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Sample records for primary transitional cell

  1. Intracranial metastasis from primary transitional cell carcinoma of female urethra: case report & review of the literature

    International Nuclear Information System (INIS)

    Moon, Kyung-Sub; Jung, Shin; Lee, Kyung-Hwa; Hwang, Eu Chang; Kim, In-Young

    2011-01-01

    Transitional cell carcinoma (TCC) of the female urethra is a rare urological malignancy, and intracranial metastasis of this cancer has not yet been reported in the literature. This review is intended to present a case of multiple intracranial metastasis in a female patient with a remote history of primary urethral TCC. A 49-year-old woman, presented with a prolapsed mass in urethral orifice that was diagnosed as primary urethral TCC with distant lung and multiple bone metastases. The patient subsequently underwent chemotherapy under various regimens. A year later, the patient developed headache and vomiting which as was found to be due to multiple intracranial metastasis. The patient underwent surgical resection of the largest lesion located on the cerebellum, and consecutively gamma knife radiosurgery was performed for other small-sized lesions. Pathological examination of the resected mass revealed a metastatic carcinoma from a known urethral TCC. Serial work-up of systemic metastasis revealed concomitant aggravation of lung, spleen, and liver metastasis. The patient died of lung complication 2 months after the diagnosis of brain metastasis. To the best of our knowledge, this is the first reported case of cerebral metastasis from primary urethral TCC, with pathological confirmation. As shown in intracranial metastasis of other urinary tract carcinoma, this case occurred in the setting of uncontrolled systemic disease and led to dismal prognosis in spite of aggressive interventional modalities

  2. Survival after primary and deferred cystectomy for stage T1 transitional cell carcinoma of the bladder

    Directory of Open Access Journals (Sweden)

    Bedeir Ali-El-Dein

    2011-01-01

    Conclusions: Cancer-specific survival is statistically comparable for primary and deferred cystectomy in T1 bladder cancer, although there is a non-significant difference in favor of primary cystectomy. In the deferred cystectomy group, the number of TURBTs beyond three is associated with lower survival. Conservative treatment should be adopted for most cases in this category.

  3. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  4. GGPP-Mediated Protein Geranylgeranylation in Oocyte Is Essential for the Establishment of Oocyte-Granulosa Cell Communication and Primary-Secondary Follicle Transition in Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Chen Jiang

    2017-01-01

    Full Text Available Folliculogenesis is a progressive and highly regulated process, which is essential to provide ova for later reproductive life, requires the bidirectional communication between the oocyte and granulosa cells. This physical connection-mediated communication conveys not only the signals from the oocyte to granulosa cells that regulate their proliferation but also metabolites from the granulosa cells to the oocyte for biosynthesis. However, the underlying mechanism of establishing this communication is largely unknown. Here, we report that oocyte geranylgeranyl diphosphate (GGPP, a metabolic intermediate involved in protein geranylgeranylation, is required to establish the oocyte-granulosa cell communication. GGPP and geranylgeranyl diphosphate synthase (Ggpps levels in oocytes increased during early follicular development. The selective depletion of GGPP in mouse oocytes impaired the proliferation of granulosa cells, primary-secondary follicle transition and female fertility. Mechanistically, GGPP depletion inhibited Rho GTPase geranylgeranylation and its GTPase activity, which was responsible for the accumulation of cell junction proteins in the oocyte cytoplasm and the failure to maintain physical connection between oocyte and granulosa cells. GGPP ablation also blocked Rab27a geranylgeranylation, which might account for the impaired secretion of oocyte materials such as Gdf9. Moreover, GGPP administration restored the defects in oocyte-granulosa cell contact, granulosa cell proliferation and primary-secondary follicle transition in Ggpps depletion mice. Our study provides the evidence that GGPP-mediated protein geranylgeranylation contributes to the establishment of oocyte-granulosa cell communication and then regulates the primary-secondary follicle transition, a key phase of folliculogenesis essential for female reproductive function.

  5. TGFβ1-induced down-regulation of microRNA-138 contributes to epithelial-mesenchymal transition in primary lung cancer cells.

    Science.gov (United States)

    Zhang, Fang; Li, Tiepeng; Han, Lu; Qin, Peng; Wu, Zhao; Xu, Benling; Gao, Quanli; Song, Yongping

    2018-02-19

    The existence of cancer stem cells within the tumor could lead to cancer therapy resistance. TGFβ1 is considered as one of the most powerful players in the generation of CSCs through induction of epithelial-mesenchymal transition in different types of cancer including lung cancer, however, the detailed mechanisms by which TGFβ1 contribute to EMT induction and CSC maintenance remains unclear. Here, we showed primary lung cancer cells treated by TGFβ1 exhibit mesenchymal features, including morphology and expression of mesenchymal marker in a time-dependent manner. We also observed long-term TGFβ1 exposure leads to an enrichment of a sub-population of CD44 + CD90 + cells which represent CSCs in lung cancer cells. Moreover, the differential expression microRNAs between CSCs and non-CSCs were identified using next-generation sequencing to screen key miRNAs which might contribute to TGFβ1-induced EMT and CSCs generation. Among those differentially expressed miRNAs, the expression of microRNA-138 was time-dependently down-regulated by TGFβ1 treatment. We further demonstrated primary lung cancer cells, in which we knockdown the expression of miR-138, exhibit mesenchymal phenotypes and stem cell properties. Taken together, these findings indicate TGFβ1-induced down-regulation of microRNA-138 contributes to EMT in primary lung cancer cells, and suggest that miR-138 might serve as a potential therapeutic target. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism.

    Science.gov (United States)

    Khan, Shoukat H; P, Madhu Vijay; Rather, Tanveer A; Laway, Bashir A

    2017-01-30

    Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy. Thirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15-20 MBq of Technetium-99m sulfur colloid diluted in 10-15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged. Patients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls ( P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation ( r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time. A significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels.

  7. Transitions from preschool to primary school

    DEFF Research Database (Denmark)

    Broström, Stig; Einarsdottir, Johanna; Vrinioti, Kalliope

    2010-01-01

    political understanding. Then the authors define and reflect the word transition in theoretical terms using Bronfenbrenner's ecological developmental model. After a short review of international transition research the article focus on international research on children's transition problems......  The article deals with transition from preschool to primary school. Starting with a historical overview presenting Fröbel's transition understanding from 1852 over European politics in the 1960s and 1970s, recommendations by the Councils of Europe from the 1990s and ending with OECD's actual...... and in continuation of this a description of a number of so-called transition activities are described in order to ease children's transition to school....

  8. Human Primary Epithelial Cells Acquire an Epithelial-Mesenchymal-Transition Phenotype during Long-Term Infection by the Oral Opportunistic Pathogen, Porphyromonas gingivalis

    Directory of Open Access Journals (Sweden)

    Jungnam Lee

    2017-12-01

    Full Text Available Porphyromonas gingivalis is a host-adapted oral pathogen associated with chronic periodontitis that successfully survives and persists in the oral epithelium. Recent studies have positively correlated periodontitis with increased risk and severity of oral squamous cell carcinoma (OSCC. Intriguingly, the presence of P. gingivalis enhances tumorigenic properties independently of periodontitis and has therefore been proposed as a potential etiological agent for OSCC. However, the initial host molecular changes induced by P. gingivalis infection which promote predisposition to cancerous transformation through EMT (epithelial-mesenchymal-transition, has never been studied in human primary cells which more closely mimic the physiological state of cells in vivo. In this study, we examine for the first time in primary oral epithelial cells (OECs the expression and activation of key EMT mediators during long-term P. gingivalis infection in vitro. We examined the inactive phosphorylated state of glycogen synthase kinase-3 beta (p-GSK3β over 120 h P. gingivalis infection and found p-GSK3β, an important EMT regulator, significantly increases over the course of infection (p < 0.01. Furthermore, we examined the expression of EMT-associated transcription factors, Slug, Snail, and Zeb1 and found significant increases (p < 0.01 over long-term P. gingivalis infection in protein and mRNA expression. Additionally, the protein expression of mesenchymal intermediate filament, Vimentin, was substantially increased over 120 h of P. gingivalis infection. Analysis of adhesion molecule E-cadherin showed a significant decrease (p < 0.05 in expression and a loss of membrane localization along with β-catenin in OECs. Matrix metalloproteinases (MMPs 2, 7, and 9 are all markedly increased with long-term P. gingivalis infection. Finally, migration of P. gingivalis infected cells was evaluated using scratch assay in which primary OEC monolayers were wounded and treated with

  9. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

    Science.gov (United States)

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

    2016-01-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

  10. Connecticut Transit (CTTRANSIT) Fuel Cell Transit Bus Preliminary Evaluation Results

    Science.gov (United States)

    2008-10-16

    This report describes operations at Connecticut Transit (CTTRANSIT) in Hartford for one prototype fuel cell bus and three new diesel buses operating from the same location. The report discusses the planned fuel cell bus demonstration and equipment us...

  11. Connecticut Transit (CTTRANSIT) Fuel Cell Transit Bus: Preliminary Evaluation Results

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2008-10-01

    This report provides preliminary results from a National Renewable Energy Laboratory evaluation of a protoptye fuel cell transit bus operating at Connecticut Transit in Hartford. Included are descriptions of the planned fuel cell bus demonstration and equipment; early results and agency experience are also provided.

  12. Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism

    OpenAIRE

    Khan, Shoukat H; Madhu, Vijay P; Rather, Tanveer A; Laway, Bashir A

    2017-01-01

    Background/Aims Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in pati...

  13. Alameda-Contra Costa Transit District (AC Transit) Fuel Cell Transit Buses: Preliminary Evaluation Results

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2007-03-01

    This report provides an evaluation of three prototype fuel cell-powered transit buses operating at AC Transit in Oakland, California, and six baseline diesel buses similar in design to the fuel cell buses.

  14. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  15. Visualizing cell state transition using Raman spectroscopy.

    Directory of Open Access Journals (Sweden)

    Taro Ichimura

    Full Text Available System level understanding of the cell requires detailed description of the cell state, which is often characterized by the expression levels of proteins. However, understanding the cell state requires comprehensive information of the cell, which is usually obtained from a large number of cells and their disruption. In this study, we used Raman spectroscopy, which can report changes in the cell state without introducing any label, as a non-invasive method with single cell capability. Significant differences in Raman spectra were observed at the levels of both the cytosol and nucleus in different cell-lines from mouse, indicating that Raman spectra reflect differences in the cell state. Difference in cell state was observed before and after the induction of differentiation in neuroblastoma and adipocytes, showing that Raman spectra can detect subtle changes in the cell state. Cell state transitions during embryonic stem cell (ESC differentiation were visualized when Raman spectroscopy was coupled with principal component analysis (PCA, which showed gradual transition in the cell states during differentiation. Detailed analysis showed that the diversity between cells are large in undifferentiated ESC and in mesenchymal stem cells compared with terminally differentiated cells, implying that the cell state in stem cells stochastically fluctuates during the self-renewal process. The present study strongly indicates that Raman spectral morphology, in combination with PCA, can be used to establish cells' fingerprints, which can be useful for distinguishing and identifying different cellular states.

  16. Metastatic transitional cell carcinoma of the tibia radiologically mimicking osteosarcoma.

    LENUS (Irish Health Repository)

    Cunningham, Laurence Patrick

    2013-01-01

    We report a case of a 73-year-old lady with transitional cell carcinoma and no evidence of metastatic disease presenting with gradual weight loss, pretibial swelling and painful weightbearing. Investigations revealed a lesion of the right tibial diaphysis. The radiological and clinical appearance was that of primary osteosarcoma. Biopsy results revealed metastatic transitional cell carcinoma of the tibia. Intramedullary nailing was performed which relieved pain on weightbearing. The patient declined radiotherapy and was started on a palliative care regimen. This case illustrates the importance of histological diagnosis in the treatment of diaphyseal lesions.

  17. Surgical management for upper urinary tract transitional cell carcinoma.

    Science.gov (United States)

    Rai, Bhavan Prasad; Shelley, Mike; Coles, Bernadette; Biyani, Chandra S; El-Mokadem, Ismail; Nabi, Ghulam

    2011-04-13

    Upper tract transitional cell carcinomas (TCC) are uncommon and aggressive tumours. There are a number of surgical approaches to manage this condition including open radical nephroureterectomy and laparoscopic procedures. To determine the best surgical management option for upper tract transitional cell carcinoma. A sensitive search strategy was developed to identify relevant studies for inclusion in this review. The following databases were searched for randomised trials evaluating surgical approaches to the management of upper tract TCC: Medline EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, British Nursing Index, AMED, LILACS, Web of Science®, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, and ISI Proceedings. The following criteria that were considered for this review.Types of studies - All randomised or quasi-randomised controlled trials comparing the various surgical methods and approaches for the management of localised upper tract transitional cell carcinoma. Types of participants - All adult patients with localised transitional cell carcinoma. Localised disease was defined as limited to the kidney or ureter with no gross regional lymph nodal enlargement on imaging. Types of interventions - Any surgical method or approach for managing localised upper tract transitional cell carcinoma. Types of outcome measures - Overall and cancer-specific survival were primary outcomes. Surgery-related morbidity. Quality of life and health economics outcomes were secondary outcomes. Two review authors examined the search results independently to identify trials for inclusion. We identified one randomised controlled trial that met our inclusion criteria. The trial showed that the laparoscopic approach had superior peri-operative outcomes compared to open approach. Laparoscopic was superior and statistically significant for blood loss (104 mL (millilitres) versus 430 mL, P management of upper tract transitional cell carcinoma

  18. Primary clear cell sarcoma of bone

    International Nuclear Information System (INIS)

    Choi, J.H.; Gu, M.J.; Kim, M.J.; Bae, Y.K.; Choi, W.H.; Shin, D.S.; Cho, K.H.

    2003-01-01

    Clear cell sarcoma is a rare soft tissue sarcoma of young adults with melanocytic differentiation. It occurs predominantly in the soft tissue of extremities, typically involving tendons and aponeuroses. Primary clear cell sarcoma of bone is extremely rare. We report a case of primary clear cell sarcoma of the right first metatarsal in a 48-year-old woman and provide a literature review of the entity. (orig.)

  19. Transition from specialist to primary diabetes care: A qualitative study of perspectives of primary care physicians

    Directory of Open Access Journals (Sweden)

    Liddy Clare

    2009-06-01

    Full Text Available Abstract Background The growing prevalence of diabetes and heightened awareness of the benefits of early and intensive disease management have increased service demands and expectations not only of primary care physicians but also of diabetes specialists. While research has addressed issues related to referral into specialist care, much less has been published about the transition from diabetes specialists back to primary care. Understanding the concerns of family physicians related to discharge of diabetes care from specialist centers can support the development of strategies that facilitate this transition and result in broader access to limited specialist services. This study was undertaken to explore primary care physician (PCP perspectives and concerns related to reassuming responsibility for diabetes care after referral to a specialized diabetes center. Methods Qualitative data were collected through three focus groups. Sessions were audio-taped and transcribed verbatim. Data were coded and sorted with themes identified using a constant comparison method. The study was undertaken through the regional academic referral center for adult diabetes care in Ottawa, Canada. Participants included 22 primary care physicians representing a variety of referral frequencies, practice types and settings. Results Participants described facilitators and barriers to successful transition of diabetes care at the provider, patient and systems level. Major facilitators included clear communication of a detailed, structured plan of care, ongoing access to specialist services for advice or re-referral, continuing education and mentoring for PCPs. Identified provider barriers were gaps in PCP knowledge and confidence related to diabetes treatment, excessive workload and competing time demands. Systems deterrents included reimbursement policies for health professionals and inadequate funding for diabetes medications and supplies. At the PCP-patient interface

  20. Circumcaval ureter with synchronous ipsilateral transitional cell ...

    African Journals Online (AJOL)

    We report a case of concomitant transitional cell carcinoma (TCC) in a circumcaval ureter and invasive bladder cancer. The diagnosis was based on the findings of excretory urography (IVU) and contrast-enhanced computed tomography (CT). IVU showed a typical J-shaped deformity in the dilated right proximal ureteric ...

  1. Transition to a hydrogen fuel cell transit bus fleet for Canadian urban transit system

    International Nuclear Information System (INIS)

    Ducharme, P.

    2004-01-01

    'Full text:' The Canadian Transportation Fuel Cell Alliance (CTFCA), created by the Canadian Government as part of its 2000 Climate Change Action Plan, has commissioned MARCON-DDM's Hydrogen Intervention Team (HIT) to provide a roadmap for urban transit systems that wish to move to hydrogen fuel cell-powered bus fleets. HIT is currently in the process of gathering information from hydrogen technology providers, bus manufacturers, fuelling system providers and urban transit systems in Canada, the US and Europe. In September, HIT will be in a position to provide a preview of its report to the CTFCA, due for October 2004. The planned table of contents includes: TOMORROW'S FUEL CELL (FC) URBAN TRANSIT BUS - Powertrain, on-board fuel technologies - FC engine system manufacturers - Bus technical specifications, performances, operating characteristics - FC bus manufacturers TOMORROW'S FC TRANSIT PROPERTY - Added maintenance, facilities and fuelling infrastructure requirements - Supply chain implications - Environmental and safety issues - Alternative operational concepts PATHWAYS TO THE FUTURE - Choosing the future operational concept - 'Gap' assessment - how long from here to there? - Facilities and fleet adjustments, including fuelling infrastructure - Risk mitigation, code compliance measures TRANSITIONAL CONSIDERATIONS - Cost implications - Transition schedule (author)

  2. Primary thermosensory events in cells.

    Science.gov (United States)

    Digel, Ilya

    2011-01-01

    Temperature sensing is essential for the survival of living organisms. Since thermal gradients are almost everywhere, thermoreception could represent one of the oldest sensory transduction processes that evolved in organisms. There are many examples of temperature changes affecting the physiology of living cells. Almost all classes of biological macromolecules in a cell (nucleic acids, lipids, proteins) can serve as a target of the temperature-related stimuli. This review is devoted to some common features of different classes of temperature-sensing molecules as well as molecular and biological processes involved in thermosensation. Biochemical, structural and thermodynamic approaches are discussed in order to overview the existing knowledge on molecular mechanisms of thermosensation.

  3. Cell Phenotype Transitions in Cardiovascular Calcification

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    Luis Hortells

    2018-03-01

    Full Text Available Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC; vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review, we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

  4. Local advanced transitional cell cancer and squamous cell cancer of ...

    African Journals Online (AJOL)

    Case report: A 51-year-old man presented with a locally advanced squamous cell cancer of the periurethral tissues as well as an underlying isolated transitional cell cancer of the urethra. Chemotherapy with Gemcitabin and Cisplatinum together with local radiation to the pelvis and the perineum was given. There was ...

