dong, Biyu; Feng, Qianqian; Tao, Qinghua; Liu, Xiao

2017-08-01

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module ( Msx/vab-15 , Pax3/7/pax-3 , and Zic/ref-2 ) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref- 2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans , Drosophila melanogaster , and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1 , which functions synergistically with Msx/vab- 15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Merchant, Thomas E.; Gajjar, Amar

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametricmore » maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.« less

Long-term neurologic health and psychosocial function of adult survivors of childhood medulloblastoma/PNET: a report from the Childhood Cancer Survivor Study.

PubMed

King, Allison A; Seidel, Kristy; Di, Chongzhi; Leisenring, Wendy M; Perkins, Stephanie Mabry; Krull, Kevin R; Sklar, Charles A; Green, Daniel M; Armstrong, Gregory T; Zeltzer, Lonnie K; Wells, Elizabeth; Stovall, Marilyn; Ullrich, Nicole J; Oeffinger, Kevin C; Robison, Leslie L; Packer, Roger J

2017-05-01

Medulloblastoma is the most common malignant childhood brain tumor, although long-term risks for chronic neurologic health and psychosocial functioning in aging adult survivors are incompletely characterized. The Childhood Cancer Survivor Study (CCSS) includes 380 five-year survivors of medulloblastoma/primitive neuroectodermal tumor (PNET; median age at follow-up: 30 y, interquartile range 24-36) and sibling comparison (n = 4031). Cumulative incidence of neurologic health conditions was reported. Cox regression models provided hazard ratios (HRs) and 95% CIs. Cross-sectional outcomes were assessed using generalized linear models. Compared with siblings, survivors were at increased risk of late-onset hearing loss (HR: 36.0, 95% CI: 23.6-54.9), stroke (HR: 33.9, 95% CI: 17.8-64.7), seizure (HR: 12.8, 95% CI: 9.0-18.1), poor balance (HR: 10.4, 95% CI: 6.7-15.9), tinnitus (HR: 4.8, 95% CI: 3.5-6.8), and cataracts (HR: 31.8, 95% CI: 16.7-60.5). Temporal/frontal lobe radiotherapy of 50 Gy or more increased risk for hearing loss (HR: 1.9, 95% CI: 1.1-1.3), seizure (HR: 2.1, 95% CI: 1.1-3.9), stroke (HR: 3.5, 95% CI: 1.3-9.1), and tinnitus (HR: 2.0, 95% CI: 1.0-3.9). Survivors were less likely than siblings to earn a college degree (relative risk [RR]: 0.49, 95% CI: 0.39-0.60), marry (RR: 0.35, 95% CI: 0.29-0.42), and live independently (RR: 0.58, 95% CI: 0.52-0.66). Adult survivors of childhood medulloblastoma/PNET demonstrate pronounced risk for hearing impairment, stroke, lower educational attainment, and social independence. Interventions to support survivors should be a high priority. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Vertebral Body Growth After Craniospinal Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartley, Katherine A.; Li Chenghong; Laningham, Fred H.

2008-04-01

Purpose: To estimate the effects of radiotherapy and clinical factors on vertebral growth in patients with medulloblastoma and supratentorial primitive neuroectodermal tumors treated with craniospinal irradiation (CSI) and chemotherapy. Methods and Materials: The height of eight individual or grouped vertebral bodies (C3, C3-C4, T4, T4-T5, C6-T3, T4-T7, L3, L1-L5) was measured before and after CSI (23.4 or 36-39.6 Gy) in 61 patients. Of the 61 patients, 40 were boys and 21 were girls (median age, 7 years; range, 3-13 years), treated between October 1996 and October 2003. Sagittal T{sub 1}-weighted magnetic resonance images were used for the craniocaudal measurements. Themore » measurements numbered 275 (median, 5/patient; range, 3-7). The median follow-up after CSI was 44.1 months (range, 13.8-74.9 months). Results: Significant growth was observed in all measured vertebrae. Excluding C3-C4, the growth rate of the grouped vertebrae was affected by age, gender, and CSI dose (risk classification). The risk classification alone affected the growth rates of C3 (p = 0.002) and L3 (p = 0.02). Before CSI, the length of all vertebral bodies was an increasing function of age (p <0.0001). The C3 length before CSI was affected by gender and risk classification: C3 was longer for female (p = 0.07) and high-risk (p = 0.07) patients. Conclusion: All vertebrae grew significantly after CSI, with the vertebrae of the boys and younger patients growing at a rate greater than that of their counterparts. The effect of age was similar across all vertebrae, and gender had the greatest effect on the growth of the lower cervical and upper thoracic vertebrae. The effect of the risk classification was greatest in the lumbar spine by a factor of {<=}10.« less

Unravelling the mystery of stem/progenitor cells in human breast milk.

PubMed

Fan, Yiping; Chong, Yap Seng; Choolani, Mahesh A; Cregan, Mark D; Chan, Jerry K Y

2010-12-28

Mammary stem cells have been extensively studied as a system to delineate the pathogenesis and treatment of breast cancer. However, research on mammary stem cells requires tissue biopsies which limit the quantity of samples available. We have previously identified putative mammary stem cells in human breast milk, and here, we further characterised the cellular component of human breast milk. We identified markers associated with haemopoietic, mesenchymal and neuro-epithelial lineages in the cellular component of human breast milk. We found 2.6 ± 0.8% (mean ± SEM) and 0.7 ± 0.2% of the whole cell population (WCP) were found to be CD133+ and CD34+ respectively, 27.8 ± 9.1% of the WCP to be positive for Stro-1 through flow-cytometry. Expressions of neuro-ectodermal stem cell markers such as nestin and cytokeratin 5 were found through reverse-transcription polymerase chain reaction (RT-PCR), and in 4.17 ± 0.2% and 0.9 ± 0.2% of the WCP on flow-cytometry. We also established the presence of a side-population (SP) (1.8 ± 0.4% of WCP) as well as CD133+ cells (1.7 ± 0.5% of the WCP). Characterisation of the sorted SP and non-SP, CD133+ and CD133- cells carried out showed enrichment of CD326 (EPCAM) in the SP cells (50.6 ± 8.6 vs 18.1 ± 6.0, P-value  = 0.02). However, culture in a wide range of in vitro conditions revealed the atypical behaviour of stem/progenitor cells in human breast milk; in that if they are present, they do not respond to established culture protocols of stem/progenitor cells. The identification of primitive cell types within human breast milk may provide a non-invasive source of relevant mammary cells for a wide-range of applications; even the possibility of banking one's own stem cell for every breastfeeding woman.

Bag3-Induced Autophagy Is Associated with Degradation of JCV Oncoprotein, T-Ag

PubMed Central

Sariyer, Ilker Kudret; Merabova, Nana; Patel, Prem Kumer; Knezevic, Tijana; Rosati, Alessandra; Turco, Maria C.; Khalili, Kamel

2012-01-01

JC virus, JCV, is a human neurotropic polyomavirus whose replication in glial cells causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition, JCV possesses oncogenic activity and expression of its transforming protein, large T-antigen (T-Ag), in several experimental animals induces tumors of neural origin. Further, the presence of JCV DNA and T-Ag have been repeatedly observed in several human malignant tissues including primitive neuroectodermal tumors and glioblastomas. Earlier studies have demonstrated that Bag3, a member of the Bcl-2-associated athanogene (Bag) family of proteins, which is implicated in autophagy and apoptosis, is downregulated upon JCV infection of glial cells and that JCV T-Ag is responsible for suppressing the activity of the BAG3 promoter. Here, we investigated the possible impact of Bag3 on T-Ag expression in JCV-infected human primary glial cells as well as in cells derived from T-Ag-induced medulloblastoma in transgenic animals. Results from these studies revealed that overexpression of Bag3 drastically decreases the level of T-Ag expression by inducing the autophagic degradation of the viral protein. Interestingly, this event leads to the inhibition of JCV infection of glial cells, suggesting that the reduced levels of T-antigen seen upon the overexpression of Bag3 has a biological impact on the viral lytic cycle. Results from protein-protein interaction studies showed that T-Ag and Bag3 physically interact with each other through the zinc-finger of T-Ag and the proline rich domains of Bag3, and this interaction is important for the autophagic degradation of T-Ag. Our observations open a new avenue of research for better understanding of virus-host interaction by investigating the interplay between T-Ag and Bag3, and their impact on the development of JCV-associated diseases. PMID:22984599

Bag3-induced autophagy is associated with degradation of JCV oncoprotein, T-Ag.

PubMed

Sariyer, Ilker Kudret; Merabova, Nana; Patel, Prem Kumer; Knezevic, Tijana; Rosati, Alessandra; Turco, Maria C; Khalili, Kamel

2012-01-01

JC virus, JCV, is a human neurotropic polyomavirus whose replication in glial cells causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition, JCV possesses oncogenic activity and expression of its transforming protein, large T-antigen (T-Ag), in several experimental animals induces tumors of neural origin. Further, the presence of JCV DNA and T-Ag have been repeatedly observed in several human malignant tissues including primitive neuroectodermal tumors and glioblastomas. Earlier studies have demonstrated that Bag3, a member of the Bcl-2-associated athanogene (Bag) family of proteins, which is implicated in autophagy and apoptosis, is downregulated upon JCV infection of glial cells and that JCV T-Ag is responsible for suppressing the activity of the BAG3 promoter. Here, we investigated the possible impact of Bag3 on T-Ag expression in JCV-infected human primary glial cells as well as in cells derived from T-Ag-induced medulloblastoma in transgenic animals. Results from these studies revealed that overexpression of Bag3 drastically decreases the level of T-Ag expression by inducing the autophagic degradation of the viral protein. Interestingly, this event leads to the inhibition of JCV infection of glial cells, suggesting that the reduced levels of T-antigen seen upon the overexpression of Bag3 has a biological impact on the viral lytic cycle. Results from protein-protein interaction studies showed that T-Ag and Bag3 physically interact with each other through the zinc-finger of T-Ag and the proline rich domains of Bag3, and this interaction is important for the autophagic degradation of T-Ag. Our observations open a new avenue of research for better understanding of virus-host interaction by investigating the interplay between T-Ag and Bag3, and their impact on the development of JCV-associated diseases.

Unravelling the Mystery of Stem/Progenitor Cells in Human Breast Milk

PubMed Central

Fan, Yiping; Chong, Yap Seng; Choolani, Mahesh A.; Cregan, Mark D.; Chan, Jerry K. Y.

2010-01-01

Background Mammary stem cells have been extensively studied as a system to delineate the pathogenesis and treatment of breast cancer. However, research on mammary stem cells requires tissue biopsies which limit the quantity of samples available. We have previously identified putative mammary stem cells in human breast milk, and here, we further characterised the cellular component of human breast milk. Methodology/Principal Findings We identified markers associated with haemopoietic, mesenchymal and neuro-epithelial lineages in the cellular component of human breast milk. We found 2.6±0.8% (mean±SEM) and 0.7±0.2% of the whole cell population (WCP) were found to be CD133+ and CD34+ respectively, 27.8±9.1% of the WCP to be positive for Stro-1 through flow-cytometry. Expressions of neuro-ectodermal stem cell markers such as nestin and cytokeratin 5 were found through reverse-transcription polymerase chain reaction (RT-PCR), and in 4.17±0.2% and 0.9±0.2% of the WCP on flow-cytometry. We also established the presence of a side-population (SP) (1.8±0.4% of WCP) as well as CD133+ cells (1.7±0.5% of the WCP). Characterisation of the sorted SP and non-SP, CD133+ and CD133- cells carried out showed enrichment of CD326 (EPCAM) in the SP cells (50.6±8.6 vs 18.1±6.0, P-value  = 0.02). However, culture in a wide range of in vitro conditions revealed the atypical behaviour of stem/progenitor cells in human breast milk; in that if they are present, they do not respond to established culture protocols of stem/progenitor cells. Conclusions/Significance The identification of primitive cell types within human breast milk may provide a non-invasive source of relevant mammary cells for a wide-range of applications; even the possibility of banking one's own stem cell for every breastfeeding woman. PMID:21203434

Molecular pathogenesis and targeted therapeutics in Ewing sarcoma/primitive neuroectodermal tumours

PubMed Central

2012-01-01

Background Ewing sarcoma/PNET is managed with treatment paradigms involving combinations of chemotherapy, surgery, and sometimes radiation. Although the 5-year survival rate of non-metastatic disease approaches 70%, those cases that are metastatic and those that recur have 5-year survival rates of less than 20%. Molecularly targeted treatments offer the potential to further improve treatment outcomes. Methods A PUBMED search was performed from 1997 to 2011. Published literature that included the topic of the Ewing sarcoma/PNET was also referenced. Results Insulin-like growth factor-1 receptor (IGF-1R) antagonists have demonstrated modest single agent efficacy in phase I/II clinical trials in Ewing sarcoma/PNET, but have a strong preclinical rationale. Based on in vitro and animal data, treatment using antisense RNA and cDNA oligonucleotides directed at silencing the EWS-FLI chimera that occurs in most Ewing sarcoma/PNET may have potential therapeutic importance. However drug delivery and degradation problems may limit this therapeutic approach. Protein-protein interactions can be targeted by inhibition of RNA helicase A, which binds to EWS/FLI as part of the transcriptional complex. Tumour necrosis factor related apoptosis inducing ligand induction using interferon has been used in preclinical models. Interferons may be incorporated into future chemotherapeutic treatment paradigms. Histone deacetylase inhibitors can restore TGF-β receptor II allowing TFF-β signalling, which appears to inhibit growth of Ewing sarcoma/PNET cell lines in vitro. Immunotherapy using allogeneic natural killer cells has activity in Ewing sarcoma/PNET cell lines and xenograft models. Finally, cyclin dependent kinase inhibitors such as flavopiridol may be clinically efficacious in relapsed Ewing sarcoma/PNET. Conclusion Preclinical evidence exists that targeted therapeutics may be efficacious in the ESFT. IGF-1R antagonists have demonstrated efficacy in phase I/II clinical trials, although predicting responses remains a challenge. The future treatment of Ewing sarcoma/PNET is likely to be improved by these scientific advances. PMID:22587874

Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data.

PubMed

Bishop, Andrew J; McDonald, Mark W; Chang, Andrew L; Esiashvili, Natia

2012-01-01

To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone. Copyright © 2012 Elsevier Inc. All rights reserved.

Diagnostic implications of IDH1-R132H and OLIG2 expression patterns in rare and challenging glioblastoma variants.

PubMed

Joseph, Nancy M; Phillips, Joanna; Dahiya, Sonika; M Felicella, Michelle; Tihan, Tarik; Brat, Daniel J; Perry, Arie

2013-03-01

Recent work has demonstrated that nearly all diffuse gliomas display nuclear immunoreactivity for the bHLH transcription factor OLIG2, and the R132H mutant isocitrate dehydrogenase 1 (IDH1) protein is expressed in the majority of diffuse gliomas other than primary glioblastoma. However, these antibodies have not been widely applied to rarer glioblastoma variants, which can be diagnostically challenging when the astrocytic features are subtle. We therefore surveyed the expression patterns of OLIG2 and IDH1 in 167 non-conventional glioblastomas, including 45 small cell glioblastomas, 45 gliosarcomas, 34 glioblastomas with primitive neuroectodermal tumor-like foci (PNET-like foci), 23 with an oligodendroglial component, 11 granular cell glioblastomas, and 9 giant cell glioblastomas. OLIG2 was strongly expressed in all glioblastomas with oligodendroglial component, 98% of small cell glioblastomas, and all granular cell glioblastomas, the latter being particularly helpful in ruling out macrophage-rich lesions. In 74% of glioblastomas with PNET-like foci, OLIG2 expression was retained in the PNET-like foci, providing a useful distinction from central nervous system PNETs. The glial component of gliosarcomas was OLIG2 positive in 93% of cases, but only 14% retained focal expression in the sarcomatous component; as such this marker would not reliably distinguish these from pure sarcoma in most cases. OLIG2 was expressed in 67% of giant cell glioblastomas. IDH1 was expressed in 55% of glioblastomas with oligodendroglial component, 15% of glioblastomas with PNET-like foci, 7% of gliosarcomas, and none of the small cell, granular cell, or giant cell glioblastomas. This provides further support for the notion that most glioblastomas with oligodendroglial component are secondary, while small cell glioblastomas, granular cell glioblastomas, and giant cell glioblastomas are primary variants. Therefore, in one of the most challenging differential diagnoses, IDH1 positivity could provide strong support for glioblastoma with oligodendroglial component, while essentially excluding small cell glioblastoma.

Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(+)/CD133(+)/CXCR4(+)/ Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells.

PubMed

Sovalat, Hanna; Scrofani, Maurice; Eidenschenk, Antoinette; Pasquet, Stéphanie; Rimelen, Valérie; Hénon, Philippe

2011-04-01

Recently, we demonstrated that normal human bone marrow (hBM)-derived CD34(+) cells, released into the peripheral blood after granulocyte colony-stimulating factor mobilization, contain cell subpopulations committed along endothelial and cardiac differentiation pathways. These subpopulations could play a key role in the regeneration of post-ischemic myocardial lesion after their direct intracardiac delivery. We hypothesized that these relevant cells might be issued from very small embryonic-like stem cells deposited in the BM during ontogenesis and reside lifelong in the adult BM, and that they could be mobilized into peripheral blood by granulocyte colony-stimulating factor. Samples of normal hBM and leukapheresis products harvested from cancer patients after granulocyte colony-stimulating factor mobilization were analyzed and sorted by multiparameter flow cytometry strategy. Immunofluorescence and reverse transcription quantitative polymerase chain reaction assays were performed to analyze the expression of typical pluripotent stem cells markers. A population of CD34(+)/CD133(+)/CXCR4(+)/Lin(-) CD45(-) immature cells was first isolated from the hBM or from leukapheresis products. Among this population, very small (2-5 μm) cells expressing Oct-4, Nanog, and stage-specific embryonic antigen-4 at protein and messenger RNA levels were identified. Our study supports the hypothesis that very small embryonic-like stem cells constitute a "mobile" pool of primitive/pluripotent stem cells that could be released from the BM into the peripheral blood under the influence of various physiological or pathological stimuli. In order to fully support that hBM- and leukapheresis product-derived very small embryonic-like stem cells are actually pluripotent, we are currently testing their ability to differentiate in vitro into cells from all three germ layers. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

Evaluating structural pattern recognition for handwritten math via primitive label graphs

NASA Astrophysics Data System (ADS)

Zanibbi, Richard; Mouchère, Harold; Viard-Gaudin, Christian

2013-01-01

Currently, structural pattern recognizer evaluations compare graphs of detected structure to target structures (i.e. ground truth) using recognition rates, recall and precision for object segmentation, classification and relationships. In document recognition, these target objects (e.g. symbols) are frequently comprised of multiple primitives (e.g. connected components, or strokes for online handwritten data), but current metrics do not characterize errors at the primitive level, from which object-level structure is obtained. Primitive label graphs are directed graphs defined over primitives and primitive pairs. We define new metrics obtained by Hamming distances over label graphs, which allow classification, segmentation and parsing errors to be characterized separately, or using a single measure. Recall and precision for detected objects may also be computed directly from label graphs. We illustrate the new metrics by comparing a new primitive-level evaluation to the symbol-level evaluation performed for the CROHME 2012 handwritten math recognition competition. A Python-based set of utilities for evaluating, visualizing and translating label graphs is publicly available.

Use of Optical Storage Devices as Shared Resources in Local Area Networks

DTIC Science & Technology

1989-09-01

13 3. SERVICE CALLS FOR MS-DOS CD-ROM EXTENSIONS . 14 4. MS-DOS PRIMITIVE GROUPS ....................... 15 5. RAM USAGE FOR VARIOUS LAN...17 2. Service Call Translation to DOS Primitives ............. 19 3. MS-DOS Device Drivers ............................. 21 4. MS-DOS/ROM...directed to I/O devices will be referred to as primitive instruction groups). These primitive instruction groups include keyboard, video, disk, serial

Method for concurrent execution of primitive operations by dynamically assigning operations based upon computational marked graph and availability of data

NASA Technical Reports Server (NTRS)

Mielke, Roland V. (Inventor); Stoughton, John W. (Inventor)

1990-01-01

Computationally complex primitive operations of an algorithm are executed concurrently in a plurality of functional units under the control of an assignment manager. The algorithm is preferably defined as a computationally marked graph contianing data status edges (paths) corresponding to each of the data flow edges. The assignment manager assigns primitive operations to the functional units and monitors completion of the primitive operations to determine data availability using the computational marked graph of the algorithm. All data accessing of the primitive operations is performed by the functional units independently of the assignment manager.

How to Spot a Primitive Black Hole

NASA Image and Video Library

2010-03-17

These two data plots from NASA Spitzer Space Telescope show a primitive supermassive black hole top compared to a typical one; usually, dust tori are missing and only gas disks are observed in primitive black holes.

Primitive erythrocytes are generated from hemogenic endothelial cells.

PubMed

Stefanska, Monika; Batta, Kiran; Patel, Rahima; Florkowska, Magdalena; Kouskoff, Valerie; Lacaud, Georges

2017-07-25

Primitive erythroblasts are the first blood cells generated during embryonic hematopoiesis. Tracking their emergence both in vivo and in vitro has remained challenging due to the lack of specific cell surface markers. To selectively investigate primitive erythropoiesis, we have engineered a new transgenic embryonic stem (ES) cell line, where eGFP expression is driven by the regulatory sequences of the embryonic βH1 hemoglobin gene expressed specifically in primitive erythroid cells. Using this ES cell line, we observed that the first primitive erythroblasts are detected in vitro around day 1.5 of blast colony differentiation, within the cell population positive for the early hematopoietic progenitor marker CD41. Moreover, we establish that these eGFP + cells emerge from a hemogenic endothelial cell population similarly to their definitive hematopoietic counterparts. We further generated a corresponding βH1-eGFP transgenic mouse model and demonstrated the presence of a primitive erythroid primed hemogenic endothelial cell population in the developing embryo. Taken together, our findings demonstrate that both in vivo and in vitro primitive erythrocytes are generated from hemogenic endothelial cells.

[Vojta's method as the early neurodevelopmental diagnosis and therapy concept].

PubMed

Banaszek, Grazyna

2010-01-01

Vaclav Vojta (1917-2000) developed an early diagnostic method of the neurodevelopmental disorder of infants and came up with therapeutic concept consisting in releasing of global motor complexes by means of the stimulation of proper areas on patients body. In the diagnostics apart from very careful observation of the spontaneous movement of the infant and examination of the reflexes that are characteristic for the first weeks of human's life, Vojta applied the examination of the 7 postural reactions. Presence of the trouble in patterns and dynamics of the postural reactions Vojta called Central Nervous Coordination Disorder--CNCD and regarded as work diagnosis or alarm signal indicating necessity of application of the therapy, especially when asymmetry of the muscle tone and primitive reflexes beyond their physiological appearance period are observed or the number of the abnormal reactions exceeds 5. Global motor complexes as reflex locomotion--crawling and rotation--consist of all the partial motion patterns, which are gradually used by healthy infant in the process of postural and motor ontogenesis. Providing the central nervous system with proper external stimulation allows to, using neuronal plasticity, recreate an access to the human's postural development program and gradually replace pathological motor patterns by those more regular. Exercises repeated several times a day rebuilt support, erectile and vertical mechanisms, improve automatic postural control and phase lower limb movement. Affecting especially on autochtonic muscles of the spine exercises balance synergic cooperation of muscle groups in the trunk and those surrounding key body joints. This way they correct body's posture and peripheral motion and pathology of the outlasted primitive reflexes gradually withdraws.

A key heterogeneous structure of fractal networks based on inverse renormalization scheme

NASA Astrophysics Data System (ADS)

Bai, Yanan; Huang, Ning; Sun, Lina

2018-06-01

Self-similarity property of complex networks was found by the application of renormalization group theory. Based on this theory, network topologies can be classified into universality classes in the space of configurations. In return, through inverse renormalization scheme, a given primitive structure can grow into a pure fractal network, then adding different types of shortcuts, it exhibits different characteristics of complex networks. However, the effect of primitive structure on networks structural property has received less attention. In this paper, we introduce a degree variance index to measure the dispersion of nodes degree in the primitive structure, and investigate the effect of the primitive structure on network structural property quantified by network efficiency. Numerical simulations and theoretical analysis show a primitive structure is a key heterogeneous structure of generated networks based on inverse renormalization scheme, whether or not adding shortcuts, and the network efficiency is positively correlated with degree variance of the primitive structure.

Discovery of survival factor for primitive chronic myeloid leukemia cells using induced pluripotent stem cells

PubMed Central

Suknuntha, Kran; Ishii, Yuki; Tao, Lihong; Hu, Kejin; McIntosh, Brian E.; Yang, David; Swanson, Scott; Stewart, Ron; Wang, Jean Y.J.; Thomson, James; Slukvin, Igor

2016-01-01

A definitive cure for chronic myeloid leukemia (CML) requires identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the primitive hematopoietic cell compartment remains a major limiting factor for their study in humans. Here we show that primitive hematopoietic cells with typical LSC features, including adhesion defect, increased long-term survival and proliferation, and innate resistance to tyrosine kinase inhibitor (TKI) imatinib, can be generated de novo from reprogrammed primary CML cells. Using CML iPSC-derived primitive leukemia cells, we discovered olfactomedin 4 (OLFM4) as a novel factor that contributes to survival and growth of somatic lin−CD34+ cells from bone marrow of patients with CML in chronic phase, but not primitive hematopoietic cells from normal bone marrow. Overall, this study shows the feasibility and advantages of using reprogramming technology to develop strategies for targeting primitive leukemia cells. PMID:26561938

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

PubMed

Ma, Yi-Ran; Ren, Si-Hua; He, Yu-Xin; Wang, Lin-Lin; Jin, Li; Hao, Yi-Wen

2012-10-01

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.

A mutli-technique search for the most primitive CO chondrites

NASA Astrophysics Data System (ADS)

Alexander, C. M. O'D.; Greenwood, R. C.; Bowden, R.; Gibson, J. M.; Howard, K. T.; Franchi, I. A.

2018-01-01

As part of a study to identify the most primitive COs and to look for weakly altered CMs amongst the COs, we have conducted a multi-technique study of 16 Antarctic meteorites that had been classified as primitive COs. For this study, we have determined: (1) the bulk H, C and N abundances and isotopes, (2) bulk O isotopic compositions, (3) bulk modal mineralogies, and (4) for some selected samples the abundances and compositions of their insoluble organic matter (IOM). Two of the 16 meteorites do appear to be CMs - BUC 10943 seems to be a fairly typical CM, while MIL 090073 has probably been heated. Of the COs, DOM 08006 appears to be the most primitive CO identified to date and is quite distinct from the other members of its pairing group. The other COs fall into two groups that are less primitive than DOM 08006 and ALH 77307, the previously most primitive CO. The first group is composed of members of the DOM 08004 pairing group, except DOM 08006. The second group is composed of meteorites belonging to the MIL 03377 and MIL 07099 pairing groups. These two pairing groups should probably be combined. There is a dichotomy in the bulk O isotopes between the primitive (all Antarctic finds) and the more metamorphosed COs (mostly falls). This dichotomy can only partly be explained by the terrestrial weathering experienced by the primitive Antarctic samples. It seems that the more equilibrated samples interacted to a greater extent with 16O-poor material, probably water, than the more primitive meteorites.

Dynamic primitives in the control of locomotion.

PubMed

Hogan, Neville; Sternad, Dagmar

2013-01-01

Humans achieve locomotor dexterity that far exceeds the capability of modern robots, yet this is achieved despite slower actuators, imprecise sensors, and vastly slower communication. We propose that this spectacular performance arises from encoding motor commands in terms of dynamic primitives. We propose three primitives as a foundation for a comprehensive theoretical framework that can embrace a wide range of upper- and lower-limb behaviors. Building on previous work that suggested discrete and rhythmic movements as elementary dynamic behaviors, we define submovements and oscillations: as discrete movements cannot be combined with sufficient flexibility, we argue that suitably-defined submovements are primitives. As the term "rhythmic" may be ambiguous, we define oscillations as the corresponding class of primitives. We further propose mechanical impedances as a third class of dynamic primitives, necessary for interaction with the physical environment. Combination of these three classes of primitive requires care. One approach is through a generalized equivalent network: a virtual trajectory composed of simultaneous and/or sequential submovements and/or oscillations that interacts with mechanical impedances to produce observable forces and motions. Reliable experimental identification of these dynamic primitives presents challenges: identification of mechanical impedances is exquisitely sensitive to assumptions about their dynamic structure; identification of submovements and oscillations is sensitive to their assumed form and to details of the algorithm used to extract them. Some methods to address these challenges are presented. Some implications of this theoretical framework for locomotor rehabilitation are considered.

Antagonizing retinoic acid and FGF/MAPK pathways control posterior body patterning in the invertebrate chordate Ciona intestinalis.

PubMed

Pasini, Andrea; Manenti, Raoul; Rothbächer, Ute; Lemaire, Patrick

2012-01-01

Vertebrate embryos exploit the mutual inhibition between the RA and FGF signalling pathways to coordinate the proliferative elongation of the main body axis with the progressive patterning and differentiation of its neuroectodermal and paraxial mesodermal structures. The evolutionary history of this patterning system is still poorly understood. Here, we investigate the role played by the RA and FGF/MAPK signals during the development of the tail structures in the tunicate Ciona intestinalis, an invertebrate chordate belonging to the sister clade of vertebrates, in which the prototypical chordate body plan is established through very derived morphogenetic processes. Ciona embryos are constituted of few cells and develop according to a fixed lineage; elongation of the tail occurs largely by rearrangement of postmitotic cells; mesoderm segmentation and somitogenesis are absent. We show that in the Ciona embryo, the antagonism of the RA and FGF/MAPK signals is required to control the anteroposterior patterning of the tail epidermis. We also demonstrate that the RA, FGF/MAPK and canonical Wnt pathways control the anteroposterior patterning of the tail peripheral nervous system, and reveal the existence of distinct subpopulations of caudal epidermal neurons with different responsiveness to the RA, FGF/MAPK and canonical Wnt signals. Our data provide the first demonstration that the use of the antagonism between the RA and FGF signals to pattern the main body axis predates the emergence of vertebrates and highlight the evolutionary plasticity of this patterning strategy, showing that in different chordates it can be used to pattern different tissues within the same homologous body region.