  5. DICER-LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sizolwenkosi Mlotshwa

    2008-03-01

    Full Text Available Dicer-like (DCL enzymes play a pivotal role in RNA silencing in plants, processing the long double-stranded RNA (dsRNA that triggers silencing into the primary short interfering RNAs (siRNAs that mediate it. The siRNA population can be augmented and silencing amplified via transitivity, an RNA-dependent RNA polymerase (RDR-dependent pathway that uses the target RNA as substrate to generate secondary siRNAs. Here we report that Arabidopsis DCL2-but not DCL4-is required for transitivity in cell-autonomous, post-transcriptional silencing of transgenes. An insertion mutation in DCL2 blocked sense transgene-induced silencing and eliminated accumulation of the associated RDR-dependent siRNAs. In hairpin transgene-induced silencing, the dcl2 mutation likewise eliminated accumulation of secondary siRNAs and blocked transitive silencing, but did not block silencing mediated by primary siRNAs. Strikingly, in all cases, the dcl2 mutation eliminated accumulation of all secondary siRNAs, including those generated by other DCL enzymes. In contrast, mutations in DCL4 promoted a dramatic shift to transitive silencing in the case of the hairpin transgene and enhanced silencing induced by the sense transgene. Suppression of hairpin and sense transgene silencing by the P1/HC-Pro and P38 viral suppressors was associated with elimination of secondary siRNA accumulation, but the suppressors did not block processing of the stem of the hairpin transcript into primary siRNAs. Thus, these viral suppressors resemble the dcl2 mutation in their effects on siRNA biogenesis. We conclude that DCL2 plays an essential, as opposed to redundant, role in transitive silencing of transgenes and may play a more important role in silencing of viruses than currently thought.

  6. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  7. Primary clear cell sarcoma of rib

    International Nuclear Information System (INIS)

    Hersekli, Murat Ali; Ozkoc, Gurkan; Akpinar, Sercan; Ozalay, Metin; Tandogan, Reha N.; Bircan, Sema; Tuncer, Ilhan

    2005-01-01

    Clear cell sarcoma (malignant melanoma of soft tissues) is a very rare soft tissue neoplasm. It generally arises in tendons and aponeuroses. Although metastasis of malignant melanoma to bone is not uncommon, primary clear cell sarcoma of bone is an extremely rare neoplasm. To our knowledge five cases have been reported in the English literature. We present a case of primary clear cell sarcoma of bone in a 28-year-old woman arising in the left ninth rib. We treated the patient with total excision of the mass and postoperative radiotherapy. The patient is alive and well without local recurrence or distant metastasis at 33 months after surgery. (orig.)

  8. Transitional cell carcinoma express vitamin D receptors

    DEFF Research Database (Denmark)

    Hermann, G G; Andersen, C B

    1997-01-01

    Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore.......05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional...... studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients....

  9. Teaching Cell Biology in Primary Schools

    Directory of Open Access Journals (Sweden)

    Francele de Abreu Carlan

    2014-01-01

    Full Text Available Basic concepts of cell biology are essential for scientific literacy. However, because many aspects of cell theory and cell functioning are quite abstract, students experience difficulties understanding them. In this study, we investigated whether diverse teaching resources such as the use of replicas of Leeuwenhoek’s microscope, visualization of cells using an optical microscope, construction of three-dimensional cell models, and reading of a comic book about cells could mitigate the difficulties encountered when teaching cell biology to 8th-grade primary school students. The results suggest that these didactic activities improve students’ ability to learn concrete concepts about cell biology, such as the composition of living beings, growth, and cicatrization. Also, the development of skills was observed, as, for example, the notion of cell size. However, no significant improvements were observed in students’ ability to learn about abstract topics, such as the structures of subcellular organelles and their functions. These results suggest that many students in this age have not yet concluded Piaget’s concrete operational stage, indicating that the concepts required for the significant learning of abstract subjects need to be explored more thoroughly in the process of designing programs that introduce primary school students to cell biology.

  10. T cell-B cell interactions in primary immunodeficiencies.

    Science.gov (United States)

    Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

    2012-02-01

    Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

  11. Starting Strong V: Transitions from Early Childhood Education and Care to Primary Education

    Science.gov (United States)

    OECD Publishing, 2017

    2017-01-01

    The transition from early childhood education to primary school is a big step for all children, and a step which more and more children are having to take. Quality transitions should be well-prepared and child-centred, managed by trained staff collaborating with one another, and guided by an appropriate and aligned curriculum. Transitions like…

  12. Use of Transition Resources by Primary Care Providers for Youth with Intellectual and Developmental Disabilities

    Science.gov (United States)

    Dressler, Paul B.; Nguyen, Teresa K.; Moody, Eric J.; Friedman, Sandra L.; Pickler, Laura

    2018-01-01

    Youth with intellectual and developmental disabilities (IDD) often experience difficulties with successful transition from pediatric to adult healthcare. A consultative Transition Clinic for youth with IDD was piloted as a quality improvement project, and assessed the engagement of primary care providers (PCPs) for transition planning after…

  13. The Transition from Primary to Secondary School in Mainstream Education for Children with Autism Spectrum Disorder

    Science.gov (United States)

    Mandy, William; Murin, Marianna; Baykaner, Ozlem; Staunton, Sara; Hellriegel, Josselyn; Anderson, Seonaid; Skuse, David

    2016-01-01

    The transition from primary to secondary education (hereafter "school transition") is a major ecological shift that poses considerable social, emotional, academic and organisational challenges. It is commonly assumed that this school transition is especially difficult for children with autism spectrum disorder, but that idea is mainly…

  14. Transfection in Primary Cultured Neuronal Cells.

    Science.gov (United States)

    Marwick, Katie F M; Hardingham, Giles E

    2017-01-01

    Transfection allows the introduction of foreign nucleic acid into eukaryotic cells. It is an important tool in understanding the roles of NMDARs in neurons. Here, we describe using lipofection-mediated transfection to introduce cDNA encoding NMDAR subunits into postmitotic rodent primary cortical neurons maintained in culture.

  15. Does Brillouin light scattering probe the primary glass transition process at temperatures well above glass transition?

    Science.gov (United States)

    Voudouris, P; Gomopoulos, N; Le Grand, A; Hadjichristidis, N; Floudas, G; Ediger, M D; Fytas, G

    2010-02-21

    The primary alpha-relaxation time (tau(alpha)) for molecular and polymeric glass formers probed by dielectric spectroscopy and two light scattering techniques (depolarized light scattering and photon correlation spectroscopy) relates to the decay of the torsional autocorrelation function computed by molecular dynamics simulation. It is well known that Brillouin light scattering spectroscopy (BLS) operating in gigahertz frequencies probes a fast (10-100 ps) relaxation of the longitudinal modulus M*. The characteristic relaxation time, irrespective of the fitting procedure, is faster than the alpha-relaxation which obeys the non-Arrhenius Vogel-Fulcher-Tammann equation. Albeit, this has been noticed, it remains a puzzling finding in glass forming systems. The available knowledge is based only on temperature dependent BLS experiments performed, however, at a single wave vector (frequency). Using a new BLS spectrometer, we studied the phonon dispersion at gigahertz frequencies in molecular [o-terphenyl (OTP)] and polymeric [polyisoprene (PI) and polypropylene (PP)] glass formers. We found that the hypersonic dispersion does relate to the glass transition dynamics but the disparity between the BLS-relaxation times and tau(alpha) is system dependent. In PI and PP, the former is more than one order of magnitude faster than tau(alpha), whereas the two relaxation times become comparable in the case of OTP. The difference between the two relaxation times appears to relate to the "breadth" of the relaxation time distribution function. In OTP the alpha-relaxation process assumes a virtually single exponential decay at high temperatures well above the glass transition temperature, in clear contrast with the case of the amorphous bulk polymers.

  16. National Fuel Cell Bus Program : Accelerated Testing Report, AC Transit

    Science.gov (United States)

    2009-01-01

    This is an evaluation of hydrogen fuel cell transit buses operating at AC Transit in revenue service since March 20, 2006 compared to similar diesel buses operating from the same depot. This evaluation report includes results from November 2007 throu...

  17. Primary cutaneous anaplastic large-cell lymphoma.

    Science.gov (United States)

    Perry, Edward; Karajgikar, Jay; Tabbara, Imad A

    2013-10-01

    Since the recognition of the anaplastic large-cell lymphomas in the 1980s, much has been learned about the diagnosis, clinical presentation, and treatment of these malignant conditions. The systemic and primary cutaneous types of anaplastic large cell lymphomas have been differentiated on clinical and immunophenotypical findings, but further research is required to elucidate their exact etiologies and pathogeneses. Primary cutaneous anaplastic large-cell lymphoma has a 95% disease-specific 5-year survival, owing partly to the relatively benign course of the disease and partly to the variety of effective treatments that are available. As with many other oncological diseases, new drugs are continually being tested and developed, with immunotherapy and biological response modifiers showing promise.

  18. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  19. Primary signet cell adenocarcinoma of bladder

    Directory of Open Access Journals (Sweden)

    Prateek Kinra

    2017-01-01

    Full Text Available Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

  20. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wheat, Rachel [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Roberts, Claudia [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Waterboer, Tim [Infection and Cancer Program, DKFZ (German Cancer Research Centre), 69120 Heidelberg (Germany); Steele, Jane [Human Biomaterials Resource Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Marsden, Jerry [University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Steven, Neil M., E-mail: n.m.steven@bham.ac.uk [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Blackbourn, David J., E-mail: n.m.steven@bham.ac.uk [Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom)

    2014-05-06

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus.

  1. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Wheat, Rachel; Roberts, Claudia; Waterboer, Tim; Steele, Jane; Marsden, Jerry; Steven, Neil M.; Blackbourn, David J.

    2014-01-01

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus

  2. The transition from primary to secondary school in mainstream education for children with autism spectrum disorder.

    Science.gov (United States)

    Mandy, William; Murin, Marianna; Baykaner, Ozlem; Staunton, Sara; Hellriegel, Josselyn; Anderson, Seonaid; Skuse, David

    2016-01-01

    The transition from primary to secondary education (hereafter 'school transition') is a major ecological shift that poses considerable social, emotional, academic and organisational challenges. It is commonly assumed that this school transition is especially difficult for children with autism spectrum disorder, but that idea is mainly based on anecdotal evidence and requires systematic investigation. We describe change and continuity for children with autism spectrum disorder (N = 28, mean age = 11.29 years, mean full-scale IQ = 87.86) transitioning in mainstream education from primary to secondary school. Levels of psychopathology, adaptive functioning and peer victimisation were measured by parent, self and teacher report in the last year of primary school, and again after one term of secondary school. At follow-up, all participants were still in their secondary school, and there was no evidence for a marked escalation of difficulties during the transition. Instead, we observed high levels of psychopathology and maladaption at baseline which persisted across the transition and were in some cases under-recognised. By parent report, levels of bullying fell from primary to secondary school. Future research should investigate factors, such as school characteristics, that influence the move to secondary education in autism spectrum disorder, to inform the development of interventions to promote successful school transition. © The Author(s) 2015.

  3. Work satisfaction and future career intentions of experienced nurses transitioning to primary health care employment.

    Science.gov (United States)

    Ashley, Christine; Peters, Kath; Brown, Angela; Halcomb, Elizabeth

    2018-02-12

    To explore registered nurses' reflections on transitioning from acute to primary health care employment, and future career intentions. Reforms in primary health care have resulted in increasing demands for a skilled primary health care nursing workforce. To meet shortfalls, acute care nurses are being recruited to primary health care employment, yet little is known about levels of satisfaction and future career intentions. A sequential mixed methods study consisting of a survey and semi-structured interviews with nurses who transition to primary health care. Most reported positive experiences, valuing work/life balance, role diversity and patient/family interactions. Limited orientation and support, loss of acute skills and inequitable remuneration were reported negatively. Many respondents indicated an intention to stay in primary health care (87.3%) and nursing (92.6%) for the foreseeable future, whilst others indicated they may leave primary health care as soon as convenient (29.6%). Our findings provide guidance to managers in seeking strategies to recruit and retain nurses in primary health care employment. To maximize recruitment and retention, managers must consider factors influencing job satisfaction amongst transitioning nurses, and the impact that nurses' past experiences may have on future career intentions in primary health care. © 2018 John Wiley & Sons Ltd.

  4. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2015

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gikakis, Christina [Federal Transit Administration, Washington, DC (United States)

    2015-12-11

    This report, published annually, summarizes the progress of fuel cell electric bus (FCEB) development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. Various stakeholders, including FCEB developers, transit agencies, and system integrators, have expressed the value of this annual status report, which provides a summary of results from evaluations performed by the National Renewable Energy Laboratory. The annual status report tracks the progress of the FCEB industry toward meeting technical targets, documents the lessons learned, and discusses the path forward for commercial viability of fuel cell technology for transit buses. The 2015 summary results primarily focus on the most recent year for each demonstration, from August 2014 through July 2015. The results for these buses account for more than 1,045,000 miles traveled and 83,000 hours of fuel cell power system operation. The primary results presented in the report are from two demonstrations of fuel-cell-dominant bus designs: the Zero Emission Bay Area Demonstration Group led by Alameda-Contra Costa Transit District (AC Transit) in California and the American Fuel Cell Bus Project at SunLine Transit Agency in California.

  5. BC Transit Fuel Cell Bus Project: Evaluation Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-02-01

    This report evaluates a fuel cell electric bus demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. This evaluation report covers two years of revenue service data on the buses from April 2011 through March 2013.

  6. Measurements of a vortex transitional ndro Josephson memory cell

    International Nuclear Information System (INIS)

    Tahara, S.; Ishida, I.; Hidaka, M.; Nagasawa, S.; Ajisawa, Y.; Wada, Y.

    1988-01-01

    A novel vortex transitional NDRO Jospehson memory cell has been successfully fabricated and tested. The memory cell consists of two superconducting loops and a two-junction interferometer gate as a sense gate. The superconducting loop contains one Josephson junction and inductances, and stores single flux quantum. The memory cell employs vortex transitions in the superconducting loops for writing and reading data. The memory cell chips have been fabricated using niobium planarization process. The +-21 percent address signal current margin and the +-33 percent sense gate current margin have been obtained experimentally. The memory operation of the cell driven by the two-junction interferometer gates has been accurately demonstrated

  7. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2016

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jeffers, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-11-01

    This report, published annually, summarizes the progress of fuel cell electric bus development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. The report provides a summary of results from evaluations performed by the National Renewable Energy Laboratory. Funding for this effort is provided by the U.S. Department of Energy's Fuel Cell Technologies Office within the Office of Energy Efficiency and Renewable Energy and by the U.S. Department of Transportation's Federal Transit Administration. The 2016 summary results primarily focus on the most recent year for each demonstration, from August 2015 through July 2016. The results for these buses account for more than 550,000 miles traveled and 59,500 hours of fuel cell power system operation. The primary results presented in the report are from three demonstrations of two different fuel-cell-dominant bus designs: Zero Emission Bay Area Demonstration Group led by Alameda-Contra Costa Transit District (AC Transit) in California; American Fuel Cell Bus Project at SunLine Transit Agency in California; and American Fuel Cell Bus Project at the University of California at Irvine.

  8. Leukemoid reaction associated with transitional cell carcinoma: A ...

    African Journals Online (AJOL)

    Leukemoid reaction associated with transitional cell carcinoma: A case report ... Nigerian Journal of Clinical Practice ... At 3 months later, patient was admitted to our 21 22 hospital with the complaints of the left leg edema, diagnosed as pelvic

  9. FFTF primary system transition to natural circulation from low reactor power

    International Nuclear Information System (INIS)

    Bouchey, G.D.; Additon, S.L.; Nutt, W.T.

    1980-01-01

    Plans for reactor and primary loop natural circulation testing in the Fast Flux Test Facility (FFTF) are summarized. Detailed pretest planning with an emphasis on understanding the implications of process noise and model uncertainties for model verification and test acceptance are discussed for a transition to natural circulation in the reactor core and primary heat transport loops from initial conditions of 5% of rated reactor power and 75% of full flow

  10. TREATMENT OF PRIMARY PLASMA CELL LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    Peter Černelč

    2003-04-01

    Full Text Available Background. The author describes long-term survival in 3 patients with primary plasma cell leukaemia (PL after different therapeutic regimen and maintenance treatment with interferon alpha (INF.Patients and treatment. In a 52-year-old male patient, a partial remission of PL was achieved after 6 months of treatment with melphalan and prednisone. The patient did not consent to stem cell transplantation (SCT. An 86-year-old female patient with PL achieved a complete remission after 6 months of treatment with vincristine, doxorubicin and dexamethasone. A 31-year-old male patient experienced a complete remission of PL after 6 months of treatment with cyclophosphamide, vincristine, doxorubicin, methilprednisone, followed by autologous SCT. All three patients were placed on maintenance therapy with INF-2b (Intron A 3 × 106 IU given subcutaneously on two days per week. In the 52-year-old man, the remission lasted 9 months and in the woman 23 months, whereupon they developed a relapse with signs of disseminated plasmacytoma. In both patients the former chemotherapy was applied again, resulting in a slight improvement. The man died 37 months and the woman 43 months after the diagnosis of PL, while the youngest patient has been in complete remission for 82 months.Conclusions. Long remission achieved in our patients confirmed the favourable effect of INF in terms of prolongation of the remission duration in this patients. The effect of maintenance treatment with INF is usually directly dependent on the degree of remission induced by different therapeutic regimen.

  11. Primary care provider perceptions of intake transition records and shared care with outpatient cardiac rehabilitation programs

    Directory of Open Access Journals (Sweden)

    Jamnik Veronica

    2011-09-01

    Full Text Available Abstract Background While it is recommended that records are kept between primary care providers (PCPs and specialists during patient transitions from hospital to community care, this communication is not currently standardized. We aimed to assess the transmission of cardiac rehabilitation (CR program intake transition records to PCPs and to explore PCPs' needs in communication with CR programs and for intake transition record content. Method 144 PCPs of consenting enrollees from 8 regional and urban Ontario CR programs participated in this cross-sectional study. Intake transition records were tracked from the CR program to the PCP's office. Sixty-six PCPs participated in structured telephone interviews. Results Sixty-eight (47.6% PCPs received a CR intake transition record. Fifty-eight (87.9% PCPs desired intake transition records, with most wanting it transmitted via fax (n = 52, 78.8%. On a 5-point Likert scale, PCPs strongly agreed that the CR transition record met their needs for providing patient care (4.32 ± 0.61, with 48 (76.2% reporting that it improved their management of patients' cardiac risk. PCPs rated the following elements as most important to include in an intake transition record: clinical status (4.67 ± 0.64, exercise test results (4.61 ± 0.52, and the proposed patient care plan (4.59 ± 0.71. Conclusions Less than half of intake transition records are reaching PCPs, revealing a large gap in continuity of patient care. PCP responses should be used to develop an evidence-based intake transition record, and procedures should be implemented to ensure high-quality transitional care.

  12. A Critical Analysis on Primary Schools Preparedness for the Transition of Autistic Children in Kenya

    Science.gov (United States)

    Otina, Salmon O.; Thinguri, Ruth W.

    2016-01-01

    Autistic children, characterized by impaired social interactions, impaired communication, repetitive and stereotyped patterns of behaviors, are also entitled to education just like the other children in the society. It is therefore important that primary schools in Kenya get prepared so that the children are able to transit to schools from their…

  13. Transitional Woes: On the Impact of L2 Input Continuity from Primary to Secondary School

    Science.gov (United States)

    Pfenninger, Simone E.; Lendl, Johanna

    2017-01-01

    In this paper, we discuss the problem of articulation between levels in the educational system, as the transition from a rather more communicative, content-based and holistic approach to English as a foreign language (EFL) teaching at primary level to more formal and explicit ways of foreign language (FL) teaching at secondary is often experienced…

  14. A Bridge Too Far: The Decline in Shared Science Activities during Primary-Secondary Transition

    Science.gov (United States)

    Galton, Maurice

    2016-01-01

    This article reviews the use of "bridging units" in science to improve curriculum continuity during transition from primary to secondary school. Based on research evidence collected over several decades, it suggests that the use of these units rose to a peak around the time of the millennium, but that in recent years few schools have…

  15. Inequality in the Transition from Primary to Secondary School: School Choices and Educational Disparities in Germany

    Science.gov (United States)

    Pietsch, Marcus; Stubbe, Tobias C.

    2007-01-01

    This article explores the mechanisms of educational pathway decision making at the transition from primary to secondary school in the German education system by analysing data from the Progress in International Reading Literacy Study (PIRLS). The highly reliable data of the German sample of the 2001 PIRLS make it possible to take into…

  16. Changes in primary health care centres over the transition period in Slovenia.

    NARCIS (Netherlands)

    Albreht, T.; Delnoij, D.M.J.; Klazinga, N.

    2006-01-01

    BACKGROUND: Primary health care centres (PHCCs) were a characteristic of the former Yugoslav health care system introduced widely in Slovenia. Transition brought structural changes to health care and the position of the PHCC's was challenged. This paper investigates (i) PHCCs' perception of

  17. Changes in primary health care centres over the transition period in Slovenia

    NARCIS (Netherlands)

    Albreht, Tit; Delnoij, Diana M. J.; Klazinga, Niek

    2006-01-01

    BACKGROUND: Primary health care centres (PHCCs) were a characteristic of the former Yugoslav health care system introduced widely in Slovenia. Transition brought structural changes to health care and the position of the PHCC's was challenged. This paper investigates (i) PHCCs' perception of

  18. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2017

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew B [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-11-21

    This report, published annually, summarizes the progress of fuel cell electric bus (FCEB) development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. The report provides a summary of results from evaluations performed by the National Renewable Energy Laboratory. This annual status report combines results from all FCEB demonstrations, tracks the progress of the FCEB industry toward meeting technical targets, documents the lessons learned, and discusses the path forward for commercial viability of fuel cell technology for transit buses. These data and analyses help provide needed information to guide future early-stage research and development. The 2017 summary results primarily focus on the most recent year for each demonstration, from August 2016 through July 2017. The primary results presented in the report are from five demonstrations of two different fuel-cell-dominant bus designs: Zero Emission Bay Area Demonstration Group led by Alameda-Contra Costa Transit District (AC Transit) in California; American Fuel Cell Bus (AFCB) Project at SunLine Transit Agency in California; AFCB Project at the University of California at Irvine; AFCB Project at Orange County Transportation Authority; and AFCB Project at Massachusetts Bay Transportation Authority.

  19. Multicentric primary extramammary Paget disease: a Toker cell disorder?

    Science.gov (United States)

    Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

    2014-07-01

    Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

  20. Transitional Cell Carcinoma of the Ovary

    Directory of Open Access Journals (Sweden)

    Chia-Hui Lin

    2006-09-01

    Conclusion: TCC of the ovary is a rare subtype of epithelial ovarian cancer. It differs from malignant Brenner tumor by the absence of a benign or borderline Brenner component. Surgical resection is the primary therapeutic approach, and patient outcomes after chemotherapy are better than for other types of common epithelial ovarian cancers.

  1. BC Transit Fuel Cell Bus Project Evaluation Results: Second Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Post, M.

    2014-09-01

    Second report evaluating a fuel cell electric bus (FCEB) demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. NREL published its first report on the demonstration in February 2014. This report is an update to the previous report; it covers 3 full years of revenue service data on the buses from April 2011 through March 2014 and focuses on the final experiences and lessons learned.

  2. Reliability Evaluation of Primary Cells | Anyaka | Nigerian Journal of ...

    African Journals Online (AJOL)

    Evaluation of the reliability of a primary cell took place in three stages: 192 cells went through a slow-discharged test. A designed experiment was conducted on 144 cells; there were three factors in the experiment: Storage temperature (three levels), thermal shock (two levels) and date code (two levels). 16 cells ...

  3. Sedentary behaviour across the primary-secondary school transition: A systematic review.

    Science.gov (United States)

    Pearson, Natalie; Haycraft, Emma; P Johnston, Julie; Atkin, Andrew J

    2017-01-01

    The transition from primary/middle school to secondary/high school is likely to be a key period in children's development, characterised by significant changes in their social and physical environment. However, little is known about the changes in sedentary behaviour that accompany this transition. This review aimed to identify, critically appraise and summarise the evidence on changes in sedentary behaviour across the primary - secondary school transition. Published English language studies were located from computerised and manual searches in 2015. Inclusion criteria specified a longitudinal design, baseline assessment when children were in primary/middle school with at least one follow-up during secondary/high school and a measure of sedentary behaviour at both (or all) points of assessment. Based on data from 11 articles (19 independent samples), tracking coefficients were typically in the range of 0.3 to 0.5 and relatively consistent across the different sedentary behaviours examined and durations of follow-up. Both screen-based sedentary behaviour and overall sedentary time increased during the school transition. Overall there was an increase of approximately 10-20min per day per year in accelerometer-assessed sedentary time. Consistent with the broader age-related changes in behaviour observed during this period, sedentary behaviour increases during the transition from primary/middle to secondary/high school. Investigating features of the social and physical environment that might exacerbate or attenuate this trend would be a valuable next step. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Primary Squamous Cell Carcinoma of Stomach: A Rare Entity ...

    African Journals Online (AJOL)

    Schmidt C, Schmid A, Lüttges JE, Kremer B, Henne-Bruns D. Primary squamous cell carcinoma of the stomach. Report of a case and review of literature. Hepatogastroenterology 2001;48:1033-6. 5. Muto M, Hasebe T, Muro K, Boku N, Ohtsu A, Fujii T, et al. Primary squamous cell carcinoma of the stomach: A case report with ...

  5. Cerebellar T-cell lymphoma: an unusual primary intracranial neoplasm

    International Nuclear Information System (INIS)

    Knorr, J.R.; Ragland, R.L.; Stone, B.B.; Woda, B.A.; Gelber, N.D.

    1992-01-01

    Primary T-cell lymphoma within the central nervous system is extremely rare. Imaging characteristics appear indistinguishable from the more common B-cell lymphoma. A case of such a primary tumor is discussed and the MRI and CT findings presented. (orig.)

  6. Connecticut Transit (CTTRANSIT) Fuel Cell Transit Bus: Third Evaluation Report and Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2010-01-01

    This report describes operations at Connecticut Transit (CTTRANSIT) in Hartford for one prototype fuel cell bus and three new diesel buses operating from the same location. The prototype fuel cell bus was manufactured by Van Hool and ISE Corp. and features an electric hybrid drive system with a UTC Power PureMotion 120 Fuel Cell Power System and ZEBRA batteries for energy storage. The fuel cell bus started operation in April 2007, and evaluation results through October 2009 are provided in this report.

  7. National Fuel Cell Bus Program: Accelerated Testing Evaluation Report and Appendices, Alameda-Contra Costa Transit District (AC Transit)

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2009-01-01

    This is an evaluation of hydrogen fuel cell transit buses operating at AC Transit in revenue service since March 20, 2006 compared to similar diesel buses operating from the same depot. This evaluation report includes results from November 2007 through October 2008. Evaluation results include implementation experience, fueling station operation, fuel cell bus operations at Golden Gate Transit, and evaluation results at AC Transit (bus usage, availability, fuel economy, maintenance costs, and roadcalls).

  8. SunLine Transit Agency Fuel Cell Transit Bus: Fourth Evaluation Report (Report and Appendices)

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2009-01-01

    This report describes operations at SunLine Transit Agency for a prototype fuel cell bus and five new compressed natural gas (CNG) buses. This is the fourth evaluation report for this site, and it describes results and experiences from April 2008 through October 2008. These results are an addition to those provided in the previous three evaluation reports.

  9. SunLine Transit Agency Fuel Cell Transit Bus: Fifth Evaluation Report (Report and Appendices)

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2009-08-01

    This report describes operations at SunLine Transit Agency for a prototype fuel cell bus and five compressed natural gas (CNG) buses. This is the fifth evaluation report for this site, and it describes results and experiences from October 2008 through June 2009. These results are an addition to those provided in the previous four evaluation reports.

  10. Connecticut Transit (CTTRANSIT) Fuel Cell Transit Bus: Second Evaluation Report and Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2009-05-01

    This report describes operations at Connecticut Transit (CTTRANSIT) in Hartford for one prototype fuel cell bus and three new diesel buses operating from the same location. The evaluation period in this report (January 2008 through February 2009) has been chosen to coincide with a UTC Power propulsion system changeout that occurred on January 15, 2008.

  11. Radiosensitivity of primary cultured fish cells with different ploidy

    International Nuclear Information System (INIS)

    Mitani, Hiroshi; Egami, Nobuo; Kobayashi, Hiromu.

    1986-01-01

    The radiosensitivity of primary cultured goldfish cells (Carassius auratus) was investigated by colony formation assay. The radiosensitivity of cells from two varieties of goldfish, which show different sensitivity to lethal effect of ionizing radiation in vivo, was almost identical. Primary cultured cells from diploid, triploid and tetraploid fish retained their DNA content as measured by microfluorometry, and the nuclear size increases as ploidy increases. However, radiosensitivity was not related to ploidy. (author)

  12. Students' perceptions about science: The impact of transition from primary to secondary school

    Science.gov (United States)

    Speering, Wendy; Rennie, Léonie

    1996-09-01

    As students move through school, attitudes to school in general, and science in particular, become less positive. This paper reports on a longitudinal study which mapped, from the students' point of view, the transition between primary and secondary school in Western Australia. The study focused on the subject of science, and used both quantitative and qualitative methods. During the transition, there is a considerable change in the organisation of the school, the curriculum and the teacherstudent relationship. Students in this study, especially the girls, were generally disenchanted with the teaching strategies used in their secondary science classrooms, and regretted the loss of the close teacher-student relationship of their primary school years. Their perceptions were that science in secondary school was not what they had expected, and this experience may have long term implications for their subject and career choices.

  13. New graduate registered nurse transition into primary health care roles: an integrative literature review.

    Science.gov (United States)

    Murray-Parahi, Pauline; DiGiacomo, Michelle; Jackson, Debra; Davidson, Patricia M

    2016-11-01

    To summarise the literature describing new graduate nurse transition to professional practice within the primary health care (PHC) setting. There is a plethora of research literature spanning several decades about new graduate nurse transition in the acute care setting. Yet, the experiences of new graduate nurse in the PHC setting is unremarkable particularly considering the increasing demand for skilled health care workers and focus of health reform to provide care where people work and live. Electronic data bases, Academic Search Complete, EBSCO, Medline, PsycINFO, CINHAL, and ERIC were searched using a combination of terms and synonyms arising from three key concepts which identify the phenomenon; 'transition', 'new graduate registered nurse' and 'primary health care. An inclusive search strategy placed no limits on language or publication date. Of the 50 articles located and examined for relevance; 40 were sourced through databases and 10 from Google Scholar/Alerts and hand-searching references. None of the 19 articles retained for analysis addressed all key concepts. Some challenges of researching the professional transition of graduate nurses in PHC settings included, an absence of definitive transition models, a dearth of literature and deference to acute care research. Nursing in PHC settings, particularly the client's home is notably different to hospital settings because of higher levels of isolation and autonomy. Societal changes, health reform and subsequent demand for skilled workers in PHC settings has caused health care providers to question the logic that such roles are only for experienced nurses. Implications arise for education and health service providers who desire to close the theory practice gap and mitigate risk for all stakeholders when next generation nurses have limited opportunities to experience PHC roles as undergraduates and newly graduated registered nurses are already transitioning in this setting. © 2016 John Wiley & Sons Ltd.

  14. Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer.

    Science.gov (United States)

    Yamamoto, Mizuki; Sakane, Kota; Tominaga, Kana; Gotoh, Noriko; Niwa, Takayoshi; Kikuchi, Yasuko; Tada, Keiichiro; Goshima, Naoki; Semba, Kentaro; Inoue, Jun-Ichiro

    2017-06-01

    Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial-mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re-undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple-negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus-labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E-box-binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT-MET dynamics that could affect the development of triple-negative breast cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. Staghorn calculi and xanthogranulomatous pyelonephritis associated with transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chao-Wei Tseng

    2015-03-01

    Full Text Available Untreated staghorn calculi can cause xanthogranulomatous pyelonephritis (XGP, diminished renal function, and renal malignancy. Squamous cell carcinoma (SCC of the upper urinary tract is associated with kidney stones and chronic infection, but their association with transitional cell carcinoma (TCC has not been proven and has rarely been reported in literature. We present a rare case of staghorn calculi and XGP associated with TCC.

  16. Primary lithium-thionyl chloride cell evaluation

    Science.gov (United States)

    Zolla, A. E.; Waterhouse, R.; Debiccari, D.; Griffin, G. L.

    1980-08-01

    A test program was conducted to evaluate the Altus 1350AH cell performance against the Minuteman Survival Ground Power requirements. Twelve cells of the 17 inch diameter, 1-3/8 inch heights were fabricated and tested during this study. Under discharge rates varying from C/100 to C/400 at ambient temperature, the volumetric and gravimetric energy density performance requirements of 15 watt hours per cubic inch and 150 watt hours per pound were exceeded in all cases. All other performance requirements of voltage, current, configuration, capacity volume, weight, electrolyte leakage (none), and maintainability (none required), were met or exceeded. The abuse testing demonstrated the Altus Cell's ability to safely withstand short circuit by external shorting, short circuit by penetration with a conductive object, forced discharge, and forced charging of a cell. Disposal of discharged cells by incineration is an environmentally safe and efficient method of disposal.

  17. Recurrence of isolated transitional cell carcinoma in an orthotopic ...

    African Journals Online (AJOL)

    A.M. Moeen

    2015-11-10

    Nov 10, 2015 ... rare with less than 10 cases reported to date [2,3]. We present the case of a female patient with isolated recurrent transitional cell carcinoma (TCC) in an ileal neobladder, diagnosed 18 months after radical cystectomy and modified Hautmann ileal bladder substitution. E-mail address: moeen3@yahoo.com.

  18. Primary Testicular B-cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Aykut Buğra Şentürk

    2015-12-01

    Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

  19. Primary Signet Ring Cell Adenocarcinoma of the Urinary Bladder: A Report of 2 Cases

    Directory of Open Access Journals (Sweden)

    Wiem Boukettaya

    2014-05-01

    Full Text Available Primary signet ring cell carcinoma of the urinary bladder is a rare and aggressive histologic subtype of adenocarcinoma. In general, this tumor occurs in the middle age, and clinical presentation does not differ from transitional cell carcinomas. The prognosis is often poor, given the advanced stage at diagnosis. To our knowledge, <100 cases of signet ring cell adenocarcinoma of the urinary bladder have been reported. We report 2 cases with bladder linitis plastica primitive, and we draw attention to its pathologic, anatomoclinical, and evolution specificity to optimize its therapeutic management.

  20. Transitional woes: On the impact of L2 input continuity from primary to secondary school

    Directory of Open Access Journals (Sweden)

    Simone E. Pfenninger

    2017-09-01

    Full Text Available In this paper, we discuss the problem of articulation between levels in the educational system, as the transition from a rather more communicative, contentbased and holistic approach to English as a foreign language (EFL teaching at primary level to more formal and explicit ways of foreign language (FL teaching at secondary is often experienced as problematic by students and teachers alike (see, e.g., Muñoz, Tragant, & Camuñas, 2015. The results of a mixed methods analysis are presented, in which we analyzed, through a questionnaire and language experience essays, perceived continuity between input received in primary school and secondary school, as well as learners’ beliefs, attitudes and self-efficacy before and after they transitioned to secondary school. Twelve primary schools and six secondary schools in Switzerland participated in the study, with a total of 280 early learners of EFL (biological age 12-13 years, age of onset 8 years. We will argue that one of the main reasons why early FL instruction seems not to bear fruit later in secondary school is that, on the one hand, coherence in curriculum design and practice vary in a few—but crucial—aspects within and between primary schools. On the other hand, the fact that secondary education becomes a meeting point for mixed ability classes also seems to mitigate the potential advantages of an earlier start.

  1. Cell complexes of transition metals in biochemistry and medicine

    International Nuclear Information System (INIS)

    Voloshin, Ya.Z.; Varzatskij, O.A.; Bubnov, Yu.N.