Fundamental physical theories: Mathematical structures grounded on a primitive ontology

NASA Astrophysics Data System (ADS)

Allori, Valia

In my dissertation I analyze the structure of fundamental physical theories. I start with an analysis of what an adequate primitive ontology is, discussing the measurement problem in quantum mechanics and theirs solutions. It is commonly said that these theories have little in common. I argue instead that the moral of the measurement problem is that the wave function cannot represent physical objects and a common structure between these solutions can be recognized: each of them is about a clear three-dimensional primitive ontology that evolves according to a law determined by the wave function. The primitive ontology is what matter is made of while the wave function tells the matter how to move. One might think that what is important in the notion of primitive ontology is their three-dimensionality. If so, in a theory like classical electrodynamics electromagnetic fields would be part of the primitive ontology. I argue that, reflecting on what the purpose of a fundamental physical theory is, namely to explain the behavior of objects in three-dimensional space, one can recognize that a fundamental physical theory has a particular architecture. If so, electromagnetic fields play a different role in the theory than the particles and therefore should be considered, like the wave function, as part of the law. Therefore, we can characterize the general structure of a fundamental physical theory as a mathematical structure grounded on a primitive ontology. I explore this idea to better understand theories like classical mechanics and relativity, emphasizing that primitive ontology is crucial in the process of building new theories, being fundamental in identifying the symmetries. Finally, I analyze what it means to explain the word around us in terms of the notion of primitive ontology in the case of regularities of statistical character. Here is where the notion of typicality comes into play: we have explained a phenomenon if the typical histories of the primitive ontology give rise to the statistical regularities we observe.

A novel class sensitive hashing technique for large-scale content-based remote sensing image retrieval

NASA Astrophysics Data System (ADS)

Reato, Thomas; Demir, Begüm; Bruzzone, Lorenzo

2017-10-01

This paper presents a novel class sensitive hashing technique in the framework of large-scale content-based remote sensing (RS) image retrieval. The proposed technique aims at representing each image with multi-hash codes, each of which corresponds to a primitive (i.e., land cover class) present in the image. To this end, the proposed method consists of a three-steps algorithm. The first step is devoted to characterize each image by primitive class descriptors. These descriptors are obtained through a supervised approach, which initially extracts the image regions and their descriptors that are then associated with primitives present in the images. This step requires a set of annotated training regions to define primitive classes. A correspondence between the regions of an image and the primitive classes is built based on the probability of each primitive class to be present at each region. All the regions belonging to the specific primitive class with a probability higher than a given threshold are highly representative of that class. Thus, the average value of the descriptors of these regions is used to characterize that primitive. In the second step, the descriptors of primitive classes are transformed into multi-hash codes to represent each image. This is achieved by adapting the kernel-based supervised locality sensitive hashing method to multi-code hashing problems. The first two steps of the proposed technique, unlike the standard hashing methods, allow one to represent each image by a set of primitive class sensitive descriptors and their hash codes. Then, in the last step, the images in the archive that are very similar to a query image are retrieved based on a multi-hash-code-matching scheme. Experimental results obtained on an archive of aerial images confirm the effectiveness of the proposed technique in terms of retrieval accuracy when compared to the standard hashing methods.

Learning multivariate distributions by competitive assembly of marginals.

PubMed

Sánchez-Vega, Francisco; Younes, Laurent; Geman, Donald

2013-02-01

We present a new framework for learning high-dimensional multivariate probability distributions from estimated marginals. The approach is motivated by compositional models and Bayesian networks, and designed to adapt to small sample sizes. We start with a large, overlapping set of elementary statistical building blocks, or "primitives," which are low-dimensional marginal distributions learned from data. Each variable may appear in many primitives. Subsets of primitives are combined in a Lego-like fashion to construct a probabilistic graphical model; only a small fraction of the primitives will participate in any valid construction. Since primitives can be precomputed, parameter estimation and structure search are separated. Model complexity is controlled by strong biases; we adapt the primitives to the amount of training data and impose rules which restrict the merging of them into allowable compositions. The likelihood of the data decomposes into a sum of local gains, one for each primitive in the final structure. We focus on a specific subclass of networks which are binary forests. Structure optimization corresponds to an integer linear program and the maximizing composition can be computed for reasonably large numbers of variables. Performance is evaluated using both synthetic data and real datasets from natural language processing and computational biology.

Cometary dust: the diversity of primitive refractory grains

PubMed Central

Ishii, H. A.

2017-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive cometary particles has expanded significantly through microscale investigations of cosmic dust samples (anhydrous interplanetary dust particles (IDPs), chondritic porous (CP) IDPs and UltraCarbonaceous Antarctic micrometeorites, Stardust and Rosetta), as well as through remote sensing (Spitzer IR spectroscopy). Comet dust are aggregate particles of materials unequilibrated at submicrometre scales. We discuss the properties and processes experienced by primitive matter in comets. Primitive particles exhibit a diverse range of: structure and typology; distribution of constituents; concentration and form of carbonaceous and refractory organic matter; Mg- and Fe-contents of the silicate minerals; sulfides; existence/abundance of type II chondrule fragments; high-temperature calcium–aluminium inclusions and ameboid-olivine aggregates; and rarely occurring Mg-carbonates and magnetite, whose explanation requires aqueous alteration on parent bodies. The properties of refractory materials imply there were disc processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disc present at the time and in the region where the comets formed. This article is part of the themed issue ‘Cometary science after Rosetta’. PMID:28554979

Orbital infantile myofibroma: a case report and clinicopathologic review of 24 cases from the literature.

PubMed

Mynatt, Corey J; Feldman, Kenneth A; Thompson, Lester D R

2011-09-01

Isolated orbital infantile myofibroma are rare tumors in the head and neck. The mass-like clinical presentation and variable histologic features result in frequent misdiagnosis and potentially inappropriate clinical management. There are only a few reported cases in the English literature. Twenty-four patients with orbital infantile myofibroma or myofibromatosis were compiled from the English literature (Medline 1960-2011) and integrated with this case report. The patients included 14 males and 10 females, aged newborn to 10 years (mean, 34.8 months), who presented with a painless mass in the infra- or supraorbital regions, usually increasing in size andassociated with exophthalmos (n = 5). Females were on average older than their male counterparts (38.9 vs. 31.9 months, respectively; P = 0.71). The tumors were twice as frequent on the left (n = 16) than right (n = 8). Patients experienced symptoms for an average of 2.7 months before clinical presentation. The tumors involved the bone (n = 17) or the soft tissues (n = 7) of the orbit, with extension into the nasal or oral cavity (n = 3). The mean size was 3.0 cm, with a statistically significant difference between males and females (mean: 3.9 vs. 1.82; P = 0.0047), but without any differences based on age at presentation (P = 0.25), duration of symptoms (P = 0.66), or bone or soft tissue involvement (P = 0.51). Grossly, all tumors were well-circumscribed, firm to rubbery, homogenous, and white-grey. Histologically, the tumors were biphasic, showing whorled and nodular areas of fusiform cells with extracellular collagen, mixed with a population of small, primitive-appearing, darkly staining cells. Necrosis was not present, but mitoses could be seen. Tumors with immunohistochemistry performed showed strong and diffuse smooth muscle actin and vimentin immunoreactivity, but were negative with muscle specific actin, desmin, MYOD1, myogenin, S100 protein, GFAP, keratin, CD31, 34, Factor VIIIR-Ag, and CD45RB. The principle histologic differential diagnosis includes juvenile hyaline fibromatosis, fibrous hamartoma of infancy, fibromatosis coli, leiomyoma, infantile hemangiopericytoma, infantile fibrosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, and lymphoma. All patients were managed with surgery. Recurrences developed in two patients at 4 and 6 months, respectively. Follow-up data was available on all but two patients (n = 22). These patients were either alive without evidence of disease (n = 18), alive but with disease (n = 3), or had died unrelated to this disease (i.e., neuroblastoma, n = 1). Orbital infantile myofibroma is a rare tumor, presenting in infancy as an enlarging mass of the orbit, with characteristic histomorphologic and immunophenotypic features. Orbital disease is usually isolated rather than part of systemic disease, and shows an excellent long-term prognosis, making appropriate separation from other conditions important.

Basic primitives for molecular diagram sketching

PubMed Central

2010-01-01

A collection of primitive operations for molecular diagram sketching has been developed. These primitives compose a concise set of operations which can be used to construct publication-quality 2 D coordinates for molecular structures using a bare minimum of input bandwidth. The input requirements for each primitive consist of a small number of discrete choices, which means that these primitives can be used to form the basis of a user interface which does not require an accurate pointing device. This is particularly relevant to software designed for contemporary mobile platforms. The reduction of input bandwidth is accomplished by using algorithmic methods for anticipating probable geometries during the sketching process, and by intelligent use of template grafting. The algorithms and their uses are described in detail. PMID:20923555

Multi-processor including data flow accelerator module

DOEpatents

Davidson, George S.; Pierce, Paul E.

1990-01-01

An accelerator module for a data flow computer includes an intelligent memory. The module is added to a multiprocessor arrangement and uses a shared tagged memory architecture in the data flow computer. The intelligent memory module assigns locations for holding data values in correspondence with arcs leading to a node in a data dependency graph. Each primitive computation is associated with a corresponding memory cell, including a number of slots for operands needed to execute a primitive computation, a primitive identifying pointer, and linking slots for distributing the result of the cell computation to other cells requiring that result as an operand. Circuitry is provided for utilizing tag bits to determine automatically when all operands required by a processor are available and for scheduling the primitive for execution in a queue. Each memory cell of the module may be associated with any of the primitives, and the particular primitive to be executed by the processor associated with the cell is identified by providing an index, such as the cell number for the primitive, to the primitive lookup table of starting addresses. The module thus serves to perform functions previously performed by a number of sections of data flow architectures and coexists with conventional shared memory therein. A multiprocessing system including the module operates in a hybrid mode, wherein the same processing modules are used to perform some processing in a sequential mode, under immediate control of an operating system, while performing other processing in a data flow mode.

Dynamic primitives in the control of locomotion

PubMed Central

Hogan, Neville; Sternad, Dagmar

2013-01-01

Humans achieve locomotor dexterity that far exceeds the capability of modern robots, yet this is achieved despite slower actuators, imprecise sensors, and vastly slower communication. We propose that this spectacular performance arises from encoding motor commands in terms of dynamic primitives. We propose three primitives as a foundation for a comprehensive theoretical framework that can embrace a wide range of upper- and lower-limb behaviors. Building on previous work that suggested discrete and rhythmic movements as elementary dynamic behaviors, we define submovements and oscillations: as discrete movements cannot be combined with sufficient flexibility, we argue that suitably-defined submovements are primitives. As the term “rhythmic” may be ambiguous, we define oscillations as the corresponding class of primitives. We further propose mechanical impedances as a third class of dynamic primitives, necessary for interaction with the physical environment. Combination of these three classes of primitive requires care. One approach is through a generalized equivalent network: a virtual trajectory composed of simultaneous and/or sequential submovements and/or oscillations that interacts with mechanical impedances to produce observable forces and motions. Reliable experimental identification of these dynamic primitives presents challenges: identification of mechanical impedances is exquisitely sensitive to assumptions about their dynamic structure; identification of submovements and oscillations is sensitive to their assumed form and to details of the algorithm used to extract them. Some methods to address these challenges are presented. Some implications of this theoretical framework for locomotor rehabilitation are considered. PMID:23801959

Model-Free Primitive-Based Iterative Learning Control Approach to Trajectory Tracking of MIMO Systems With Experimental Validation.

PubMed

Radac, Mircea-Bogdan; Precup, Radu-Emil; Petriu, Emil M

2015-11-01

This paper proposes a novel model-free trajectory tracking of multiple-input multiple-output (MIMO) systems by the combination of iterative learning control (ILC) and primitives. The optimal trajectory tracking solution is obtained in terms of previously learned solutions to simple tasks called primitives. The library of primitives that are stored in memory consists of pairs of reference input/controlled output signals. The reference input primitives are optimized in a model-free ILC framework without using knowledge of the controlled process. The guaranteed convergence of the learning scheme is built upon a model-free virtual reference feedback tuning design of the feedback decoupling controller. Each new complex trajectory to be tracked is decomposed into the output primitives regarded as basis functions. The optimal reference input for the control system to track the desired trajectory is next recomposed from the reference input primitives. This is advantageous because the optimal reference input is computed straightforward without the need to learn from repeated executions of the tracking task. In addition, the optimization problem specific to trajectory tracking of square MIMO systems is decomposed in a set of optimization problems assigned to each separate single-input single-output control channel that ensures a convenient model-free decoupling. The new model-free primitive-based ILC approach is capable of planning, reasoning, and learning. A case study dealing with the model-free control tuning for a nonlinear aerodynamic system is included to validate the new approach. The experimental results are given.

36 CFR 261.21 - National Forest primitive areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false National Forest primitive areas. 261.21 Section 261.21 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE PROHIBITIONS General Prohibitions § 261.21 National Forest primitive areas. The following are...

The Distributed Memory Computing Conference (5th) Held in Charleston, South Carolina on April 8-12, 1990. Volume 1. Applications

DTIC Science & Technology

1991-03-31

nodes, directional arrows show the parent and child rela- and the graphics driver runs on the CP, i.e., the tionship of processes. Although there is a...about ODB plus some number of transitory primitives, whether or not its child primitives are resident. Transitory primitives are discarded as needed...true if this Hnode’s child primitives approached. are not resident. This method of ODB decomposition has the ability to distribute a very large number of

EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation

PubMed Central

Richter, Günther H. S.; Plehm, Stephanie; Fasan, Annette; Rössler, Sabine; Unland, Rebekka; Bennani-Baiti, Idriss M.; Hotfilder, Marc; Löwel, Diana; von Luettichau, Irene; Mossbrugger, Ilona; Quintanilla-Martinez, Leticia; Kovar, Heinrich; Staege, Martin S.; Müller-Tidow, Carsten; Burdach, Stefan

2009-01-01

Ewing tumors (ET) are highly malignant, localized in bone or soft tissue, and are molecularly defined by ews/ets translocations. DNA microarray analysis revealed a relationship of ET to both endothelium and fetal neural crest. We identified expression of histone methyltransferase enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. Suppressive activity of EZH2 maintains stemness in normal and malignant cells. Here, we found EWS/FLI1 bound to the EZH2 promoter in vivo, and induced EZH2 expression in ET and mesenchymal stem cells. Down-regulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis was suppressed in immunodeficient Rag2−/−γC−/− mice. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR), as well as genes involved in neuroectodermal and endothelial differentiation (EMP1, EPHB2, GFAP, and GAP43). These data suggest that EZH2 might have a central role in ET pathology by shaping the oncogenicity and stem cell phenotype of this tumor. PMID:19289832

Generalized compliant motion primitive

NASA Technical Reports Server (NTRS)

Backes, Paul G. (Inventor)

1994-01-01

This invention relates to a general primitive for controlling a telerobot with a set of input parameters. The primitive includes a trajectory generator; a teleoperation sensor; a joint limit generator; a force setpoint generator; a dither function generator, which produces telerobot motion inputs in a common coordinate frame for simultaneous combination in sensor summers. Virtual return spring motion input is provided by a restoration spring subsystem. The novel features of this invention include use of a single general motion primitive at a remote site to permit the shared and supervisory control of the robot manipulator to perform tasks via a remotely transferred input parameter set.

Density of Primitive Pythagorean Triples

ERIC Educational Resources Information Center

Killen, Duncan A.

2004-01-01

Based on the properties of a Primitive Pythagorean Triple (PPT), a computer program was written to generate, print, and count all PPTs greater than or equal to I[subscript x], where I[subscript x] is an arbitrarily chosen integer. The Density of Primitive Pythagorean Triples may be defined as the ratio of the number of PPTs whose hypotenuse is…

A Discussion on the Substitution Method for Trigonometric Rational Functions

ERIC Educational Resources Information Center

Ponce-Campuzano, Juan Carlos; Rivera-Figueroa, Antonio

2011-01-01

It is common to see, in the books on calculus, primitives of functions (some authors use the word "antiderivative" instead of primitive). However, the majority of authors pay scant attention to the domains over which the primitives are valid, which could lead to errors in the evaluation of definite integrals. In the teaching of calculus, in…

Scientific Terminology and Minimum Terms in Speech Communication: Some Philosophical Ramblings.

ERIC Educational Resources Information Center

Krivonos, Paul D.; Sussman, Lyle.

Philosophers of science have emphasized the need for primitive terms, or "givens," in the construction of theory for any discipline. While there are inherent dangers regarding the use of primitive terms, they can have great value in serving as the basis for minimum terms, which are primitive terms unique to a discipline. (Borrowed terms are those…

A manual for PARTI runtime primitives

NASA Technical Reports Server (NTRS)

Berryman, Harry; Saltz, Joel

1990-01-01

Primitives are presented that are designed to help users efficiently program irregular problems (e.g., unstructured mesh sweeps, sparse matrix codes, adaptive mesh partial differential equations solvers) on distributed memory machines. These primitives are also designed for use in compilers for distributed memory multiprocessors. Communications patterns are captured at runtime, and the appropriate send and receive messages are automatically generated.

New ligands for melanocortin receptors.

PubMed

Kaelin, C B; Candille, S I; Yu, B; Jackson, P; Thompson, D A; Nix, M A; Binkley, J; Millhauser, G L; Barsh, G S

2008-12-01

Named originally for their effects on peripheral end organs, the melanocortin system controls a diverse set of physiological processes through a series of five G-protein-coupled receptors and several sets of small peptide ligands. The central melanocortin system plays an essential role in homeostatic regulation of body weight, in which two alternative ligands, alpha-melanocyte-stimulating hormone and agouti-related protein, stimulate and inhibit receptor signaling in several key brain regions that ultimately affect food intake and energy expenditure. Much of what we know about the relationship between central melanocortin signaling and body weight regulation stems from genetic studies. Comparative genomic studies indicate that melanocortin receptors used for controlling pigmentation and body weight regulation existed more than 500 million years ago in primitive vertebrates, but that fine-grained control of melanocortin receptors through neuropeptides and endogenous antagonists developed more recently. Recent studies based on dog coat-color genetics revealed a new class of melanocortin ligands, the beta-defensins, which reveal the potential for cross talk between the melanocortin and the immune systems.

Emergence of Functional Hierarchy in a Multiple Timescale Neural Network Model: A Humanoid Robot Experiment

PubMed Central

Yamashita, Yuichi; Tani, Jun

2008-01-01

It is generally thought that skilled behavior in human beings results from a functional hierarchy of the motor control system, within which reusable motor primitives are flexibly integrated into various sensori-motor sequence patterns. The underlying neural mechanisms governing the way in which continuous sensori-motor flows are segmented into primitives and the way in which series of primitives are integrated into various behavior sequences have, however, not yet been clarified. In earlier studies, this functional hierarchy has been realized through the use of explicit hierarchical structure, with local modules representing motor primitives in the lower level and a higher module representing sequences of primitives switched via additional mechanisms such as gate-selecting. When sequences contain similarities and overlap, however, a conflict arises in such earlier models between generalization and segmentation, induced by this separated modular structure. To address this issue, we propose a different type of neural network model. The current model neither makes use of separate local modules to represent primitives nor introduces explicit hierarchical structure. Rather than forcing architectural hierarchy onto the system, functional hierarchy emerges through a form of self-organization that is based on two distinct types of neurons, each with different time properties (“multiple timescales”). Through the introduction of multiple timescales, continuous sequences of behavior are segmented into reusable primitives, and the primitives, in turn, are flexibly integrated into novel sequences. In experiments, the proposed network model, coordinating the physical body of a humanoid robot through high-dimensional sensori-motor control, also successfully situated itself within a physical environment. Our results suggest that it is not only the spatial connections between neurons but also the timescales of neural activity that act as important mechanisms leading to functional hierarchy in neural systems. PMID:18989398

Comet Dust: The Diversity of "Primitive" Particles and Implications

NASA Technical Reports Server (NTRS)

Wooden, Diane H.; Ishii, Hope A.; Bradley, John P.; Zolensky, Michael E.

2016-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive particles has expanded significantly through microscale investigations of cosmic dust samples ( IDP's(Interplanetary Dust Particles) and AMM's (Antarctic Micrometeorites)) and of comet dust samples (Stardust and Rosetta's COSIMA), as well as through remote sensing (spectroscopy and imaging) via Spitzer and via spacecraft encounters with 103P/Hartley 2 and 67P/Churyumov-Gerasimenko. Microscale investigations show that comet dust and cosmic dust are particles of unequilibrated materials, including aggregates of materials unequilibrated at submicron scales. We call unequilibrated materials "primitive" and we deduce they were incorporated into ice-rich (H2O-, CO2-, and CO-ice) parent bodies that remained cold, i.e., into comets, because of the lack of aqueous or thermal alteration since particle aggregation; yet some Stardust olivines suggest mild thermal metamorphism. Primitive particles exhibit a diverse range of: structure and typology; size and size distribution of constituents; concentration and form of carbonaceous and organic matter; D-, N-, and O- isotopic enhancements over solar; Mg-, Fe-contents of the silicate minerals; the compositions and concentrations of sulfides, and of less abundant mineral species such as chondrules, CAIs and carbonates. The uniformity within a group of samples points to: aerodynamic sorting of particles and/or particle constituents; the inclusion of a limited range of oxygen fugacities; the inclusion or exclusion of chondrules; a selection of organics. The properties of primitive particles imply there were disk processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disk present at the time and in the region where the comets formed.

Comet Dust: The Diversity of Primitive Particles and Implications

NASA Technical Reports Server (NTRS)

John Bradley; Zolensky, Michael E.

2016-01-01

Comet dust is primitive and shows significant diversity. Our knowledge of the properties of primitive particles has expanded significantly through microscale investigations of cosmic dust samples (IDPs and AMMs) and of comet dust samples (Stardust and Rosetta's COSIMA), as well as through remote sensing (spectroscopy and imaging) via Spitzer and via spacecraft encounters with 103P/Hartley 2 and 67P/Churyumov-Gerasimenko. Microscale investigations show that comet dust and cosmic dust are particles of unequilibrated materials, including aggregates of materials unequilibrated at submicron scales. We call unequilibrated materials "primitive" and we deduce they were incorporated into ice-­-rich (H2O-, CO2-, and CO-ice) parent bodies that remained cold, i.e., into comets, because of the lack of aqueous or thermal alteration since particle aggregation; yet some Stardust olivines suggest mild thermal metamorphism. Primitive particles exhibit a diverse range of: structure and typology; size and size distribution of constituents; concentration and form of carbonaceous and organic matter; D-, N-, and O- isotopic enhancements over solar; Mg-, Fe-contentsof thesilicate minerals; the compositions and concentrations of sulfides, and of less abundant mineral species such as chondrules, CAIs and carbonates. The unifomity within a group of samples points to: aerodynamic sorting of particles and/or particle constituents; the inclusion of a limited range of oxygen fugacities; the inclusion or exclusion of chondrules; a selection of organics. The properites of primitive particles imply there were disk processes that resulted in different comets having particular selections of primitive materials. The diversity of primitive particles has implications for the diversity of materials in the protoplanetary disk present at the time and in the region where the comets formed.

Proliferative Potentials of Bone Marrow and Blood Cells Studied by in vitro Uptake of H 3-Thymidine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, V. P.; Fliedner, T. M.; Cronkite, E. P.

1959-01-01

Cell proliferative activity and potential in the circulating blood and in the bone marrow of individuals with normal hematopoiesis, and in patients with hematopoietic dyscrasias was studied by means of in vitro one hour incubation with tritiated thymidine (H 3Th) and 6tripping film autoradiography. The labeled material is incorporated only into DNA during synthesis. In normal bone marrow, labeling was seen at 1 hour in all cell lineages, and in cells variously referred to as "reticulum," "stem,'' " stroma,'' etc., cells. Erythropoietic cells were labeled as far as the polychromatic normoblast; the myeloid series was labeled to the myelocyte state.more » Leukemia cells in the bone marrow and peripheral blood of patients with acute or chronic myelocytic leukemia incorporated label avidly; the small typical leukemia cell of chronic lymphocytic leukemia did not label at all. Less than 3 per cent of the myeloma cells in patients with multiple myeloma incorporated thymidine. Most striking was the finding of small numbers of labeled large mononuclear cells of different morphological types in the peripheral blood of normal human beings, and an increase in the number of morphologically identical cells in the blood of patients with infection and infectious mononucleosis. The labeling indicates active DNA synthesis and thus these cells presumably are capable of division. It is suggested that these cells may represent a mobile pool of primitive progenitor cells and are multipotential in their function.« less

FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia

PubMed Central

Kim, Hyung-Gyoon; Kojima, Kyoko; Swindle, C. Scott; Cotta, Claudiu V.; Huo, Yongliang; Reddy, Vishnu

2008-01-01

The inversion of chromosome 16 in the inv(16)(p13q22) is one of the most frequent cytogenetic abnormalities observed in acute myeloid leukemia (AML). The inv(16) fuses the core binding factor (CBF) beta subunit with the coiled-coil rod domain of smooth muscle myosin heavy chain (SMMHC). Expression of CBFβ-SMMHC in mice does not promote AML in the absence of secondary mutations. Patient samples with the inv(16) also possess mutually exclusive activating mutations in either N-RAS, K-RAS, or the receptor tyrosine kinases, c-KIT and FLT3, in almost 70% of cases. To test whether an activating mutation of FLT3 (FLT3-ITD) would cooperate with CBFβ-SMMHC to promote AML, we coexpressed both mutations in hematopoietic progenitor cells used to reconstitute lethally irradiated mice. Analysis of transplanted animals showed strong selection for CBFβ-SMMHC/FLT3-ITD–expressing cells in bone marrow and peripheral blood. Compared with animals transplanted with only CBFβ-SMMHC–expressing cells, FLT3-ITD further restricted early myeloid differentiation and promoted peripheralization of primitive myeloblasts as early as 2.5 weeks after transplantation. FLT3-ITD also accelerated disease progression in all CBFβ-SMMHC/FLT3-ITD–reconstituted animals, which died of a highly aggressive and transplantable AML within 3 to 5 months. These results indicate that FLT3-activating mutations can cooperate with CBFβ-SMMHC in an animal model of inv(16)-associated AML. PMID:17967943

Circuit design tool. User's manual, revision 2

NASA Technical Reports Server (NTRS)

Miyake, Keith M.; Smith, Donald E.

1992-01-01

The CAM chip design was produced in a UNIX software environment using a design tool that supports definition of digital electronic modules, composition of these modules into higher level circuits, and event-driven simulation of these circuits. Our design tool provides an interface whose goals include straightforward but flexible primitive module definition and circuit composition, efficient simulation, and a debugging environment that facilitates design verification and alteration. The tool provides a set of primitive modules which can be composed into higher level circuits. Each module is a C-language subroutine that uses a set of interface protocols understood by the design tool. Primitives can be altered simply by recoding their C-code image; in addition new primitives can be added allowing higher level circuits to be described in C-code rather than as a composition of primitive modules--this feature can greatly enhance the speed of simulation.

Retention of primitive reflexes and delayed motor development in very low birth weight infants.

PubMed

Marquis, P J; Ruiz, N A; Lundy, M S; Dillard, R G

1984-06-01

Primitive reflexes and motor development were evaluated in 127 very low birth weight (VLBW) infants (birth weight less than 1501 grams) at four months corrected age. The asymmetrical tonic neck reflex, tonic labyrinth reflex, and Moro reflex were assessed for each child. The ability of each child to reach (obtain a red ring) and roll were observed. The child's performance on the gross motor scale of the Denver Development Screening Test was recorded. Thirty-seven term infants were administered identical evaluations at four months of age. The VLBW infants retained stronger primitive reflexes and exhibited a significantly higher incidence of motor delays than term infants. Significant correlations existed between the strength of the primitive reflexes and early motor development for VLBW infants. This study confirms a high incidence of motor delays among VLBW infants and demonstrates a clear association between retained primitive reflexes and delayed motor development in VLBW infants.

RIPE integrity primitives, part 2 (RACE Integrity Primitives Evaluation)

NASA Astrophysics Data System (ADS)

Denboer, B.; Boly, J. P.; Bosselaers, A.; Brandt, J.; Chaum, D.; Damgaard, I.; Dichtl, M.; Fumy, W.; Vanderham, M.; Jansen, C. J. A.

1993-04-01

A manual intended for those seeking to secure information systems by applying modern cryptography is presented. It represents the successful attainment of goals by RIPE (RACE (Research and development of Advanced Communications technology in Europe) Integrity Primitives Evaluation). The recommended portfolio of integrity primitives, which is the main product of the project, forms the heart of the manual. By integrity, is meant the kinds of security that can be achieved through cryptography, apart from keeping messages secret. Thus included are ways to ensure that stored or communicated data is not illicitly modified, that parties exchanging messages are actually present, and that 'signed' electronic messages can be recognized as authentic by anyone. Of particular concern to the project were the high speed requirements of broadband communication. The project also aimed for completeness in its recommendations. As a result, the portfolio contains primitives, that is building blocks, that can meet most of today's perceived needs for integrity.

RIPE integrity primitives, part 1 (RACE Integrity Primitives Evaluation)

NASA Astrophysics Data System (ADS)

Denboer, B.; Boly, J. P.; Bosselaers, A.; Brandt, J.; Chaum, D.; Damgaard, I.; Dichtl, M.; Fumy, W.; Vanderham, M.; Jansen, C. J. A.

1993-04-01

A manual intended for those seeking to secure information systems by applying modern cryptography is presented. It represents the successful attainment of goals by RIPE (RACE (Research and development of Advanced Communication technology in Europe) Integrity Primitives Evaluation). The recommended portfolio of integrity primitives, which is the main product of the project, forms the heart of the manual. By integrity, is meant the kinds of security that can be achieved through cryptography, apart from keeping messages secret. Thus included are ways to ensure that stored or communicated data is not illicitly modified, that parties exchanging messages are actually present, and that 'signed' electronic messages can be recognized as authentic by anyone. Of particular concern to the project were the high speed requirements of broadband communication. The project also aimed for completeness in its recommendations. As a result, the portfolio contains primitives, that is building blocks, that can meet most of today's perceived needs for integrity.

Infant Brain Tumors: Incidence, Survival, and the Role of Radiation Based on Surveillance, Epidemiology, and End Results (SEER) Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, Andrew J.; McDonald, Mark W., E-mail: mwmcdona@iupui.edu; Indiana University Health Proton Therapy Center, Bloomington, IN

2012-01-01

Purpose: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Results: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastomamore » and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). Conclusion: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone.« less

Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma

PubMed Central

Ahmed, Nabil; Brawley, Vita S.; Hegde, Meenakshi; Robertson, Catherine; Ghazi, Alexia; Gerken, Claudia; Liu, Enli; Dakhova, Olga; Ashoori, Aidin; Corder, Amanda; Gray, Tara; Wu, Meng-Fen; Liu, Hao; Hicks, John; Rainusso, Nino; Dotti, Gianpietro; Mei, Zhuyong; Grilley, Bambi; Gee, Adrian; Rooney, Cliona M.; Brenner, Malcolm K.; Heslop, Helen E.; Wels, Winfried S.; Wang, Lisa L.; Anderson, Peter; Gottschalk, Stephen

2015-01-01

Purpose The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. Patients and Methods We conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive sarcoma received escalating doses (1 × 104/m2 to 1 × 108/m2) of T cells expressing an HER2-specific chimeric antigen receptor with a CD28.ζ signaling domain (HER2-CAR T cells). Results We enrolled 19 patients with HER2-positive tumors (16 osteosarcomas, one Ewing sarcoma, one primitive neuroectodermal tumor, and one desmoplastic small round cell tumor). HER2-CAR T-cell infusions were well tolerated with no dose-limiting toxicity. At dose level 3 (1 × 105/m2) and above, we detected HER2-CAR T cells 3 hours after infusion by quantitative polymerase chain reaction in 14 of 16 patients. HER2-CAR T cells persisted for at least 6 weeks in seven of the nine evaluable patients who received greater than 1 × 106/m2 HER2-CAR T cells (P = .005). HER2-CAR T cells were detected at tumor sites of two of two patients examined. Of 17 evaluable patients, four had stable disease for 12 weeks to 14 months. Three of these patients had their tumor removed, with one showing ≥ 90% necrosis. The median overall survival of all 19 infused patients was 10.3 months (range, 5.1 to 29.1 months). Conclusion This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence. PMID:25800760

Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma.

PubMed

Ahmed, Nabil; Brawley, Vita S; Hegde, Meenakshi; Robertson, Catherine; Ghazi, Alexia; Gerken, Claudia; Liu, Enli; Dakhova, Olga; Ashoori, Aidin; Corder, Amanda; Gray, Tara; Wu, Meng-Fen; Liu, Hao; Hicks, John; Rainusso, Nino; Dotti, Gianpietro; Mei, Zhuyong; Grilley, Bambi; Gee, Adrian; Rooney, Cliona M; Brenner, Malcolm K; Heslop, Helen E; Wels, Winfried S; Wang, Lisa L; Anderson, Peter; Gottschalk, Stephen

2015-05-20

The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. We conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) -positive sarcoma received escalating doses (1 × 10(4)/m(2) to 1 × 10(8)/m(2)) of T cells expressing an HER2-specific chimeric antigen receptor with a CD28.ζ signaling domain (HER2-CAR T cells). We enrolled 19 patients with HER2-positive tumors (16 osteosarcomas, one Ewing sarcoma, one primitive neuroectodermal tumor, and one desmoplastic small round cell tumor). HER2-CAR T-cell infusions were well tolerated with no dose-limiting toxicity. At dose level 3 (1 × 10(5)/m(2)) and above, we detected HER2-CAR T cells 3 hours after infusion by quantitative polymerase chain reaction in 14 of 16 patients. HER2-CAR T cells persisted for at least 6 weeks in seven of the nine evaluable patients who received greater than 1 × 10(6)/m(2) HER2-CAR T cells (P = .005). HER2-CAR T cells were detected at tumor sites of two of two patients examined. Of 17 evaluable patients, four had stable disease for 12 weeks to 14 months. Three of these patients had their tumor removed, with one showing ≥ 90% necrosis. The median overall survival of all 19 infused patients was 10.3 months (range, 5.1 to 29.1 months). This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence. © 2015 by American Society of Clinical Oncology.

Recurrent PAX3-MAML3 Fusion in Biphenotypic Sinonasal Sarcoma

PubMed Central

Wang, Xiaoke; Bledsoe, Krista L.; Graham, Rondell P.; Asmann, Yan W.; Viswanatha, David S.; Lewis, Jean E.; Lewis, Jason T.; Chou, Margaret M.; Yaszemski, Michael J.; Jen, Jin; Westendorf, Jennifer J.; Oliveira, André M.

2014-01-01

Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and paranasal areas. Herein, we report the novel recurring chromosomal translocation t(2;4)(q35;q31.1) in SNS. The translocation results in the formation of the fusion protein PAX3-MAML3, which is a potent transcriptional activator of PAX3 response elements. The SNS phenotype is characterized by aberrant expression of genes involved in neuroectodermal and myogenic differentiation, which closely simulates the developmental roles of PAX3. PMID:24859338

[Novel concepts in biology of diffuse endocrine system: results and future investigations].

PubMed

Iaglov, V V; Iaglova, N V

2012-01-01

Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

Using Abstraction in Explicity Parallel Programs.

DTIC Science & Technology

1991-07-01

However, we only rely on sequential consistency of memory operations. includ- ing reads. writes and any synchronization primitives provided by the...explicit synchronization primitives . This demonstrates the practical power of sequentially consistent memory, as opposed to weaker models of memory that...a small set of synchronization primitives , all pro- cedures have non-waiting specifications. This is in contrast to richer process-oriented

Semantically-Sensitive Macroprocessing

DTIC Science & Technology

1989-12-15

constr uct for protecting critical regions. Given the synchronization primitives P and V, we might implement the following transformation, where...By this we mean that the semantic model for the base language provides a primitive set of concepts, represented by data types and operations...the gener- ation of a (dynamic-) semantically equivalent program fragment ultimately expressible in terms of built-in primitives . Note that static

A manual for PARTI runtime primitives, revision 1

NASA Technical Reports Server (NTRS)

Das, Raja; Saltz, Joel; Berryman, Harry

1991-01-01

Primitives are presented that are designed to help users efficiently program irregular problems (e.g., unstructured mesh sweeps, sparse matrix codes, adaptive mesh partial differential equations solvers) on distributed memory machines. These primitives are also designed for use in compilers for distributed memory multiprocessors. Communications patterns are captured at runtime, and the appropriate send and receive messages are automatically generated.

Fast concurrent array-based stacks, queues and deques using fetch-and-increment-bounded, fetch-and-decrement-bounded and store-on-twin synchronization primitives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Dong; Gara, Alana; Heidelberger, Philip

Implementation primitives for concurrent array-based stacks, queues, double-ended queues (deques) and wrapped deques are provided. In one aspect, each element of the stack, queue, deque or wrapped deque data structure has its own ticket lock, allowing multiple threads to concurrently use multiple elements of the data structure and thus achieving high performance. In another aspect, new synchronization primitives FetchAndIncrementBounded (Counter, Bound) and FetchAndDecrementBounded (Counter, Bound) are implemented. These primitives can be implemented in hardware and thus promise a very fast throughput for queues, stacks and double-ended queues.

Probabilistic structural analysis of a truss typical for space station

NASA Technical Reports Server (NTRS)

Pai, Shantaram S.

1990-01-01

A three-bay, space, cantilever truss is probabilistically evaluated using the computer code NESSUS (Numerical Evaluation of Stochastic Structures Under Stress) to identify and quantify the uncertainties and respective sensitivities associated with corresponding uncertainties in the primitive variables (structural, material, and loads parameters) that defines the truss. The distribution of each of these primitive variables is described in terms of one of several available distributions such as the Weibull, exponential, normal, log-normal, etc. The cumulative distribution function (CDF's) for the response functions considered and sensitivities associated with the primitive variables for given response are investigated. These sensitivities help in determining the dominating primitive variables for that response.

Initiation of olfactory placode development and neurogenesis is blocked in mice lacking both Six1 and Six4.

PubMed

Chen, Binglai; Kim, Eun-Hee; Xu, Pin-Xian

2009-02-01

Mouse olfactory epithelium (OE) originates from ectodermally derived placode, the olfactory placode that arises at the anterior end of the neural plate. Tissue grafting and recombination experiments suggest that the placode is derived from a common preplacodal domain around the neural plate and its development is directed by signals arising from the underlying mesoderm and adjacent neuroectoderm. In mice, loss of Six1 affects OE morphogenesis but not placode formation. We show here that embryos lacking both Six1 and Six4 failed to form the olfactory placode but the preplacodal region appeared to be specified as judged by the expression of Eya2, which marks the common preplacodal domain, suggesting a synergistic requirement of Six1 and Six4 in patterning the preplacodal ectoderm to a morphologic placode. Our results show that Six1 and Six4 are coexpressed in the preplacodal ectoderm from E8.0. In the olfactory pit, Six4 expression was observed in the peripheral precursors that overlap with Mash1-expressing cells, the early committed neuronal lineage. In contrast, Six1 is highly distributed in the peripheral regions where stem cells reside at E10.5 and it overlaps with Sox2 expression. Both genes are expressed in the basal and apical neuronal progenitors in the OE. Analyses of Six1;Six4 double mutant embryos demonstrated that the slightly thickened epithelium observed in the mutant was not induced for neuronal development. In contrast, in Six1(-/-) embryos, all neuronal lineage markers were initially expressed but the pattern of their expression was altered. Although very few, the pioneer neurons were initially present in the Six1 mutant OE. However, neurogenesis ceased by E12.5 due to markedly increased cell apoptosis and reduced proliferation, thus defining the cellular defects occurring in Six1(-/-) OE that have not been previously observed. Our findings demonstrate that Six1/4 function at the top of early events controlling olfactory placode formation and neuronal development. Our analyses show that the threshold of Six1/4 may be crucial for the expression of olfactory specific genes and that Six1 and Six4 may act synergistically to mediate olfactory placode specification and patterning through Fgf and Bmp signaling pathways.

A method of plane geometry primitive presentation

NASA Astrophysics Data System (ADS)

Jiao, Anbo; Luo, Haibo; Chang, Zheng; Hui, Bin

2014-11-01

Point feature and line feature are basic elements in object feature sets, and they play an important role in object matching and recognition. On one hand, point feature is sensitive to noise; on the other hand, there are usually a huge number of point features in an image, which makes it complex for matching. Line feature includes straight line segment and curve. One difficulty in straight line segment matching is the uncertainty of endpoint location, the other is straight line segment fracture problem or short straight line segments joined to form long straight line segment. While for the curve, in addition to the above problems, there is another difficulty in how to quantitatively describe the shape difference between curves. Due to the problems of point feature and line feature, the robustness and accuracy of target description will be affected; in this case, a method of plane geometry primitive presentation is proposed to describe the significant structure of an object. Firstly, two types of primitives are constructed, they are intersecting line primitive and blob primitive. Secondly, a line segment detector (LSD) is applied to detect line segment, and then intersecting line primitive is extracted. Finally, robustness and accuracy of the plane geometry primitive presentation method is studied. This method has a good ability to obtain structural information of the object, even if there is rotation or scale change of the object in the image. Experimental results verify the robustness and accuracy of this method.

A rare case report of mixed olfactory neuroblastoma: Carcinoma with review of literature.

PubMed

Gandhoke, Charandeep S; Dewan, Aditi; Gupta, Divya; Syal, Simran K; Jagetia, Anita; Saran, Ravindra K; Meher, Ravi; Srivastava, Arvind K; Singh, Daljit

2017-01-01

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Mixed olfactory neuroblastoma which contains areas of divergent differentiation is even rare. Till date, only 4 cases of mixed olfactory neuroblastomas have been reported. We report the case of a 46-year-old male who presented with the chief complaints of nasal bleeding and nasal obstruction since 4 months. Radiological imaging was suggestive of a large heterogeneous mass in the left superior nasal cavity with extensions into bilateral maxillary, ethmoidal, and sphenoidal sinuses, as well as into the anterior cranial fossa. Bifrontal osteoplastic craniotomy and excision of the intracranial part of the tumor from above and transnasal endoscopic removal of the mass in the nasal cavities and paranasal sinuses from below was done. Postoperative radiological imaging was suggestive of gross complete excision of the mass. Histopathological diagnosis was "mixed olfactory neuroblastoma-carcinoma (squamous and glandular differentiation) Hyams grade IV." On immunohistochemistry, the tumor cells were positive for neuron specific enolase (NSE), synaptophysin, chromogranin, and CD56 and peripherally for S100. Because of personal reasons, the patient did not take adjuvant radiotherapy. He presented again after 2 months with a full blown recurrence of esthesioneuroblastoma with similar extensions as before. The patient is now planned for salvage surgery followed by adjuvant chemoradiation. We report the 5 th case in the world of mixed olfactory neuroblastoma-carcinoma with squamous and glandular differentiation. From an analysis of the findings in the 5 reported cases of mixed olfactory neuroblastomas, one might infer that a separate subcategory of ONB, i.e., mixed ONB, should be considered because mixed ONBs have an aggressive behavior, high rates of recurrence, and these tumors should be treated aggressively by multimodality treatment.

A rare case report of mixed olfactory neuroblastoma: Carcinoma with review of literature

PubMed Central

Gandhoke, Charandeep S.; Dewan, Aditi; Gupta, Divya; Syal, Simran K.; Jagetia, Anita; Saran, Ravindra K.; Meher, Ravi; Srivastava, Arvind K.; Singh, Daljit

2017-01-01

Background: Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Mixed olfactory neuroblastoma which contains areas of divergent differentiation is even rare. Till date, only 4 cases of mixed olfactory neuroblastomas have been reported. Case Description: We report the case of a 46-year-old male who presented with the chief complaints of nasal bleeding and nasal obstruction since 4 months. Radiological imaging was suggestive of a large heterogeneous mass in the left superior nasal cavity with extensions into bilateral maxillary, ethmoidal, and sphenoidal sinuses, as well as into the anterior cranial fossa. Bifrontal osteoplastic craniotomy and excision of the intracranial part of the tumor from above and transnasal endoscopic removal of the mass in the nasal cavities and paranasal sinuses from below was done. Postoperative radiological imaging was suggestive of gross complete excision of the mass. Histopathological diagnosis was “mixed olfactory neuroblastoma-carcinoma (squamous and glandular differentiation) Hyams grade IV.” On immunohistochemistry, the tumor cells were positive for neuron specific enolase (NSE), synaptophysin, chromogranin, and CD56 and peripherally for S100. Because of personal reasons, the patient did not take adjuvant radiotherapy. He presented again after 2 months with a full blown recurrence of esthesioneuroblastoma with similar extensions as before. The patient is now planned for salvage surgery followed by adjuvant chemoradiation. Conclusion: We report the 5th case in the world of mixed olfactory neuroblastoma-carcinoma with squamous and glandular differentiation. From an analysis of the findings in the 5 reported cases of mixed olfactory neuroblastomas, one might infer that a separate subcategory of ONB, i.e., mixed ONB, should be considered because mixed ONBs have an aggressive behavior, high rates of recurrence, and these tumors should be treated aggressively by multimodality treatment. PMID:28607817

The pathology of lumbosacral lipomas: macroscopic and microscopic disparity have implications for embryogenesis and mode of clinical deterioration.

PubMed

Jones, Victoria; Wykes, Victoria; Cohen, Nicki; Thompson, Dominic; Jacques, Tom S

2018-06-01

Lumbosacral lipomas (LSL) are congenital disorders of the terminal spinal cord region that have the potential to cause significant spinal cord dysfunction in children. They are of unknown embryogenesis with variable clinical presentation and natural history. It is unclear whether the spinal cord dysfunction reflects a primary developmental dysplasia or whether it occurs secondarily to mechanical traction (spinal cord tethering) with growth. While different anatomical subtypes are recognised and classified according to radiological criteria, these subtypes correlate poorly with clinical prognosis. We have undertaken an analysis of surgical specimens in order to describe the spectrum of histological changes that occur and have correlated the histology with the anatomical type of LSL to determine if there are distinct histological subtypes. The histopathology was reviewed of 64 patients who had undergone surgical resection of LSL. The presence of additional tissues and cell types were recorded. LSLs were classified from pre-operative magnetic resonance imaging (MRI) scans according to Chapman classification. Ninety-five per cent of the specimens consisted predominantly of mature adipocytes with all containing thickened bands of connective tissue and peripheral nerve fibres, 91% of samples contained ectatic blood vessels with thickened walls, while 22% contained central nervous system (CNS) glial tissue. Additional tissue was identified of both mesodermal and neuroectodermal origin. Our analysis highlights the heterogeneity of tissue types within all samples, not reflected in the nomenclature. The diversity of tissue types, consistent across all subtypes, challenges currently held notions regarding the embryogenesis of LSLs and the assumption that clinical deterioration is due simply to tethering. © 2018 The Authors. Histopathology Published by John Wiley & Sons Ltd.

Downregulation of Axl in non-MYCN amplified neuroblastoma cell lines reduces migration.

PubMed

Duijkers, Floor A M; Meijerink, Jules P P; Pieters, Rob; van Noesel, Max M

2013-05-25

Neuroblastomas (NBL) are common pediatric solid tumors with a variable clinical course. At diagnosis half of all neuroblastoma patients presents with metastatic disease. The mechanisms of metastasis are largely unknown. Gene expression profiles (HU133plus2.0 arrays, Affymetrix) of 17 NBL and 5 peripheral neuro-ectodermal cell lines were used to identify a subgroup of non-MYCN amplified (non-NMA) NBL cell lines with a distinct gene expression profile and characterized by high expression of AXL. Axl is a tyrosine kinase receptor which plays a role in the metastatic process of several types of cancer. We hypothesized that Axl contributes to the metastasizing potential of non-NMA NBL and tested if AXL silencing diminishes malignant properties of high Axl expressing cell lines. AXL was silenced in two non-NMA NBL cell lines by using a lentiviral shRNA construct that was able to transduce these cell lines with more than 90% infection efficiency. Axl mRNA and protein level were efficiently knocked-down resulting in a decrease of migration of Axl positive cell lines GI-M-EN and SH-EP-2, and decreased invasion of GI-M-EN. Morphologically, Axl knockdown induced more rounded cells with a loss of contact. Intracellularly, we observed induction of stress fibers (immunofluorescence F-actin). These changes in cytoskeleton were associated with decreased migration, but were not accompanied by changes in genes involved in epithelial to mesenchymal transition such as CDH2, VIM or MMP9. No effects were observed for cell proliferation, apoptosis or downstream pathways. In conclusion, AXL is identified as a possible mediator of NBL metastasis. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative Anatomy of Maintenance Tasks (CAMT): A Feasibility Study

DTIC Science & Technology

1992-03-01

systems. Methods for task primitive definition were developed, then taken into the field for testing . Task primitives were defined to cover three remove...engine maintenance) and to test whether task primitives developed for one weapon system could have applicability to other weapon systems (Phase 2...requirements, levying MPT constraints and predicting MPT requirements are only ritualistic exercises until the operational test and evaluation of a

Origin of fatty acid synthesis - Thermodynamics and kinetics of reaction pathways

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

1991-01-01

The primitiveness of contemporary fatty acid biosynthesis was evaluated by using the thermodynamics and kinetics of its component reactions to estimate the extent of its dependence on powerful and selective catalysis by enzymes. Since this analysis indicated that the modern pathway is not primitive because it requires sophisticated enzymatic catalysis, an alternative pathway of primitive fatty acid synthesis is proposed that uses glycolaldehyde as a substrate. In contrast to the modern pathway, this primitive pathway is not dependent on an exogenous source of phosphoanhydride energy. Furthermore, the chemical spontaneity of its reactions suggests that it could have been readily catalyzed by the rudimentary biocatalysts available at an early stage in the origin of life.

Physics of the primitive solar nebula and of giant gaseous protoplanets

NASA Technical Reports Server (NTRS)

Cameron, A. G. W.

1978-01-01

It has been proposed that the supernova responsible for injecting Al-26 into the early solar system was in fact responsible for triggering the collapse of an interstellar cloud in order to produce a system of stars, one of which would be the solar system. Details concerning the mechanism involved in such a process are discussed. Attention is given to the evolution of the primitive solar nebula, the instabilities in the primitive solar nebula, and the giant gaseous protoplanets. The principal conclusion to be drawn from the material presented is that the primitive solar nebula was a rather chaotic place, highly turbulent, with the multiple formation of giant gaseous protoplanets.

Possible complex organic compounds on Mars.

PubMed

Kobayashi, K; Sato, T; Kajishima, S; Kaneko, T; Ishikawa, Y; Saito, T

1997-01-01

It is suggested that primitive Mars had somehow similar environments as primitive Earth. If life was born on the primitive earth using organic compounds which were produced from the early Earth environment, the same types of organic compounds were also formed on primitive Mars. Such organic compounds might have been preserved on Mars still now. We are studying possible organic formation on primitive and present Mars. A gaseous mixture of CO2, CO, N2 and H2O with various mixing ratios were irradiated with high energy protons (major components of cosmic rays). Hydrogen cyanide and formaldehyde were detected among volatile products, and yellow-brown-colored water-soluble non-volatile substances were produced, which gave amino acids after acid-hydrolysis. Major part of "amino acid precursors" were not simple molecules like aminonitriles, but complex compounds which eluted earlier than free amino acids in cation-exchange HPLC. These organic compounds should be major targets in the future Mars mission. Strategy for the detection of the complex organics on Mars will be discussed.

Using Parallel Processing for Problem Solving.

DTIC Science & Technology

1979-12-01

are the basic parallel proces- sing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities...Language primitives are provided for manipulating running activities. Viewpoints are a generalization of context FOM -(over "*’ DD I FON 1473 ’EDITION OF I...arc the basic parallel processing primitive . Different goals of the system can be pursued in parallel by placing them in separate activities. Language

Security Primitives for Reconfigurable Hardware-Based Systems

DTIC Science & Technology

2010-05-01

work, we propose security primitives using ideas centered around the notion of “moats and drawbridges .” The primitives encompass four design properties...Santa Bar- bara, CA 93106; email: sherwood@cs.ucsb.edu; R. Kastner, Department of Computer Science and Engineering , University of California, San...fingerprint reader), the other to control the ethernet IP core—and an AES encryption engine used by both of the processor cores. These cores are all implemented

Spectrum Analysis of Inertial and Subinertial Motions Based on Analyzed Winds and Wind-Driven Currents from a Primitive Equation General Ocean Circulation Model.

DTIC Science & Technology

1982-12-01

1Muter.Te Motions Based on Ana lyzed Winds and wind-driven December 1982 Currents from. a Primitive Squat ion General a.OW -love"*..* Oean Circulation...mew se"$ (comeS.... do oISN..u am ae~ 00do OWaor NUN Fourier and Rotary Spc , Analysis Modeled Inertial and Subinrtial Motion 4 Primitive Equation

A Generalized-Compliant-Motion Primitive

NASA Technical Reports Server (NTRS)

Backes, Paul G.

1993-01-01

Computer program bridges gap between planning and execution of compliant robotic motions developed and installed in control system of telerobot. Called "generalized-compliant-motion primitive," one of several task-execution-primitive computer programs, which receives commands from higher-level task-planning programs and executes commands by generating required trajectories and applying appropriate control laws. Program comprises four parts corresponding to nominal motion, compliant motion, ending motion, and monitoring. Written in C language.

Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

PubMed

Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

2015-05-01

Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

MACOP modular architecture with control primitives

PubMed Central

Waegeman, Tim; Hermans, Michiel; Schrauwen, Benjamin

2013-01-01

Walking, catching a ball and reaching are all tasks in which humans and animals exhibit advanced motor skills. Findings in biological research concerning motor control suggest a modular control hierarchy which combines movement/motor primitives into complex and natural movements. Engineers inspire their research on these findings in the quest for adaptive and skillful control for robots. In this work we propose a modular architecture with control primitives (MACOP) which uses a set of controllers, where each controller becomes specialized in a subregion of its joint and task-space. Instead of having a single controller being used in this subregion [such as MOSAIC (modular selection and identification for control) on which MACOP is inspired], MACOP relates more to the idea of continuously mixing a limited set of primitive controllers. By enforcing a set of desired properties on the mixing mechanism, a mixture of primitives emerges unsupervised which successfully solves the control task. We evaluate MACOP on a numerical model of a robot arm by training it to generate desired trajectories. We investigate how the tracking performance is affected by the number of controllers in MACOP and examine how the individual controllers and their generated control primitives contribute to solving the task. Furthermore, we show how MACOP compensates for the dynamic effects caused by a fixed control rate and the inertia of the robot. PMID:23888140

A real-time robot arm collision detection system

NASA Technical Reports Server (NTRS)

Shaffer, Clifford A.; Herb, Gregory M.

1990-01-01

A data structure and update algorithm are presented for a prototype real time collision detection safety system for a multi-robot environment. The data structure is a variant of the octree, which serves as a spatial index. An octree recursively decomposes 3-D space into eight equal cubic octants until each octant meets some decomposition criteria. The octree stores cylspheres (cylinders with spheres on each end) and rectangular solids as primitives (other primitives can easily be added as required). These primitives make up the two seven degrees-of-freedom robot arms and environment modeled by the system. Octree nodes containing more than a predetermined number N of primitives are decomposed. This rule keeps the octree small, as the entire environment for the application can be modeled using a few dozen primitives. As robot arms move, the octree is updated to reflect their changed positions. During most update cycles, any given primitive does not change which octree nodes it is in. Thus, modification to the octree is rarely required. Incidents in which one robot arm comes too close to another arm or an object are reported. Cycle time for interpreting current joint angles, updating the octree, and detecting/reporting imminent collisions averages 30 milliseconds on an Intel 80386 processor running at 20 MHz.

Fully automatic segmentation of the femur from 3D-CT images using primitive shape recognition and statistical shape models.

PubMed

Ben Younes, Lassad; Nakajima, Yoshikazu; Saito, Toki

2014-03-01

Femur segmentation is well established and widely used in computer-assisted orthopedic surgery. However, most of the robust segmentation methods such as statistical shape models (SSM) require human intervention to provide an initial position for the SSM. In this paper, we propose to overcome this problem and provide a fully automatic femur segmentation method for CT images based on primitive shape recognition and SSM. Femur segmentation in CT scans was performed using primitive shape recognition based on a robust algorithm such as the Hough transform and RANdom SAmple Consensus. The proposed method is divided into 3 steps: (1) detection of the femoral head as sphere and the femoral shaft as cylinder in the SSM and the CT images, (2) rigid registration between primitives of SSM and CT image to initialize the SSM into the CT image, and (3) fitting of the SSM to the CT image edge using an affine transformation followed by a nonlinear fitting. The automated method provided good results even with a high number of outliers. The difference of segmentation error between the proposed automatic initialization method and a manual initialization method is less than 1 mm. The proposed method detects primitive shape position to initialize the SSM into the target image. Based on primitive shapes, this method overcomes the problem of inter-patient variability. Moreover, the results demonstrate that our method of primitive shape recognition can be used for 3D SSM initialization to achieve fully automatic segmentation of the femur.

Next Generation, 4-D Distributed Modeling and Visualization of Battlefield

DTIC Science & Technology

2006-07-14

accurate. However, the effectiveness of such a view is determined by its usability. If the picture contained all the information that had been...major key to success in such missions is the ability to model real-world urban areas accurately and effectively , so as to support US military mission...primitives (including the standard CG primitives such as plane, cube, wedge, polyhedron, cylinder and sphere, and high-order surface primitives such as

A Guide to FASTGEN Target Geometric Modeling

DTIC Science & Technology

1993-10-01

component part is described in plate mode. These rules apply to all primitives with the exception of rod mode primitives which are always accompanied by a...format. A detailed discussion of the rules for preparing the target description file, where components are described using primitives defined as triangles...NN position is 99, the diameter of a rod mode component is limited to a maximum of 1.98-inches. Theie are several rules and cautions associated with

Hydrostatic calculations of axisymmetric flow and its stability for the AGCE model

NASA Technical Reports Server (NTRS)

Miller, T. L.; Gall, R. L.

1981-01-01

Baroclinic waves in the atmospherics general circulation experiment (AGCE) apparatus by the use of numerical hydrostatic primitive equation models were determined. The calculation is accomplished by using an axisymmetric primitive equation model to compute, for a given set of experimental parameters, a steady state axisymmetric flow and then testing this axisymmetric flow for stability using a linear primitive equation model. Some axisymmetric flows are presented together with preliminary stability calculations.

Cave men: stone tools, Victorian science, and the 'primitive mind' of deep time.

PubMed

Pettitt, Paul B; White, Mark J

2011-03-20

Palaeoanthropology, the study of the evolution of humanity, arose in the nineteenth century. Excavations in Europe uncovered a series of archaeological sediments which provided proof that the antiquity of human life on Earth was far longer than the biblical six thousand years, and by the 1880s authors had constructed a basic paradigm of what 'primitive' human life was like. Here we examine the development of Victorian palaeoanthropology for what it reveals of the development of notions of cognitive evolution. It seems that Victorian specialists rarely addressed cognitive evolution explicitly, although several assumptions were generally made that arose from preconceptions derived from contemporary 'primitive' peoples. We identify three main phases of development of notions of the primitive mind in the period.

Insights to primitive replication derived from structures of small oligonucleotides

NASA Technical Reports Server (NTRS)

Smith, G. K.; Fox, G. E.

1995-01-01

Available information on the structure of small oligonucleotides is surveyed. It is observed that even small oligomers typically exhibit defined structures over a wide range of pH and temperature. These structures rely on a plethora of non-standard base-base interactions in addition to the traditional Watson-Crick pairings. Stable duplexes, though typically antiparallel, can be parallel or staggered and perfect complementarity is not essential. These results imply that primitive template directed reactions do not require high fidelity. Hence, the extensive use of Watson-Crick complementarity in genes rather than being a direct consequence of the primitive condensation process, may instead reflect subsequent selection based on the advantage of accuracy in maintaining the primitive genetic machinery once it arose.

ARCGRAPH SYSTEM - AMES RESEARCH GRAPHICS SYSTEM

NASA Technical Reports Server (NTRS)

Hibbard, E. A.