    2007-01-01

    Basic directions and prospects of use of cell complexes of transition metals in medicine and biochemistry are considered: incapsulation of radioactive metal ions for radiotherapy and diagnostics; preparation of contrast compounds for magnetic resonance tomography, antidotes and pharmaceutical preparation of prolonged effect, preparations for boron-neutron-capture therapy of neoplasms, antioxidants; membrane transport of metal ions; study of interaction of cell metal complexes with nucleic acids; possibility of use of self-assembly of cell complexes for imitation of ligases and use of clathrochelates as linkers; design of inhibitors of viruses for AIDS therapy [ru

  2. Psychometric analysis of the TRANSIT quality indicators for cardiovascular disease prevention in primary care.

    Science.gov (United States)

    Khanji, Cynthia; Bareil, Céline; Hudon, Eveline; Goudreau, Johanne; Duhamel, Fabie; Lussier, Marie-Thérèse; Perreault, Sylvie; Lalonde, Gilles; Turcotte, Alain; Berbiche, Djamal; Martin, Élisabeth; Lévesque, Lise; Gagnon, Marie-Mireille; Lalonde, Lyne

    2017-12-01

    To assess a selection of psychometric properties of the TRANSIT indicators. Using medical records, indicators were documented retrospectively during the 14 months preceding the end of the TRANSIT study. Primary care in Quebec, Canada. Indicators were documented in a random subsample (n = 123 patients) of the TRANSIT study population (n = 759). For every patient, the mean compliance to all indicators of a category (subscale score) and to the complete set of indicators (overall scale score) were established. To evaluate test-retest and inter-rater reliabilities, indicators were applied twice, two months apart, by the same evaluator and independently by different evaluators, respectively. To evaluate convergent validity, correlations between TRANSIT indicators, Burge et al. indicators and Institut national d'excellence en santé et en services sociaux (INESSS) indicators were examined. Test-retest reliability, inter-rater reliability, and convergent validity. Test-retest reliability, as measured by intraclass correlation coefficients (ICCs) was equal to 0.99 (0.99-0.99) for the overall scale score while inter-rater reliability was equal to 0.95 (0.93-0.97) for the overall scale score. Convergent validity, as measured by Pearson's correlation coefficients, was equal to 0.77 (P TRANSIT indicators were compared to Burge et al. indicators and to 0.82 (P TRANSIT indicators were compared to INESSS indicators. Reliability was excellent except for eleven indicators while convergent validity was strong except for domains related to the management of CVD risk factors. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  3. Comparison of Gasoline and Primary Reference Fuel in the Transition from HCCI to PPC

    KAUST Repository

    Li, Changle

    2017-10-10

    Our previous research investigated the sensitivity of combustion phasing to intake temperature and injection timing during the transition from homogeneous charge compression ignition (HCCI) to partially premixed combustion (PPC) fuelled with generic gasoline. The results directed particular attention to the relationship between intake temperature and combustion phasing which reflected the changing of stratification level with the injection timing. To confirm its applicability with the use of different fuels, and to investigate the effect of fuel properties on stratification formation, primary reference fuels (PRF) were tested using the same method: a start of injection sweep from -180° to -20° after top dead center with constant combustion phasing by tuning the intake temperature. The present results are further developed compared with those of our previous work, which were based on generic gasoline. In the present work, a three-stage fuel-air stratification development process was observed during the transition from HCCI to PPC. Moreover, a transition stage was observed between the HCCI and PPC stages. Within this transition stage, both the combustion and emission characteristics deteriorated. The allocation of this transition area was mainly determined by the geometric design of the fuel injector and combustion chamber. Some differences in charge stratification were observed between the PRF and gasoline. The NO emissions of the PRF were comparable to those of gasoline. However, the NO emissions surged during the transition stage, indicating that the PRF combustion was probably more stratified. The soot emissions from PRF and gasoline were both much higher in the PPC than the HCCI mode, though the PRF produced much less soot than did gasoline in the PPC mode.

  4. Rapid intestinal transit as a primary cause of severe chronic diarrhea in patients with amyloidosis.

    Science.gov (United States)

    Guirl, Michael J; Högenauer, Christoph; Santa Ana, Carol A; Porter, Jack L; Little, Katherine H; Stone, Marvin J; Fordtran, John S

    2003-10-01

    The cause of severe diarrhea in patients with systemic amyloidosis is obscure. We therefore performed pathophysiological studies in three such patients in an effort to determine the mechanism of amyloid diarrhea. Epithelial cell absorption rate of electrolytes was measured during steady state GI perfusion of a saline-mannitol solution. GI transit time of PEG and absorption of radiolabeled bile acid were measured simultaneously while subjects ingested three meals per day. To obtain a diarrhea control group for transit time and bile acid absorption, normal subjects were studied when they had diarrhea caused by ingestion of Milk of Magnesia (MOM). Diarrhea could not be explained by malabsorption of ingested nutrients, bacterial overgrowth, bile acid malabsorption, or epithelial cell malabsorption of electrolytes. However, 25% of polyethylene glycol (PEG) ingested with a standard meal was recovered in stool in 45 min, which is 10 times faster than in normal subjects with equally severe diarrhea caused by ingestion of MOM. All of the patients had autonomic neuropathy that remained unrecognized for 15-36 months after onset of chronic diarrhea; it seems likely that this was the cause of rapid transit. Severe chronic diarrhea in three patients with systemic amyloidosis was mediated by extremely rapid transit of chyme and digestive secretions through the intestine.

  5. CERDEC Fuel Cell Team: Military Transitions for Soldier Fuel Cells

    Science.gov (United States)

    2008-10-27

    Fuel Cell (DMFC) (PEO Soldier) Samsung: 20W DMFC (CRADA) General Atomics & Jadoo: 50W Ammonia Borane Fueled PEMFC Current Fuel Cell Team Efforts...Continued Ardica: 20W Wearable PEMFC operating on Chemical Hydrides Spectrum Brands w/ Rayovac: Hydrogen Generators and Alkaline Fuel Cells for AA...100W Ammonia Borane fueled PEMFC Ultralife: 150W sodium borohydride fueled PEMFC Protonex: 250W RMFC and Power Manager (ARO) NanoDynamics: 250W SOFC

  6. Primary immunodeficiencies and B-cell lymphomas.

    Science.gov (United States)

    Martín-Mateos, María Anunciación; Piquer Gibert, Mónica

    In primary immunodeficiencies there is a failure in the anti-tumor defense. Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies characterized by an alteration in the differentiation of B lymphocytes (BL). Epstein-Barr virus (EBV) is an ubiquitous virus that selectively infects the BL. In patients with immunodeficiency, uncontrolled proliferation of infected BL and the action of viral proteins promote the development of lymphomas. At the University Hospital Sant Joan de Deu, Barcelona, 28 patients were diagnosed with CVID from 2000 to 2013. This paper describes four patients who developed non-Hodgkin's lymphoma (NHL). The lymphoma was associated with EBV in two of the cases. Patients were<18 years old, diagnosed with lymphoma between 4 and 13 years old. Two patients were treated with rituximab as monotherapy and achieved complete remission. Two patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and radiotherapy or rituximab and achieved complete remission. Early detection of EBV infections and NHL in all patients diagnosed with CVID is recommended, regardless of age at diagnosis. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  7. Mantle cell lymphoma of the larynx: Primary case report

    Directory of Open Access Journals (Sweden)

    Naciri Sarah

    2012-07-01

    Full Text Available Abstract Introduction Primary laryngeal lymphomas are exceedingly rare. Only about a hundred cases have been reported. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report the first case of a primary laryngeal mantle cell lymphoma. Case presentation We report a case of a primary mantle cell lymphoma of the larynx in a 70-year-old North African non-smoker male. We present a detailed report of his clinical and paraclinical data as well as treatment options. Conclusions Mantle cell lymphoma is a very aggressive lymphoma subset associated with poor prognosis. Laryngeal mantle cell lymphoma is exceedingly rare. To the best of our knowledge, this is the first case to ever be reported.

  8. Strength functions of primary transitions following thermal neutron capture in strontium

    International Nuclear Information System (INIS)

    Winter, C.; Lieb, K.P.

    1989-01-01

    The primary E1, M1 and E2 γ-radiation in 87,88,89 Sr observed after thermal neutron capture was compared with the predictions of single particle and giant resonance models. The nuclei feature a wide range of neutron binding energies between 6.3 and 11.1 MeV, which makes a 5.5 MeV spectrum of primary transition energies available for investigation. The (n, γ) reaction was used to estimate the parameters of the spin-flip M1 giant resonance in strontium. The total energy weighted M1 strength of this resonance exceeds the results of shell model and random phase approximation calculations for 90 Zr by a factor of 3-4. The E1 strengths were found to agree with the established giant dipole resonance model. The few data on primary E2 transitions do not allow to differentiate between the giant quadrupole resonance and the single particle models. (orig.)

  9. A new Zero-Voltage-Transition PWM switching cell

    Energy Technology Data Exchange (ETDEWEB)

    Grigore, V. [Electronics and Telecommunications Faculty `Politebuica` University Bucharest (Romania); Kyyrae, J. [Helsinki University of Technology, Otaniemi (Finland): Institute of Intelligent Power Electronics

    1997-12-31

    In this paper a new Zero-Voltage-Transition (ZVT) PWM switching cell is presented. The proposed switching cell is composed of the normal hard-switched PWM cell (consisting of one active switch and one passive switch), plus an auxiliary circuit (consisting of one active switch and some reactive components). The auxiliary circuit is inactive during the ON and OFF intervals of the switches in the normal PWM switch. However, the transitions between the two states are controlled by the auxiliary circuit. Prior to turn-on, the voltage across the active switch in the PWM cell is forced to zero, thus the turn-on losses of the active switch are practically eliminated. At turn-off the auxiliary circuit behaves like a non-dissipative passive snubber reducing the turn-off losses to a great extent. Zero-Voltage-Transition switching technique almost eliminates switching losses. The active switch operates under ZVT conditions, the passive switch (diode) has a controlled reverse recovery, and the switch in the auxiliary circuit operates under Zero-Current-Switching (ZCS) conditions. (orig.) 6 refs.

  10. Primary radiation damage and disturbance in cell divisions

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Yun-Jong; Kim, Jae-Hun; Petin, Vladislav G.; Nili, Mohammad

    2008-01-01

    Survived cells from a homogeneous population exposed to ionizing radiation form various colonies of different sizes and morphology on a solid nutrient medium, which appear at different time intervals after irradiation. Such a phenomenon agrees well with the modern theory of microdosimetry and classical hit-and-target models of radiobiology. According to the hit-principle, individual cells exposed to the same dose of radiation are damaged in different manners. It means that the survived cells can differ in the content of sublethal damage (hits) produced by the energy absorbed into the cell and which is not enough to give rise to effective radiation damage which is responsible for cell killing or inactivation. In diploid yeast cells, the growth rate of cells from 250 colonies of various sizes appeared at different time intervals after irradiation with 600 Gy of gamma radiation from a 60 Co isotopic source was analyzed. The survival rate after irradiation was 20%. Based on the analyses results, it was possible to categorize the clones grown from irradiated cells according to the number of sub-lesions from 1 to 4. The clones with various numbers of sub-lesions were shown to be different in their viability, radiosensitivity, sensitivity to environmental conditions, and the frequency of recombination and respiratory deficient mutations. Cells from unstable clones exhibited an enhanced radiosensitivity, and an increased portion of morphologically changed cells, nonviable cells and respiration mutants, as well. The degree of expression of the foregoing effects was higher if the number of primary sublethal lesions was greater in the originally irradiated cell. Disturbance in cell division can be characterized by cell inactivation or incorrect distribution of mitochondria between daughter cells. Thus, the suggested methodology of identification of cells with a definite number of primary sublethal lesions will promote further elucidation of the nature of primary radiation

  11. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line.

    Science.gov (United States)

    Meng, Ran; Zhou, Jin; Sui, Meng; Li, ZhiYong; Feng, GuoSheng; Yang, BaoFeng

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.

  12. A transition program to primary health care for new graduate nurses: a strategy towards building a sustainable primary health care nurse workforce?

    Science.gov (United States)

    Gordon, Christopher J; Aggar, Christina; Williams, Anna M; Walker, Lynne; Willcock, Simon M; Bloomfield, Jacqueline

    2014-01-01

    This debate discusses the potential merits of a New Graduate Nurse Transition to Primary Health Care Program as an untested but potential nursing workforce development and sustainability strategy. Increasingly in Australia, health policy is focusing on the role of general practice and multidisciplinary teams in meeting the service needs of ageing populations in the community. Primary health care nurses who work in general practice are integral members of the multidisciplinary team - but this workforce is ageing and predicted to face increasing shortages in the future. At the same time, Australia is currently experiencing a surplus of and a corresponding lack of employment opportunities for new graduate nurses. This situation is likely to compound workforce shortages in the future. A national nursing workforce plan that addresses supply and demand issues of primary health care nurses is required. Innovative solutions are required to support and retain the current primary health care nursing workforce, whilst building a skilled and sustainable workforce for the future. This debate article discusses the primary health care nursing workforce dilemma currently facing policy makers in Australia and presents an argument for the potential value of a New Graduate Transition to Primary Health Care Program as a workforce development and sustainability strategy. An exploration of factors that may contribute or hinder transition program for new graduates in primary health care implementation is considered. A graduate transition program to primary health care may play an important role in addressing primary health care workforce shortages in the future. There are, however, a number of factors that need to be simultaneously addressed if a skilled and sustainable workforce for the future is to be realised. The development of a transition program to primary health care should be based on a number of core principles and be subjected to both a summative and cost

  13. Subcutaneous Transitional Cell Cancer After Percutaneous Nephrolithotomy: A Case Report

    Directory of Open Access Journals (Sweden)

    Lokman Ižrkilata

    2013-10-01

    Full Text Available Transitional cell carcinomas of the upper urinary tract are rare but, highly predisposing to tumoral seeding. Percutaneous lithotripsy (PNL recently has expanded the therapeutic choices for patients with kidney stones and gained popularity by urologic surgeons. Although unusual, renal collecting system tumours may be encountered during PNL. We present and discuss the clinical course of a 48 years old male patient who underwent PNL surgery for kidney stone in whom transitional cell carcinoma in the renal collecting system obscured by stone left undiagnosed. Three months later following PNL he admitted with a bulge on lumbar region. Excisional biopsy revealed carcinoma and therefore, he was directed to chemoradiotherapy and died 21 months later. Renal collecting system tumors undiagnosed during surgery may progress and demonstrate local invasion in a short period of time. Therefore, we recommend to take more caution during any percutaneous access and to exclude the possible existence of tumor.

  14. Development of a Mobile-Optimised Website to Support Students with Special Needs Transitioning from Primary to Secondary Settings

    Science.gov (United States)

    Chambers, Dianne; Coffey, Anne

    2013-01-01

    With an increasing number of students with special needs being included in regular classroom environments, consideration of, and planning for, a smooth transition between different school settings is important for parents, classroom teachers and school administrators. The transition between primary and secondary school can be difficult for…

  15. Utilisation and Satisfaction with Rehabilitation Services in Children with Primary Language Impairment Transitioning to School: Parents' Perspective

    Science.gov (United States)

    Mazer, Barbara; Dion, Karyne; Moryoussef, Aguy

    2017-01-01

    Children with disabilities require coordinated services to optimise transition into school. This study compared type, frequency and approach to service utilisation for children with primary language impairment transitioning from rehabilitation to the educational system, and examined parent satisfaction. Parents responded to a telephone…

  16. Isolated Meningeal Recurrence of Transitional Cell Carcinoma of the Bladder

    Directory of Open Access Journals (Sweden)

    Catherine Butchart

    2010-06-01

    Full Text Available Meningeal carcinomatosis occurs in 1–18% of patients with solid tumours, most commonly carcinomas of the breast and lung or melanomas. There are relatively few reports of meningeal carcinomatosis in transitional cell carcinoma of the bladder. Isolated meningeal recurrence is particularly uncommon, and we present an unusual case of this in a 58-year-old man. The case was further complicated by the somewhat atypical presentation with a confirmed ischaemic stroke. The patient died one month after presentation.

  17. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  18. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

    NARCIS (Netherlands)

    Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

    2005-01-01

    Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

  19. Differential heat shock response of primary human cell cultures and established cell lines

    DEFF Research Database (Denmark)

    Richter, W W; Issinger, O G

    1986-01-01

    degrees C treatment, whereas in immortalized cell lines usually 90% of the cells were found in suspension. Enhanced expression of the major heat shock protein (hsp 70) was found in all heat-treated cells. In contrast to the primary cell cultures, established and transformed cell lines synthesized...

  20. Transcriptomic profiling of primary alveolar epithelial cell differentiation in human and rat

    Directory of Open Access Journals (Sweden)

    Crystal N. Marconett

    2014-12-01

    Full Text Available Cell-type specific gene regulation is a key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how changes in transcriptional activation during alveolar epithelial cell (AEC differentiation determine phenotype. We performed transcriptomic profiling using in vitro differentiation of human and rat primary AEC. This model recapitulates in vitro an in vivo process in which AEC transition from alveolar type 2 (AT2 cells to alveolar type 1 (AT1 cells during normal maintenance and regeneration following lung injury. Here we describe in detail the quality control, preprocessing, and normalization of microarray data presented within the associated study (Marconett et al., 2013. We also include R code for reproducibility of the referenced data and easily accessible processed data tables.

  1. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  2. A new Zero-Current-Transition PWM switching cell

    Energy Technology Data Exchange (ETDEWEB)

    Grigore, V. [Electronics and Telecommunications Faculty, `Politechnica` University Bucharest (Romania); Kyyrae, J. [Helsinki University of Technology, Otaniemi (Finland): Institute of Intelligent Power Electronics

    1997-12-31

    In this paper a new Zero-Current-Transition (ZCT) PWM switching cell is presented. The proposed switching cell is composed of the normal hard-switched PWM cell (consisting of one active switch and one passive switch), plus as auxiliary circuit. The auxiliary circuit is inactive during the ON ad OFF intervals of the switches in the normal PWM switch. The transitions between the two states are controlled by the auxiliary circuit. Prior to turn-off, the current through the active switch in the PWM cell is forced to zero, thus the turn-off losses of the active switch are practically eliminated. At turn-on the auxiliary circuit slows down the growing rate of the current through the main switch. Thus, turn-on losses are also very much reduced. The active switch operates under ZCT conditions, the passive switch (diode) has a controlled reverse recovery, while the switch in the auxiliary circuit operates under Zero-Current-Switching (ZCS) conditions. (orig.) 3 refs.

  3. Study of the strength distribution of primary γ-transitions in the decay from superdeformed states in 194Hg

    International Nuclear Information System (INIS)

    Lopez-Martens, A.P.; Doessing, T.; Khoo, T.L.; Korichi, A.; Hannachi, F.; Calderin, I.J.; Lauritsen, T.; Ahmad, I.; Carpenter, M.P.; Fischer, S.M.; Hackman, G.; Janssens, R.V.F.; Nisius, D.; Reiter, P.; Amro, H.; Moore, E.F.