1994-01-01

Ames Research Graphics System, ARCGRAPH, is a collection of libraries and utilities which assist researchers in generating, manipulating, and visualizing graphical data. In addition, ARCGRAPH defines a metafile format that contains device independent graphical data. This file format is used with various computer graphics manipulation and animation packages at Ames, including SURF (COSMIC Program ARC-12381) and GAS (COSMIC Program ARC-12379). In its full configuration, the ARCGRAPH system consists of a two stage pipeline which may be used to output graphical primitives. Stage one is associated with the graphical primitives (i.e. moves, draws, color, etc.) along with the creation and manipulation of the metafiles. Five distinct data filters make up stage one. They are: 1) PLO which handles all 2D vector primitives, 2) POL which handles all 3D polygonal primitives, 3) RAS which handles all 2D raster primitives, 4) VEC which handles all 3D raster primitives, and 5) PO2 which handles all 2D polygonal primitives. Stage two is associated with the process of displaying graphical primitives on a device. To generate the various graphical primitives, create and reprocess ARCGRAPH metafiles, and access the device drivers in the VDI (Video Device Interface) library, users link their applications to ARCGRAPH's GRAFIX library routines. Both FORTRAN and C language versions of the GRAFIX and VDI libraries exist for enhanced portability within these respective programming environments. The ARCGRAPH libraries were developed on a VAX running VMS. Minor documented modification of various routines, however, allows the system to run on the following computers: Cray X-MP running COS (no C version); Cray 2 running UNICOS; DEC VAX running BSD 4.3 UNIX, or Ultrix; SGI IRIS Turbo running GL2-W3.5 and GL2-W3.6; Convex C1 running UNIX; Amhdahl 5840 running UTS; Alliant FX8 running UNIX; Sun 3/160 running UNIX (no native device driver); Stellar GS1000 running Stellex (no native device driver); and an SGI IRIS 4D running IRIX (no native device driver). Currently with version 7.0 of ARCGRAPH, the VDI library supports the following output devices: A VT100 terminal with a RETRO-GRAPHICS board installed, a VT240 using the Tektronix 4010 emulation capability, an SGI IRIS turbo using the native GL2 library, a Tektronix 4010, a Tektronix 4105, and the Tektronix 4014. ARCGRAPH version 7.0 was developed in 1988.

A simple and efficient method for deriving neurospheres from bone marrow stromal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang Qin; Mu Jun; Li Qi

2008-08-08

Bone marrow stromal cells (MSCs) can be differentiated into neuronal and glial-like cell types under appropriate experimental conditions. However, previously reported methods are complicated and involve the use of toxic reagents. Here, we present a simplified and nontoxic method for efficient conversion of rat MSCs into neurospheres that express the neuroectodermal marker nestin. These neurospheres can proliferate and differentiate into neuron, astrocyte, and oligodendrocyte phenotypes. We thus propose that MSCs are an emerging model cell for the treatment of a variety of neurological diseases.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

PubMed

Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

PRIMitive Asteroids Spectroscopic Survey - PRIMASS: First Results

NASA Astrophysics Data System (ADS)

de Leon, Julia; Pinilla-Alonso, Noemi; Campins, Humberto; Lorenzi, Vania; Licandro, Javier; Morate, David; Tanga, Paolo; Cellino, Alberto; Delbo, Marco

2015-11-01

NASA OSIRIS-REx and JAXA Hayabusa 2 sample-return missions have targeted two near-Earth asteroids: (101955) Bennu and (162173) 1999 JU3, respectively. These are primitive asteroids that are believed to originate in the inner belt, where five distinct sources have been identified: four primitive collisional families (Polana, Erigone, Sulamitis, and Clarissa), and a population of low-albedo and low-inclination background asteroids. Identifying and characterizing the populations from which these two NEAs might originate will enchance the science return of the two missions.With this main objective in mind, we initiated in 2010 a spectroscopic survey in the visible and the near-infrared to characterize the primitive collisional families in the inner belt and the low-albedo background population. This is the PRIMitive Asteroids Spectroscopic Survey - PRIMASS. So far we have obtained more than 200 spectra using telescopes located at different observatories. PRIMASS uses a variety of ground based facilities. Most of the spectra have been obtained using the 10.4m Gran Telescopio Canarias (GTC), and the 3.6m Telescopio Nazionale Galileo (TNG), both located at the El Roque de los Muchachos Observatory (La Palma, Spain), and the 3.0m NASA Infrared Telescope Facility on Mauna Kea (Hawai, USA).We present the first results from our on-going survey (de Leon et al. 2015; Pinilla-Alonso et al. 2015; Morate et al. 2015), focused on the Polana and the Erigone primitive families, with visible and near-infrared spectra of more than 200 objects, most of them with no previous spectroscopic data. Our survey is already the largest database of primitive asteroids spectra, and we keep obtaining data on the Sulamitis and the Clarissa families, as well as on the background low-albedo population.

Friend of GATA (FOG) Interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to Support Primitive Erythropoiesis in Xenopus laevis

PubMed Central

Mimoto, Mizuho S.; Christian, Jan L.

2012-01-01

Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect. PMID:22235346

UNCOMPAHGRE PRIMITIVE AREA, COLORADO.

USGS Publications Warehouse

Luedke, R.G.; Sheridan, M.J.

1984-01-01

A mineral-resource study was made of that part of the Uncompahgre National Forest, Colorado constituting the officially designated primitive area. Because the primitive area and its southern border zone contained operating mines producing gold, silver, copper, lead, zinc, and minor amounts of a few other metals, and had been a part of a highly productive mining region, the area was concluded to have large segments of both probable and substantiated mineral-resource potential. No energy resources were identified in the study.

Primitive myxoid mesenchymal tumor of infancy in a preterm infant.

PubMed

Lam, Joseph; Lara-Corrales, Irene; Cammisuli, Salvatore; Somers, Gino R; Pope, Elena

2010-01-01

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred following excision of a congenital juvenile xanthogranuloma. © 2010 Wiley Periodicals, Inc.

HIGH UINTAS PRIMITIVE AREA, UTAH.

USGS Publications Warehouse

Crittenden, Max D.; Sheridan, Michael J.

1984-01-01

Mineral surveys in the High Uintas Primitive Area, Utah and the additions subsequently proposed concluded that the area has little promise for mineral resources. Of the areas around the fringes, a strip along the north flank fault can be classed as having probable energy-resource potential for oil and gas. The oil and gas potential could be tested by additional seismic studies followed by drilling. Much of the necessary information probably could be obtained without drilling within the primitive area itself.

Intrapartum Synthetic Oxytocin Reduce the Expression of Primitive Reflexes Associated with Breastfeeding

PubMed Central

Olza Fernández, Ibone; Malalana Martínez, Ana M.; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

2015-01-01

Abstract Aim: Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. Materials and Methods: A cohort prospective study was conducted at a tertiary hospital. Mother–infant dyads who received intrapartum oxytocin (n=53) were compared with mother–infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. Results: The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Conclusions: Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent. PMID:25785487

Essential roles for Cdx in murine primitive hematopoiesis.

PubMed

Brooke-Bisschop, Travis; Savory, Joanne G A; Foley, Tanya; Ringuette, Randy; Lohnes, David

2017-02-15

The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis. We found that Cdx1/Cdx2 double mutants exhibited defects in primitive hematopoiesis and yolk sac vasculature concomitant with reduced expression of several genes encoding hematopoietic transcription factors including Scl/Tal1. Chromatin immunoprecipitation analysis revealed that Scl was occupied by Cdx2 in vivo, and Cdx mutant hematopoietic yolk sac differentiation defects could be rescued by expression of exogenous Scl. These findings demonstrate critical roles for Cdx members in murine primitive hematopoiesis upstream of Scl. Copyright © 2017 Elsevier Inc. All rights reserved.

Purification of zebrafish erythrocytes as a means of identifying a novel regulator of haematopoiesis.

PubMed

Kulkeaw, Kasem; Inoue, Tomoko; Ishitani, Tohru; Nakanishi, Yoichi; Zon, Leonard I; Sugiyama, Daisuke

2018-02-01

Zebrafish embryos are useful to study haematopoietic gene function in vertebrates, although lack of antibodies to zebrafish proteins has limited the purification of specific cell populations. Here, we purified primitive zebrafish erythrocytes using 1, 5-bis{[2-(di-methylamino)ethyl]amino}-4, 8-dihydroxyanthracene-9, 10-dione (DRAQ5 TM ), a DNA-staining fluorescent dye. At 48-h post-fertilization, we sorted small-sized cells from embryos using forward scatter and found that they consisted of DRAQ5 high and DRAQ5 low populations. DRAQ5 high cells contained haemoglobin, lacked myeloperoxidase activity and expressed high levels of embryonic globin (hbae3 and hbbe1.1) mRNA, all characteristics of primitive erythrocytes. Following DRAQ5 TM analysis of gata1:dsRed transgenic embryos, we purified primitive DRAQ5 high dsRed+ erythrocytes from haematopoietic progenitor cells. Using this method, we identified docking protein 2 (Dok2) as functioning in differentiation of primitive erythrocytes. We conclude that DRAQ5 TM -based flow cytometry enables purification of primitive zebrafish erythrocytes. © 2017 John Wiley & Sons Ltd.

A subjective study and an objective metric to quantify the granularity level of textures

NASA Astrophysics Data System (ADS)

Subedar, Mahesh M.; Karam, Lina J.

2015-03-01

Texture granularity is an important visual characteristic that is useful in a variety of applications, including analysis, recognition, and compression, to name a few. A texture granularity measure can be used to quantify the perceived level of texture granularity. The granularity level of the textures is influenced by the size of the texture primitives. A primitive is defined as the smallest recognizable repetitive object in the texture. If the texture has large primitives then the perceived granularity level tends to be lower as compared to a texture with smaller primitives. In this work we are presenting a texture granularity database referred as GranTEX which consists of 30 textures with varying levels of primitive sizes and granularity levels. The GranTEX database consists of both natural and man-made textures. A subjective study is conducted to measure the perceived granularity level of textures present in the GranTEX database. An objective metric that automatically measures the perceived granularity level of textures is also presented as part of this work. It is shown that the proposed granularity metric correlates well with the subjective granularity scores.

Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1+ cells.

PubMed

Sturgeon, Christopher M; Chicha, Laurie; Ditadi, Andrea; Zhou, Qinbo; McGrath, Kathleen E; Palis, James; Hammond, Scott M; Wang, Shusheng; Olson, Eric N; Keller, Gordon

2012-07-17

Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin(+) and Ter119(+) cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Acute undifferentiated leukaemia in a dog.

PubMed

Miglio, A; Antognoni, M T; Miniscalco, B; Caivano, D; Lepri, E; Birettoni, F; Mangili, V

2014-12-01

Acute undifferentiated leukaemia (AUL) is considered a separate entity in the context of acute leukaemias. AUL is extremely rare in both humans and dogs, has a rapid clinical course and does not respond to treatment. It is characterised by the presence of blast cells within the bone marrow and/or peripheral blood at levels ≥ 20% and even up to 100% of all nucleated cells. Blast cells are unable to be differentiated on morphological, cytochemical and phenotypic criteria into myeloid or lymphoid lineages because of their immaturity and/or atypia. An 8-year-old German Shepherd dog was referred for depression, asthenia, mild anaemia, thrombocytopenia and marked leucocytosis. Abdominal ultrasound showed hepatomegaly, splenomegaly, bilateral nephromegaly and enlargement of mesenteric lymph nodes. Echocardiography revealed biventricular hypertrophy with abnormal tissue density of the myocardium. Blood and bone marrow smears were composed of 95% unclassifiable and/or atypical blast cells and signs of dysplasia of the erythroid and thrombocytic/megakaryocytic lineages were present. Blast cells were negative for all cytochemical stains used and flow cytometry of peripheral blood revealed 85% of total leucocytes consisting of small-to-medium-sized cells, negative for all lymphoid and myeloid markers except CD45 and CD34. After necropsy, cytology and histology revealed that blast cells had diffusely infiltrated all tissues examined. Both erythroid and megakaryocytic extramedullary haemopoiesis was also detected in the spleen, lymph nodes and liver. All immunohistochemical stains used were negative. On the basis of all the results, a diagnosis of acute leukaemia involving a very primitive haematopoietic precursor was made. © 2014 Australian Veterinary Association.

Primitive African Medical Lore and Witchcraft *

PubMed Central

Thompson, Ethel E.

1965-01-01

This article presents a comprehensive study of the methods, practices, equipment, and paraphernalia of African witch doctors in carrying out primitive medical practices. The chief tribes studied are the Azandes of the Sudan, the Manos of Liberia, the Congo tribes, the Bundas of Angola, and the Zulus and other Bantu tribes of South Africa. Primitive beliefs and customs are discussed only insofar as they have a direct bearing on medical practices. The medical practices considered deal mainly with the application of general remedies for ailments and diseases, but certain specialized fields such as obstetrics, surgery, treatment for fractures, and dentistry are also included. Primitive medicaments are presented with reference to their application for various illnesses. An alphabetical list of these medicaments is given at the end of the article. PMID:14223742

Carotid-vertebrobasilar Anastomoses with Reference to Their Segmental Property.

PubMed

Namba, Katsunari

2017-06-15

The primitive carotid-vertebrobasilar anastomoses are primitive embryonic cerebral vessels that temporarily provide arterial supply from the internal carotid artery to the longitudinal neural artery, the future vertebrobasilar artery in the hindbrain. Four types known are the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries. The arteries are accompanied by their corresponding nerves and resemble an intersegmental pattern. These vessels exist in the very early period of cerebral arterial development and rapidly involute within a week. Occasionally, persistence of the carotid to vertebrobasilar anastomosis is discovered in the adult period, and is considered as the vestige of the corresponding primitive embryonic vessel. The embryonic development and the segmental property of the primitive carotid-vertebrobasilar anastomoses are discussed. This is followed by a brief description of the persisting anastomoses in adults.

Impact of Discrete Corrections in a Modular Approach for Trajectory Generation in Quadruped Robots

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.; Santos, Cristina P.; Rocha, Diana; Matos, Vítor

2011-09-01

Online generation of trajectories in robots is a very complex task that involves the combination of different types of movements, i.e., distinct motor primitives. The later are used to model complex behaviors in robots, such as locomotion in irregular terrain and obstacle avoidance. In this paper, we consider two motor primitives: rhythmic and discrete. We study the effect on the robots' gaits of superimposing the two motor primitives, considering two distinct types of coupling. Additionally, we simulate two scenarios, where the discrete primitive is inserted in all of the four limbs, or is inserted in ipsilateral pairs of limbs. Numerical results show that amplitude and frequency of the periodic solutions, corresponding to the gaits trot and pace, are almost constant for diffusive and synaptic couplings.

Quantifying chain reptation in entangled polymer melts: Topological and dynamical mapping of atomistic simulation results onto the tube model

NASA Astrophysics Data System (ADS)

Stephanou, Pavlos S.; Baig, Chunggi; Tsolou, Georgia; Mavrantzas, Vlasis G.; Kröger, Martin

2010-03-01

The topological state of entangled polymers has been analyzed recently in terms of primitive paths which allowed obtaining reliable predictions of the static (statistical) properties of the underlying entanglement network for a number of polymer melts. Through a systematic methodology that first maps atomistic molecular dynamics (MD) trajectories onto time trajectories of primitive chains and then documents primitive chain motion in terms of a curvilinear diffusion in a tubelike region around the coarse-grained chain contour, we are extending these static approaches here even further by computing the most fundamental function of the reptation theory, namely, the probability ψ(s,t) that a segment s of the primitive chain remains inside the initial tube after time t, accounting directly for contour length fluctuations and constraint release. The effective diameter of the tube is independently evaluated by observing tube constraints either on atomistic displacements or on the displacement of primitive chain segments orthogonal to the initial primitive path. Having computed the tube diameter, the tube itself around each primitive path is constructed by visiting each entanglement strand along the primitive path one after the other and approximating it by the space of a small cylinder having the same axis as the entanglement strand itself and a diameter equal to the estimated effective tube diameter. Reptation of the primitive chain longitudinally inside the effective constraining tube as well as local transverse fluctuations of the chain driven mainly from constraint release and regeneration mechanisms are evident in the simulation results; the latter causes parts of the chains to venture outside their average tube surface for certain periods of time. The computed ψ(s,t) curves account directly for both of these phenomena, as well as for contour length fluctuations, since all of them are automatically captured in the atomistic simulations. Linear viscoelastic properties such as the zero shear rate viscosity and the spectra of storage and loss moduli obtained on the basis of the obtained ψ(s,t) curves for three different polymer melts (polyethylene, cis-1,4-polybutadiene, and trans-1,4-polybutadiene) are consistent with experimental rheological data and in qualitative agreement with the double reptation and dual constraint models. The new methodology is general and can be routinely applied to analyze primitive path dynamics and chain reptation in atomistic trajectories (accumulated through long MD simulations) of other model polymers or polymeric systems (e.g., bidisperse, branched, grafted, etc.); it is thus believed to be particularly useful in the future in evaluating proposed tube models and developing more accurate theories for entangled systems.

Distributed Computation and TENEX-Related Activities

DTIC Science & Technology

1978-01-01

IPCF) which provides the inter-job communication functions required by MSG. MSG will be modified to use the IPCF primitives when running under TOPS...mmummi iiiwnrnrtnr’in i^WMBi. ■a^j.i.aiAj.k ■*"-’"’’"— •’ ’■■ BBN Report No. 3752 Bolt Beranek and Newman Inc. . . - . *. - primitive (e.g...from a process to MSG when a communication primitive is executed, and from MSG to a process when a pending event (e.g., outstanding receive operation

Primitive ideals of C q [ SL(3)

NASA Astrophysics Data System (ADS)

Hodges, Timothy J.; Levasseur, Thierry

1993-10-01

The primitive ideals of the Hopf algebra C q [ SL(3)] are classified. In particular it is shown that the orbits in Prim C q [ SL(3)] under the action of the representation group H ≅ C *× C * are parameterized naturally by W×W, where W is the associated Weyl group. It is shown that there is a natural one-to-one correspondence between primitive ideals of C q [ SL(3)] and symplectic leaves of the associated Poisson algebraic group SL(3, C).

A comment on methanogenic bacteria and the primitive ecology

NASA Technical Reports Server (NTRS)

Woese, C. R.

1977-01-01

As the phenotype of methanogenic bacteria is suggested to have been one of the major factors creating a dynamic balance between CO2 and CH4 in the primitive atmosphere, these organisms are thought to be very ancient. Their antiquity may be further postulated by comparative characterization of their ribosomal RNA. Accepting this antiquity, it is concluded that a carbon-dioxide-methane cycle, driven by photosynthesis, was the major carbon cycle in primitive ecology, and that photosynthesis and methanogens were thus contemporaneous.

Surface Antigens Common to Mouse Cleavage Embryos and Primitive Teratocarcinoma Cells in Culture

PubMed Central

Artzt, Karen; Dubois, Philippe; Bennett, Dorothea; Condamine, Hubert; Babinet, Charles; Jacob, François

1973-01-01

Syngeneic antisera have been produced in mouse strain 129/Sv-CP males against the primitive cells of teratocarcinoma. These sera react specifically with the primitive cells and are negative on various types of differentiated teratoma cells derived from the same original tumor. They are negative on all other mouse cells tested, with the exception of male germ cells and cleavage-stage embryos. Thus, teratoma cells possess cell-surface antigens in common with normal cleavage-stage embryos. Images PMID:4355379

Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.

PubMed

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.

Dynamic Association with Donor Cell Filopodia and Lipid-Modification Are Essential Features of Wnt8a during Patterning of the Zebrafish Neuroectoderm

PubMed Central

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Background Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. Results We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Conclusions Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning. PMID:24427298

The Role of H1 Linker Histone Subtypes in Preserving the Fidelity of Elaboration of Mesendodermal and Neuroectodermal Lineages during Embryonic Development

PubMed Central

Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Yang, Seung-Min; Kim, Byung-Ju; Skoultchi, Arthur I.; Mehler, Mark F.

2014-01-01

H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs) depleted of H1c, H1d and H1e subtypes (H1-KO ESCs) by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers. PMID:24802750

Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

PubMed

Holland, Linda Z

2005-07-15

In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.

Johnson-McMillin syndrome, a neuroectodermal syndrome with conductive hearing loss and microtia: report of a new case.

PubMed

Schweitzer, Daniela N; Yano, Shoji; Earl, Dawn L; Graham, John M

2003-07-30

In 1983, Johnson et al. described 16 related individuals with alopecia, anosmia or hyposmia, conductive hearing loss, microtia and/or atresia of the external auditory canal, and hypogonadotrophic hypogonadism inherited in an autosomal dominant pattern. Other less constant manifestations included facial asymmetry, mental retardation, congenital heart defect, cleft palate, and choanal stenosis. An isolated case was reported later (Johnston et al. [1987: Am J Med Genet 26: 925-927]) and thereafter an affected mother and son (Hennekam and Holtus [1993: Am J Med Genet 47: 714-716]). We describe an additional unrelated female patient with features resembling those of the previously reported cases. She presented with intrauterine growth deficiency, microcephaly, alopecia, bilateral microtia with canal atresia, conductive hearing loss, partial left facial palsy, posterior cleft palate, left choanal stenosis, tetralogy of Fallot, developmental delay, and right thumb polydactyly. Because the phenotypic abnormalities in this syndrome affect the brain, facial structures, ectoderm and its derivatives, outflow tract of the heart, and Rathke's pouch derivatives, this has suggested to previous authors etiologic involvement of the ectoderm and neuroectoderm of the first and second branchial arches, Rathke's pouch, and the diencephalon. Microtia with conductive hearing loss differentiates the condition from other ectodermal dysplasias. In the initial report, females appeared somewhat less affected than males, and there was male-to-male transmission. The mother of our patient manifests subtle features, which suggest she may be a mildly affected female. Additionally, there is a family history of early-onset alopecia in the maternal grandfather's relatives. Copyright 2003 Wiley-Liss, Inc.

Primitive macrophages control HSPC mobilization and definitive haematopoiesis.

PubMed

Travnickova, Jana; Tran Chau, Vanessa; Julien, Emmanuelle; Mateos-Langerak, Julio; Gonzalez, Catherine; Lelièvre, Etienne; Lutfalla, Georges; Tavian, Manuela; Kissa, Karima

2015-02-17

In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis.

Design principles of a cooperative robot controller

NASA Technical Reports Server (NTRS)

Hayward, Vincent; Hayati, Samad

1987-01-01

The paper describes the design of a controller for cooperative robots being designed at McGill University in a collaborative effort with the Jet Propulsion Laboratory. The first part of the paper discusses the background and motivation for multiple arm control. Then, a set of programming primitives, which are based on the RCCL system and which permit a programmer to specify cooperative tasks are described. The first group of primitives are motion primitives which specify asynchronous motions, master/slave motions, and cooperative motions. In the context of cooperative robots, trajectory generation issues will be discussed and the implementation described. A second set of primitives provides for the specification of spatial relationships. The relations between programming and control in the case of multiple robot are examined. Finally, the paper describes the allocation of various tasks among a set of microprocessors sharing a common bus.

Physically Unclonable Cryptographic Primitives by Chemical Vapor Deposition of Layered MoS2.

PubMed

Alharbi, Abdullah; Armstrong, Darren; Alharbi, Somayah; Shahrjerdi, Davood

2017-12-26

Physically unclonable cryptographic primitives are promising for securing the rapidly growing number of electronic devices. Here, we introduce physically unclonable primitives from layered molybdenum disulfide (MoS 2 ) by leveraging the natural randomness of their island growth during chemical vapor deposition (CVD). We synthesize a MoS 2 monolayer film covered with speckles of multilayer islands, where the growth process is engineered for an optimal speckle density. Using the Clark-Evans test, we confirm that the distribution of islands on the film exhibits complete spatial randomness, hence indicating the growth of multilayer speckles is a spatial Poisson process. Such a property is highly desirable for constructing unpredictable cryptographic primitives. The security primitive is an array of 2048 pixels fabricated from this film. The complex structure of the pixels makes the physical duplication of the array impossible (i.e., physically unclonable). A unique optical response is generated by applying an optical stimulus to the structure. The basis for this unique response is the dependence of the photoemission on the number of MoS 2 layers, which by design is random throughout the film. Using a threshold value for the photoemission, we convert the optical response into binary cryptographic keys. We show that the proper selection of this threshold is crucial for maximizing combination randomness and that the optimal value of the threshold is linked directly to the growth process. This study reveals an opportunity for generating robust and versatile security primitives from layered transition metal dichalcogenides.

A new Chinese specimen indicates that 'protofeathers' in the Early Cretaceous theropod dinosaur Sinosauropteryx are degraded collagen fibres.

PubMed

Lingham-Soliar, Theagarten; Feduccia, Alan; Wang, Xiaolin

2007-08-07

Alleged primitive feathers or protofeathers in the theropod dinosaur Sinosauropteryx have potentially profound implications concerning feather morphogenesis, evolution offlight, dinosaur physiology and perhaps even the origin of birds, yet their existence has never been adequately documented. We report on a new specimen of Sinosauropteryx which shows that the integumental structures proposed as protofeathers are the remains of structural fibres that provide toughness. The preservation in the proximal tail area reveals an architecture of closely associated bands offibres parallel to the tail's long axis, which originate from the skin. In adjacent more exposed areas, the fibres are short, fragmented and disorganized. Fibres preserved dorsal to the neck and back and in the distal part of the tail are the remains of a stiffening system of a frill, peripheral to the body and extending from the head to the tip of the tail. These findings are confirmed in the holotype Sinosauropteryx and NIGP 127587. The fibres show a striking similarity to the structure and levels of organization of dermal collagen. The proposal that these fibres are protofeathers is dismissed.

Cortical organization in insectivora: the parallel evolution of the sensory periphery and the brain.

PubMed

Catania, K C

2000-06-01

Insectivores are traditionally described as a primitive group that has not changed much in the course of mammalian evolution. In contrast, recent studies reveal a great diversity of sensorimotor specializations among insectivores adapted to a number of different ecological niches, indicating that there has been significant diversification and change in the course of their evolution. Here the organization of sensory cortex is compared in the African hedgehog (Atelerix albiventris), the masked shrew (Sorex cinereus), the eastern mole (Scalopus aquaticus), and the star-nosed mole (Condylura cristata). Each of these four closely related species lives in a unique ecological niche, exhibits a different repertoire of behaviors, and has a different configuration of peripheral sensory receptors. Corresponding specializations of cortical sensory areas reveal a number of ways in which the cortex has evolved in parallel with changes to the sensory periphery. These specializations include expansion of cortical representations (cortical magnification), the addition or loss of cortical areas in the processing network, and the subdivision of areas into modules (barrels and stripes). Copyright 2000 S. Karger AG, Basel

Efficient conservative ADER schemes based on WENO reconstruction and space-time predictor in primitive variables

NASA Astrophysics Data System (ADS)

Zanotti, Olindo; Dumbser, Michael

2016-01-01

We present a new version of conservative ADER-WENO finite volume schemes, in which both the high order spatial reconstruction as well as the time evolution of the reconstruction polynomials in the local space-time predictor stage are performed in primitive variables, rather than in conserved ones. To obtain a conservative method, the underlying finite volume scheme is still written in terms of the cell averages of the conserved quantities. Therefore, our new approach performs the spatial WENO reconstruction twice: the first WENO reconstruction is carried out on the known cell averages of the conservative variables. The WENO polynomials are then used at the cell centers to compute point values of the conserved variables, which are subsequently converted into point values of the primitive variables. This is the only place where the conversion from conservative to primitive variables is needed in the new scheme. Then, a second WENO reconstruction is performed on the point values of the primitive variables to obtain piecewise high order reconstruction polynomials of the primitive variables. The reconstruction polynomials are subsequently evolved in time with a novel space-time finite element predictor that is directly applied to the governing PDE written in primitive form. The resulting space-time polynomials of the primitive variables can then be directly used as input for the numerical fluxes at the cell boundaries in the underlying conservative finite volume scheme. Hence, the number of necessary conversions from the conserved to the primitive variables is reduced to just one single conversion at each cell center. We have verified the validity of the new approach over a wide range of hyperbolic systems, including the classical Euler equations of gas dynamics, the special relativistic hydrodynamics (RHD) and ideal magnetohydrodynamics (RMHD) equations, as well as the Baer-Nunziato model for compressible two-phase flows. In all cases we have noticed that the new ADER schemes provide less oscillatory solutions when compared to ADER finite volume schemes based on the reconstruction in conserved variables, especially for the RMHD and the Baer-Nunziato equations. For the RHD and RMHD equations, the overall accuracy is improved and the CPU time is reduced by about 25 %. Because of its increased accuracy and due to the reduced computational cost, we recommend to use this version of ADER as the standard one in the relativistic framework. At the end of the paper, the new approach has also been extended to ADER-DG schemes on space-time adaptive grids (AMR).

Tholeiitic basalt magmatism of Kilauea and Mauna Loa volcanoes of Hawaii

USGS Publications Warehouse

Murata, K.J.

1970-01-01

The primitive magmas of Kilauca and Mauna Loa are generated by partial melting of mantle peridotite at depths of -60 km or more. Results of high-pressure melting experiments indicate that the primitive melt must contain at least 20% MgO in order to have olivine as a liquidus mineral. The least fractionated lavas of both volcanoes have olivine (Fa13) on the liquidus at 1 atmosphere, suggesting that the only substance lost from the primitive melt, during a rather rapid ascent to the surface, is olivine. This relation allows the primitive composition to be computed by adding olivine to the composition of an erupted lava until total MgO is at least 20 percent. Although roughly similar, historic lavas of the two volcanoes show a consistent difference in composition. The primitive melt of Mauna Loa contains 20% more dissolved orthopyroxene, a high-temperature melting phase in the mantle, and is deficient in elements such as potassium, uranium, and niobium, which presumably occur in minor low-melting phases. Mauna Loa appears to be the older volcano, deriving its magma at higher temperature and greater depth from a more depleted source rock. ?? 1970 Springer-Verlag.

Compositional study of asteroids in the Erigone collisional family using visible spectroscopy at the 10.4 m GTC

NASA Astrophysics Data System (ADS)

Morate, David; de León, Julia; De Prá, Mário; Licandro, Javier; Cabrera-Lavers, Antonio; Campins, Humberto; Pinilla-Alonso, Noemí; Alí-Lagoa, Víctor

2016-02-01

Two primitive near-Earth asteroids, (101955) Bennu and (162173) Ryugu, will be visited by a spacecraft with the aim of returning samples back to Earth. Since these objects are believed to originate in the inner main belt primitive collisional families (Erigone, Polana, Clarissa, and Sulamitis) or in the background of asteroids outside these families, the characterization of these primitive populations will enhance the scientific return of the missions. The main goal of this work is to shed light on the composition of the Erigone collisional family by means of visible spectroscopy. Asteroid (163) Erigone has been classified as a primitive object, and we expect the members of this family to be consistent with the spectral type of the parent body. We have obtained visible spectra (0.5-0.9 μm) for 101 members of the Erigone family, using the OSIRIS instrument at the 10.4 m Gran Telescopio Canarias. We found that 87% of the objects have typically primitive visible spectra consistent with that of (163) Erigone. In addition, we found that a significant fraction of these objects (~50%) present evidence of aqueous alteration.

Developmental Approach for Behavior Learning Using Primitive Motion Skills.

PubMed

Dawood, Farhan; Loo, Chu Kiong

2018-05-01

Imitation learning through self-exploration is essential in developing sensorimotor skills. Most developmental theories emphasize that social interactions, especially understanding of observed actions, could be first achieved through imitation, yet the discussion on the origin of primitive imitative abilities is often neglected, referring instead to the possibility of its innateness. This paper presents a developmental model of imitation learning based on the hypothesis that humanoid robot acquires imitative abilities as induced by sensorimotor associative learning through self-exploration. In designing such learning system, several key issues will be addressed: automatic segmentation of the observed actions into motion primitives using raw images acquired from the camera without requiring any kinematic model; incremental learning of spatio-temporal motion sequences to dynamically generates a topological structure in a self-stabilizing manner; organization of the learned data for easy and efficient retrieval using a dynamic associative memory; and utilizing segmented motion primitives to generate complex behavior by the combining these motion primitives. In our experiment, the self-posture is acquired through observing the image of its own body posture while performing the action in front of a mirror through body babbling. The complete architecture was evaluated by simulation and real robot experiments performed on DARwIn-OP humanoid robot.

The primitive code and repeats of base oligomers as the primordial protein-encoding sequence.

PubMed Central

Ohno, S; Epplen, J T

1983-01-01

Even if the prebiotic self-replication of nucleic acids and the subsequent emergence of primitive, enzyme-independent tRNAs are accepted as plausible, the origin of life by spontaneous generation still appears improbable. This is because the just-emerged primitive translational machinery had to cope with base sequences that were not preselected for their coding potentials. Particularly if the primitive mitochondria-like code with four chain-terminating base triplets preceded the universal code, the translation of long, randomly generated, base sequences at this critical stage would have merely resulted in the production of short oligopeptides instead of long polypeptide chains. We present the base sequence of a mouse transcript containing tetranucleotide repeats conserved during evolution. Even if translated in accordance with the primitive mitochondria-like code, this transcript in its three reading frames can yield 245-, 246-, and 251-residue-long tetrapeptidic periodical polypeptides that are already acquiring longer periodicities. We contend that the first set of base sequences translated at the beginning of life were such oligonucleotide repeats. By quickly acquiring longer periodicities, their products must have soon gained characteristic secondary structures--alpha-helical or beta-sheet or both. PMID:6574491

Capture, Learning, and Classification of Upper Extremity Movement Primitives in Healthy Controls and Stroke Patients

PubMed Central

Guerra, Jorge; Uddin, Jasim; Nilsen, Dawn; Mclnerney, James; Fadoo, Ammarah; Omofuma, Isirame B.; Hughes, Shatif; Agrawal, Sunil; Allen, Peter; Schambra, Heidi M.

2017-01-01

There currently exist no practical tools to identify functional movements in the upper extremities (UEs). This absence has limited the precise therapeutic dosing of patients recovering from stroke. In this proof-of-principle study, we aimed to develop an accurate approach for classifying UE functional movement primitives, which comprise functional movements. Data were generated from inertial measurement units (IMUs) placed on upper body segments of older healthy individuals and chronic stroke patients. Subjects performed activities commonly trained during rehabilitation after stroke. Data processing involved the use of a sliding window to obtain statistical descriptors, and resulting features were processed by a Hidden Markov Model (HMM). The likelihoods of the states, resulting from the HMM, were segmented by a second sliding window and their averages were calculated. The final predictions were mapped to human functional movement primitives using a Logistic Regression algorithm. Algorithm performance was assessed with a leave-one-out analysis, which determined its sensitivity, specificity, and positive and negative predictive values for all classified primitives. In healthy control and stroke participants, our approach identified functional movement primitives embedded in training activities with, on average, 80% precision. This approach may support functional movement dosing in stroke rehabilitation. PMID:28813877

On the Primitive Ideal spaces of the C(*) -algebras of graphs

NASA Astrophysics Data System (ADS)

Bates, Teresa

2005-11-01

We characterise the topological spaces which arise as the primitive ideal spaces of the Cuntz-Krieger algebras of graphs satisfying condition (K): directed graphs in which every vertex lying on a loop lies on at least two loops. We deduce that the spaces which arise as Prim;C(*(E)) are precisely the spaces which arise as the primitive ideal spaces of AF-algebras. Finally, we construct a graph wt{E} from E such that C(*(wt{E})) is an AF-algebra and Prim;C(*(E)) and Prim;C(*(wt{E})) are homeomorphic.

Chemical evolution of primitive solar system bodies

NASA Technical Reports Server (NTRS)

Oro, J.; Mills, T.

1989-01-01

Observations on organic molecules and compounds containing biogenic elements in the interstellar medium and in the primitive bodies of the solar system are reviewed. The discovery of phosphorus molecular species in dense interstellar clouds, the existence of organic ions in the dust and gas phase of the comas of Comet Halley, and the presence of presolar, deuterium-hydrogen ratios in the amino acids of carbonaceous chondrites are discussed. The relationships between comets, dark asteroids, and carbonaceous chondrites are examined. Also, consideration is given to the chemical evolution of Titan, the primitive earth, and early Mars.

Incidence of the Hb E [β26(B8)Glu→Lys, GAG>AAG] variant in Totos, one of the smallest primitive tribes in the world.

PubMed

Bhattacharyya, Deboshree; Mukhopadhyay, Ashis; Chakraborty, Abhijit; Dasgupta, Swati; Mukhopadhyay, Soma; Pal, Nabamita; Basak, Jayasri

2013-01-01

Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as β-thalassemia (β-thal). We have studied 443 Totos to define their Hb E [β26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the β-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ - - - - -] (HincII 5'ϵ, HindIII (G)γ, HindIII (A)γ, HincII 5'ψβ, HincII 3'ψβ and HinfI 3'β). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future.

Generic extravehicular (EVA) and telerobot task primitives for analysis, design, and integration. Version 1.0: Reference compilation for the EVA and telerobotics communities

NASA Technical Reports Server (NTRS)

Smith, Jeffrey H.; Drews, Michael

1990-01-01

The results are described of an effort to establish commonality and standardization of generic crew extravehicular (crew-EVA) and telerobotic task analysis primitives used for the study of spaceborne operations. Although direct crew-EVA plans are the most visible output of spaceborne operations, significant ongoing efforts by a wide variety of projects and organizations also require tools for estimation of crew-EVA and telerobotic times. Task analysis tools provide estimates for input to technical and cost tradeoff studies. A workshop was convened to identify the issues and needs to establish a common language and syntax for task analysis primitives. In addition, the importance of such a syntax was shown to have precedence over the level to which such a syntax is applied. The syntax, lists of crew-EVA and telerobotic primitives, and the data base in diskette form are presented.

Small Cofactors May Assist Protein Emergence from RNA World: Clues from RNA-Protein Complexes

PubMed Central

Shen, Liang; Ji, Hong-Fang

2011-01-01

It is now widely accepted that at an early stage in the evolution of life an RNA world arose, in which RNAs both served as the genetic material and catalyzed diverse biochemical reactions. Then, proteins have gradually replaced RNAs because of their superior catalytic properties in catalysis over time. Therefore, it is important to investigate how primitive functional proteins emerged from RNA world, which can shed light on the evolutionary pathway of life from RNA world to the modern world. In this work, we proposed that the emergence of most primitive functional proteins are assisted by the early primitive nucleotide cofactors, while only a minority are induced directly by RNAs based on the analysis of RNA-protein complexes. Furthermore, the present findings have significant implication for exploring the composition of primitive RNA, i.e., adenine base as principal building blocks. PMID:21789260

Polycyclic aromatic hydrocarbons - Primitive pigment systems in the prebiotic environment

NASA Technical Reports Server (NTRS)

Deamer, D. W.

1992-01-01

The chemical evolution of meteoritic organics in the primitive earth is examined experimentally with attention given to the photochemical effects of hydrocarbon/water mixtures. Also addressed are the generation of amphiphilic products by photochemical reactions and the transduction of light energy into potentially useful forms. Polycyclic aromatic hydrocarbons (PAHs) absorb light and exist in carbonaceous chondrites; PAHs are therefore examined as primitive pigments by means of salt solutions with pyrene, fluoranthene, and pyrene derivatives with hexadecane. The hexadecane undergoes photochemical oxidation and yields long-chain amphiphiles with oxygen supplied by water, and acid pH shifts also occur. PAHs are also tested in lipid bilayer membranes to examine light-energy transduction. Protons are found to accumulate within the membrane-bounded volume to form proton gradients, and this reaction is theorized to be a good model of primitive photochemical reactions that related to the transduction of light energy into useable forms.

Clay minerals in primitive meteorites and interplanetary dust 1

NASA Technical Reports Server (NTRS)

Zolensky, M. E.; Keller, L. P.

1991-01-01

Many meteorites and interplanetary dust particles (IDPs) with primitive compositions contain significant amounts of phyllosilicate minerals, which are generally interpreted as evidence of protoplanetary aqueous alteration at an early period of the solar system. These meteorites are chondrites (near solar composition) of the carbonaceous and ordinary varieties. The former are subdivided (according to bulk composition and petrology) into CI, CM, CV, CO, CR, and ungrouped classes. IDPs are extraterrestrial particulates, collected in stratosphere, which have chemical compositions indicative of a primitive origin; they are typically distinct from the primitive meteorites. Characterization of phyllosilicates in these materials is a high priority because of the important physico-chemical information they hold. The most common phyllosilicates present in chondritic extraterrestrial materials are serpentine-group minerals, smectites, and micas. We discuss these phyllosilicates and describe the interpretation of their occurrence in meteorites and IDPs and what this indicates about history of their parent bodies, which are probably the hydrous asteroids.

A newborn with neurocutaneous melanocytosis and Dandy-Walker malformation.

PubMed

De Cock, Jens; Snauwaert, Julie; Van Rompaey, Walter; Morren, Marie-Anne; Demaerel, Philippe

2014-03-01

Neurocutaneous melanocytosis is a rare congenital dysplasia of the neuroectodermal melanocyte precursor cells that leads to proliferation of melanin-producing cells in the skin and leptomeninges. We describe a newborn with a giant congenital melanocytic nevus on his back, buttocks, and thighs. His brain magnetic resonance imaging study revealed bilateral T1 hyperintense lesions in the cerebellum and in the amygdala, hydrocephalus, and a Blake's pouch cyst, consistent with neurocutaneous melanocytosis and Dandy-Walker malformation. Neurocutaneous melanocytosis has a wide clinical spectrum that includes hydrocephalus, epilepsy, cranial nerve palsy, increased intracranial pressure, and sensorimotor deficits. Copyright © 2014. Published by Elsevier Inc.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

A morphological analysis of the transition between the embryonic primitive intestine and yolk sac in bovine embryos and fetuses.

PubMed

Mançanares, Celina A F; Leiser, Rudolf; Favaron, Phelipe O; Carvalho, Ana F; Oliveira, Vanessa C De; Santos, José M Dos; Ambrósio, Carlos E; Miglino, Maria A

2013-07-01

The yolk sac (YS) is the main source of embryonic nutrition during the period when the placenta has not yet formed. It is also responsible for hematopoiesis because the blood cells develop from it as part of the primitive embryonic circulation. The objective of this study was to characterize the transitional area between the YS and primitive gut using the techniques of light microscopy, transmission electron microscopy, and immunohistochemistry to detect populations of pluripotent cells by labeling with Oct4 antibody. In all investigated embryos, serial sections were made to permit the identification of this small, restricted area. We identified the YS connection with the primitive intestine and found that it is composed of many blood islands, which correspond to the vessels covered by vitelline and mesenchymal cells. We identified large numbers of hemangioblasts inside the vessels. The mesenchymal layer was thin and composed of elongated cells, and the vitelline endodermal membrane was composed of large, mono- or binucleated cells. The epithelium of the primitive intestine comprised stratified columnar cells and undifferentiated mesenchymal cells. The transitional area between the YS and the primitive intestine was very thin and composed of cells with irregular shapes, which formed a delicate lumen containing hemangioblasts. In the mesenchyme of the transitional area, there were a considerable number of small vessels containing hemangioblasts. Using Oct4 as a primary antibody, we identified positive cells in the metanephros, primordial gonad, and hepatic parenchyma as well as in YS cells, suggesting that these regions contain populations of pluripotent cells. Copyright © 2013 Wiley Periodicals, Inc.

Correct Patterning of the Primitive Streak Requires the Anterior Visceral Endoderm

PubMed Central

Stuckey, Daniel W.; Di Gregorio, Aida; Clements, Melanie; Rodriguez, Tristan A.

2011-01-01

Anterior-posterior axis specification in the mouse requires signalling from a specialised extra-embryonic tissue called the anterior visceral endoderm (AVE). AVE precursors are induced at the distal tip of the embryo and move to the prospective anterior. Embryological and genetic analysis has demonstrated that the AVE is required for anterior patterning and for correctly positioning the site of primitive streak formation by inhibiting Nodal activity. We have carried out a genetic ablation of the Hex-expressing cells of the AVE (Hex-AVE) by knocking the Diphtheria toxin subunit A into the Hex locus in an inducible manner. Using this model we have identified that, in addition to its requirement in the anterior of the embryo, the Hex-AVE sub-population has a novel role between 5.5 and 6.5dpc in patterning the primitive streak. Embryos lacking the Hex-AVE display delayed initiation of primitive streak formation and miss-patterning of the anterior primitive streak. We demonstrate that in the absence of the Hex-AVE the restriction of Bmp2 expression to the proximal visceral endoderm is also defective and expression of Wnt3 and Nodal is not correctly restricted to the posterior epiblast. These results, coupled with the observation that reducing Nodal signalling in Hex-AVE ablated embryos increases the frequency of phenotypes observed, suggests that these primitive streak patterning defects are due to defective Nodal signalling. Together, our experiments demonstrate that the AVE is not only required for anterior patterning, but also that specific sub-populations of this tissue are required to pattern the posterior of the embryo. PMID:21445260

Evolution of Computational Toxicology-from Primitive ...

EPA Pesticide Factsheets

Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 Presentation at the Health Canada seminar in Ottawa, ON, Canada on Nov. 15. 2016 on the Evolution of Computational Toxicology-from Primitive Beginnings to Sophisticated Application

Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD34+ and CD34+ Thy-1dim CD38- progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation.

PubMed

Körbling, M; Anderlini, P; Durett, A; Maadani, F; Bojko, P; Seong, D; Giralt, S; Khouri, I; Andersson, B; Mehra, R; vanBesien, K; Mirza, N; Przepiorka, D; Champlin, R

1996-12-01

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) is emerging as a new stem cell transplant modality. Rather than undergoing general anesthesia for bone marrow harvest, normal blood stem cell donors are subjected to rhG-CSF mobilization treatment followed by single or multiple apheresis. Whereas the effects of cytokine treatment and apheresis on stem cell peripheralization and collection have been described, little is known about delayed effects of rhG-CSF treatment and apheresis on a normal hematopoietic system, and there are no long-term data that address safety issues. Ten normal, patient-related donors underwent a 3 or 4 day rhG-CSF (filgrastim) treatment (12 micrograms/kg/day) followed by single or tandem apheresis. We monitored peripheral blood (PB) cellularity including CD34+ and lymphoid subsets at baseline, during cytokine treatment, prior to apheresis, and at days 2, 4, 7, 30 and 100 post-apheresis. The PB progenitor cell concentration peak prior to apheresis was followed by a nadir by day 7 and normalized by day 30, with the exception of the most primitive CD34+ Thy-1dim CD38- progenitor subset that reached a nadir by day 30. Lymphoid subsets such as CD3, 4, 8, suppressor cells (CD3+ 4- 8- TCR+ alpha beta), and B cells (CD19+) showed a similar pattern with a nadir concentration by day 7, followed, except for B cells, by a rebound by day 30 and subnormal counts at day 100. The PB concentrations of hemoglobin and platelets dropped mainly due to the apheresis procedure itself, and normalized by day 30. With cytokine treatment, the PB alkaline phosphatase and lactate dehydrogenase concentrations increased 2.2- and 2.8-fold, respectively, over baseline, and returned to normal range by day 30. Based on the preliminary nature of this study, the clinical relevance of these findings is still unclear.

Low-Resolution Spectroscopy of Primitive Asteroids: Progress Report for SARA/VSU Survey

NASA Technical Reports Server (NTRS)

Leake, M. A.; Nogues, J. P.; Gaines, J. K.; Looper, J. K.; Freitas, K. A.

2001-01-01

Progress on a low-resolution survey of primitive C-class asteroids continues using new equipment (and its associated problems) to understand aqueous alteration in the solar system. Additional information is contained in the original extended abstract.

Design of Quasi-Terminator Orbits near Primitive Bodies

NASA Technical Reports Server (NTRS)

Lantoine, Gregory; Broschart, Stephen B.; Grebow, Daniel J.

2013-01-01

Quasi-terminator orbits are a class of quasi-periodic orbits around a primitive body that exist in the vicinity of the well-known terminator orbits. The inherent stability of quasi-terminator trajectories and their wide variety of viewing geometries make them a very compelling option for primitive body mapping missions. In this paper, we discuss orbit design methodologies for selection of an appropriate quasi-terminator orbit that would meet the needs of a specific mission. Convergence of these orbits in an eccentric, higher-fidelity model is also discussed with an example case at Bennu, the target of the upcoming NASA's OSIRIS-REx mission.

KSOS Computer Program Development Specifications (Type B-5). (Kernelized Secure Operating System). I. Security Kernel (CDRL 0002AF). II. UNIX Emulator (CDRL 0002AG). III. Security-Related Software (CDRL 0002AH).

DTIC Science & Technology

1980-12-01

Commun- ications Corporation, Palo Alto, CA (March 1978). g. [Walter at al. 74] Walter, K.G. et al., " Primitive Models for Computer .. Security", ESD-TR...discussion is followed by a presenta- tion of the Kernel primitive operations upon these objects. All Kernel objects shall be referenced by a common...set of sizes. All process segments, regardless of domain, shall be manipulated by the same set of Kernel segment primitives . User domain segments

SMP: A solid modeling program version 2.0

NASA Technical Reports Server (NTRS)

Randall, D. P.; Jones, K. H.; Vonofenheim, W. H.; Gates, R. L.; Matthews, C. G.

1986-01-01

The Solid Modeling Program (SMP) provides the capability to model complex solid objects through the composition of primitive geometric entities. In addition to the construction of solid models, SMP has extensive facilities for model editing, display, and analysis. The geometric model produced by the software system can be output in a format compatible with existing analysis programs such as PATRAN-G. The present version of the SMP software supports six primitives: boxes, cones, spheres, paraboloids, tori, and trusses. The details for creating each of the major primitive types is presented. The analysis capabilities of SMP, including interfaces to existing analysis programs, are discussed.

Utilizing semantic networks to database and retrieve generalized stochastic colored Petri nets

NASA Technical Reports Server (NTRS)

Farah, Jeffrey J.; Kelley, Robert B.

1992-01-01

Previous work has introduced the Planning Coordinator (PCOORD), a coordinator functioning within the hierarchy of the Intelligent Machine Mode. Within the structure of the Planning Coordinator resides the Primitive Structure Database (PSDB) functioning to provide the primitive structures utilized by the Planning Coordinator in the establishing of error recovery or on-line path plans. This report further explores the Primitive Structure Database and establishes the potential of utilizing semantic networks as a means of efficiently storing and retrieving the Generalized Stochastic Colored Petri Nets from which the error recovery plans are derived.

AGUA TIBIA PRIMITIVE AREA, CALIFORNIA.

USGS Publications Warehouse

Irwin, William P.; Thurber, Horace K.

1984-01-01

The Agua Tibia Primitive Area in southwestern California is underlain by igneous and metamorphic rocks that are siilar to those widely exposed throughout much of the Peninsular Ranges. To detect the presence of any concealed mineral deposits, samples of stream sediments were collected along the various creeks that head in the mountain. As an additional aid in evaluating the mineral potential, an aeromagnetic survey was made and interpreted. A search for records of past or existing mining claims within the primitive area was made but none was found. Evidence of deposits of metallic or nonmetallic minerals was not seen during the study.

Perceptual integration of kinematic components in the recognition of emotional facial expressions.

PubMed

Chiovetto, Enrico; Curio, Cristóbal; Endres, Dominik; Giese, Martin

2018-04-01

According to a long-standing hypothesis in motor control, complex body motion is organized in terms of movement primitives, reducing massively the dimensionality of the underlying control problems. For body movements, this low-dimensional organization has been convincingly demonstrated by the learning of low-dimensional representations from kinematic and EMG data. In contrast, the effective dimensionality of dynamic facial expressions is unknown, and dominant analysis approaches have been based on heuristically defined facial "action units," which reflect contributions of individual face muscles. We determined the effective dimensionality of dynamic facial expressions by learning of a low-dimensional model from 11 facial expressions. We found an amazingly low dimensionality with only two movement primitives being sufficient to simulate these dynamic expressions with high accuracy. This low dimensionality is confirmed statistically, by Bayesian model comparison of models with different numbers of primitives, and by a psychophysical experiment that demonstrates that expressions, simulated with only two primitives, are indistinguishable from natural ones. In addition, we find statistically optimal integration of the emotion information specified by these primitives in visual perception. Taken together, our results indicate that facial expressions might be controlled by a very small number of independent control units, permitting very low-dimensional parametrization of the associated facial expression.

A direct Primitive Variable Recovery Scheme for hyperbolic conservative equations: The case of relativistic hydrodynamics.

PubMed

Aguayo-Ortiz, A; Mendoza, S; Olvera, D

2018-01-01

In this article we develop a Primitive Variable Recovery Scheme (PVRS) to solve any system of coupled differential conservative equations. This method obtains directly the primitive variables applying the chain rule to the time term of the conservative equations. With this, a traditional finite volume method for the flux is applied in order avoid violation of both, the entropy and "Rankine-Hugoniot" jump conditions. The time evolution is then computed using a forward finite difference scheme. This numerical technique evades the recovery of the primitive vector by solving an algebraic system of equations as it is often used and so, it generalises standard techniques to solve these kind of coupled systems. The article is presented bearing in mind special relativistic hydrodynamic numerical schemes with an added pedagogical view in the appendix section in order to easily comprehend the PVRS. We present the convergence of the method for standard shock-tube problems of special relativistic hydrodynamics and a graphical visualisation of the errors using the fluctuations of the numerical values with respect to exact analytic solutions. The PVRS circumvents the sometimes arduous computation that arises from standard numerical methods techniques, which obtain the desired primitive vector solution through an algebraic polynomial of the charges.

Basis set construction for molecular electronic structure theory: natural orbital and Gauss-Slater basis for smooth pseudopotentials.

PubMed

Petruzielo, F R; Toulouse, Julien; Umrigar, C J

2011-02-14

A simple yet general method for constructing basis sets for molecular electronic structure calculations is presented. These basis sets consist of atomic natural orbitals from a multiconfigurational self-consistent field calculation supplemented with primitive functions, chosen such that the asymptotics are appropriate for the potential of the system. Primitives are optimized for the homonuclear diatomic molecule to produce a balanced basis set. Two general features that facilitate this basis construction are demonstrated. First, weak coupling exists between the optimal exponents of primitives with different angular momenta. Second, the optimal primitive exponents for a chosen system depend weakly on the particular level of theory employed for optimization. The explicit case considered here is a basis set appropriate for the Burkatzki-Filippi-Dolg pseudopotentials. Since these pseudopotentials are finite at nuclei and have a Coulomb tail, the recently proposed Gauss-Slater functions are the appropriate primitives. Double- and triple-zeta bases are developed for elements hydrogen through argon. These new bases offer significant gains over the corresponding Burkatzki-Filippi-Dolg bases at various levels of theory. Using a Gaussian expansion of the basis functions, these bases can be employed in any electronic structure method. Quantum Monte Carlo provides an added benefit: expansions are unnecessary since the integrals are evaluated numerically.

A direct Primitive Variable Recovery Scheme for hyperbolic conservative equations: The case of relativistic hydrodynamics

PubMed Central

Mendoza, S.; Olvera, D.

2018-01-01

In this article we develop a Primitive Variable Recovery Scheme (PVRS) to solve any system of coupled differential conservative equations. This method obtains directly the primitive variables applying the chain rule to the time term of the conservative equations. With this, a traditional finite volume method for the flux is applied in order avoid violation of both, the entropy and “Rankine-Hugoniot” jump conditions. The time evolution is then computed using a forward finite difference scheme. This numerical technique evades the recovery of the primitive vector by solving an algebraic system of equations as it is often used and so, it generalises standard techniques to solve these kind of coupled systems. The article is presented bearing in mind special relativistic hydrodynamic numerical schemes with an added pedagogical view in the appendix section in order to easily comprehend the PVRS. We present the convergence of the method for standard shock-tube problems of special relativistic hydrodynamics and a graphical visualisation of the errors using the fluctuations of the numerical values with respect to exact analytic solutions. The PVRS circumvents the sometimes arduous computation that arises from standard numerical methods techniques, which obtain the desired primitive vector solution through an algebraic polynomial of the charges. PMID:29659602

Neoadjuvant chemotherapy for brain tumors in infants and young children.

PubMed

Iwama, Junya; Ogiwara, Hideki; Kiyotani, Chikako; Terashima, Keita; Matsuoka, Kentaro; Iwafuchi, Hideto; Morota, Nobuhito

2015-05-01

Because of their large size and high vascularity, complete removal of brain tumors in infants and young children is often difficult. In most cases the degree of resection is associated with prognosis. Neoadjuvant chemotherapy may facilitate resection by reducing the vascularity of the tumor. The authors evaluated the effectiveness of neoadjuvant chemotherapy in the management of these tumors. The authors performed a retrospective review of infants and young children who underwent tumor removal after neoadjuvant chemotherapy. Nine consecutive patients underwent resection after neoadjuvant chemotherapy during the period February 2004 to December 2012. The mean age at diagnosis was 18 months (range 2-50 months). The average largest tumor diameter was 71 mm (range 30-130 mm) at initial surgery. Five patients underwent partial resection, and 4 underwent biopsy as the initial surgery. The histopathological diagnoses were ependymoma in 2 patients, anaplastic ependymoma in 1, primitive neuroectodermal tumor (PNET) in 2, choroid plexus carcinoma in 1, atypical teratoid/rhabdoid tumor (AT/RT) in 1, glioblastoma in 1, and embryonal tumor with abundant neuropil and true rosettes in 1. After 2-4 courses of multiagent chemotherapy (mainly with vincristine, cyclophosphamide, etoposide, and cisplatin), the second-look surgery was performed. In 1 patient with a PNET, intratumoral hemorrhage was observed after 2 courses of chemotherapy. The mean interval between the initial and the second-look surgery was 3 months. The tumor volume was reduced to varying degrees in 5 patients (56%) after chemotherapy. Intraoperatively, the vascularity of the tumor was considerably reduced, and the tumor was more circumscribed in all cases. Gross-total resection was achieved in 8 patients (89%) and neartotal resection in 1 (11%). Histopathological examination demonstrated fibrotic tissue circumscribing the tumor in 6 of 9 cases (67%). The average blood loss was 20% of the estimated blood volume, and 3 patients (33%) required a blood transfusion. There was no surgical mortality. One patient had transient dysphasia postoperatively. The mean follow-up period was 28 months. At the last follow-up, 2 patients (22%) had died (1 died of tumor progression and 1 of sepsis), and 4 patients (44%) had no tumor recurrence. Neoadjuvant chemotherapy for brain tumors in infants and young children was effective in reduction of tumor vascularity and clarification of the tumor-brain interface, which significantly facilitated maximal tumor resection.

The role of immunohistochemistry in the analysis of the spectrum of small round cell tumours at a tertiary care centre.

PubMed

D'cruze, Lawrence; Dutta, Ruma; Rao, Shalinee; R, Anuradha; Varadarajan, Suresh; Kuruvilla, Sarah

2013-07-01

The term, "Small Round - Cell Tumours" (SRCT) describes a group of highly aggressive malignant neoplasms which are composed predominantly of small and monotonous undifferentiated cells with high nucleocytoplasmic ratios. Immunohistochemistry (IHC) plays a crucial role in catagorizing the small round - cell tumours. This study was done to analyse the spectrum of small round cell tumours over a period of five years at a tertiary care centre and to study the relevance of immunohistochemistry in making precise diagnoses of the small round cell tumours. Formalin - fixed, paraffin - embedded sections of tumours which were diagnosed as small round cell tumours on small biopsies and resected specimens were retrieved from the files of the Department of Pathology of Sri Ramachandra Medical College and Research institute, in the period from January 2005 to December 2009. This study was confined to the bone and the soft tissues. Decalcification was performed on the bony tissues before the routine processing was done. The patients belonging to all age groups were included in this study. The small round cell tumours of the bone marrow, the spleen and the lymph node was excluded from our study. Immunohistochemical stains were performed to differentiate and categorise the small round blue cell tumours. The immunomarkers which were utilised in this study included CD45/LCA (the lymphocyte common antigen), CD20, CD3, CD99 (cluster of differentiation 99 also known as MIC2), desmin, EMA (epithelial membrane antigen), CK(cytokeratin), synaptophysin, chromogranin and GFAP (Glial fibrillary acidic protein). Forty three cases of small round cell tumours were analysed, which included 19 cases of NHL (non Hodgkin's lymphoma), 6 cases of Ewing/PNETs (primitive neuroectodermal tumours), 3 cases of atypical carcinoid, 3 cases of olfactory neuroblastoma, 2 cases each of rhabdomyosarcoma, Wilms tumour, neuroblastoma and synovial sarcoma and 1 case each of small cell osteosarcoma, small (oat) cell carcinoma, medulloblastoma and hepatoblastoma. By using a panel of monoclonal antibodies, we could arrive at a final diagnosis for all the 40 cases in which immunohistochemistry was performed. Our study showed that the use of immunohistochemistry was extremely beneficial. A majority of the small round cell tumours occurred between the ages of 15-45 years and the most common small round cell tumour was Non-Hodgkins lymphoma (extra lymphoreticular).

Highly Conformal Craniospinal Radiotherapy Techniques Can Underdose the Cranial Clinical Target Volume if Leptomeningeal Extension through Skull Base Exit Foramina is not Contoured.