    1999-01-01

    The strength distribution of the primary γ rays in the decay from superdeformed (SD) states is investigated by applying the maximum likelihood method. For the 194 Hg nucleus, 41 primary transitions are identified above 2600 keV. It is concluded that they represent the strongest 10% of the transitions selected stochastically from a Porter-Thomas distribution. This would support the scenario of a statistical decay of SD states via coupling to a compound state at normal deformation. However, the occurrence of several very strong 'one-step linking' transitions is found to have a very small probability. Based on the absence of strong primary transitions from SD states in adjacent nuclei, the situation in 194 Hg is viewed as a very lucky incidence

  4. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-08-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  5. Surgical management of bladder transitional cell carcinoma in a vesicular diverticulum: case report.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2012-02-01

    We report a case of primary transitional cell carcinoma (TCC) of a bladder diverticum along with a literature review. A 55-year-old male presented with painless gross hematuria. A histological diagnosis of TCC within a bladder diverticulum was made following cystoscopical examination. Initially transurethral resection of bladder tumour with subsequent intravesical chemotherapy followed. As a result of recurrence and in view of bladder-sparing therapy, a distal partial cystectomy was performed. This report demonstrates that conservative bladder-sparing treatment can be achieved and subsequently followed by vigilant cystoscopy.

  6. Growth of primary embryo cells in a microculture system.

    Science.gov (United States)

    Villa, Max; Pope, Sara; Conover, Joanne; Fan, Tai-Hsi

    2010-04-01

    We present optimal perfusion conditions for the growth of primary mouse embryonic fibroblasts (mEFs) and mouse embryonic stem cells (mESCs) using a microfluidic perfusion culture system. In an effort to balance nutrient renewal while ensuring the presence of cell secreted factors, we found that the optimal perfusion rate for culturing primary embryonic fibroblasts (mEFs) in our experimental setting is 10 nL/min with an average flow velocity 0.55 microm/s in the microchannel. Primary mEFs may have a greater dependence on cell secreted factors when compared to their immortalized counterpart 3T3 fibroblasts cultured under similar conditions. Both the seeding density and the perfusion rate are critical for the proliferation of primary cells. A week long cultivation of mEFs and mESCs using the microculture system exhibited similar morphology and viability to those grown in a petri dish. Both mEFs and mESCs were analyzed using fluorescence immunoassays to determine their proliferative status and protein expression. Our results demonstrate that a perfusion-based microculture environment is capable of supporting the highly proliferative status of pluripotent embryonic stem cells.

  7. Neoexpression of a functional primary cilium in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Blanche Sénicourt

    2016-05-01

    Full Text Available The Hedgehog (HH signaling pathway is involved in the maintenance of numerous cell types both during development and in the adult. Often deregulated in cancers, its involvement in colorectal cancer has come into view during the last few years, although its role remains poorly defined. In most tissues, the HH pathway is highly connected to the primary cilium (PC, an organelle that recruits functional components and regulates the HH pathway. However, normal epithelial cells of the colon display an inactive HH pathway and lack a PC. In this study, we report the presence of the PC in adenocarcinoma cells of primary colorectal tumors at all stages. Using human colorectal cancer cell lines we found a clear correlation between the presence of the PC and the expression of the final HH effector, GLI1, and provide evidence of a functional link between the two by demonstrating the recruitment of the SMO receptor to the membrane of the primary cilium. We conclude that the primary cilium directly participates in the HH pathway in colorectal cancer cells.

  8. Primary Small Cell Carcinoma of the Upper Urinary Tract

    Directory of Open Access Journals (Sweden)

    Victor Ka-Siong Kho

    2010-03-01

    Full Text Available We report a case of primary extrapulmonary small cell carcinoma of the distal ureter, with a synchronous small cell carcinoma of the ipsilateral renal pelvis. These tumors, rarely reported in the urinary tract, are locally aggressive and have a poor prognosis. A 77-year-old male bedridden patient presented with fever and chills with left side-flank pain for 3 days. Following a diagnosis of ureteral urothelial carcinoma, hand-assisted laparoscopic nephroureterectomy with bladder cuff excision was carried out. Adjuvant chemotherapy was given after pathologic report of primary small cell carcinoma of the distal ureter and a synchronous small cell carcinoma of the ipsilateral renal pelvis. After 3 cycles of combination chemotherapy, the patient died 4 months postoperatively due to sepsis.

  9. Analysis of primary cilia in directional cell migration in fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

  10. Speeding the transition: Designing a fuel-cell hypercar

    Energy Technology Data Exchange (ETDEWEB)

    Williams, B.D.; Moore, T.C.; Lovins, A.B. [Rocky Mountain Inst., Snowmass, CO (United States). Hypercar Center

    1997-12-31

    A rapid transformation now underway in automotive technology could accelerate the transition to transportation powered by fuel cells. Ultralight, advanced-composite, low-drag, hybrid-electric hypercars--using combustion engines--could be three- to fourfold more efficient and one or two orders of magnitude cleaner than today`s cars, yet equally safe, sporty, desirable, and (probably) affordable. Further, important manufacturing advantages--including low tooling and equipment costs, greater mechanical simplicity, autobody parts consolidation, shorter product cycles, and reduced assembly effort and space--permit a free-market commercialization strategy. This paper discusses a conceptual hypercar powered by a proton-exchange-membrane fuel cell (PEMFC). It outlines the implications of platform physics and component selection for the vehicle`s mass budget and performance. The high fuel-to-traction conversion efficiency of the hypercar platform could help automakers overcome the Achilles` heel of hydrogen-powered vehicles: onboard storage. Moreover, because hypercars would require significantly less tractive power, and even less fuel-cell power, they could adopt fuel cells earlier, before fuel cells` specific cost, mass, and volume have fully matured. In the meantime, commercialization in buildings can help prepare fuel cells for hypercars. The promising performance of hydrogen-fueled PEMFC hypercars suggests important opportunities in infrastructure development for direct-hydrogen vehicles.

  11. Single-cell qPCR on dispersed primary pituitary cells -an optimized protocol

    Directory of Open Access Journals (Sweden)

    Haug Trude M

    2010-11-01

    Full Text Available Abstract Background The incidence of false positives is a potential problem in single-cell PCR experiments. This paper describes an optimized protocol for single-cell qPCR measurements in primary pituitary cell cultures following patch-clamp recordings. Two different cell harvesting methods were assessed using both the GH4 prolactin producing cell line from rat, and primary cell culture from fish pituitaries. Results Harvesting whole cells followed by cell lysis and qPCR performed satisfactory on the GH4 cell line. However, harvesting of whole cells from primary pituitary cultures regularly produced false positives, probably due to RNA leakage from cells ruptured during the dispersion of the pituitary cells. To reduce RNA contamination affecting the results, we optimized the conditions by harvesting only the cytosol through a patch pipette, subsequent to electrophysiological experiments. Two important factors proved crucial for reliable harvesting. First, silanizing the patch pipette glass prevented foreign extracellular RNA from attaching to charged residues on the glass surface. Second, substituting the commonly used perforating antibiotic amphotericin B with β-escin allowed efficient cytosol harvest without loosing the giga seal. Importantly, the two harvesting protocols revealed no difference in RNA isolation efficiency. Conclusion Depending on the cell type and preparation, validation of the harvesting technique is extremely important as contaminations may give false positives. Here we present an optimized protocol allowing secure harvesting of RNA from single cells in primary pituitary cell culture following perforated whole cell patch clamp experiments.

  12. Pulp tissue from primary teeth: new source of stem cells

    Directory of Open Access Journals (Sweden)

    Paloma Dias Telles

    2011-06-01

    Full Text Available SHED (stem cells from human exfoliated deciduous teeth represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells to regenerate tooth structures and bone, and possibly to treat neural tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells and discuss tissue engineering approaches that use SHED to replace irreversibly inflamed or necrotic pulps with a healthy and functionally competent tissue that is capable of forming new dentin.

  13. Nanoscaffold's stiffness affects primary cortical cell network formation

    NARCIS (Netherlands)

    Xie, Sijia; Schurink, Bart; Wolbers, F.; Lüttge, Regina; Hassink, Gerrit Cornelis

    2014-01-01

    Networks of neurons cultured on-chip can provide insights into both normal and disease-state brain function. The ability to guide neuronal growth in specific, artificially designed patterns allows us to study how brain function follows form. Primary cortical cells cultured on nanograting scaffolds,

  14. Structure of cellulose microfibrils in primary cell walls from Collenchyma

    Czech Academy of Sciences Publication Activity Database

    Thomas, L. H.; Forsyth, V. T.; Šturcová, Adriana; Kennedy, C. J.; May, R. P.; Altaner, C. M.; Apperley, D. C.; Wess, T. J.; Jarvis, M. C.

    2013-01-01

    Roč. 161, č. 1 (2013), s. 465-476 ISSN 0032-0889 R&D Projects: GA ČR GAP108/12/0703 Institutional support: RVO:61389013 Keywords : primary cell wall * cellulose microfibril structure * chain packing disorder Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.394, year: 2013

  15. Cutaneous features seen in primary liver cell (Hepatocellular ...

    African Journals Online (AJOL)

    Primary liver cell carcinoma (PLCC), predominantly hepatocellular carcinoma is a killer. In the southwestern region of Nigeria it occupies the second position, behind prostate cancer in males. Females account for about a third of diagnosed cases. Children are not spared. Over 80 % of PLCC cases present to the hospital at ...

  16. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2010

    Science.gov (United States)

    2010-11-11

    This past year has been one of transition for the introduction of fuel cell transit buses. The existing generation of fuel cell buses from Van Hool and UTC Power has continued to operate in service at three transit agencies. At the same time, a new g...

  17. Uptake of gold nanoparticles in primary human endothelial cells

    DEFF Research Database (Denmark)

    Klingberg, Henrik; Oddershede, Lene B.; Löschner, Katrin

    2015-01-01

    Gold nanoparticles (AuNPs) are relevant in nanomedicine for drug delivery in the vascular system, where endothelial cells are the first point of contact. We investigated the uptake of 80 nm AuNPs in primary human umbilical vein endothelial cells (HUVECs) by flow cytometry, 3D confocal microscopy......–3 or more particles. Pre-treatment with chlorpromazine inhibited the AuNP-uptake in HUVECs, indicating that internalisation occurred mainly by clathrin-mediated endocytosis. Cell activation by exposure to tumour necrosis factor or lipopolysaccharide had a slight or no effect on the uptake of Au...

  18. Longevity in vivo of primary cell wall cellulose synthases.

    Science.gov (United States)

    Hill, Joseph Lee; Josephs, Cooper; Barnes, William J; Anderson, Charles T; Tien, Ming

    2018-02-01

    Our work focuses on understanding the lifetime and thus stability of the three main cellulose synthase (CESA) proteins involved in primary cell wall synthesis of Arabidopsis. It had long been thought that a major means of CESA regulation was via their rapid degradation. However, our studies here have uncovered that AtCESA proteins are not rapidly degraded. Rather, they persist for an extended time in the plant cell. Plant cellulose is synthesized by membrane-embedded cellulose synthase complexes (CSCs). The CSC is composed of cellulose synthases (CESAs), of which three distinct isozymes form the primary cell wall CSC and another set of three isozymes form the secondary cell wall CSC. We determined the stability over time of primary cell wall (PCW) CESAs in Arabidopsis thaliana seedlings, using immunoblotting after inhibiting protein synthesis with cycloheximide treatment. Our work reveals very slow turnover for the Arabidopsis PCW CESAs in vivo. Additionally, we show that the stability of all three CESAs within the PCW CSC is altered by mutations in individual CESAs, elevated temperature, and light conditions. Together, these results suggest that CESA proteins are very stable in vivo, but that their lifetimes can be modulated by intrinsic and environmental cues.

  19. Cell reprogramming modelled as transitions in a hierarchy of cell cycles

    International Nuclear Information System (INIS)

    Hannam, Ryan; Annibale, Alessia; Kühn, Reimer

    2017-01-01

    We construct a model of cell reprogramming (the conversion of fully differentiated cells to a state of pluripotency, known as induced pluripotent stem cells, or iPSCs) which builds on key elements of cell biology viz. cell cycles and cell lineages. Although reprogramming has been demonstrated experimentally, much of the underlying processes governing cell fate decisions remain unknown. This work aims to bridge this gap by modelling cell types as a set of hierarchically related dynamical attractors representing cell cycles. Stages of the cell cycle are characterised by the configuration of gene expression levels, and reprogramming corresponds to triggering transitions between such configurations. Two mechanisms were found for reprogramming in a two level hierarchy: cycle specific perturbations and a noise induced switching. The former corresponds to a directed perturbation that induces a transition into a cycle-state of a different cell type in the potency hierarchy (mainly a stem cell) whilst the latter is a priori undirected and could be induced, e.g. by a (stochastic) change in the cellular environment. These reprogramming protocols were found to be effective in large regimes of the parameter space and make specific predictions concerning reprogramming dynamics which are broadly in line with experimental findings. (paper)

  20. Transitional cell carcinoma involving the ductus deferens in a dog.

    Science.gov (United States)

    Guerin, Vincent J; 't Hooft, Krista W Visser; L'Eplattenier, Henry F; Petite, Audrey F

    2012-02-15

    A 12-year-old neutered male Springer Spaniel was referred with a 1-year history of recurring urinary tract infections. Repeated treatment with appropriate antimicrobials selected on the basis of bacterial culture and antimicrobial susceptibility results would result in clinical improvement, but recurrence of clinical signs was observed within days after discontinuation of treatment. Ultrasound examination revealed a tubular, fluid-filled structure dorsal to the bladder that extended from the midlevel of the bladder to the cranial pole of the prostate. Mineralized foci within a heterogeneous prostatic parenchyma were also noted. Dilation of the right ductus deferens (DD) was observed during exploratory laparotomy. Both DD were surgically removed, and the prostate was biopsied. The histopathological diagnosis was transitional cell carcinoma involving the right DD and the prostate. The dog was treated with meloxicam (0.1 mg/kg [0.05 mg/lb], p.o., q 24 h) for 9 months after diagnosis before being euthanized. Because the normal DD is rarely visualized during abdominal ultrasonography in dogs, identification of a tubular, fluid-filled structure dorsal to the bladder may indicate an abnormal DD. Transitional cell carcinoma of the DD should be included in the differential diagnoses of affected patients examined for clinical signs involving the urinary tract.

  1. General Information about Transitional Cell Cancer of the Renal Pelvis and Ureter

    Science.gov (United States)

    ... These cells can change shape and stretch without breaking apart. Transitional cell cancer starts in these cells. ... away. Extreme tiredness. Weight loss with no known reason. Painful or frequent urination. Tests that examine the ...

  2. Results of radiotherapy for primary subglottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Paisley, Sonya; Warde, Padraig R.; O'Sullivan, Brian; Waldron, John; Gullane, Patrick J.; Payne, David; Liu, F.-F.; Bayley, Andrew; Ringash, Jolie; Cummings, Bernard J.

    2002-01-01

    Purpose: To retrospectively evaluate the outcome after radical radiotherapy (RT) and surgical salvage and assess the risk of late toxicity for patients with primary subglottic squamous cell carcinoma treated at our center. Methods and Materials: Between 1971 and 1996, 43 patients with primary squamous cell carcinoma of the subglottis (35 men, 8 women) were treated with radical RT. All received megavoltage irradiation, most commonly to a dose of 50-52 Gy in 20 fractions during 4 weeks (39 patients). The median follow-up was 4.2 years. Results: Local control was achieved with RT alone in 24 (56%) of the 43 patients: 7 of 11 with T1, 8 of 12 with T2, 4 of 8 with T3, and 5 of 12 with T4. The 5-year actuarial local relapse-free rate was 52%. Subsequent local control was achieved in 11 of the 13 patients with failed RT and attempted surgical salvage, for an ultimate local control rate of 81.4% (35 of 43). The 5-year overall and cause-specific actuarial survival rate was 50.3% and 66.9%, respectively. No patients developed Grade 3 or 4 late radiation morbidity. Conclusion: These data support the use of primary RT in the treatment of patients with primary squamous cell carcinoma of the subglottis as an appropriate treatment approach providing an option for laryngeal conservation

  3. Cytotoxicity and accumulation of ergot alkaloids in human primary cells.

    Science.gov (United States)

    Mulac, Dennis; Humpf, Hans-Ulrich

    2011-04-11

    Ergot alkaloids are secondary metabolites produced by fungi of the species Claviceps. Toxic effects after consumption of contaminated grains are described since mediaeval times. Of the more than 40 known ergot alkaloids six are found predominantly. These are ergotamine, ergocornine, ergocryptine, ergocristine, ergosine and ergometrine, along with their corresponding isomeric forms (-inine-forms). Toxic effects are known to be induced by an interaction of the ergot alkaloids as neurotransmitters, like dopamine or serotonin. Nevertheless data concerning cytotoxic effects are missing and therefore a screening of the six main ergot alkaloids was performed in human primary cells in order to evaluate the toxic potential. As it is well known that ergot alkaloids isomerize easily the stability was tested in the cell medium. Based on these results factors were calculated to correct the used concentration values to the biologically active lysergic (-ine) form. These factors range from 1.4 for the most stable compound ergometrine to 5.0 for the most unstable ergot alkaloid ergocristine. With these factors, reflecting the instability, several controverse literature data concerning the toxicity could be explained. To evaluate the cytotoxic effects of ergot alkaloids, human cells in primary culture were used. These cells remain unchanged in contrast to cell lines and the data allow a better comparison to the in vivo situation than using immortalized cell lines. To characterize the effects on primary cells, renal proximal tubule epithelial cells (RPTEC) and normal human astrocytes (NHA) were used. The parameters necrosis (LDH-release) and apoptosis (caspase-3-activation, DNA condensation and fragmentation) were distinguished. The results show that depending on the individual structure of the peptide ergot alkaloids the toxic properties change. While ergometrine as a lysergic acid amide did not show any effect, the peptide ergot alkaloids revealed a different toxic potential. Of

  4. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P Skeletal muscle cells were...... in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P contracted, but not in the moderately contracted muscle cells...

  5. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical...... knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms....

  6. Cell surface of sea urchin micromeres and primary mesenchyme

    International Nuclear Information System (INIS)

    DeSimone, D.W.