PubMed

Noble, D J; Ajithkumar, T; Lambert, J; Gleeson, I; Williams, M V; Jefferies, S J

2017-07-01

Craniospinal irradiation (CSI) remains a crucial treatment for patients with medulloblastoma. There is uncertainty about how to manage meningeal surfaces and cerebrospinal fluid (CSF) that follows cranial nerves exiting skull base foramina. The purpose of this study was to assess plan quality and dose coverage of posterior cranial fossa foramina with both photon and proton therapy. We analysed the radiotherapy plans of seven patients treated with CSI for medulloblastoma and primitive neuro-ectodermal tumours and three with ependymoma (total n = 10). Four had been treated with a field-based technique and six with TomoTherapy™. The internal acoustic meatus (IAM), jugular foramen (JF) and hypoglossal canal (HC) were contoured and added to the original treatment clinical target volume (Plan_CTV) to create a Test_CTV. This was grown to a test planning target volume (Test_PTV) for comparison with a Plan_PTV. Using Plan_CTV and Plan_PTV, proton plans were generated for all 10 cases. The following dosimetry data were recorded: conformity (dice similarity coefficient) and homogeneity index (D 2  - D 98 /D 50 ) as well as median and maximum dose (D 2% ) to Plan_PTV, V 95% and minimum dose (D 99.9% ) to Plan_CTV and Test_CTV and Plan_PTV and Test_PTV, V 95% and minimum dose (D 98% ) to foramina PTVs. Proton and TomoTherapy™ plans were more conformal (0.87, 0.86) and homogeneous (0.07, 0.04) than field-photon plans (0.79, 0.17). However, field-photon plans covered the IAM, JF and HC PTVs better than proton plans (P = 0.002, 0.004, 0.003, respectively). TomoTherapy™ plans covered the IAM and JF better than proton plans (P = 0.000, 0.002, respectively) but the result for the HC was not significant. Adding foramen CTVs/PTVs made no difference for field plans. The mean D min dropped 3.4% from Plan_PTV to Test_PTV for TomoTherapy™ (not significant) and 14.8% for protons (P = 0.001). Highly conformal CSI techniques may underdose meninges and CSF in the dural reflections of posterior fossa cranial nerves unless these structures are specifically included in the CTV. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The results of surgical treatment of chest wall tumors in childhood.

PubMed

Soyer, Tutku; Karnak, Ibrahim; Ciftci, Arbay O; Senocak, Mehmet Emin; Tanyel, F Cahit; Büyükpamukçu, Nebil

2006-02-01

Chest wall tumors (CWT) are rarely seen in childhood and surgery constitutes a complementary part of the therapy. The early and late results of CWT resection and chest wall reconstruction were evaluated retrospectively. The children who underwent chest wall resection for CWT between January 1990 and November 2003 were evaluated retrospectively. Seventeen children (male/female = 12/5, mean age: 7.58 years) underwent chest wall resection for CWT. Fifteen patients underwent initial biopsy (tru-cut, n = 8 or open biopsy, n = 7) and two underwent initial resection. The diagnosis was malignant tumor in 12 (70%) and benign in 5 (30%). They were Ewing's sarcoma (ES) (n = 4), primitive neuroectodermal tumor (PNET) (n = 3), Askin's tumor (n = 1), rhabdomyosarcoma (RMS) (n = 2), neuroblastoma (n = 2), osteochondroma (n = 1), aneurysmal bone cyst (n = 2) and hamartoma (n = 2). Preoperative chemotherapy was given to most patients with malignant tumor. All patients had only local tumor at the time of resection. Thoracotomy was performed in all patients. All tumor tissues with the affected rib/ribs were resected en bloc with the adjacent tissues. The number of resected ribs was 1 (n = 6), 2 (n = 7) and 3 (n = 4). Chest wall defects were repaired primarily (n = 8) or with grafts (n = 9). Dura (n = 4), Neuro-patch (n = 3) and Goretex (n = 2) were used for closure. Wound infection and pleural fistula occurred in one patient. Patients with benign tumor were free of complaints or complications during follow up. All patients with malignant tumor received postoperative chemotherapy. Local recurrence did not occur in all patients. Five patients developed distant metastasis and two died. Scoliosis was encountered in one patient during follow-up. Since most of the CWT are malignant and not initially suitable for surgical excision, the management includes tissue diagnosis either by tru-cut or open biopsy. Determination of malignant condition should be followed by an intensive chemotherapy. Chest wall resection is planned to control local disease. Chest wall reconstruction may be needed for large defects following resection of CWT. Prosthetic materials can be used safely. Early complications of the surgery are limited. The patients should be closely followed up for late complications such as scoliosis, restrictive pulmonary disease and for the development of metastasis, which is a part of natural course of malignant CWT in children.

Heuristics for Cooperative Problem Solving

DTIC Science & Technology

1989-02-01

briefly, cooperation is a very common problem-solving technique in natural systems and occurs in a wide variety of animals ranging from termites and...primitive way with pheromones but sometimes more directly. As with social spiders, they show relatively primitive coordination of behavior. In spite

Evolutionary anatomy of the Neandertal ulna and radius in the light of the new El Sidrón sample.

PubMed

Pérez-Criado, Laura; Rosas, Antonio

2017-05-01

This paper aims to improve our understanding of the phylogenetic trait polarity related to hominin forearm evolution, in particular those traits traditionally defined as "Neandertal features." To this aim, twelve adult and adolescent fragmented forelimb elements (including ulnae and radii) of Homo neanderthalensis recovered from the site of El Sidrón (Asturias, Spain) were examined comparatively using three-dimensional geometric and traditional morphometrics. Mean centroid size and shape comparisons, principal components analysis, and phylogenetic signal analysis were undertaken. Our investigations revealed that the proximal region of the ulna discriminated best between Neandertals and modern humans, with fewer taxonomically-informative features in the distal ulna and radius. Compared to modern humans, the divergent features in the Neandertal ulna are an increase in olecranon breadth (a derived trait), lower coronoid length (primitive), and anterior orientation of the trochlear notch (primitive). In the Neandertal radius, we observe a larger neck length (primitive), medial orientation of the radial tubercle (secondarily primitive), and a curved diaphysis (secondarily primitive). Anatomically, we identified three units of evolutionary change: 1) the olecranon and its fossa, 2) the coronoid-radius neck complex, and 3) the tubercle and radial diaphysis. Based on our data, forearm evolution followed a mosaic pattern in which some features were inherited from a pre-Homo ancestor, others originated in some post-ergaster and pre-antecessor populations, and other characters emerged in the specific Homo sapiens and H. neanderthalensis lineages, sometimes appearing as secondarily primitive. Future investigations might consider the diverse phylogenetic origin of apomorphies while at the same time seeking to elucidate their functional meaning. Copyright © 2017 Elsevier Ltd. All rights reserved.

New hybrid voxelized/analytical primitive in Monte Carlo simulations for medical applications

NASA Astrophysics Data System (ADS)

Bert, Julien; Lemaréchal, Yannick; Visvikis, Dimitris

2016-05-01

Monte Carlo simulations (MCS) applied in particle physics play a key role in medical imaging and particle therapy. In such simulations, particles are transported through voxelized phantoms derived from predominantly patient CT images. However, such voxelized object representation limits the incorporation of fine elements, such as artificial implants from CAD modeling or anatomical and functional details extracted from other imaging modalities. In this work we propose a new hYbrid Voxelized/ANalytical primitive (YVAN) that combines both voxelized and analytical object descriptions within the same MCS, without the need to simultaneously run two parallel simulations, which is the current gold standard methodology. Given that YVAN is simply a new primitive object, it does not require any modifications on the underlying MC navigation code. The new proposed primitive was assessed through a first simple MCS. Results from the YVAN primitive were compared against an MCS using a pure analytical geometry and the layer mass geometry concept. A perfect agreement was found between these simulations, leading to the conclusion that the new hybrid primitive is able to accurately and efficiently handle phantoms defined by a mixture of voxelized and analytical objects. In addition, two application-based evaluation studies in coronary angiography and intra-operative radiotherapy showed that the use of YVAN was 6.5% and 12.2% faster than the layered mass geometry method, respectively, without any associated loss of accuracy. However, the simplification advantages and differences in computational time improvements obtained with YVAN depend on the relative proportion of the analytical and voxelized structures used in the simulation as well as the size and number of triangles used in the description of the analytical object meshes.

Petrogenesis of the Late Triassic diorites in the Hoh Xil area, northern Tibet: Insights into the origin of the high-Mg# andesitic signature of continental crust

NASA Astrophysics Data System (ADS)

Wang, Jun; Gou, Guo-Ning; Wang, Qiang; Zhang, Chunfu; Dan, Wei; Wyman, Derek A.; Zhang, Xiu-Zheng

2018-02-01

An integrated petrologic, geochronologic, major and trace element geochemical, and Sr-Nd-Hf isotopic study of Late Triassic ( 215 Ma) diorites from the Hoh Xil area, northern Tibet, provides new constraints on the genesis of intermediate magmas and insights into the origin of the high-Mg# andesitic signature of continental crust. These dioritic rocks are characterized by high MgO contents (3.3-5.0 wt%) and Mg# values (50-57) comparable to the estimates for the bulk continental crust at the same level of SiO2 contents (61.1-64.5 wt%). They also display continental crust-like trace element distribution patterns and uniformly enriched isotope compositions ([87Sr/86Sr]i = 0.7081 to 0.7094, ɛNd[t] = - 8.0 to - 6.9, and ɛHf[t]zircon = - 10.1 to - 5.0). Combining our results with published data from crystallization experiments, we propose that they were probably produced by fractional crystallization from a primitive andesite parent, rather than a primitive basalt parent. This parental magma may be geochemically similar to the roughly contemporaneous primitive andesites in the adjacent Malanshan area of northern Tibet. Our compilation of modern arc lavas shows that progressive fractional crystallization of primitive andesites is also required to reproduce the Mg# versus SiO2 array for natural arc magmas, in addition to differentiation of mantle-derived primitive basaltic magmas and/or mixing of basaltic with felsic magmas. Therefore, we emphasize that fractional crystallization of primitive andesitic magmas is potentially a frequent occurrence in arc crust and hence may play an important role in producing the high-Mg# signature of intermediate magmas comprising the continental crust.

The Midline Protein Regulates Axon Guidance by Blocking the Reiteration of Neuroblast Rows within the Drosophila Ventral Nerve Cord

PubMed Central

Manavalan, Mary Ann; Gaziova, Ivana; Bhat, Krishna Moorthi

2013-01-01

Guiding axon growth cones towards their targets is a fundamental process that occurs in a developing nervous system. Several major signaling systems are involved in axon-guidance, and disruption of these systems causes axon-guidance defects. However, the specific role of the environment in which axons navigate in regulating axon-guidance has not been examined in detail. In Drosophila, the ventral nerve cord is divided into segments, and half-segments and the precursor neuroblasts are formed in rows and columns in individual half-segments. The row-wise expression of segment-polarity genes within the neuroectoderm provides the initial row-wise identity to neuroblasts. Here, we show that in embryos mutant for the gene midline, which encodes a T-box DNA binding protein, row-2 neuroblasts and their neuroectoderm adopt a row-5 identity. This reiteration of row-5 ultimately creates a non-permissive zone or a barrier, which prevents the extension of interneuronal longitudinal tracts along their normal anterior-posterior path. While we do not know the nature of the barrier, the axon tracts either stall when they reach this region or project across the midline or towards the periphery along this zone. Previously, we had shown that midline ensures ancestry-dependent fate specification in a neuronal lineage. These results provide the molecular basis for the axon guidance defects in midline mutants and the significance of proper specification of the environment to axon-guidance. These results also reveal the importance of segmental polarity in guiding axons from one segment to the next, and a link between establishment of broad segmental identity and axon guidance. PMID:24385932

An anterior signaling center patterns and sizes the anterior neuroectoderm of the sea urchin embryo.

PubMed

Range, Ryan C; Wei, Zheng

2016-05-01

Anterior signaling centers help specify and pattern the early anterior neuroectoderm (ANE) in many deuterostomes. In sea urchin the ANE is restricted to the anterior of the late blastula stage embryo, where it forms a simple neural territory comprising several types of neurons as well as the apical tuft. Here, we show that during early development, the sea urchin ANE territory separates into inner and outer regulatory domains that express the cardinal ANE transcriptional regulators FoxQ2 and Six3, respectively. FoxQ2 drives this patterning process, which is required to eliminate six3 expression from the inner domain and activate the expression of Dkk3 and sFRP1/5, two secreted Wnt modulators. Dkk3 and low expression levels of sFRP1/5 act additively to potentiate the Wnt/JNK signaling pathway governing the positioning of the ANE territory around the anterior pole, whereas high expression levels of sFRP1/5 antagonize Wnt/JNK signaling. sFRP1/5 and Dkk3 levels are rigidly maintained via autorepressive and cross-repressive interactions with Wnt signaling components and additional ANE transcription factors. Together, these data support a model in which FoxQ2 initiates an anterior patterning center that implements correct size and positions of ANE structures. Comparisons of functional and expression studies in sea urchin, hemichordate and chordate embryos reveal striking similarities among deuterostome ANE regulatory networks and the molecular mechanism that positions and defines ANE borders. These data strongly support the idea that the sea urchin embryo uses an ancient anterior patterning system that was present in the common ambulacrarian/chordate ancestor. © 2016. Published by The Company of Biologists Ltd.

Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders

PubMed Central

2014-01-01

Prostaglandin E2 (PGE2) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE2 signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE2 and canonical Wnt signalling pathways in non-neuronal cells. Since the Wnt pathway is crucial in the development and organization of the brain, the main goal of this study is to determine whether collaboration between these pathways exists in neuronal cell types. We report that PGE2 interacts with canonical Wnt signalling through PKA and PI-3K in neuroectodermal (NE-4C) stem cells. We used time-lapse microscopy to determine that PGE2 increases the final distance from origin, path length travelled, and the average speed of migration in Wnt-activated cells. Furthermore, PGE2 alters distinct cellular phenotypes that are characteristic of Wnt-induced NE-4C cells, which corresponds to the modified splitting behaviour of the cells. We also found that in Wnt-induced cells the level of β-catenin protein was increased and the expression levels of Wnt-target genes (Ctnnb1, Ptgs2, Ccnd1, Mmp9) was significantly upregulated in response to PGE2 treatment. This confirms that PGE2 activated the canonical Wnt signalling pathway. Furthermore, the upregulated genes have been previously associated with ASD. Our findings show, for the first time, evidence for cross-talk between PGE2 and Wnt signalling in neuronal cells, where PKA and PI-3K might act as mediators between the two pathways. Given the importance of PGE2 and Wnt signalling in prenatal development of the nervous system, our study provides insight into how interaction between these two pathways may influence neurodevelopment. PMID:24656144

Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders.

PubMed

Wong, Christine T; Ahmad, Eizaaz; Li, Hongyan; Crawford, Dorota A

2014-03-23

Prostaglandin E2 (PGE2) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE2 signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE2 and canonical Wnt signalling pathways in non-neuronal cells. Since the Wnt pathway is crucial in the development and organization of the brain, the main goal of this study is to determine whether collaboration between these pathways exists in neuronal cell types. We report that PGE2 interacts with canonical Wnt signalling through PKA and PI-3K in neuroectodermal (NE-4C) stem cells. We used time-lapse microscopy to determine that PGE2 increases the final distance from origin, path length travelled, and the average speed of migration in Wnt-activated cells. Furthermore, PGE2 alters distinct cellular phenotypes that are characteristic of Wnt-induced NE-4C cells, which corresponds to the modified splitting behaviour of the cells. We also found that in Wnt-induced cells the level of β-catenin protein was increased and the expression levels of Wnt-target genes (Ctnnb1, Ptgs2, Ccnd1, Mmp9) was significantly upregulated in response to PGE2 treatment. This confirms that PGE2 activated the canonical Wnt signalling pathway. Furthermore, the upregulated genes have been previously associated with ASD. Our findings show, for the first time, evidence for cross-talk between PGE2 and Wnt signalling in neuronal cells, where PKA and PI-3K might act as mediators between the two pathways. Given the importance of PGE2 and Wnt signalling in prenatal development of the nervous system, our study provides insight into how interaction between these two pathways may influence neurodevelopment.

Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis

PubMed Central

Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

2014-01-01

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. PMID:24829209

Technical design and system implementation of region-line primitive association framework

NASA Astrophysics Data System (ADS)

Wang, Min; Xing, Jinjin; Wang, Jie; Lv, Guonian

2017-08-01

Apart from regions, image edge lines are an important information source, and they deserve more attention in object-based image analysis (OBIA) than they currently receive. In the region-line primitive association framework (RLPAF), we promote straight-edge lines as line primitives to achieve powerful OBIAs. Along with regions, straight lines become basic units for subsequent extraction and analysis of OBIA features. This study develops a new software system called remote-sensing knowledge finder (RSFinder) to implement RLPAF for engineering application purposes. This paper introduces the extended technical framework, a comprehensively designed feature set, key technology, and software implementation. To our knowledge, RSFinder is the world's first OBIA system based on two types of primitives, namely, regions and lines. It is fundamentally different from other well-known region-only-based OBIA systems, such as eCogntion and ENVI feature extraction module. This paper has important reference values for the development of similarly structured OBIA systems and line-involved extraction algorithms of remote sensing information.

Lysophosphatidic acid acts as a nutrient-derived developmental cue to regulate early hematopoiesis.

PubMed

Li, Haisen; Yue, Rui; Wei, Bin; Gao, Ge; Du, Jiulin; Pei, Gang

2014-06-17

Primitive hematopoiesis occurs in the yolk sac blood islands during vertebrate embryogenesis, where abundant phosphatidylcholines (PC) are available as important nutrients for the developing embryo. However, whether these phospholipids also generate developmental cues to promote hematopoiesis is largely unknown. Here, we show that lysophosphatidic acid (LPA), a signaling molecule derived from PC, regulated hemangioblast formation and primitive hematopoiesis. Pharmacological and genetic blockage of LPA receptor 1 (LPAR1) or autotoxin (ATX), a secretory lysophospholipase that catalyzes LPA production, inhibited hematopoietic differentiation of mouse embryonic stem cells and impaired the formation of hemangioblasts. Mechanistic experiments revealed that the regulatory effect of ATX-LPA signaling was mediated by PI3K/Akt-Smad pathway. Furthermore, during in vivo embryogenesis in zebrafish, LPA functioned as a developmental cue for hemangioblast formation and primitive hematopoiesis. Taken together, we identified LPA as an important nutrient-derived developmental cue for primitive hematopoiesis as well as a novel mechanism of hemangioblast regulation. © 2014 The Authors.

On the evolution of sport.

PubMed

Lombardo, Michael P

2012-01-02

Sports have received little attention from evolutionary biologists. I argue that sport began as a way for men to develop the skills needed in primitive hunting and warfare, then developed to act primarily as a lek where athletes display and male spectators evaluate the qualities of potential allies and rivals. This hypothesis predicts that (1) the most popular modern male sports require the skills needed for success in male-male physical competition and primitive hunting and warfare; (2) champion male athletes obtain high status and thereby reproductive opportunities in ways that parallel those gained by successful primitive hunters and warriors; (3) men pay closer attention than do women to male sports so they can evaluate potential allies and rivals; and (4) male sports became culturally more important when opportunities to evaluate potential allies and rivals declined as both the survival importance of hunting and the proportion of men who experience combat decreased. The characteristics of primitive and modern sports are more consistent with these predictions than those generated by intersexual sexual selection theories of sport.

Fine structures of embryonic discs of in vivo post-hatching porcine blastocysts at the pre-primitive streak stage.

PubMed

Xia, P; Liu, Z; Qin, P

2011-04-01

To date, reports about the ultrastructure of porcine embryonic discs have not shown details of the primitive streak. The main objective of this study was to examine the ultrastructure of interior and exterior embryonic discs in porcine in vivo blastocysts with diameters of 1, 3 and 9 mm using scanning electron microscopy and transmission electron microscopy. For the first time, we revealed the ultrastructure of the unusual group of cells in the pre-primitive streak area of embryonic discs. The cells were 1-2 μm in diameter, had high electron density and contained abundant, free ribosomes and endoplasmic reticulum. These primitive streak cells could represent original embryonic stem cells or represent a stem cell niche. The results also showed three types of cells on the exterior surface of the embryonic discs. Moreover, our results provided morphological evidence of condensed nuclei in the smooth cells on the surface of the embryonic disc. © 2010 Blackwell Verlag GmbH.

Raft cultivation area extraction from high resolution remote sensing imagery by fusing multi-scale region-line primitive association features

NASA Astrophysics Data System (ADS)

Wang, Min; Cui, Qi; Wang, Jie; Ming, Dongping; Lv, Guonian

2017-01-01

In this paper, we first propose several novel concepts for object-based image analysis, which include line-based shape regularity, line density, and scale-based best feature value (SBV), based on the region-line primitive association framework (RLPAF). We then propose a raft cultivation area (RCA) extraction method for high spatial resolution (HSR) remote sensing imagery based on multi-scale feature fusion and spatial rule induction. The proposed method includes the following steps: (1) Multi-scale region primitives (segments) are obtained by image segmentation method HBC-SEG, and line primitives (straight lines) are obtained by phase-based line detection method. (2) Association relationships between regions and lines are built based on RLPAF, and then multi-scale RLPAF features are extracted and SBVs are selected. (3) Several spatial rules are designed to extract RCAs within sea waters after land and water separation. Experiments show that the proposed method can successfully extract different-shaped RCAs from HR images with good performance.

Experimental analysis of control mechanisms in somite segmentation in avian embryos. II. Reduction of material in the gastrula stages of the chick.

PubMed

Bellairs, R; Veini, M

1984-02-01

A new theory of control of somite segmentation in chick embryos is proposed. This supposses that tiny clusters of already programmed cells are present throughout the presumptive somite area at stage 4, but that in order to fulfill their destiny they probably depend on the addition of further cells from the primitive streak. Evidence is based on the two groups of experiments: a) Experiments involving transection across the primitive streak at various stages, (which results in a 'tail' which possesses mesodermal derivatives) and across the segmental plate (which results in a 'tail' lacking mesodermal derivatives). b) Experiments in which parts of embryos have been explanted with or without their primitive streak. It is suggested that the initial clusters of pre-programmed cells move further and further posteriorly, developing into somitomeres (the precursors of true somites) only as they receive re-inforcements from the primitive streak or, ultimately, from the tail bud.

Exploiting replication in distributed systems

NASA Technical Reports Server (NTRS)

Birman, Kenneth P.; Joseph, T. A.

1989-01-01

Techniques are examined for replicating data and execution in directly distributed systems: systems in which multiple processes interact directly with one another while continuously respecting constraints on their joint behavior. Directly distributed systems are often required to solve difficult problems, ranging from management of replicated data to dynamic reconfiguration in response to failures. It is shown that these problems reduce to more primitive, order-based consistency problems, which can be solved using primitives such as the reliable broadcast protocols. Moreover, given a system that implements reliable broadcast primitives, a flexible set of high-level tools can be provided for building a wide variety of directly distributed application programs.

Oxygen reservoirs in the early solar nebula inferred from an Allende CAI.

PubMed

Young, E D; Russell, S S

1998-10-16

Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI) from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a plot of delta (17)O against delta (18)O represents the primitive oxygen isotope reservoir of the early solar nebula. Most meteorites are enriched in (17)O and (18)O relative to this line, and their oxygen isotope ratios can be explained by mass fractionation or isotope exchange initiating from the primitive reservoir. These data establish a link between the oxygen isotopic composition of the abundant ordinary chondrites and the primitive (16)O-rich component of CAIs.

Oxygen reservoirs in the early solar nebula inferred from an allende CAI

PubMed

Young; Russell

1998-10-16

Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI) from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a plot of delta17O against delta18O represents the primitive oxygen isotope reservoir of the early solar nebula. Most meteorites are enriched in 17O and 18O relative to this line, and their oxygen isotope ratios can be explained by mass fractionation or isotope exchange initiating from the primitive reservoir. These data establish a link between the oxygen isotopic composition of the abundant ordinary chondrites and the primitive 16O-rich component of CAIs.

Deuterium enrichment in the primitive ices of the protosolar nebula

NASA Technical Reports Server (NTRS)

Lutz, Barry L.; Owen, Tobias; De Bergh, Catherine

1990-01-01

On the basis of CH3D/CH4-ratio observations in the outer planets, the present effort to estimate the D/H ratio of the protosolar nebula's primitive ices arrives at two simple, yet effectively limiting models which constrain the degree of dilution undergone by deuterated volatiles through mixing with the initial hydrogen envelopes. These volatiles would have been contributed to planetary atmospheres by evaporated primordial ices. Ice D/H ratio model results of 0.0001 to 0.001 are compared with values for other potentially primitive material-containing bodies in the solar system, as well as with D/H ratio values from interstellar polyatomic molecules.

Interstellar chemistry recorded in organic matter from primitive meteorites.

PubMed

Busemann, Henner; Young, Andrea F; Alexander, Conel M O'd; Hoppe, Peter; Mukhopadhyay, Sujoy; Nittler, Larry R

2006-05-05

Organic matter in extraterrestrial materials has isotopic anomalies in hydrogen and nitrogen that suggest an origin in the presolar molecular cloud or perhaps in the protoplanetary disk. Interplanetary dust particles are generally regarded as the most primitive solar system matter available, in part because until recently they exhibited the most extreme isotope anomalies. However, we show that hydrogen and nitrogen isotopic compositions in carbonaceous chondrite organic matter reach and even exceed those found in interplanetary dust particles. Hence, both meteorites (originating from the asteroid belt) and interplanetary dust particles (possibly from comets) preserve primitive organics that were a component of the original building blocks of the solar system.

Fractions We Cannot Ignore: The Nonsymbolic Ratio Congruity Effect

ERIC Educational Resources Information Center

Matthews, Percival G.; Lewis, Mark R.

2017-01-01

Although many researchers theorize that primitive numerosity processing abilities may lay the foundation for whole number concepts, other classes of numbers, like fractions, are sometimes assumed to be inaccessible to primitive architectures. This research presents evidence that the automatic processing of nonsymbolic magnitudes affects processing…

Intuitive Test Theory. CSE Report 631

ERIC Educational Resources Information Center

Braun, Henry I.; Mislevy, Robert J.

2004-01-01

Psychologist Andrea diSessa coined the term "phenomenological primitives", or p-prims, to talk about nonexperts' reasoning about physical situations. P-prims are primitive in the sense that they stand without significant explanatory substructure or explanation. Examples are "Heavy objects fall faster than light objects" and "Continuing force is…

Photovoltaic panel extraction from very high-resolution aerial imagery using region-line primitive association analysis and template matching

NASA Astrophysics Data System (ADS)

Wang, Min; Cui, Qi; Sun, Yujie; Wang, Qiao

2018-07-01

In object-based image analysis (OBIA), object classification performance is jointly determined by image segmentation, sample or rule setting, and classifiers. Typically, as a crucial step to obtain object primitives, image segmentation quality significantly influences subsequent feature extraction and analyses. By contrast, template matching extracts specific objects from images and prevents shape defects caused by image segmentation. However, creating or editing templates is tedious and sometimes results in incomplete or inaccurate templates. In this study, we combine OBIA and template matching techniques to address these problems and aim for accurate photovoltaic panel (PVP) extraction from very high-resolution (VHR) aerial imagery. The proposed method is based on the previously proposed region-line primitive association framework, in which complementary information between region (segment) and line (straight line) primitives is utilized to achieve a more powerful performance than routine OBIA. Several novel concepts, including the mutual fitting ratio and best-fitting template based on region-line primitive association analyses, are proposed. Automatic template generation and matching method for PVP extraction from VHR imagery are designed for concept and model validation. Results show that the proposed method can successfully extract PVPs without any user-specified matching template or training sample. High user independency and accuracy are the main characteristics of the proposed method in comparison with routine OBIA and template matching techniques.

Mathematical Observations: The Genesis of Mathematical Discovery in the Classroom

ERIC Educational Resources Information Center

Beaugris, Louis M.

2013-01-01

In his "Proofs and Refutations," Lakatos identifies the "Primitive Conjecture" as the first stage in the pattern of mathematical discovery. In this article, I am interested in ways of reaching the "Primitive Conjecture" stage in an undergraduate classroom. I adapted Realistic Mathematics Education methods in an…

Multiphase Complete Exchange: A Theoretical Analysis

DTIC Science & Technology

1993-08-01

Birkhiuser, Boston, 1984. 24 [9] C-T. Ho and M. T. Raghunath . Efficient communication primitives on hy- percubes. In Proc. 6th. DMCC, pages 390-397...1991. [10] C-T. Ho and M. T. Raghunath . Efficient communication primitives on hy- percubes. Technical Report RJ 7932 (72915), IBM, T. J. Watson Center

36 CFR 294.23 - Road construction and reconstruction in Idaho Roadless Areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... reconstruction in Idaho Roadless Areas. (a) Wild Land Recreation, Special Areas of Historic or Tribal... designated as Wild Land Recreation, Special Areas of Historic or Tribal Significance, or Primitive. However... Wild Land Recreation, Special Area of Historic or Tribal Significance, or Primitive if pursuant to...

36 CFR 294.23 - Road construction and reconstruction in Idaho Roadless Areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... reconstruction in Idaho Roadless Areas. (a) Wild Land Recreation, Special Areas of Historic or Tribal... designated as Wild Land Recreation, Special Areas of Historic or Tribal Significance, or Primitive. However... Wild Land Recreation, Special Area of Historic or Tribal Significance, or Primitive if pursuant to...

36 CFR 294.23 - Road construction and reconstruction in Idaho Roadless Areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... reconstruction in Idaho Roadless Areas. (a) Wild Land Recreation, Special Areas of Historic or Tribal... designated as Wild Land Recreation, Special Areas of Historic or Tribal Significance, or Primitive. However... Wild Land Recreation, Special Area of Historic or Tribal Significance, or Primitive if pursuant to...

The Grammar of Mental Predicates in Japanese.

ERIC Educational Resources Information Center

Onishi, Masayuki

1997-01-01

Examines Japanese equivalents of the six mental predicates defined as semantic universals in Natural Semantic Metalanguage theory, with special attention to syntax and semantics of complementation types. It is shown that each primitive predicate has a specific set of syntactic frames for expressing primitive meaning and that extended meanings that…

Nilpotent representations of classical quantum groups at roots of unity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abe, Yuuki; Nakashima, Toshiki

2005-11-01

Properly specializing the parameters in 'Schnizer modules', for types A,B,C, and D, we get its unique primitive vector. Then we show that the module generated by the primitive vector is an irreducible highest weight module of finite dimensional classical quantum groups at roots of unity.

Could 433 Eros have a Primitive Achondritic Composition?

NASA Technical Reports Server (NTRS)

Burbine, T. H.; McCoy, T. J.; Nittler, L. R.; Bell, J. F., III

2001-01-01

One of the goals of the NEAR (Near Earth Asteroid Rendezvous) mission to 433 Eros is to determine if it has a meteoritic analog. We are currently investigating if primitive achondrites have bulk compositions and spectral properties similar to Eros. Additional information is contained in the original extended abstract.

A Test of Durkheim's Theory of Suicide in Primitive Societies.

ERIC Educational Resources Information Center

Lester, David

1992-01-01

Classified primitive societies as high, moderate, or low on independent measures of social integration and social regulation to test Durkheim's theory of suicide. Estimated frequency of suicide did not differ between those societies predicted to have high, moderate, and low suicide rates. Durkheim's theory was not confirmed. (Author/NB)

Basic and clinical aspects of malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nathanson, L.

1987-01-01

This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignantmore » melanoma by fast neutrons.« less

The Dovyren Intrusive Complex (Southern Siberia, Russia): Insights into dynamics of an open magma chamber with implications for parental magma origin, composition, and Cu-Ni-PGE fertility

NASA Astrophysics Data System (ADS)

Ariskin, Alexey; Danyushevsky, Leonid; Nikolaev, Georgy; Kislov, Evgeny; Fiorentini, Marco; McNeill, Andrew; Kostitsyn, Yuri; Goemann, Karsten; Feig, Sandrin T.; Malyshev, Alexey

2018-03-01

The Dovyren Intrusive Complex (DIC, Northern Baikal region, 728 Ma) includes the layered dunite-troctolite-gabbronorite Yoko-Dovyren massif (YDM), associated mafic-ultramafic sills, and dykes of olivine-rich to olivine-free gabbronorite. Major rock types of the DIC are presented, including a diversity of olivine orthocumulates to olivine-plagioclase and gabbroic adcumulates, carbonate-contaminated ultramafics and Cu-Ni-PGE mineralisation. Detailed comparisons of complete cross-sections of the YDM in its centre and at the NE and SW margins demonstrate differences in the cumulate succession, mineral chemistry, and geochemical structure that likely reflect variations in parental magma compositions. Combining petrochemical reconstructions for most primitive rocks and calculations using the COMAGMAT-5 model, it is shown that the central and peripheral parts of the intrusion formed by olivine-laden parental magmas ranged in their temperatures by 100 °C, approximately from 1290 °C ( 11 wt% MgO, olivine Fo88) to 1190 °C ( 8 wt% MgO, olivine Fo86). Thermodynamic modelling suggests that the most primitive high-Mg magma was S-undersaturated, whereas its derivatives became S-saturated at T < 1240-1200 °C. These estimates are consistent with geological observations that mostly sulphide-poor mineralisation occurs in the centre of the intrusion, whereas Cu-Ni sulphide ores (locally net-textured) occur in its NE and SW parts, as well as in the underlying peridotite sills. The primitive S-undersaturated olivine cumulates became sulphide-saturated at a post-cumulus stage. As a result, Ni-rich immiscible sulphides formed within and migrated through the early olivine-rich cumulate piles to generate poorly-mineralised plagiodunite. In the troctolite and gabbroic parts of the Dovyren chamber, sulphide immiscibility likely occurred at lower temperatures, producing Cu-rich sulphide precursors, which gave rise to the 'platinum group mineral' (PGM-containing) troctolite and low-mineralised PGE-rich anorthosite in the Main Reef. The geochemical structure of the YDM demonstrates C-shaped distributions of TiO2, K2O, P2O5, and incompatible trace elements, which are 3-5 fold depleted in the cumulate rocks from the inner horizons of the intrusion with respect to the relatively thin lower and upper contact zones. In addition, a marked misbalance between estimates of the average composition of the YDM and that of the proposed olivine-laden parental magmas is established. This misbalance reflects a significant deficit of the YDM in incompatible elements, which argues that 60-70% of basaltic melts had to have been expelled from the Dovyren magma chamber during its consolidation. A possible scenario of the evolution of the open magma chamber is proposed.

Execution time supports for adaptive scientific algorithms on distributed memory machines

NASA Technical Reports Server (NTRS)

Berryman, Harry; Saltz, Joel; Scroggs, Jeffrey

1990-01-01

Optimizations are considered that are required for efficient execution of code segments that consists of loops over distributed data structures. The PARTI (Parallel Automated Runtime Toolkit at ICASE) execution time primitives are designed to carry out these optimizations and can be used to implement a wide range of scientific algorithms on distributed memory machines. These primitives allow the user to control array mappings in a way that gives an appearance of shared memory. Computations can be based on a global index set. Primitives are used to carry out gather and scatter operations on distributed arrays. Communications patterns are derived at runtime, and the appropriate send and receive messages are automatically generated.

Hydrazines and carbohydrazides produced from oxidized carbon in earth's primitive environment

NASA Technical Reports Server (NTRS)

Folsome, C. E.; Brittain, A.; Smith, A.; Chang, S.

1981-01-01

Whether abiological organic compounds can be formed from the interactions of energy sources with nitrogen, oxidized carbon and water is held to be of importance in geochemical models of the primordial earth atmosphere. It is reported that experiments using quenched spark discharges through molecular nitrogen on aqueous suspensions of CaCO3 and other reactants to simulate the hydrosphere/atmosphere interface yield hydrazine and carbohydrazine in significant but low yields. Such reactions in primitive aquatic environments may have supplied a pathway for chemical evolution and the origin of life, on a primitive earth in which fully oxidized states of carbon were available for the primary synthesis of organic matter.

Execution time support for scientific programs on distributed memory machines

NASA Technical Reports Server (NTRS)

Berryman, Harry; Saltz, Joel; Scroggs, Jeffrey

1990-01-01

Optimizations are considered that are required for efficient execution of code segments that consists of loops over distributed data structures. The PARTI (Parallel Automated Runtime Toolkit at ICASE) execution time primitives are designed to carry out these optimizations and can be used to implement a wide range of scientific algorithms on distributed memory machines. These primitives allow the user to control array mappings in a way that gives an appearance of shared memory. Computations can be based on a global index set. Primitives are used to carry out gather and scatter operations on distributed arrays. Communications patterns are derived at runtime, and the appropriate send and receive messages are automatically generated.

Deictic primitives for general purpose navigation

NASA Technical Reports Server (NTRS)

Crismann, Jill D.

1994-01-01

A visually-based deictic primative used as an elementary command set for general purpose navigation was investigated. It was shown that a simple 'follow your eyes' scenario is sufficient for tracking a moving target. Limitations of velocity, acceleration, and modeling of the response of the mechanical systems were enforced. Realistic paths of the robots were produced during the simulation. Scientists could remotely command a planetary rover to go to a particular rock formation that may be interesting. Similarly an expert at plant maintenance could obtain diagnostic information remotely by using deictic primitives on a mobile are used in the deictic primitives, we could imagine that the exact same control software could be used for all of these applications.

On the zero-Rossby limit for the primitive equations of the atmosphere*

NASA Astrophysics Data System (ADS)

Chen, Gui-Qiang; Zhang, Ping

2001-09-01

The zero-Rossby limit for the primitive equations governing atmospheric motions is analysed. The limit is important in geophysics for large-scale models (cf Lions 1996 Int. Conf. IAM 95 (Hamburg 1995) (Math. Res. vol 87) (Berlin: Akademie) pp 177-212) and is in the level of the zero relaxation limit for nonlinear partial differential equations (cf Chen et al 1994 Commun. Pure Appl. Math. 47 787-830). It is proved that, if the initial data appropriately approximate data of geostrophic type, the corresponding solutions of the simplified primitive equations approximate the solutions of the quasigeostrophic equations with order ɛ accuracy as the Rossby number ɛ goes to zero.

Secure and Authenticated Data Communication in Wireless Sensor Networks.

PubMed

Alfandi, Omar; Bochem, Arne; Kellner, Ansgar; Göge, Christian; Hogrefe, Dieter

2015-08-10

Securing communications in wireless sensor networks is increasingly important as the diversity of applications increases. However, even today, it is equally important for the measures employed to be energy efficient. For this reason, this publication analyzes the suitability of various cryptographic primitives for use in WSNs according to various criteria and, finally, describes a modular, PKI-based framework for confidential, authenticated, secure communications in which most suitable primitives can be employed. Due to the limited capabilities of common WSN motes, criteria for the selection of primitives are security, power efficiency and memory requirements. The implementation of the framework and the singular components have been tested and benchmarked in our testbed of IRISmotes.

Secure and Authenticated Data Communication in Wireless Sensor Networks

PubMed Central

Alfandi, Omar; Bochem, Arne; Kellner, Ansgar; Göge, Christian; Hogrefe, Dieter

2015-01-01

Securing communications in wireless sensor networks is increasingly important as the diversity of applications increases. However, even today, it is equally important for the measures employed to be energy efficient. For this reason, this publication analyzes the suitability of various cryptographic primitives for use in WSNs according to various criteria and, finally, describes a modular, PKI-based framework for confidential, authenticated, secure communications in which most suitable primitives can be employed. Due to the limited capabilities of common WSN motes, criteria for the selection of primitives are security, power efficiency and memory requirements. The implementation of the framework and the singular components have been tested and benchmarked in our testbed of IRISmotes. PMID:26266413

Distributed computation of graphics primitives on a transputer network

NASA Technical Reports Server (NTRS)

Ellis, Graham K.

1988-01-01

A method is developed for distributing the computation of graphics primitives on a parallel processing network. Off-the-shelf transputer boards are used to perform the graphics transformations and scan-conversion tasks that would normally be assigned to a single transputer based display processor. Each node in the network performs a single graphics primitive computation. Frequently requested tasks can be duplicated on several nodes. The results indicate that the current distribution of commands on the graphics network shows a performance degradation when compared to the graphics display board alone. A change to more computation per node for every communication (perform more complex tasks on each node) may cause the desired increase in throughput.

A new Chinese specimen indicates that ‘protofeathers’ in the Early Cretaceous theropod dinosaur Sinosauropteryx are degraded collagen fibres

PubMed Central

Lingham-Soliar, Theagarten; Feduccia, Alan; Wang, Xiaolin

2007-01-01

Alleged primitive feathers or protofeathers in the theropod dinosaur Sinosauropteryx have potentially profound implications concerning feather morphogenesis, evolution of flight, dinosaur physiology and perhaps even the origin of birds, yet their existence has never been adequately documented. We report on a new specimen of Sinosauropteryx which shows that the integumental structures proposed as protofeathers are the remains of structural fibres that provide toughness. The preservation in the proximal tail area reveals an architecture of closely associated bands of fibres parallel to the tail's long axis, which originate from the skin. In adjacent more exposed areas, the fibres are short, fragmented and disorganized. Fibres preserved dorsal to the neck and back and in the distal part of the tail are the remains of a stiffening system of a frill, peripheral to the body and extending from the head to the tip of the tail. These findings are confirmed in the holotype Sinosauropteryx and NIGP 127587. The fibres show a striking similarity to the structure and levels of organization of dermal collagen. The proposal that these fibres are protofeathers is dismissed. PMID:17521978

Differentiation of the matter of the moon

NASA Technical Reports Server (NTRS)

Vinogradov, A. P.

1977-01-01

The following facts were uncovered in comparing the basaltic surface rocks of the moon with terrestrial tholeiitic basalts and ordinary chondrites: (1) there is an excess of the so-called refractory chemical elements, including the group of truly refractory elements, the rare earths, U, and Th, in comparison with their content in primitive terrestrial basalts and chondrites; (2) the so-called siderophilic elements have lower contents in the lunar surface rocks than in terrestrial rocks; (3) the low alkali content (Na, K, Rb) in lunar rocks is established; (4) there is a low content of H2O and the ordinary gases CO2, halides, etc.; (5) the low content of metals with high vapor pressure, (In, Tl, etc.) has been established. It is proposed that U and Th were carried from the internal areas to the peripheral rocks of the moon during magmatic activity, i.e., up to 3 billion years ago. This redistribution of U and Th lead to their concentration in surface layers of the moon, and the heat which they generated was lost into surrounding space. The conclusion is then reached that in order to understand processes on the moon, the chondritic model cannot be used.

Gene disruption of dematin causes precipitous loss of erythrocyte membrane stability and severe hemolytic anemia.

PubMed

Lu, Yunzhe; Hanada, Toshihiko; Fujiwara, Yuko; Nwankwo, Jennifer O; Wieschhaus, Adam J; Hartwig, John; Huang, Sha; Han, Jongyoon; Chishti, Athar H

2016-07-07

Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin-actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin's actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate-dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex. © 2016 by The American Society of Hematology.

Gene disruption of dematin causes precipitous loss of erythrocyte membrane stability and severe hemolytic anemia

PubMed Central

Lu, Yunzhe; Hanada, Toshihiko; Fujiwara, Yuko; Nwankwo, Jennifer O.; Wieschhaus, Adam J.; Hartwig, John; Huang, Sha; Han, Jongyoon

2016-01-01

Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin–actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin’s actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate–dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex. PMID:27073223

A Comparison Between Plant Photosystem I and Photosystem II Architecture and Functioning

PubMed Central

Caffarri, Stefano; Tibiletti, Tania; Jennings, Robert C.; Santabarbara, Stefano

2014-01-01

Oxygenic photosynthesis is indispensable both for the development and maintenance of life on earth by converting light energy into chemical energy and by producing molecular oxygen and consuming carbon dioxide. This latter process has been responsible for reducing the CO2 from its very high levels in the primitive atmosphere to the present low levels and thus reducing global temperatures to levels conducive to the development of life. Photosystem I and photosystem II are the two multi-protein complexes that contain the pigments necessary to harvest photons and use light energy to catalyse the primary photosynthetic endergonic reactions producing high energy compounds. Both photosystems are highly organised membrane supercomplexes composed of a core complex, containing the reaction centre where electron transport is initiated, and of a peripheral antenna system, which is important for light harvesting and photosynthetic activity regulation. If on the one hand both the chemical reactions catalysed by the two photosystems and their detailed structure are different, on the other hand they share many similarities. In this review we discuss and compare various aspects of the organisation, functioning and regulation of plant photosystems by comparing them for similarities and differences as obtained by structural, biochemical and spectroscopic investigations. PMID:24678674

Developmental imaging: the avian embryo hatches to the challenge.

PubMed

Kulesa, Paul M; McKinney, Mary C; McLennan, Rebecca

2013-06-01

The avian embryo provides a multifaceted model to study developmental mechanisms because of its accessibility to microsurgery, fluorescence cell labeling, in vivo imaging, and molecular manipulation. Early two-dimensional planar growth of the avian embryo mimics human development and provides unique access to complex cell migration patterns using light microscopy. Later developmental events continue to permit access to both light and other imaging modalities, making the avian embryo an excellent model for developmental imaging. For example, significant insights into cell and tissue behaviors within the primitive streak, craniofacial region, and cardiovascular and peripheral nervous systems have come from avian embryo studies. In this review, we provide an update to recent advances in embryo and tissue slice culture and imaging, fluorescence cell labeling, and gene profiling. We focus on how technical advances in the chick and quail provide a clearer understanding of how embryonic cell dynamics are beautifully choreographed in space and time to sculpt cells into functioning structures. We summarize how these technical advances help us to better understand basic developmental mechanisms that may lead to clinical research into human birth defects and tissue repair. Copyright © 2013 Wiley Periodicals, Inc.

Prenatal metanephrogenesis of the camel: morphological evidence of epithelial-mesenchymal interaction.

PubMed

Osman, A-H K; Farouk, S M; Eidaroos, H; Abbott, L C; Ahmed, A A

2014-04-01

The present investigation examined histogenesis of epithelial, stromal and angiogenic elements of the prenatal camel permanent or metanephric kidney. The primitive metanephros was first observed at the 13-mm crown vertebral rump length (CVRL) stage as an ovoid structure composed of a centrally located epithelial ureteric bud and peripheral circumscribed masses of undifferentiated mesenchymal cells. The first morphological evidence of glomerulogenesis was observed at the 28-mm CVRL stage. Developing renal corpuscles became obvious at the 35-mm CVRL stage. At the 60-mm CVRL stage, the epithelial renal pelvis gave rise to tubular branches that extended towards the cortical zone. These branches represented the presumptive collecting ducts. Differentiation of renal tubules into the proximal and distal convoluted tubules was observed at the 95-mm CVRL stage. At the 130-mm CVRL stage, the renal medulla was clearly delineated into medullary pyramids, which in association with the corresponding cortical caps formed the morphological basis of the renal lobar formation. A gradual nephrogenic decline was noticed from the 940-mm CVRL on; however, the process of nephrogenesis persisted throughout all the studied foetal stages. © 2013 Blackwell Verlag GmbH.

Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity

PubMed Central

Ratajczak, Mariusz Z.; Zuba-Surma, Ewa K.; Shin, Dong-Myung; Ratajczak, Janina; Kucia, Magda

2011-01-01

Recently, we purified rare CXC chemokine receptor 4 expressing (CXCR4+) small stem cells (SCs) from the murine bone marrow (BM) that express markers characteristic for embryonic (E)SCs, epiblast (EP)SCs, and primordial germ cells (PGCs). We named these primitive cells very small embryonic-like (VSEL) SCs (VSELs). Our data indicate that VSELs are also present in many other organs in mice and that they may differentiate into cells from all three germ layers. Similar SCs were also isolated from human cord blood (CB) and mobilized peripheral blood (mPB). We hypothesize that VSELs are deposited during gastrulation and organogenesis in developing organs/tissues of mammals as a population of pluripotent stem cells (PSCs) that give rise to tissue committed monopotent SCs and that their number decreases with age. Therefore VSELs could play a pivotal role in normal rejuvenation of adult tissues as well as involvement in regeneration of damaged organs. Thus, these cells are potential SCs candidates for regenerative medicine and we envision that the regenerative potential of these cells could be harnessed to decelerate the aging processes. PMID:18601995

Aqueous Alteration and Hydrogen Generation on Parent Bodies of Unequilibrated Ordinary Chondrites: Thermodynamic Modeling for the Semarkona Composition

NASA Technical Reports Server (NTRS)

Zolotov, M. Y.; Mironenko, M. V.; Shock, E. L.

2005-01-01

Ordinary chondrites are the most abundant class of meteorites that could represent rocky parts of solar system bodies. However, even the most primitive unequilibrated ordinary chondrites (UOC) reveal signs of mild alteration that affected the matrix and peripheral zones of chondrules. Major chemical changes include oxidation of kamacite, alteration of glass, removal of alkalis, Al, and Si from chondrules, and formation of phases enriched in halogens, alkalis, and hydrogen. Secondary mineralogical changes include formation of magnetite, ferrous olivine, fayalite, pentlandite, awaruite, smectites, phosphates, carbonates, and carbides. Aqueous alteration is consistent with the oxygen isotope data for magnetite. The presence of secondary magnetite, Ni-rich metal alloys, and ferrous silicates in UOC implies that H2O was the oxidizing agent. However, oxidation by H2O means that H2 is produced in each oxidative pathway. In turn, production of H2, and its redistribution and possible escape should have affected total pressure, as well as the oxidation state of gas, aqueous and mineral phases in the parent body. Here we use equilibrium thermodynamic modeling to explore water-rock reactions in UOC. The chemical composition of gas, aqueous, and mineral phases is considered.

Transfer and Conceptual Change: The Change Process from the Theoretical Perspectives of Coordination Classes and Phenomenological Primitives

ERIC Educational Resources Information Center

Ozdemir, Omer F.

2013-01-01

The purpose of this study is to understand the nature of pre-instructional knowledge transferred by students into problem situations and the change process on students' knowledge system during classroom discussions. This study was framed by two interrelated theoretical frameworks on knowledge structures, phenomenological primitives and…

Addressing Nature Deficit Disorder through Primitive Camping Experiences

ERIC Educational Resources Information Center

Allen, Kevin; Varner, Keegan; Sallee, Jeff

2011-01-01

Today's youth suffer from Nature Deficit Disorder, a condition that has been connected to ADHD, shortage of creativity, and general lack of knowledge about the outdoors. A team of educators and specialists are addressing this issue with primitive camping. County educators were trained using experiential learning and train-the-trainer techniques.…

Topological versus rheological entanglement length in primitive-path analysis protocols, tube models, and slip-link models

NASA Astrophysics Data System (ADS)

Everaers, Ralf

2012-08-01

We show that the front factor appearing in the shear modulus of a phantom network, Gph=(1-2/f)(ρkBT)/Ns, also controls the ratio of the strand length, Ns, and the number of monomers per Kuhn length of the primitive paths, NphPPKuhn, characterizing the average network conformation. In particular, NphPPKuhn=Ns/(1-2/f) and Gph=(ρkBT)/NphPPKuhn. Neglecting the difference between cross-links and slip-links, these results can be transferred to entangled systems and the interpretation of primitive path analysis data. In agreement with the tube model, the analogy to phantom networks suggest that the rheological entanglement length, Nerheo=(ρkBT)/Ge, should equal NePPKuhn. Assuming binary entanglements with f=4 functional junctions, we expect that Nerheo should be twice as large as the topological entanglement length, Netopo. These results are in good agreement with reported primitive path analysis results for model systems and a wide range of polymeric materials. Implications for tube and slip-link models are discussed.

Representation primitives, process models and patient data in computer-interpretable clinical practice guidelines: a literature review of guideline representation models.

PubMed

Wang, Dongwen; Peleg, Mor; Tu, Samson W; Boxwala, Aziz A; Greenes, Robert A; Patel, Vimla L; Shortliffe, Edward H

2002-12-18

Representation of clinical practice guidelines in a computer-interpretable format is a critical issue for guideline development, implementation, and evaluation. We studied 11 types of guideline representation models that can be used to encode guidelines in computer-interpretable formats. We have consistently found in all reviewed models that primitives for representation of actions and decisions are necessary components of a guideline representation model. Patient states and execution states are important concepts that closely relate to each other. Scheduling constraints on representation primitives can be modeled as sequences, concurrences, alternatives, and loops in a guideline's application process. Nesting of guidelines provides multiple views to a guideline with different granularities. Integration of guidelines with electronic medical records can be facilitated by the introduction of a formal model for patient data. Data collection, decision, patient state, and intervention constitute four basic types of primitives in a guideline's logic flow. Decisions clarify our understanding on a patient's clinical state, while interventions lead to the change from one patient state to another.

Toward a self-organizing pre-symbolic neural model representing sensorimotor primitives.

PubMed

Zhong, Junpei; Cangelosi, Angelo; Wermter, Stefan

2014-01-01

The acquisition of symbolic and linguistic representations of sensorimotor behavior is a cognitive process performed by an agent when it is executing and/or observing own and others' actions. According to Piaget's theory of cognitive development, these representations develop during the sensorimotor stage and the pre-operational stage. We propose a model that relates the conceptualization of the higher-level information from visual stimuli to the development of ventral/dorsal visual streams. This model employs neural network architecture incorporating a predictive sensory module based on an RNNPB (Recurrent Neural Network with Parametric Biases) and a horizontal product model. We exemplify this model through a robot passively observing an object to learn its features and movements. During the learning process of observing sensorimotor primitives, i.e., observing a set of trajectories of arm movements and its oriented object features, the pre-symbolic representation is self-organized in the parametric units. These representational units act as bifurcation parameters, guiding the robot to recognize and predict various learned sensorimotor primitives. The pre-symbolic representation also accounts for the learning of sensorimotor primitives in a latent learning context.

Toward a self-organizing pre-symbolic neural model representing sensorimotor primitives

PubMed Central

Zhong, Junpei; Cangelosi, Angelo; Wermter, Stefan

2014-01-01

The acquisition of symbolic and linguistic representations of sensorimotor behavior is a cognitive process performed by an agent when it is executing and/or observing own and others' actions. According to Piaget's theory of cognitive development, these representations develop during the sensorimotor stage and the pre-operational stage. We propose a model that relates the conceptualization of the higher-level information from visual stimuli to the development of ventral/dorsal visual streams. This model employs neural network architecture incorporating a predictive sensory module based on an RNNPB (Recurrent Neural Network with Parametric Biases) and a horizontal product model. We exemplify this model through a robot passively observing an object to learn its features and movements. During the learning process of observing sensorimotor primitives, i.e., observing a set of trajectories of arm movements and its oriented object features, the pre-symbolic representation is self-organized in the parametric units. These representational units act as bifurcation parameters, guiding the robot to recognize and predict various learned sensorimotor primitives. The pre-symbolic representation also accounts for the learning of sensorimotor primitives in a latent learning context. PMID:24550798

Microcrystals and Amorphous Material in Comets and Primitive Meteorites: Keys to Understanding Processes in the Early Solar System

NASA Technical Reports Server (NTRS)

Nuth, J. A.; Brearley, A. J.; Scott, E. R. D.

2004-01-01

Comets, fine-grained matrices of chondrites, and chondritic interplanetary dust particles (IDPs) are each composed of both crystalline and amorphous silicates. The primitive solar nebula, in which comets and asteroids accreted, was formed from the collapsed core of a Giant Molecular Cloud, that, in turn, condensed from materials present in the interstellar medium (ISM). Despite observations that reveal the presence of crystalline magnesium silicate minerals in the shells of very high mass-loss-rate stars [1,2], typical silicate grains in the ISM are most likely to be amorphous, given their relatively long residence time in such a high radiation environment. An upper limit of 3% crystalline grains can be derived from their non-detection in spectra of ISM solids [3]. If the vast majority of grains that enter the primitive solar nebula are amorphous, then the observation of crystalline dust in comets and primitive chondrite matrices indicates the action of specific processes required to transform the amorphous starting materials into the crystals that are observed.

The logical primitives of thought: Empirical foundations for compositional cognitive models.

PubMed

Piantadosi, Steven T; Tenenbaum, Joshua B; Goodman, Noah D

2016-07-01

The notion of a compositional language of thought (LOT) has been central in computational accounts of cognition from earliest attempts (Boole, 1854; Fodor, 1975) to the present day (Feldman, 2000; Penn, Holyoak, & Povinelli, 2008; Fodor, 2008; Kemp, 2012; Goodman, Tenenbaum, & Gerstenberg, 2015). Recent modeling work shows how statistical inferences over compositionally structured hypothesis spaces might explain learning and development across a variety of domains. However, the primitive components of such representations are typically assumed a priori by modelers and theoreticians rather than determined empirically. We show how different sets of LOT primitives, embedded in a psychologically realistic approximate Bayesian inference framework, systematically predict distinct learning curves in rule-based concept learning experiments. We use this feature of LOT models to design a set of large-scale concept learning experiments that can determine the most likely primitives for psychological concepts involving Boolean connectives and quantification. Subjects' inferences are most consistent with a rich (nonminimal) set of Boolean operations, including first-order, but not second-order, quantification. Our results more generally show how specific LOT theories can be distinguished empirically. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A shape-based inter-layer contours correspondence method for ICT-based reverse engineering

PubMed Central

Duan, Liming; Yang, Shangpeng; Zhang, Gui; Feng, Fei; Gu, Minghui

2017-01-01

The correspondence of a stack of planar contours in ICT (industrial computed tomography)-based reverse engineering, a key step in surface reconstruction, is difficult when the contours or topology of the object are complex. Given the regularity of industrial parts and similarity of the inter-layer contours, a specialized shape-based inter-layer contours correspondence method for ICT-based reverse engineering was presented to solve the above problem based on the vectorized contours. In this paper, the vectorized contours extracted from the slices consist of three graphical primitives: circles, arcs and segments. First, the correspondence of the inter-layer primitives is conducted based on the characteristics of the primitives. Second, based on the corresponded primitives, the inter-layer contours correspond with each other using the proximity rules and exhaustive search. The proposed method can make full use of the shape information to handle industrial parts with complex structures. The feasibility and superiority of this method have been demonstrated via the related experiments. This method can play an instructive role in practice and provide a reference for the related research. PMID:28489867

The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers.

PubMed

Amalric, Marie; Wang, Liping; Pica, Pierre; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

2017-01-01

During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a "geometrical language" with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them.

A shape-based inter-layer contours correspondence method for ICT-based reverse engineering.

PubMed

Duan, Liming; Yang, Shangpeng; Zhang, Gui; Feng, Fei; Gu, Minghui

2017-01-01

The correspondence of a stack of planar contours in ICT (industrial computed tomography)-based reverse engineering, a key step in surface reconstruction, is difficult when the contours or topology of the object are complex. Given the regularity of industrial parts and similarity of the inter-layer contours, a specialized shape-based inter-layer contours correspondence method for ICT-based reverse engineering was presented to solve the above problem based on the vectorized contours. In this paper, the vectorized contours extracted from the slices consist of three graphical primitives: circles, arcs and segments. First, the correspondence of the inter-layer primitives is conducted based on the characteristics of the primitives. Second, based on the corresponded primitives, the inter-layer contours correspond with each other using the proximity rules and exhaustive search. The proposed method can make full use of the shape information to handle industrial parts with complex structures. The feasibility and superiority of this method have been demonstrated via the related experiments. This method can play an instructive role in practice and provide a reference for the related research.

The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers

PubMed Central

Amalric, Marie; Wang, Liping; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

2017-01-01

During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a “geometrical language” with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them. PMID:28125595

Odorant-binding proteins from a primitive termite.

PubMed

Ishida, Yuko; Chiang, Vicky P; Haverty, Michael I; Leal, Walter S

2002-09-01

Hitherto, odorant-binding proteins (OBPs) have been identified from insects belonging to more highly evolved insect orders (Lepidoptera, Coleoptera, Diptera, Hymenoptera, and Hemiptera), whereas only chemosensory proteins have been identified from more primitive species, such as orthopteran and phasmid species. Here, we report for the first time the isolation and cloning of odorant-binding proteins from a primitive termite species, the dampwood termite. Zootermopsis nevadensis nevadensis (Isoptera: Termopsidae). A major antennae-specific protein was detected by native PAGE along with four other minor proteins, which were also absent in the extract from control tissues (hindlegs). Multiple cDNA cloning led to the full characterization of the major antennae-specific protein (ZnevOBP1) and to the identification of two other antennae-specific cDNAs, encoding putative odorant-binding proteins (ZnevOBP2 and ZnevOBP3). N-terminal amino acid sequencing of the minor antennal bands and cDNA cloning showed that olfaction in Z. n. nevadensis may involve multiple odorant-binding proteins. Database searches suggest that the OBPs from this primitive termite are homologues of the pheromone-binding proteins from scarab beetles and antennal-binding proteins from moths.