    1985-01-01

    The cell surface and extracellular matrix (ECM) of the sea urchin embryo were studied during the early morphogenetic events involved in the differentiation of the micromere cell lineage. Sixteen-cell and early cleavage stage blastomeres were isolated and the protein composition of their cell surfaces examined by 125 I-labelling followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Micromere-specific cell surface proteins are reported for Arbacia punctulata, Strongylocentrotus droebachiensis, and Strongylocentrotus purpuratus. Cell surface glycoproteins were characterized on the basis of lectin binding specificity with a novel lectin affinity transfer technique. Using this procedure, cell-type specific surface proteins, which are also lectin-binding specific, can be detected. In addition, fluorescein conjugated lectins were microinjected into the blastocoels of living S. drobachiensis and Lytechinus pictus embryos and the patterns of lectin bindings observed by fluorescence microscopy. The evidence presented in this thesis suggests that the differentiation of the primary mesenchyme cells is correlated with changes in the molecular composition of the cell-surface and the ECM

  7. Radiation Gene-expression Signatures in Primary Breast Cancer Cells.

    Science.gov (United States)

    Minafra, Luigi; Bravatà, Valentina; Cammarata, Francesco P; Russo, Giorgio; Gilardi, Maria C; Forte, Giusi I

    2018-05-01

    In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene expression profiling (GEP) in primary BC cells following irradiation with doses of 9 Gy and 23 Gy delivered by intraoperative electron radiation therapy (IOERT) in order to define gene signatures of response to high doses of ionizing radiation. We performed GEP by cDNA microarrays and evaluated cell survival after IOERT treatment in primary BC cell cultures. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate candidate genes. We showed, for the first time, a 4-gene and a 6-gene signature, as new molecular biomarkers, in two primary BC cell cultures after exposure at 9 Gy and 23 Gy respectively, for which we observed a significantly high survival rate. Gene signatures activated by different doses of ionizing radiation may predict response to RT and contribute to defining a personalized biological-driven treatment plan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Imprint lithography provides topographical nanocues to guide cell growth in primary cortical cell culture

    NARCIS (Netherlands)

    Xie, S.; Luttge, R.

    2014-01-01

    In this paper, we describe a technology platform to study the effect of nanocues on the cell growth direction in primary cortical cell culture. Topographical cues to cells are provided using nanoscale features created by Jet and Flash Imprint Lithography, coated with polyethylenimine. We

  9. Primary tonsillar mast cell tumour in a dog.

    Science.gov (United States)

    Shekell, C C; Thomson, M J; Miller, R I; Mackie, J T

    2018-05-01

    A 6-year-old speyed female Bull Arab-cross dog was found to have a small tonsillar nodule. Histological examination revealed a well-differentiated mast cell tumour (MCT). At initial staging, no evidence of concurrent cutaneous or visceral MCTs was found on a complete blood count, a single lateral thoracic radiograph, abdominal ultrasound or cytology of the spleen and regional lymph nodes. A diagnosis of primary tonsillar MCT was made. At 40 months postoperatively, the dog is alive with no evidence of gross tumour progression, in contrast to some previous reports of rapid disease progression and metastasis in dogs with primary oral MCTs. To the authors' knowledge, no previous reports of a primary MCT of the tonsil in dogs exist in the veterinary literature. © 2018 Australian Veterinary Association.

  10. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  11. Different Chondrogenic Potential among Human Induced Pluripotent Stem Cells from Diverse Origin Primary Cells

    Directory of Open Access Journals (Sweden)

    Yeri Alice Rim

    2018-01-01

    Full Text Available Scientists have tried to reprogram various origins of primary cells into human induced pluripotent stem cells (hiPSCs. Every somatic cell can theoretically become a hiPSC and give rise to targeted cells of the human body. However, there have been debates on the controversy about the differentiation propensity according to the origin of primary cells. We reprogrammed hiPSCs from four different types of primary cells such as dermal fibroblasts (DF, n=3, peripheral blood mononuclear cells (PBMC, n=3, cord blood mononuclear cells (CBMC, n=3, and osteoarthritis fibroblast-like synoviocytes (OAFLS, n=3. Established hiPSCs were differentiated into chondrogenic pellets. All told, cartilage-specific markers tended to express more by the order of CBMC > DF > PBMC > FLS. Origin of primary cells may influence the reprogramming and differentiation thereafter. In the context of chondrogenic propensity, CBMC-derived hiPSCs can be a fairly good candidate cell source for cartilage regeneration. The differentiation of hiPSCs into chondrocytes may help develop “cartilage in a dish” in the future. Also, the ideal cell source of hiPSC for chondrogenesis may contribute to future application as well.

  12. Transitional cell carcinomas in four fishing cats (Prionailurus viverrinus).

    Science.gov (United States)

    Sutherland-Smith, Meg; Harvey, Catherine; Campbell, Mark; McAloose, Denise; Rideout, Bruce; Morris, Patrick

    2004-09-01

    Transitional cell carcinomas (TCC) of the urinary bladder were diagnosed in four related fishing cats (Prionailurus viverrinus). The major clinical sign in each case was persistent hematuria unresponsive to medical therapy. Cystotomy and biopsy provided an antemortem diagnosis in three of the fishing cats before euthanasia because of progression of clinical signs. The diagnosis was made in the fourth cat after euthanasia because of renal failure. Hematuria improved temporarily in one of the cats diagnosed antemortem and treated with piroxicam and carboplatin. Attempts to isolate a herpesvirus in two of the cats failed. Histopathologic appearance of the TCC was similar to that described for other species. TCC metastasis to the lungs was noted at necropsy in one cat; metastatic disease was not noted in the other fishing cats on gross or histopathologic examination. TCC of the urinary bladder appears to be more prevalent in fishing cats than in other species of domestic or nondomestic felids.

  13. Renal transitional cell carcinoma: a sonographic and radiological correlation

    International Nuclear Information System (INIS)

    Prando, A.; Marins, J.L.C.; Prando, D.; Pereira, R.M.

    1984-01-01

    A sonographic study was performed on nine patients with renal transitional cell carcinoma and the findings correlated with those of excretory urography, retrograde and/or antegrade pyelography. In six patients the correct diagnosis was considered mainly by the radiological features. In the remaining three patients, due to its unusual manifestations, this diagnosis was accomplished only by sonography. A small echogenic mass at the peryphery of a chronic hydronephrotic kidney, a huge complex mass due to a multiple arborescent papilary tumor and a demonstration of a mass in a presumptive renal pelvic inflammatory disease, respectively, represented these uncommon aspects. The spectrum of features of this entity and the related differential diagnosis are also presented. (Author) [pt

  14. Developmental dynamics between mathematical performance, task motivation, and teachers' goals during the transition to primary school.

    Science.gov (United States)

    Aunola, Kaisa; Leskinen, Esko; Nurmi, Jari-Erik

    2006-03-01

    It has been suggested that children's learning motivation and interest in a particular subject play an important role in their school performance, particularly in mathematics. However, few cross-lagged longitudinal studies have been carried out to investigate the prospective relationships between academic achievement and task motivation. Moreover, the role that the classroom context plays in this development is largely unknown. The aim of the study was to investigate the developmental dynamics of maths-related motivation and mathematical performance during children's transition to primary school. The role of teachers' pedagogical goals and classroom characteristics on this development was also investigated. A total of 196 Finnish children were examined four times: (0) in October during their preschool year; (1) in October and (2) April during their first grade of primary school; and (3) in October during their second grade. Children's mathematical performance was tested at each measurement point. Task motivation was examined at measurement points 2, 3, and 4 using the Task-value scale for children. First-grade teachers were interviewed in November about their pedagogical goals and classroom characteristics. The results showed that children's mathematical performance and related task motivation formed a cumulative developmental cycle: a high level of maths performance at the beginning of the first grade increased subsequent task motivation towards mathematics, which further predicted a high level of maths performance at the beginning of the second grade. The level of maths-related task motivation increased in those classrooms where the teachers emphasized motivation or self-concept development as their most important pedagogical goal.

  15. Examining the Role of Primary Care Physicians and Challenges Faced When Their Patients Transition to Home Hospice Care.

    Science.gov (United States)

    Shalev, Ariel; Phongtankuel, Veerawat; Lampa, Katherine; Reid, M C; Eiss, Brian M; Bhatia, Sonica; Adelman, Ronald D

    2018-04-01

    The transition into home hospice care is often a critical time in a patient's medical care. Studies have shown patients and caregivers desire continuity with their physicians at the end of life (EoL). However, it is unclear what roles primary care physicians (PCPs) play and what challenges they face caring for patients transitioning into home hospice care. To understand PCPs' experiences, challenges, and preferences when their patients transition to home hospice care. Nineteen semi-structured phone interviews with PCPs were conducted. Study data were analyzed using standard qualitative methods. Participants included PCPs from 3 academic group practices in New York City. Measured: Physician recordings were transcribed and analyzed using content analysis. Most PCPs noted that there was a discrepancy between their actual role and ideal role when their patients transitioned to home hospice care. Primary care physicians expressed a desire to maintain continuity, provide psychosocial support, and collaborate actively with the hospice team. Better establishment of roles, more frequent communication with the hospice team, and use of technology to communicate with patients were mentioned as possible ways to help PCPs achieve their ideal role caring for their patients receiving home hospice care. Primary care physicians expressed varying degrees of involvement during a patient's transition to home hospice care, but many desired to be more involved in their patient's care. As with patients, physicians desire to maintain continuity with their patients at the EoL and solutions to improve communication between PCPs, hospice providers, and patients need to be explored.

  16. Language, Culture and Identity in the Transition to Primary School: Challenges to Indigenous Children's Rights to Education in Peru

    Science.gov (United States)

    Ames, Patricia

    2012-01-01

    This paper analyses a "critical moment" in the educational trajectories of young indigenous children in Peru: the transition to primary school. It addresses the inequalities in educational services that affect indigenous children, before looking at the micro-level processes that take place in school settings, through a focus on two…

  17. The Social and Emotional Functioning of Students with an Autistic Spectrum Disorder during the Transition between Primary and Secondary Schools

    Science.gov (United States)

    Fortuna, Ron

    2014-01-01

    The transition from the primary to the secondary phase in education can be a pivotal moment for many students, but for students who have autism, their difficulties with socialisation and emotional regulation can make this time period especially challenging. This article explores the experiences of key stakeholders regarding the issue of students…

  18. Measuring mechanisms for quality assurance in primary care systems in transition: test of a new instrument in Slovenia and Uzbekistan.

    NARCIS (Netherlands)

    Kringos, D.S.; Boerma, W.G.W.; Pellny, M.

    2009-01-01

    Aim: This WHO study, carried out by the authors, aimed to develop and field test an instrument to assess the availability of structures and mechanisms for managing quality in primary care in countries in transition. Methods: The instrument is based on a literature study, consensus meetings with

  19. Teaching Economics with Spanish Primary School Textbooks during the Franco Dictatorship and the Transition to Democracy (1962-1982)

    Science.gov (United States)

    Angulo, Kira Mahamud; Hernández Laina, Yovana

    2017-01-01

    In this article we analyze knowledge about economics conveyed via primary school textbooks published during the late Franco dictatorship and the years of transition to democracy in Spain. Starting from the premise that the process of political socialization and identity construction is based partly on economic factors, we examine the evolution of…

  20. Evaluation of high-energy lithium thionyl chloride primary cells

    Science.gov (United States)

    Frank, H. A.

    1980-02-01

    An advanced commercial primary lithium cell (LiSoCl2) was evaluated in order to establish baseline data for improved lithium batteries for aerospace applications. The cell tested had nominal capacity of 6 Ah. Maximum energy density at low rates (less than C/30, where C is the cell capacity in amp-hrs and 30 corresponds to a 30 hr discharge time) was found to be near 300 Wh/kg. An equation which predicts the operating voltage of these cells as a function of current and state of charge is presented. Heat generation rates of these cells were determined as a function of current in a calorimeter. It was found that heat rates could be theoretically predicted with some degree of accuracy at currents less than 1 amp or the C/6 rate. No explosions were observed in the cells during the condition of overdischarge or reversal nor during high rate discharge. It was found, however, that the cells can vent when overdischarge currents are greater than C/30 and when discharge rates are greater than 1.5C.

  1. Graphene Films Show Stable Cell Attachment and Biocompatibility with Electrogenic Primary Cardiac Cells

    OpenAIRE

    Kim, Taeyong; Kahng, Yung Ho; Lee, Takhee; Lee, Kwanghee; Kim, Do Han

    2013-01-01

    Graphene has attracted substantial attention due to its advantageous materialistic applicability. In the present study, we tested the biocompatibility of graphene films synthesized by chemical vapor deposition with electrogenic primary adult cardiac cells (cardiomyocytes) by measuring the cell properties such as cell attachment, survival, contractility and calcium transients. The results show that the graphene films showed stable cell attachment and excellent biocompatibility with the electro...

  2. Application of liquid chromatography techniques to the measurement of soluble transition metals in PWR primary coolant

    International Nuclear Information System (INIS)

    Amey, M.D.H.; Brown, G.R.

    1987-01-01

    Two chromatographic techniques have been developed, and evaluated for the on-line analysis of soluble transition metals, particularly cobalt, in PWR primary coolant. Automatic operation and control, together with data processing and storage has been achieved by interfacing a Dionex ion chromatograph to a microprocessor control system. An absolute detection limit of 0.1 ng cobalt has been obtained which, with on-line sample preconcentration (100 ml), has enabled measurements to be made down to part-per-trillion levels (0.001 ppb). Application of the techniques to PWR coolant analysis was demonstrated by a programme of work on the Half Megawatt Loop at Winfrith. During this work some aspects of the behaviour of soluble metal species have been studied in both de-oxygenated and hydrogenated conditions. The effects of changes in coolant chemistry, operating temperature, and sample line flowrates on circulating impurity levels are reported, together with the dramatic effects observed when part of the circuit pipework was replaced with new stainless steel tubing. (author)

  3. Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact

    Directory of Open Access Journals (Sweden)

    Hidehiko Takigawa

    2017-05-01

    Full Text Available We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow–derived mesenchymal stem cells (MSCs migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important. We performed a microarray analysis of gene expression in KM12SM colon cancer cells directly cocultured with MSCs. Expression of epithelial-mesenchymal transition (EMT–related genes such as fibronectin (FN, SPARC, and galectin 1 was increased by direct coculture with MSCs. We also confirmed the upregulation of these genes with real-time polymerase chain reaction. Gene expression was not elevated in cancer cells indirectly cocultured with MSCs. Among the EMT-related genes upregulated by direct coculture with MSCs, we examined the immune localization of FN, a well-known EMT marker. In coculture assay in chamber slides, expression of FN was seen only at the edges of cancer clusters where cancer cells directly contacted MSCs. FN expression in cancer cells increased at the tumor periphery and invasive edge in orthotopic nude mouse tumors and human colon cancer tissues. These results suggest that MSCs induce EMT in colon cancer cells via direct cell-to-cell contact and may play an important role in colon cancer metastasis.

  4. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  5. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

    DEFF Research Database (Denmark)

    Fornara, O; Bartek, J; Rahbar, A

    2016-01-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

  6. Cell longevity and sustained primary growth in palm stems.

    Science.gov (United States)

    Tomlinson, P Barry; Huggett, Brett A

    2012-12-01

    Longevity, or organismal life span, is determined largely by the period over which constituent cells can function metabolically. Plants, with modular organization (the ability continually to develop new organs and tissues) differ from animals, with unitary organization (a fixed body plan), and this difference is reflected in their respective life spans, potentially much longer in plants than animals. We draw attention to the observation that palm trees, as a group of monocotyledons without secondary growth comparable to that of lignophytes (plants with secondary growth from a bifacial cambium), retain by means of sustained primary growth living cells in their trunks throughout their organismal life span. Does this make palms the longest-lived trees because they can grow as individuals for several centuries? No conventional lignophyte retains living metabolically active differentiated cell types in its trunk for this length of time, even though the tree as a whole can exist for millennia. Does this contrast also imply that the long-lived cells in a palm trunk have exceptional properties, which allows this seeming immortality? We document the long-life of many tall palm species and their inherent long-lived stem cell properties, comparing such plants to conventional trees. We provide a summary of aspects of cell age and life span in animals and plants. Cell replacement is a feature of animal function, whereas conventional trees rely on active growth centers (meristems) to sustain organismal development. However, the long persistence of living cells in palm trunks is seen not as evidence for unique metabolic processes that sustain longevity, but is a consequence of unique constructional features. This conclusion suggests that the life span of plant cells is not necessarily genetically determined.

  7. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2011

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.; Gikakis, C.

    2011-11-01

    This status report, fifth in a series of annual status reports from the U.S. Department of Energy's National Renewable Energy Laboratory (NREL), discusses the achievements and challenges of fuel cell propulsion for transit and summarizes the introduction of fuel cell transit buses in the United States. Progress this year includes an increase in the number of fuel cell electric buses (FCEBs), from 15 to 25, operating at eight transit agencies, as well as increased diversity of the fuel cell design options for transit buses. The report also provides an analysis of the combined results from fuel cell transit bus demonstrations evaluated by NREL with a focus on the most recent data through July 2011 including fuel cell power system reliability and durability; fuel economy; roadcall; and hydrogen fueling results. These evaluations cover 22 of the 25 FCEBs currently operating.

  8. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-01-01

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti

  9. Fuel Cell Buses in U.S. Transit Fleets : Current Status 2014

    Science.gov (United States)

    2014-12-03

    This report, published annually, summarizes the progress of fuel cell electric bus (FCEB) development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. Various stakeholders, including d...

  10. Fuel Cell Buses in U.S. Transit Fleets : Current Status 2015

    Science.gov (United States)

    2015-12-01

    This report, published annually, summarizes the progress of fuel cell electric bus (FCEB) development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. The report provides a summary of ...

  11. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2017

    Science.gov (United States)

    2017-11-01

    This report, published annually, summarizes the progress of fuel cell electric bus (FCEB) development in the United States and discusses the achievements and challenges of introducing fuel cell propulsion in transit. The report provides a summary of ...