Development of an Instrument for Assessing the Effectiveness of Chemistry Classroom Teaching

NASA Astrophysics Data System (ADS)

Zheng, Changlong; Fu, Lihai; He, Peng

2014-04-01

Classroom teaching is a main frontier of the implementation of new curricular ideas in China. The study reported in this article is concerned with the effectiveness of system of classroom teaching (SCT) in chemistry lessons. According to the Systems Science theory, we took a macroscopic view on the SCT, arguing that SCT is a hierarchy of system, which includes class system, plate system, unit system, and primitive system. In this study, we focused on primitive system of classroom teaching (PrS)—the lowest level in a SCT. Using focus group interviews, this study investigated the variables related to the effectiveness of PrS. We found a total of 21 such variables. To identify the main factors underlying the effectiveness of PrS, we further used exploratory factor analysis and confirmatory factor analysis. We found five main factors: rational use of time, quality of teaching behavior chain, match degree, quality of using resource and technology, and rationality of primitive content. Based on these findings, we constructed an evaluation scale for assessing the effectiveness of primitive system of chemistry classroom teaching.

Discovering motion primitives for unsupervised grouping and one-shot learning of human actions, gestures, and expressions.

PubMed

Yang, Yang; Saleemi, Imran; Shah, Mubarak

2013-07-01

This paper proposes a novel representation of articulated human actions and gestures and facial expressions. The main goals of the proposed approach are: 1) to enable recognition using very few examples, i.e., one or k-shot learning, and 2) meaningful organization of unlabeled datasets by unsupervised clustering. Our proposed representation is obtained by automatically discovering high-level subactions or motion primitives, by hierarchical clustering of observed optical flow in four-dimensional, spatial, and motion flow space. The completely unsupervised proposed method, in contrast to state-of-the-art representations like bag of video words, provides a meaningful representation conducive to visual interpretation and textual labeling. Each primitive action depicts an atomic subaction, like directional motion of limb or torso, and is represented by a mixture of four-dimensional Gaussian distributions. For one--shot and k-shot learning, the sequence of primitive labels discovered in a test video are labeled using KL divergence, and can then be represented as a string and matched against similar strings of training videos. The same sequence can also be collapsed into a histogram of primitives or be used to learn a Hidden Markov model to represent classes. We have performed extensive experiments on recognition by one and k-shot learning as well as unsupervised action clustering on six human actions and gesture datasets, a composite dataset, and a database of facial expressions. These experiments confirm the validity and discriminative nature of the proposed representation.

Two different pathways for the transport of primitive and definitive blood cells from the yolk sac to the embryo in humans.

PubMed

Pereda, Jaime; Monge, Juan I; Niimi, Gen

2010-08-01

During the early human embryonic period nutrients and blood cells are temporarily provided by the extraembryonic yolk sac (YS). The YS before week six is involved not only in primitive but also in definitive erythropoiesis. While the destiny of primitive erythroid cells that fill the blood vessels of the YS is well known, the final destination of erythrocytes present in the endodermal vesicular system is unknown. In the present study we have investigated, step by step, the destiny of the erythrocytes present in the endodermal vesicles during the embryonic period. Twelve human YSs and their corresponding yolk stalks were analyzed between weeks 4 and 7 of embryonic age by light and scanning electron microscopy. It is shown that erythrocytes (according to their size and morphological features) located within the endodermal vesicles of the YS wall are pulled out through endodermal pits into the YS cavity, from where they reach the lumen of the primitive gut of the embryo through the vitelline duct, a temporary pathway communicating both compartments. During the study period no erythrocytes were seen within the embryo's vascular network where only primitive erythroblasts were identified. Our results indicate that the vitelline duct plays an important transient role as a pathway for the transport of nutrients and blood cells between the YS and the embryo before week five of embryonic development that ends just at the time when YS-embryo circulation becomes established. (c) 2010 Wiley-Liss, Inc.

Comparative analysis of the 5S rRNA and its associated proteins reveals unique primitive rather than parasitic features in Giardia lamblia.

PubMed

Feng, Jin-Mei; Sun, Jun; Xin, De-Dong; Wen, Jian-Fan

2012-01-01

5S rRNA is a highly conserved ribosomal component. Eukaryotic 5S rRNA and its associated proteins (5S rRNA system) have become very well understood. Giardia lamblia was thought by some researchers to be the most primitive extant eukaryote while others considered it a highly evolved parasite. Previous reports have indicated that some aspects of its 5S rRNA system are simpler than that of common eukaryotes. We here explore whether this is true to its entire system, and whether this simplicity is a primitive or parasitic feature. By collecting and confirming pre-existing data and identifying new data, we obtained almost complete datasets of the system of three isolates of G. lamblia, two other parasitic excavates (Trichomonas vaginalis, Trypanosoma cruzi), and one free-living one (Naegleria gruberi). After comprehensively comparing each aspect of the system among these excavates and also with those of archaea and common eukaryotes, we found all the three Giardia isolates to harbor a same simplified 5S rRNA system, which is not only much simpler than that of common eukaryotes but also the simplest one among those of these excavates, and is surprisingly very similar to that of archaea; we also found among these excavates the system in parasitic species is not necessarily simpler than that in free-living species, conversely, the system of free-living species is even simpler in some respects than those of parasitic ones. The simplicity of Giardia 5S rRNA system should be considered a primitive rather than parasitically-degenerated feature. Therefore, Giardia 5S rRNA system might be a primitive system that is intermediate between that of archaea and the common eukaryotic model system, and it may reflect the evolutionary history of the eukaryotic 5S rRNA system from the archaeal form. Our results also imply G. lamblia might be a primitive eukaryote with secondary parasitically-degenerated features.

Volatile and light lithophile elements in high-anorthite plagioclase-hosted melt inclusions from Iceland

NASA Astrophysics Data System (ADS)

Neave, David A.; Hartley, Margaret E.; Maclennan, John; Edmonds, Marie; Thordarson, Thorvaldur

2017-05-01

Melt inclusions formed during the early stages of magmatic evolution trap primitive melt compositions and enable the volatile contents of primary melts and the mantle to be estimated. However, the syn- and post-entrapment behaviour of volatiles in primitive high-anorthite plagioclase-hosted melt inclusions from oceanic basalts remains poorly constrained. To address this deficit, we present volatile and light lithophile element analyses from a well-characterised suite of nine matrix glasses and 102 melt inclusions from the 10 ka Grímsvötn tephra series (i.e., Saksunarvatn ash) of Iceland's Eastern Volcanic Zone (EVZ). High matrix glass H2O and S contents indicate that eruption-related exsolution was arrested by quenching in a phreatomagmatic setting; Li, B, F and Cl did not exsolve during eruption. The almost uniformly low CO2 content of plagioclase-hosted melt inclusions cannot be explained by either shallow entrapment or the sequestration of CO2 into shrinkage bubbles, suggesting that inclusion CO2 contents were controlled by decrepitation instead. High H2O/Ce values in primitive plagioclase-hosted inclusions (182-823) generally exceed values expected for EVZ primary melts (∼ 180), and can be accounted for by diffusive H2O gain following the entrainment of primitive macrocrysts into evolved and H2O-rich melts a few days before eruption. A strong positive correlation between H2O and Li in plagioclase-hosted inclusions suggests that diffusive Li gain may also have occurred. Extreme F enrichments in primitive plagioclase-hosted inclusions (F/Nd = 51-216 versus ∼15 in matrix glasses) possibly reflect the entrapment of inclusions from high-Al/(Al + Si) melt pools formed by dissolution-crystallisation processes (as indicated by HFSE depletions in some inclusions), and into which F was concentrated by uphill diffusion since F is highly soluble in Al-rich melts. The high S/Dy of primitive inclusions (∼300) indicates that primary melts were S-rich in comparison with most oceanic basalts. Cl and B are unfractionated from similarly compatible trace elements, and preserve records of primary melt heterogeneity. Although primitive plagioclase-hosted melt inclusions from the 10 ka Grímsvötn tephra series record few primary signals in their volatile contents, they nevertheless record information about crustal magma processing that is not captured in olivine-hosted melt inclusions suites.

Using Spatial-Temporal Primitives to Improve Geographic Skills for Preservice Teachers

ERIC Educational Resources Information Center

Kaufman, Martin M.

2004-01-01

An exercise to help improve the geographic skills of preservice teachers was developed and tested during a six year period on over 500 students. The exercise required these students to map two arrangements of roads and facilities within a small neighborhood. A set of special-temporal primitives (place, size, shape, distance, direction,…

Android Protection Mechanism: A Signed Code Security Mechanism for Smartphone Applications

DTIC Science & Technology

2011-03-01

status registers, exceptions, endian support, unaligned access support, synchronization primitives , the Jazelle Extension, and saturated integer...supports comprehensive non-blocking shared-memory synchronization primitives that scale for multiple-processor system designs. This is an improvement... synchronization . Memory semaphores can be loaded and altered without interruption because the load and store operations are atomic. Processor

Primitive Reflexes and Attention-Deficit/Hyperactivity Disorder: Developmental Origins of Classroom Dysfunction

ERIC Educational Resources Information Center

Taylor, Myra; Houghton, Stephen; Chapman, Elaine

2004-01-01

The present research studied the symptomatologic overlap of AD/HD behaviours and retention of four primitive reflexes (Moro, Tonic Labyrinthine Reflex [TLR], Asymmetrical Tonic Neck Reflex [ATNR], Symmetrical Tonic Neck Reflex [STNR]) in 109 boys aged 7-10 years. Of these, 54 were diagnosed with AD/HD, 34 manifested sub-syndromal coordination,…

Advanced Robotics for In-Space Vehicle Processing

NASA Technical Reports Server (NTRS)

Smith, Jeffrey H.; Estus, Jay; Heneghan, Cate; Bosley, John

1990-01-01

An analysis of spaceborne vehicle processing is described. Generic crew-EVA tasks are presented for a specific vehicle, the orbital maneuvering vehicle (OMV), with general implications to other on-orbit vehicles. The OMV is examined with respect to both servicing and maintenance. Crew-EVA activities are presented by task and mapped to a common set of generic crew-EVA primitives to identify high-demand areas for telerobot services. Similarly, a set of telerobot primitives is presented that can be used to model telerobot actions for alternative telerobot reference configurations. The telerobot primitives are tied to technologies and used for composting telerobot operations for an automated refueling scenario. Telerobotics technology issues and design accomodation guidelines (hooks and scars) for the Space Station Freedom are described.

On the origin of extraterrestrial stratospheric particles: Interplanetary dust or meteor ablation debris?. M.S. Thesis

NASA Technical Reports Server (NTRS)

Kyte, F. T.

1977-01-01

Meteor ablation debris was distinguished from unablated interplanetary dust in a collection of extraterrestrial particles collected in the stratosphere using NASA U-2 aircraft. A 62 g sample of the Murchison (C2) meteorite was artificially ablated to characterize ablation debris for comparison with the stratospheric particles. By using proper experimental conditions, artificial ablation debris can be produced that is similar to natural ablation debris. Analyses of natural fusion crusts, artificial fusion crust, and artificial ablation debris of the Murchison meteorite produced criteria for recognizing debris ablated by a primitive meteoroid. Ninety-five percent of the stratospheric particles can be described as either ablation debris from a primitive meteoroid, or as very primitive interplanetary dust.

A primitive protostegid from Australia and early sea turtle evolution

PubMed Central

Kear, Benjamin P; Lee, Michael S.Y

2005-01-01

Sea turtles (Chelonioidea) are a prominent group of modern marine reptiles whose early history is poorly understood. Analysis of exceptionally well preserved fossils of Bouliachelys suteri gen. et sp. nov., a large-bodied basal protostegid (primitive chelonioid) from the Early Cretaceous (Albian) of Australia, indicates that early sea turtles were both larger and more diverse than previously thought. The analysis implies at least five distinct sea turtle lineages existed around 100 million years ago. Currently, the postcranially primitive Ctenochelys and Toxochelys are interpreted as crown-group sea turtles closely related to living cheloniids (e.g. Chelonia); in contrast, the new phylogeny suggests that they are transitional (intermediate stem-taxa) between continental testudines and derived, pelagic chelonioids. PMID:17148342

Detailed Primitive-Based 3d Modeling of Architectural Elements

NASA Astrophysics Data System (ADS)

Remondino, F.; Lo Buglio, D.; Nony, N.; De Luca, L.

2012-07-01

The article describes a pipeline, based on image-data, for the 3D reconstruction of building façades or architectural elements and the successive modeling using geometric primitives. The approach overcome some existing problems in modeling architectural elements and deliver efficient-in-size reality-based textured 3D models useful for metric applications. For the 3D reconstruction, an opensource pipeline developed within the TAPENADE project is employed. In the successive modeling steps, the user manually selects an area containing an architectural element (capital, column, bas-relief, window tympanum, etc.) and then the procedure fits geometric primitives and computes disparity and displacement maps in order to tie visual and geometric information together in a light but detailed 3D model. Examples are reported and commented.

POPO AGIE PRIMITIVE AREA, WYOMING.

USGS Publications Warehouse

Pearson, Robert C.; Patten, L.L.

1984-01-01

A mineral-resource appraisal was made of the Popo Agie Primitive Area and some adjoining lands. This scenic mountainous region of the Wind River Range in west-central Wyoming is composed largely of ancient granitic rocks in which virtually no evidence of mineral deposits was found. Deep crustal seismic-reflection profiles obtained across the southern Wind River Range suggest the possibility that young sedimentary rocks, similar to those at the surface along the northeast flank of the range, are present at depth beneath the granite in the Popo Agie primitive Area. If present, such buried sedimentary rocks could be petroleum bearing. Additional seismic and gravity studies would probably add valuable information, but ultimately very expensive, very deep drilling will be necessary to test this possibility.

Quadruped robots' modular trajectories: Stability issues

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.

2012-09-01

Pinto, Santos, Rocha and Matos [13, 12] study a CPG model for the generation of modular trajectories of quadruped robots. They consider that each movement is composed of two types of primitives: rhythmic and discrete. The rhythmic primitive models the periodic patterns and the discrete primitive is inserted as a perturbation of those patterns. In this paper we begin to tackle numerically the problem of the stability of that mathematical model. We observe that if the discrete part is inserted in all limbs, with equal values, and as an offset of the rhythmic part, the obtained gait is stable and has the same spatial and spatio-temporal symmetry groups as the purely rhythmic gait, differing only on the value of the offset.

Hard Spheres on the Primitive Surface

NASA Astrophysics Data System (ADS)

Dotera, Tomonari; Takahashi, Yusuke

2015-03-01

Recently hierarchical structures associated with the gyroid in several soft-matter systems have been reported. One of fundamental questions is regular arrangement or tiling on minimal surfaces. We have found certain numbers of hard spheres per unit cell on the gyroid surface are entropically self-organized. Here, new results for the primitive surface are presented. 56/64/72 per unit cell on the primitive minimal surface are entropically self-organized. Numerical evidences for the fluid-solid transition as a function of hard sphere radius are obtained in terms of the acceptance ratio of Monte Carlo moves and order parameters. These arrangements, which are the extensions of the hexagonal arrangement on a flat surface, can be viewed as hyperbolic tiling on the Poincaré disk with a negative Gaussian curvature.

Genetic origin, admixture and population history of aurochs (Bos primigenius) and primitive European cattle

PubMed Central

Upadhyay, M R; Chen, W; Lenstra, J A; Goderie, C R J; MacHugh, D E; Park, S D E; Magee, D A; Matassino, D; Ciani, F; Megens, H-J; van Arendonk, J A M; Groenen, M A M; Marsan, P A; Balteanu, V; Dunner, S; Garcia, J F; Ginja, C; Kantanen, J

2017-01-01

The domestication of taurine cattle initiated ~10 000 years ago in the Near East from a wild aurochs (Bos primigenius) population followed by their dispersal through migration of agriculturalists to Europe. Although gene flow from wild aurochs still present at the time of this early dispersion is still debated, some of the extant primitive cattle populations are believed to possess the aurochs-like primitive features. In this study, we use genome-wide single nucleotide polymorphisms to assess relationship, admixture patterns and demographic history of an ancient aurochs sample and European cattle populations, several of which have primitive features and are suitable for extensive management. The principal component analysis, the model-based clustering and a distance-based network analysis support previous works suggesting different histories for north-western and southern European cattle. Population admixture analysis indicates a zebu gene flow in the Balkan and Italian Podolic cattle populations. Our analysis supports the previous report of gene flow between British and Irish primitive cattle populations and local aurochs. In addition, we show evidence of aurochs gene flow in the Iberian cattle populations indicating wide geographical distribution of the aurochs. Runs of homozygosity (ROH) reveal that demographic processes like genetic isolation and breed formation have contributed to genomic variations of European cattle populations. The ROH also indicate recent inbreeding in southern European cattle populations. We conclude that in addition to factors such as ancient human migrations, isolation by distance and cross-breeding, gene flow between domestic and wild-cattle populations also has shaped genomic composition of European cattle populations. PMID:27677498

Genetic origin, admixture and population history of aurochs (Bos primigenius) and primitive European cattle.

PubMed

Upadhyay, M R; Chen, W; Lenstra, J A; Goderie, C R J; MacHugh, D E; Park, S D E; Magee, D A; Matassino, D; Ciani, F; Megens, H-J; van Arendonk, J A M; Groenen, M A M

2017-02-01

The domestication of taurine cattle initiated ~10 000 years ago in the Near East from a wild aurochs (Bos primigenius) population followed by their dispersal through migration of agriculturalists to Europe. Although gene flow from wild aurochs still present at the time of this early dispersion is still debated, some of the extant primitive cattle populations are believed to possess the aurochs-like primitive features. In this study, we use genome-wide single nucleotide polymorphisms to assess relationship, admixture patterns and demographic history of an ancient aurochs sample and European cattle populations, several of which have primitive features and are suitable for extensive management. The principal component analysis, the model-based clustering and a distance-based network analysis support previous works suggesting different histories for north-western and southern European cattle. Population admixture analysis indicates a zebu gene flow in the Balkan and Italian Podolic cattle populations. Our analysis supports the previous report of gene flow between British and Irish primitive cattle populations and local aurochs. In addition, we show evidence of aurochs gene flow in the Iberian cattle populations indicating wide geographical distribution of the aurochs. Runs of homozygosity (ROH) reveal that demographic processes like genetic isolation and breed formation have contributed to genomic variations of European cattle populations. The ROH also indicate recent inbreeding in southern European cattle populations. We conclude that in addition to factors such as ancient human migrations, isolation by distance and cross-breeding, gene flow between domestic and wild-cattle populations also has shaped genomic composition of European cattle populations.

Genetic control of Drosophila nerve cord development

NASA Technical Reports Server (NTRS)

Skeath, James B.; Thor, Stefan

2003-01-01

The Drosophila ventral nerve cord has been a central model system for studying the molecular genetic mechanisms that control CNS development. Studies show that the generation of neural diversity is a multistep process initiated by the patterning and segmentation of the neuroectoderm. These events act together with the process of lateral inhibition to generate precursor cells (neuroblasts) with specific identities, distinguished by the expression of unique combinations of regulatory genes. The expression of these genes in a given neuroblast restricts the fate of its progeny, by activating specific combinations of downstream genes. These genes in turn specify the identity of any given postmitotic cell, which is evident by its cellular morphology and choice of neurotransmitter.

Existence and Regularity of Invariant Measures for the Three Dimensional Stochastic Primitive Equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glatt-Holtz, Nathan, E-mail: negh@vt.edu; Kukavica, Igor, E-mail: kukavica@usc.edu; Ziane, Mohammed, E-mail: ziane@usc.edu

2014-05-15

We establish the continuity of the Markovian semigroup associated with strong solutions of the stochastic 3D Primitive Equations, and prove the existence of an invariant measure. The proof is based on new moment bounds for strong solutions. The invariant measure is supported on strong solutions and is furthermore shown to have higher regularity properties.

Comprehensive BRL-CAD Primitive Database

DTIC Science & Technology

2015-03-01

are not to be construed as an official Department of the Army position unless so designated by other authorized documents. Citation of...database provides the target describers of BRL–CAD with a representative example of each primitive’s shape and its properties. In addition to the...database was completed, a tool was created to generate primitive shapes automatically. This provides target describers—CAD experts who generate

Counting Primitive Pythagorean Triples

ERIC Educational Resources Information Center

Ayoub, Ayoub B.

2005-01-01

A triple (x,y,z) of natural numbers is called a Primitive Pythagorean Triple (PPT) if it satisfies two conditions: (1) x[squared] + y[squared] = z[squared]; and (2) x, y, and z have no common factor other than one. All the PPT's are given by the parametric equations: (1) x = m[squared] - n[squared]; (2) y = 2mn; and (3) z = m[squared] +…

Trace element distributions in primitive achondrites

NASA Technical Reports Server (NTRS)

Davis, Andrew M.; Prinz, Martin; Weisberg, Michael K.

1993-01-01

The primitive achondrites have approximately chondritic bulk chemical composition but achondritic textures. Clayton et al. show that nine of these meteorites, the acapulcoites and the lodranites, have similar oxygen isotopic compositions. The acapulcoites appear to be highly metamorphosed, but undifferentiated meteorites of chondritic composition; whereas, the lodranites appear to have lost a feldspathic partial melt. In order to learn more about metamorphic processes and partial melt removal, we have measured the trace element compositions of constituent phases of a number of primitive achondrites by ion microprobe. We have analyzed two acapulcoites, Acapulco and ALH81261 (paired with ALH77081), and three londranites, Lodran, LEW88280, and MAC88177. In addition, we analyzed LEW88663, which has the bulk composition, mineral chemistry, and oxygen isotopic composition of L-chondrites, but is metal-free and has an achondrite texture; and Divnoe, a plagioclase-poor, olivine-rich primitive achondrite with an oxygen isotopic composition similar to that of the group IAB iron meteorites. These meteorites show a variety of REE patterns in their constituent phases, and there are consistent differences between acapulcoites and lodranites that are consistent with removal of a LREE- and Eu-enriched melt that is apparently responsible for the low plagioclase content of lodranites.

Primitive Photosynthetic Architectures Based on Self-Organization and Chemical Evolution of Amino Acids and Metal Ions.

PubMed

Liu, Kai; Ren, Xiaokang; Sun, Jianxuan; Zou, Qianli; Yan, Xuehai

2018-06-01

The emergence of light-energy-utilizing metabolism is likely to be a critical milestone in prebiotic chemistry and the origin of life. However, how the primitive pigment is spontaneously generated still remains unknown. Herein, a primitive pigment model based on adaptive self-organization of amino acids (Cystine, Cys) and metal ions (zinc ion, Zn 2+ ) followed by chemical evolution under hydrothermal conditions is developed. The resulting hybrid microspheres are composed of radially aligned cystine/zinc (Cys/Zn) assembly decorated with carbonate-doped zinc sulfide (C-ZnS) nanocrystals. The part of C-ZnS can work as a light-harvesting antenna to capture ultraviolet and visible light, and use it in various photochemical reactions, including hydrogen (H 2 ) evolution, carbon dioxide (CO 2 ) photoreduction, and reduction of nicotinamide adenine dinucleotide (NAD + ) to nicotinamide adenine dinucleotide hydride (NADH). Additionally, guest molecules (e.g., glutamate dehydrogenase, GDH) can be encapsulated within the hierarchical Cys/Zn framework, which facilitates sustainable photoenzymatic synthesis of glutamate. This study helps deepen insight into the emergent functionality (conversion of light energy) and complexity (hierarchical architecture) from interaction and reaction of prebiotic molecules. The primitive pigment model is also promising to work as an artificial photosynthetic microreactor.

A balanced motor primitive framework can simultaneously explain motor learning in unimanual and bimanual movements.

PubMed

Takiyama, Ken; Sakai, Yutaka

2017-02-01

Certain theoretical frameworks have successfully explained motor learning in either unimanual or bimanual movements. However, no single theoretical framework can comprehensively explain motor learning in both types of movement because the relationship between these two types of movement remains unclear. Although our recent model of a balanced motor primitive framework attempted to simultaneously explain motor learning in unimanual and bimanual movements, this model focused only on a limited subset of bimanual movements and therefore did not elucidate the relationships between unimanual movements and various bimanual movements. Here, we extend the balanced motor primitive framework to simultaneously explain motor learning in unimanual and various bimanual movements as well as the transfer of learning effects between unimanual and various bimanual movements; these phenomena can be simultaneously explained if the mean activity of each primitive for various unimanual movements is balanced with the corresponding mean activity for various bimanual movements. Using this balanced condition, we can reproduce the results of prior behavioral and neurophysiological experiments. Furthermore, we demonstrate that the balanced condition can be implemented in a simple neural network model. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

What is ontic structural realism?

NASA Astrophysics Data System (ADS)

Ainsworth, Peter Mark

In recent years a doctrine known as ontic structural realism (OSR) has achieved a degree of notoriety, but many people remain confused as to what exactly the doctrine amounts. In this paper three main variants of OSR are defined and discussed: (i) OSR1, which is the view that relations are ontologically primitive but objects and properties are not; (ii) OSR2, which is the view that objects and relations are ontologically primitive but properties are not; (iii) OSR3, which is the view that properties and relations are ontologically primitive but objects are not. Proponents of OSR claim that it is a "naturalistic" metaphysics, arguing that metaphysical views that take objects and/or properties as ontologically primitive are undermined by contemporary physics. In this paper it is argued that OSR1 and OSR2 are themselves undermined by contemporary physics. On the other hand, it is also argued that considerations about the objects of quantum mechanics and general relativity do seem to suggest that we should abandon some of our "common-sense" metaphysical intuitions, and that OSR3 is one of the metaphysical views that is compatible with what these theories seem to tell us about fundamental ontology.

Process Management and Exception Handling in Multiprocessor Operating Systems Using Object-Oriented Design Techniques. Revised Sep. 1988

NASA Technical Reports Server (NTRS)

Russo, Vincent; Johnston, Gary; Campbell, Roy

1988-01-01

The programming of the interrupt handling mechanisms, process switching primitives, scheduling mechanism, and synchronization primitives of an operating system for a multiprocessor require both efficient code in order to support the needs of high- performance or real-time applications and careful organization to facilitate maintenance. Although many advantages have been claimed for object-oriented class hierarchical languages and their corresponding design methodologies, the application of these techniques to the design of the primitives within an operating system has not been widely demonstrated. To investigate the role of class hierarchical design in systems programming, the authors have constructed the Choices multiprocessor operating system architecture the C++ programming language. During the implementation, it was found that many operating system design concerns can be represented advantageously using a class hierarchical approach, including: the separation of mechanism and policy; the organization of an operating system into layers, each of which represents an abstract machine; and the notions of process and exception management. In this paper, we discuss an implementation of the low-level primitives of this system and outline the strategy by which we developed our solution.

Biometric verification in dynamic writing

NASA Astrophysics Data System (ADS)

George, Susan E.

2002-03-01

Pen-tablet devices capable of capturing the dynamics of writing record temporal and pressure information as well as the spatial pattern. This paper explores biometric verification based upon the dynamics of writing where writers are distinguished not on the basis of what they write (ie the signature), but how they write. We have collected samples of dynamic writing from 38 Chinese writers. Each writer was asked to provide 10 copies of a paragraph of text and the same number of signature samples. From the data we have extracted stroke-based primitives from the sentence data utilizing pen-up/down information and heuristic rules about the shape of the character. The x, y and pressure values of each primitive were interpolated into an even temporal range based upon a 20 msec sampling rate. We applied the Daubechies 1 wavelet transform to the x signal, y signal and pressure signal using the coefficients as inputs to a multi-layer perceptron trained with back-propagation on the sentence data. We found a sensitivity of 0.977 and specificity of 0.990 recognizing writers based on test primitives extracted from sentence data and measures of 0.916 and 0.961 respectively, from test primitives extracted from signature data.

Pseudo-random number generator for the Sigma 5 computer

NASA Technical Reports Server (NTRS)

Carroll, S. N.

1983-01-01

A technique is presented for developing a pseudo-random number generator based on the linear congruential form. The two numbers used for the generator are a prime number and a corresponding primitive root, where the prime is the largest prime number that can be accurately represented on a particular computer. The primitive root is selected by applying Marsaglia's lattice test. The technique presented was applied to write a random number program for the Sigma 5 computer. The new program, named S:RANDOM1, is judged to be superior to the older program named S:RANDOM. For applications requiring several independent random number generators, a table is included showing several acceptable primitive roots. The technique and programs described can be applied to any computer having word length different from that of the Sigma 5.

The Nature and Origin of Interplanetary Dust: High Temperature Components

NASA Technical Reports Server (NTRS)

Keller, L. P.; Messenger, S.

2004-01-01

The specific parent bodies of individual interplanetary dust particles (IDPs) are un-known, but the anhydrous chondritic-porous (CP) sub-set has been linked directly to cometary sources [1]. The CP IDPs escaped the thermal processing and water-rock interactions that have severely modified or destroyed the original mineralogy of primitive meteorites. Their origin in the outer regions of the solar system suggests they should retain primitive chemical and physical characteristics from the earliest stages of solar system formation (including abundant presolar materials). Indeed, CP IDPs are the most primitive extraterrestrial materials available for laboratory studies based on their unequilibrated mineralogy [2], high concentrations of carbon, nitrogen and volatile trace elements relative to CI chondrites [3, 4, 5], presolar hydrogen and nitrogen isotopic signatures [6, 7] and abundant presolar silicates [8].

Phosphorus, a key to life on the primitive earth

NASA Technical Reports Server (NTRS)

Griffith, E. J.; Ponnamperuma, C.; Gabel, N. W.

1977-01-01

The phosphorus of the primitive earth was present as phosphates. It is strongly probable that a portion of the phosphate was present as condensed phosphates. The primitive earth was highly deficient in the total available phosphorus until a sufficient quantity of phosphorus weathered from the igneous rocks in which it was entrapped. Approximately three billion years were required for the seas to become saturated. Until this time passed the seas acted as a giant sink for phosphorus, diluting it to the extent that all forms of life were deprived of the vital nutrient. When the seas became saturated, the rate of turnover of the phosphorus increased rapidly. As the seas pulsated, they left the excess precipitate phosphorus as sedimentary rock in locally rich deposits on which life could thrive.