  12. Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model

    International Nuclear Information System (INIS)

    Ke, Xi-song; Li, Wen-cheng; Hovland, Randi; Qu, Yi; Liu, Run-hui; McCormack, Emmet; Thorsen, Frits; Olsen, Jan Roger; Molven, Anders; Kogan-Sakin, Ira; Rotter, Varda; Akslen, Lars A.; Oyan, Anne Margrete; Kalland, Karl-Henning

    2011-01-01

    Epithelial to mesenchymal transition (EMT) is pivotal in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to cells with mesenchymal phenotype (EPT1) without malignant transformation. To promote prostate cell transformation, cells were maintained in saturation density cultures to select for cells overriding quiescence. Foci formed repeatedly following around 8 weeks in confluent EPT1 monolayers. Only later passage EPT1, but not EP156T cells of any passage, could form foci. Cells isolated from the foci were named EPT2 and formed robust colonies in soft agar, a malignant feature present neither in EP156T nor in EPT1 cells. EPT2 cells showed additional malignant traits in vitro, including higher ability to proliferate following confluence, higher resistance to apoptosis and lower dependence on exogenous growth factors than EP156T and EPT1 cells. Microarray profiling identified gene sets, many of which belong to cell junction modules, that changed expression from EP156T to EPT1 cells and continued to change from EPT1 to EPT2 cells. Our findings provide a novel stepwise cell culture model in which EMT emerges independently of transformation and is associated with subsequent accumulation of malignant features in prostate cells. Reprogramming of cell junction modules is involved in both steps.

  13. Primary desmoplastic small round cell tumor of the femur

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Akihiko; Garcia, Joaquin [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Edgar, Mark A. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Meyers, Paul A. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Morris, Carol D. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Surgery, Orthopaedic Service, New York, NY (United States); Panicek, David M. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2008-09-15

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  14. [Primary cutaneous B-cell lymphomas: study of 22 cases].

    Science.gov (United States)

    Martín Carrasco, Pablo; Morillo Andújar, Mercedes; Pérez Ruiz, Carmen; de Zulueta Dorado, Teresa; Cabrera Pérez, Rocío; Conejo-Mir, Julián

    2016-09-02

    Primary cutaneous B-cell lymphoma (CBCL) is a very low prevalence neoplasm and constitutes 25% of all primary cutaneous lymphomas. Our objective was to discover the epidemiological, clinic and histologic characteristics of CBCL in our area. Retrospective descriptive study with patients with histologic diagnosis of CBCL followed up in our department between 2004 and 2015. Twenty-two patients with CBCL were included; 65% were men and 35% were women. Follicle centre lymphoma was the most common subtype (41%). Only 3 cases presented with node involvement and one with bone marrow invasion. Five recurrences were detected and one patient died because of the CBCL. This is one of the first CBCL series in theSpanish population. The incidence, sex, age, subtype distribution, clinical features and immunohistochemical patterns are very similar to those of the other series. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  15. Primary desmoplastic small round cell tumor of the femur

    International Nuclear Information System (INIS)

    Yoshida, Akihiko; Garcia, Joaquin; Edgar, Mark A.; Meyers, Paul A.; Morris, Carol D.; Panicek, David M.

    2008-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  16. Experience of combined cisplatin and radiation therapy for advanced urinary tract transitional cell carcinoma

    International Nuclear Information System (INIS)

    Yoshioka, Toshiaki; Utsunomiya, Masato; Itoh, Hiroshi; Itatani, Hiroaki; Namiki, Mikio.

    1987-01-01

    Since March, 1981, 13 patients with locally advanced transitional cell carcinoma were treated by combined cisdiamminedichloroplatinum (cisplatin) and full dose radiotherapy. They were 10 men and 3 women. The patient ages ranged from 42 to 79 years, with a median of 59.5 years. The primary sites of transitional cell carcinoma were bladder in 5, ureter in 6, renal pelvis in 1 and prostate in 1. Radiotherapy consisted of a mean tumor dose of 48.7 gray, with a range of 40 to 66.4 gray, was administered with cobalt 60. Cisplatin was infused 5 days a week with a daily dose of 20 to 30 mg. 4 patients recieved 2 courses of cisplatin infusion and others 1 or less. Of the 4 evaluable patients 3 (75 %) achieved a complete response. Toxicity was evaluated for the 13 patients. Mainly gastrointestinal toxicity was noted: appetite loss in 9 (69.2 %), nausea and/or vomiting in 5 (38.5 %) and diarrhea in 5 (38.5 %). Leukocytopenia was noted in 7 patients (53.9 %), but in no one leukocyte count was less than 2000/mm 3 . Mild thrombocytopenia was noted only in 3 patients (23.1 %). All of these toxicities were mild, and the patients recovered soon after the therapy. Herein it is discussed about future problems such as solution of interaction mechanism, detection of practical dose and administering method of cisplatin and radiation. (author)

  17. Mesenchymal stem cells promote cell invasion and migration and autophagy-induced epithelial-mesenchymal transition in A549 lung adenocarcinoma cells.

    Science.gov (United States)

    Luo, Dan; Hu, Shiyuan; Tang, Chunlan; Liu, Guoxiang

    2018-03-01

    Mesenchymal stem cells (MSCs) are recruited into the tumour microenvironment and promote tumour growth and metastasis. Tumour microenvironment-induced autophagy is considered to suppress primary tumour formation by impairing migration and invasion. Whether these recruited MSCs regulate tumour autophagy and whether autophagy affects tumour growth are controversial. Our data showed that MSCs promote autophagy activation, reactive oxygen species production, and epithelial-mesenchymal transition (EMT) as well as increased migration and invasion in A549 cells. Decreased expression of E-cadherin and increased expression of vimentin and Snail were observed in A549 cells cocultured with MSCs. Conversely, MSC coculture-mediated autophagy positively promoted tumour EMT. Autophagy inhibition suppressed MSC coculture-mediated EMT and reduced A549 cell migration and invasion slightly. Furthermore, the migratory and invasive abilities of A549 cells were additional increased when autophagy was further enhanced by rapamycin treatment. Taken together, this work suggests that microenvironments containing MSCs can promote autophagy activation for enhancing EMT; MSCs also increase the migratory and invasive abilities of A549 lung adenocarcinoma cells. Mesenchymal stem cell-containing microenvironments and MSC-induced autophagy signalling may be potential targets for blocking lung cancer cell migration and invasion. Copyright © 2018 John Wiley & Sons, Ltd.

  18. TRANSIT

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. TRANSIT. SYSTEM: DETERMINE 2D-POSITION GLOBALLY BUT INTERMITTENT (POST-FACTO). IMPROVED ACCURACY. PRINCIPLE: POLAR SATELLITES WITH INNOVATIONS OF: GRAVITY-GRADIENT ATTITUDE CONTROL; DRAG COMPENSATION. WORKS ...

  19. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2013

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gikakis, Christina [Federal Transit Administration, Washington, DC (United States)

    2013-12-01

    This report is the seventh in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results from August 2012 through July 2013 for five FCEB demonstrations at four transit agencies.

  20. A novel derivative of doxorubicin, AD198, inhibits canine transitional cell carcinoma and osteosarcoma cells in vitro.

    Science.gov (United States)

    Rathore, Kusum; Cekanova, Maria

    2015-01-01

    Doxorubicin (DOX) is one of the most commonly used chemotherapeutic treatments for a wide range of cancers. N-benzyladriamycin-14-valerate (AD198) is a lipophilic anthracycline that has been shown to target conventional and novel isoforms of protein kinase C (PKC) in cytoplasm of cells. Because of the adverse effects of DOX, including hair loss, nausea, vomiting, liver dysfunction, and cardiotoxicity, novel derivatives of DOX have been synthesized and validated. In this study, we evaluated the effects of DOX and its derivative, AD198, on cell viability of three canine transitional cell carcinoma (K9TCC) (K9TCC#1-Lillie, K9TCC#2-Dakota, K9TCC#4-Molly) and three canine osteosarcoma (K9OSA) (K9OSA#1-Zoe, K9OSA#2-Nashville, K9OSA#3-JJ) primary cancer cell lines. DOX and AD198 significantly inhibited cell proliferation in all tested K9TCC and K9OSA cell lines in a dose-dependent manner. AD198 inhibited cell viability of tested K9TCC and K9OSA cell lines more efficiently as compared to DOX at the same concentration using MTS (3-(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2h-tetrazolium) assay. AD198 had lower IC50 values as compared to DOX for all tested K9TCC and K9OSA cell lines. In addition, AD198 increased apoptosis in all tested K9TCC and K9OSA cell lines. AD198 increased the caspase activity in tested K9TCC and K9OSA cell lines, which was confirmed by caspase-3/7 assay, and cleavage of poly (ADP-ribose) polymerase (PARP) was confirmed by Western blotting analysis. In addition, AD198 cleaved PKC-δ, which subsequently activated the p38 signaling pathway, resulting in the apoptosis of tested K9TCC and K9OSA cell lines. Inhibition of the p38 signaling pathway by SB203580 rescued DOX- and AD198-induced apoptosis in tested K9TCC and K9OSA cell lines. Our in vitro results suggest that AD198 might be considered as a new treatment option for K9TCC and K9OSA cell lines cancers in vivo.

  1. A novel derivative of doxorubicin, AD198, inhibits canine transitional cell carcinoma and osteosarcoma cells in vitro

    Directory of Open Access Journals (Sweden)

    Rathore K

    2015-09-01

    Full Text Available Kusum Rathore, Maria Cekanova Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Doxorubicin (DOX is one of the most commonly used chemotherapeutic treatments for a wide range of cancers. N-benzyladriamycin-14-valerate (AD198 is a lipophilic anthracycline that has been shown to target conventional and novel isoforms of protein kinase C (PKC in cytoplasm of cells. Because of the adverse effects of DOX, including hair loss, nausea, vomiting, liver dysfunction, and cardiotoxicity, novel derivatives of DOX have been synthesized and validated. In this study, we evaluated the effects of DOX and its derivative, AD198, on cell viability of three canine transitional cell carcinoma (K9TCC (K9TCC#1-Lillie, K9TCC#2-Dakota, K9TCC#4-Molly and three canine osteosarcoma (K9OSA (K9OSA#1-Zoe, K9OSA#2-Nashville, K9OSA#3-JJ primary cancer cell lines. DOX and AD198 significantly inhibited cell proliferation in all tested K9TCC and K9OSA cell lines in a dose-dependent manner. AD198 inhibited cell viability of tested K9TCC and K9OSA cell lines more efficiently as compared to DOX at the same concentration using MTS (3-(4,5-dimethyl-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2h-tetrazolium assay. AD198 had lower IC50 values as compared to DOX for all tested K9TCC and K9OSA cell lines. In addition, AD198 increased apoptosis in all tested K9TCC and K9OSA cell lines. AD198 increased the caspase activity in tested K9TCC and K9OSA cell lines, which was confirmed by caspase-3/7 assay, and cleavage of poly (ADP-ribose polymerase (PARP was confirmed by Western blotting analysis. In addition, AD198 cleaved PKC-δ, which subsequently activated the p38 signaling pathway, resulting in the apoptosis of tested K9TCC and K9OSA cell lines. Inhibition of the p38 signaling pathway by SB203580 rescued DOX- and AD198-induced apoptosis in tested K9TCC and K9OSA cell lines. Our in vitro results suggest

  2. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  3. Tumor necrosis factor (cachetin) decreases adipose cell differentiation in primary cell culture

    International Nuclear Information System (INIS)

    Martin, R.J.; Jones, D.D.; Jewell, D.E.; Hausman, G.J.

    1986-01-01

    Cachetin has been shown to effect gene product expression in the established adipose cell line 3T3-L1. Expression of messenger RNA for lipoprotein lipase is suppressed in cultured adipocytes. The purpose of this study was to determine the effect of Cachetin on adipose cell differentiation in primary cell culture. Stromalvascular cells obtained from the inguinal fat pad of 4-5 week old Sprague-Dawley rats were grown in culture for two weeks. During the proliferative growth phase all cells were grown on the same medium and labelled with 3 H-thymidine. Cachetin treatment (10 -6 to 10 -10 M) was initiated on day 5, the initial phase of preadipocyte differentiation. Adipocytes and stromal cells were separated using density gradient, and 3 H-thymidine was determined for both cell types. Thymidine incorporation into adipose cells was decreased maximally (∼ 50%) at 10 -10 M. Stromalvascular cells were not influenced at any of the doses tested. Adipose cell lipid content as indicated by oil red-O staining was decreased by Cachetin. Esterase staining by adipose cells treated with Cachetin was increased indicating an increase in intracellular lipase. These studies show that Cachetin has specific effects on primary adipose cell differentiation

  4. CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Michela Lupia

    2018-04-01

    Full Text Available Summary: Cancer-initiating cells (CICs have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC, CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5′-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. : Cavallaro et al. characterized the transcriptome of OCIC-enriched primary cultures and found CD73 as an upregulated gene. CD73 was then shown to regulate the expression of stemness and EMT-associated genes. The expression and function of CD73 in OCICs is required for tumor initiation, and CD73-targeted drugs decrease the rate of tumor take and inhibit cancer growth. Keywords: CD73, ovarian cancer, cancer-initiating cells, cancer stem cells, EMT, adenosine

  5. Transition from an asylum seeker–specific health service to mainstream primary care for community-based asylum seekers: a qualitative interview study

    OpenAIRE

    Genevieve L Fair; Mark F Harris; Mitchell M Smith

    2018-01-01

    Background and aim: Transition of asylum seekers from special-purpose health services to mainstream primary care is both necessary and difficult. This study explores the issues encountered by asylum seekers undergoing this transition in Sydney, Australia. Methods: Qualitative semistructured interviews were conducted with nine asylum seeker patients and nine staff working in the sector. Results: Asylum seekers faced significant challenges in the transition to mainstream primary care. C...

  6. Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma

    International Nuclear Information System (INIS)

    Wersaell, Peter J.; Blomgren, Henric; Lax, Ingmar; Kaelkner, Karl-Mikael; Linder, Christina; Lundell, Goeran; Nilsson, Bo; Nilsson, Sten; Naeslund, Ingemar; Pisa, Pavel; Svedman, Christer

    2005-01-01

    Background and purpose: We investigated the results of using stereotactic radiotherapy (SRT) for 58 patients with renal cell carcinomas (RCC) who were evaluated restrospectively for response rates, local control rates and side effects. Patients and methods: From October 1997 to January 2003, 50 patients suffering from metastatic RCC and eight patients with inoperable primary RCC received high-dose fraction SRT while placed in a stereotactic body-frame. The most common dose/fractionation schedules used were 8 Gyx4, 10 Gyx4 and 15 Gyx3 during approximately 1 week. Results: SRT-treated tumor lesions regressed totally in 30% of the patients at 3-36 months, whereas 60% of the patients had a partial volume reduction or no change after a median follow-up of 37 months (SD 17.4) for censored and 13 months (SD 12.9) for uncensored patients. Side effects were generally mild. Of 162 treated tumors, only three recurred, yielding a local control rate of 90-98%, considering the 8% non-evaluable sites as defined here. For patients with one to three metastases, the time to new spread was 9 months. Conclusions: Our use of SRT for patients with primary and metastatic RCC yielded a high local control rate with low toxicity. Patients with one to three metastases, local recurrences after nephrectomy or inoperable primary tumors benefited the most, i.e. had fewer distant recurrences (13/23) and longer survival times compared to patients with >3 metastases (24/27 recurrences)

  7. Transition from early intervention program to primary school in children with autism spectrum disorder.

    Science.gov (United States)

    Eapen, Valsamma; Grove, Rachel; Aylward, Elizabeth; Joosten, Annette V; Miller, Scott I; Van Der Watt, Gerdamari; Fordyce, Kathryn; Dissanayake, Cheryl; Maya, Jacqueline; Tucker, Madonna; DeBlasio, Antonia

    2017-11-08

    To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism. Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child's school adjustment. The relationship between child characteristics and school outcomes was evaluated. Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement. Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential.

  8. Effect of cell phone-like electromagnetic radiation on primary human thyroid cells.

    Science.gov (United States)

    Silva, Veronica; Hilly, Ohad; Strenov, Yulia; Tzabari, Cochava; Hauptman, Yirmi; Feinmesser, Raphael

    2016-01-01

    To evaluate the potential carcinogenic effects of radiofrequency energy (RFE) emitted by cell phones on human thyroid primary cells. Primary thyroid cell culture was prepared from normal thyroid tissue obtained from patients who underwent surgery at our department. Subconfluent thyroid cells were irradiated under different conditions inside a cell incubator using a device that simulates cell phone-RFE. Proliferation of control and irradiated cells was assessed by the immunohistochemical staining of antigen Kiel clone-67 (Ki-67) and tumor suppressor p53 (p53) expression. DNA ploidy and the stress biomarkers heat shock protein 70 (HSP70) and reactive oxygen species (ROS) was evaluated by fluorescence-activated cell sorting (FACS). Our cells highly expressed thyroglobulin (Tg) and sodium-iodide symporter (NIS) confirming the origin of the tissue. None of the irradiation conditions evaluated here had an effect neither on the proliferation marker Ki-67 nor on p53 expression. DNA ploidy was also not affected by RFE, as well as the expression of the biomarkers HSP70 and ROS. Our conditions of RFE exposure seem to have no potential carcinogenic effect on human thyroid cells. Moreover, common biomarkers usually associated to environmental stress also remained unchanged. We failed to find an association between cell phone-RFE and thyroid cancer. Additional studies are recommended.

  9. Transition zone cells reach G2 phase before initiating elongation in maize root apex

    Directory of Open Access Journals (Sweden)

    M. Victoria Alarcón

    2017-06-01

    Full Text Available Root elongation requires cell divisions in the meristematic zone and cell elongation in the elongation zone. The boundary between dividing and elongating cells is called the transition zone. In the meristem zone, initial cells are continuously dividing, but on the basal side of the meristem cells exit the meristem through the transition zone and enter in the elongation zone, where they stop division and rapidly elongate. Throughout this journey cells are accompanied by changes in cell cycle progression. Flow cytometry analysis showed that meristematic cells are in cycle, but exit when they enter the elongation zone. In addition, the percentage of cells in G2 phase (4C strongly increased from the meristem to the elongation zone. However, we did not observe remarkable changes in the percentage of cells in cell cycle phases along the entire elongation zone. These results suggest that meristematic cells in maize root apex stop the cell cycle in G2 phase after leaving the meristem.

  10. Integrated Transcriptomic and Epigenomic Analysis of Primary Human Lung Epithelial Cell Differentiation

    Science.gov (United States)

    Marconett, Crystal N.; Zhou, Beiyun; Rieger, Megan E.; Selamat, Suhaida A.; Dubourd, Mickael; Fang, Xiaohui; Lynch, Sean K.; Stueve, Theresa Ryan; Siegmund, Kimberly D.; Berman, Benjamin P.

    2013-01-01

    Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation. PMID:23818859

  11. Management of primary malignant germ cell tumor of the mediastinum

    International Nuclear Information System (INIS)

    Sakurai, Hiroyuki; Asamura, Hisao; Suzuki, Kenji; Watanabe, Shun-ichi; Tsuchiya, Ryosuke

    2004-01-01

    Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear. Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile. Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had nonseminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%. Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine

  12. Simultaneous Expression of Cancer Stem Cell-Like Properties and Cancer-Associated Fibroblast-Like Properties in a Primary Culture of Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Mami; Inoue, Takahiro; Shirai, Takuma; Takamatsu, Kazuhiko; Kunihiro, Shiori; Ishii, Hirokazu [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Nishikata, Takahito, E-mail: nisikata@konan-u.ac.jp [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Kobe 650-0047 (Japan)

    2014-07-31

    The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs.

  13. Sickle cell children traveling abroad: primary risk is infection.

    Science.gov (United States)

    Runel-Belliard, Camille; Lesprit, Emmanuelle; Quinet, Béatrice; Grimprel, Emmanuel

    2009-01-01

    Pediatricians taking care of sickle cell children in France are concerned about giving travel advice. Very few articles are published and no study has been done about it. A lot of pediatricians are using their own experience to decide if sickle cell children can travel abroad. Studying the consequences of such travel for sickle cell children is important to discuss common recommendations. We conducted a prospective study from June 2006 to December 2007 on desires to travel expressed during our consultations with sickle cell children. We studied notable events that occurred during travel and at least 2 months after return. Of 52 desires to travel, 10 were cancelled. All of the 42 trips were to Africa. Median duration of travel was 1.29 months (0.5-3). Median age at travel was 7.6 years (0.2-17.7). Events during travel were two hospitalizations (4.8%), a transfusion (2.4%), and four paramedical or medical examinations (9.6%). After return, four events occurred: two SS children had Plasmodium falciparum malaria (4.8%) and two had digestive bacteremia (4.8%) in SC and Sbeta+ children. No event occurred during plane travel. None of our patients died. The primary risk for sickle cell children traveling to Africa is infection: malaria first and digestive septicemia second. These risks are increased by long travel and poor sanitary conditions. Each travel should be prepared a long time before departure, and each pediatrician should insist on malaria prophylaxis and sanitary conditions, especially for young children. Trips should be shorter than 1 month when possible. A longer prospective study will be done to confirm these results.

  14. Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus

    Science.gov (United States)

    Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A.; Wang, Timothy G.; Sepulveda, Antonia R.; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen

    2017-01-01

    In several organ systems the transitional zone between different types of epithelia is a hotspot for pre-neoplastic metaplasia and malignancy1–3. However, the cell-of-origin for the metaplastic epithelium and subsequent malignancy, remains obscure1–3. In the case of Barrett’s oesophagus (BE), intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells4. Based on different experimental models, several alternative cell types have been proposed as the source of the metaplasia, but in all cases the evidence is inconclusive and no model completely mimics BE with the presence of intestinal goblet cells5–8. Here, we describe a novel transitional columnar epithelium with distinct basal progenitor cells (p63+ KRT5+ KRT7+) in the squamous-columnar junction (SCJ) in the upper gastrointestinal tract of the mouse. We use multiple models and lineage tracing strategies to show that this unique SCJ basal cell population serves as a source of progenitors for the transitional epithelium. Moreover, upon ectopic expression of CDX2 these transitional basal progenitors differentiate into intestinal-like epithelium including goblet cells, thus reproducing Barrett’s metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues, including the anorectal junction, and, importantly, at the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (MLE) believed to be a precursor of BE are both characterized by the expansion of the transitional basal progenitor cells. Taken together our findings reveal the presence of a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+ KRT7+ basal cells in this zone are the cell-of-origin for MLE and BE. PMID:29019984

  15. Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Ulm, Ashley; Mayhew, Christopher N; Debley, Jason; Khurana Hershey, Gurjit K; Ji, Hong

    2016-03-10

    Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They are also involved in many airway diseases through their innate immune response and interaction with immune and airway stromal cells. NECs are of particular interest for studies in children due to their accessibility during clinical visits. Human induced pluripotent stem cells (iPSCs) have been generated from multiple cell types and are a powerful tool for modeling human development and disease, as well as for their potential applications in regenerative medicine. This is the first protocol to lay out methods for successful generation of iPSCs from NECs derived from pediatric participants for research purposes. It describes how to obtain nasal epithelial cells from children, how to generate primary NEC cultures from these samples, and how to reprogram primary NECs into well-characterized iPSCs. Nasal mucosa samples are useful in epidemiological studies related to the effects of air pollution in children, and provide an important tool for studying airway disease. Primary nasal cells and iPSCs derived from them can be a tool for providing unlimited material for patient-specific research in diverse areas of airway epithelial biology, including asthma and COPD research.

  16. Growth inhibitory activity of Ankaferd hemostat on primary melanoma cells and cell lines

    Directory of Open Access Journals (Sweden)

    Seyhan Turk

    2017-02-01

    Full Text Available Objective: Ankaferd hemostat is the first topical hemostatic agent about the red blood cell–fibrinogen relations tested in the clinical trials. Ankaferd hemostat consists of standardized plant extracts including Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica, and Vitis vinifera. The aim of this study was to determine the effect of Ankaferd hemostat on viability of melanoma cell lines. Methods: Dissimilar melanoma cell lines and primary cells were used in this study. These cells were treated with different concentrations of Ankaferd hemostat to assess the impact of different dosages of the drug. All cells treated with different concentrations were incubated for different time intervals. After the data had been obtained, one-tailed T-test was used to determine whether the Ankaferd hemostat would have any significant inhibitory impact on cell growth. Results: We demonstrated in this study that cells treated with Ankaferd hemostat showed a significant decrease in cell viability compared to control groups. The cells showed different resistances against Ankaferd hemostat which depended on the dosage applied and the time treated cells had been incubated. We also demonstrated an inverse relationship between the concentration of the drug and the incubation time on one hand and the viability of the cells on the other hand, that is, increasing the concentration of the drug and the incubation time had a negative impact on cell viability. Conclusion: The findings in our study contribute to our knowledge about the anticancer impact of Ankaferd hemostat on different melanoma cells.

  17. Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture.

    Science.gov (United States)

    Jin, Liting; Qu, Ying; Gomez, Liliana J; Chung, Stacey; Han, Bingchen; Gao, Bowen; Yue, Yong; Gong, Yiping; Liu, Xuefeng; Amersi, Farin; Dang, Catherine; Giuliano, Armando E; Cui, Xiaojiang

    2018-02-20

    Conditional reprogramming methods allow for the inexhaustible in vitro proliferation of primary epithelial cells from human tissue specimens. This methodology has the potential to enhance the utility of primary cell culture as a model for mammary gland research. However, few studies have systematically characterized this method in generating in vitro normal human mammary epithelial cell models. We show that cells derived from fresh normal breast tissues can be propagated and exhibit heterogeneous morphologic features. The cultures are composed of CK18, desmoglein 3, and CK19-positive luminal cells and vimentin, p63, and CK14-positive myoepithelial cells, suggesting the maintenance of in vivo heterogeneity. In addition, the cultures contain subpopulations with different CD49f and EpCAM expression profiles. When grown in 3D conditions, cells self-organize into distinct structures that express either luminal or basal cell markers. Among these structures, CK8-positive cells enclosing a lumen are capable of differentiation into milk-producing cells in the presence of lactogenic stimulus. Furthermore, our short-term cultures retain the expression of ERα, as well as its ability to respond to estrogen stimulation. We have investigated conditionally reprogrammed normal epithelial cells in terms of cell type heterogeneity, cellular marker expression, and structural arrangement in two-dimensional (2D) and three-dimensional (3D) systems. The conditional reprogramming methodology allows generation of a heterogeneous culture from normal human mammary tissue in vitro . We believe that this cell culture model will provide a valuable tool to study mammary cell function and malignant transformation.

  18. Comparison of Gasoline and Primary Reference Fuel in the Transition from HCCI to PPC

    KAUST Repository

    Li, Changle; Tunestal, Per; Tuner, Martin; Johansson, Bengt

    2017-01-01

    Our previous research investigated the sensitivity of combustion phasing to intake temperature and injection timing during the transition from homogeneous charge compression ignition (HCCI) to partially premixed combustion (PPC) fuelled with generic

  19. OPIUM USE IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER

    Directory of Open Access Journals (Sweden)

    A. Nourbakhsh

    2006-08-01

    Full Text Available Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1% of the cases and 12 (5% of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

  20. CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells.

    Science.gov (United States)

    Lupia, Michela; Angiolini, Francesca; Bertalot, Giovanni; Freddi, Stefano; Sachsenmeier, Kris F; Chisci, Elisa; Kutryb-Zajac, Barbara; Confalonieri, Stefano; Smolenski, Ryszard T; Giovannoni, Roberto; Colombo, Nicoletta; Bianchi, Fabrizio; Cavallaro, Ugo

    2018-04-10

    Cancer-initiating cells (CICs) have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC), CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs) remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5'-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Primary orbital precursor T-cell lymphoblastic lymphoma

    DEFF Research Database (Denmark)

    Stenman, Lisa; Persson, Marta; Enlund, Fredrik

    2016-01-01

    Primary T-cell lymphoblastic lymphoma (T-LBL) in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical...... examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph....... There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal...

  2. A novel three-dimensional cell culture method enhances antiviral drug screening in primary human cells.

    Science.gov (United States)

    Koban, Robert; Neumann, Markus; Daugs, Aila; Bloch, Oliver; Nitsche, Andreas; Langhammer, Stefan; Ellerbrok, Heinz

    2018-02-01

    Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) and FDA approved for treatment of non-small cell lung cancer. In a previous study we could show the in vitro efficacy of gefitinib for treatment of poxvirus infections in monolayer (2D) cultivated cell lines. Permanent cell lines and 2D cultures, however, are known to be rather unphysiological; therefore it is difficult to predict whether determined effective concentrations or the drug efficacy per se are transferable to the in vivo situation. 3D cell cultures, which meanwhile are widely distributed across all fields of research, are a promising tool for more predictive in vitro investigations of antiviral compounds. In this study the spreading of cowpox virus and the antiviral efficacy of gefitinib were analyzed in primary human keratinocytes (NHEK) grown in a novel 3D extracellular matrix-based cell culture model and compared to the respective monolayer culture. 3D-cultivated NHEK grew in a polarized and thus a more physiological manner with altered morphology and close cell-cell contact. Infected cultures showed a strongly elevated sensitivity towards gefitinib. EGFR phosphorylation, cell proliferation, and virus replication were significantly reduced in 3D cultures at gefitinib concentrations which were at least 100-fold lower than those in monolayer cultures and well below the level of cytotoxicity. Our newly established 3D cell culture model with primary human cells is an easy-to-handle alternative to conventional monolayer cell cultures and previously described more complex 3D cell culture systems. It can easily be adapted to other cell types and a broad spectrum of viruses for antiviral drug screening and many other aspects of virus research under more in vivo-like conditions. In consequence, it may contribute to a more targeted realization of necessary in vivo experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy

    Directory of Open Access Journals (Sweden)

    P. Wang

    2007-07-01

    Full Text Available Transitional cell carcinoma (TCC of the urothelium is often multifocal and subsequent tumors may occur anywhere in the urinary tract after the treatment of a primary carcinoma. Patients initially presenting a bladder cancer are at significant risk of developing metachronous tumors in the upper urinary tract (UUT. We evaluated the prognostic factors of primary invasive bladder cancer that may predict a metachronous UUT TCC after radical cystectomy. The records of 476 patients who underwent radical cystectomy for primary invasive bladder TCC from 1989 to 2001 were reviewed retrospectively. The prognostic factors of UUT TCC were determined by multivariate analysis using the COX proportional hazards regression model. Kaplan-Meier analysis was also used to assess the variable incidence of UUT TCC according to different risk factors. Twenty-two patients (4.6%. developed metachronous UUT TCC. Multiplicity, prostatic urethral involvement by the bladder cancer and the associated carcinoma in situ (CIS were significant and independent factors affecting the occurrence of metachronous UUT TCC (P = 0.0425, 0.0082, and 0.0006, respectively. These results were supported, to some extent, by analysis of the UUT TCC disease-free rate by the Kaplan-Meier method, whereby patients with prostatic urethral involvement or with associated CIS demonstrated a significantly lower metachronous UUT TCC disease-free rate than patients without prostatic urethral involvement or without associated CIS (log-rank test, P = 0.0116 and 0.0075, respectively. Multiple tumors, prostatic urethral involvement and associated CIS were risk factors for metachronous UUT TCC, a conclusion that may be useful for designing follow-up strategies for primary invasive bladder cancer after radical cystectomy.

  4. The Transition of Primary Care Group Practices to Next Generation Models: Satisfaction of Staff, Clinicians, and Patients.

    Science.gov (United States)

    Zink, Therese; Kralewski, John; Dowd, Bryan

    Restructuring primary care is essential to achieve the triple aim. This case study examines the human factors of extensive redesign on 2 midsized primary care clinics (clinics A and B) in the Midwest United States that are owned by a large health care system. The transition occurred when while the principles for patient-centered medical home were being rolled out nationally, and before the Affordable Care Act. After the transition, interviews and discussions were conducted with 5 stakeholder groups: health system leaders, clinic managers, clinicians, nurses, and reception staff. Using a culture assessment instrument, the responses of personnel at clinics A and B were compared with comparison clinics from another health system that had not undergone transition. Patient satisfaction scores are presented. Clinics A and B were similar in size and staffing. Three human factor themes emerged from interviews: responses to change, professional and personal challenges due to role redefinition, and the importance of communication. The comparison clinics had an equal or higher mean culture scores compared with the transition clinics (A and B). Patient satisfaction in improved in Clinic A. The transition took more time than expected. Health system leaders underestimated the stress and the role adjustments for clinicians and nurses. Change leaders need to anticipate the challenge of role redefinition until health profession schools graduate trainees with more experience in new models of team-based care. Incorporating experience with team based, interprofessional care into training is essential to properly prepare future health professionals. © Copyright 2017 by the American Board of Family Medicine.

  5. Massachusetts Fuel Cell Bus Project: Demonstrating a Total Transit Solution for Fuel Cell Electric Buses in Boston

    Energy Technology Data Exchange (ETDEWEB)

    2017-05-22

    The Federal Transit Administration's National Fuel Cell Bus Program focuses on developing commercially viable fuel cell bus technologies. Nuvera is leading the Massachusetts Fuel Cell Bus project to demonstrate a complete transit solution for fuel cell electric buses that includes one bus and an on-site hydrogen generation station for the Massachusetts Bay Transportation Authority (MBTA). A team consisting of ElDorado National, BAE Systems, and Ballard Power Systems built the fuel cell electric bus, and Nuvera is providing its PowerTap on-site hydrogen generator to provide fuel for the bus.

  6. Relationship between transit time and mechanical properties of a cell through a stenosed microchannel.

    Science.gov (United States)

    Ye, Ting; Shi, Huixin; Phan-Thien, Nhan; Lim, Chwee Teck; Li, Yu

    2018-01-24

    The changes in the mechanical properties of a cell are not only the cause of some diseases, but can also be a biomarker for some disease states. In recent times, microfluidic devices with built-in constrictions have been widely used to measure these changes. The transit time in such devices, defined as the time that a cell takes to pass through a constriction, has been found to be a crucial factor associated with the cell mechanical properties. Here, we use smoothed dissipative particle dynamics (SDPD), a particle-based numerical method, to explore the relationship between the transit time and mechanical properties of a cell. Three expressions of the transit time are developed from our simulation data, with respect to the stenosed size of constrictions, the shear modulus and bending modulus of cells, respectively. We show that a convergent constriction (the inlet is wider than the outlet), and a sharp-corner constriction (the constriction outlet is narrow) are better in identifying the differences in the transit time of cells. Moreover, the transit time increases and gradually approaches a constant as the shear modulus of cells increases, but increases first and then decreases as the bending modulus increases. These results suggest that the mechanical properties of cells can indeed be measured by analyzing their transit time, based on the recommended microfluidic device.

  7. Susceptibility of Primary Human Choroid Plexus Epithelial Cells and Meningeal Cells to Infection by JC Virus.

    Science.gov (United States)

    O'Hara, Bethany A; Gee, Gretchen V; Atwood, Walter J; Haley, Sheila A

    2018-04-15

    JC polyomavirus (JCPyV) establishes a lifelong persistence in roughly half the human population worldwide. The cells and tissues that harbor persistent virus in vivo are not known, but renal tubules and other urogenital epithelial cells are likely candidates as virus is shed in the urine of healthy individuals. In an immunosuppressed host, JCPyV can become reactivated and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system. Recent observations indicate that JCPyV may productively interact with cells in the choroid plexus and leptomeninges. To further study JCPyV infection in these cells, primary human choroid plexus epithelial cells and meningeal cells were challenged with virus, and their susceptibility to infection was compared to the human glial cell line, SVG-A. We found that JCPyV productively infects both choroid plexus epithelial cells and meningeal cells in vitro Competition with the soluble receptor fragment LSTc reduced virus infection in these cells. Treatment of cells with neuraminidase also inhibited both viral infection and binding. Treatment with the serotonin receptor antagonist, ritanserin, reduced infection in SVG-A and meningeal cells. We also compared the ability of wild-type and sialic acid-binding mutant pseudoviruses to transduce these cells. Wild-type pseudovirus readily transduced all three cell types, but pseudoviruses harboring mutations in the sialic acid-binding pocket of the virus failed to transduce the cells. These data establish a novel role for choroid plexus and meninges in harboring virus that likely contributes not only to meningoencephalopathies but also to PML. IMPORTANCE JCPyV infects greater than half the human population worldwide and causes central nervous system disease in patients with weakened immune systems. Several recent reports have found JCPyV in the choroid plexus and leptomeninges of patients with encephalitis. Due to their role in forming the blood

  8. Physicians' perceptions about the quality of primary health care services in transitional Albania

    NARCIS (Netherlands)

    Kellici, Neritan; Dibra, Arvin; Mihani, Joana; Kellici, Suela; Burazeri, Genc

    AIM: To date, the available information regarding the quality of primary health care services in Albania is scarce. The aim of our study was to assess the quality of primary health care services in Albania based on physicians' perceptions towards the quality of the services provided to the general

  9. Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

    Science.gov (United States)

    Gittler, Julia; Martires, Kathryn; Terushkin, Vitaly; Brinster, Nooshin; Ramsay, David

    2016-12-15

    HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

  10. Adoptive T Cell Immunotherapy for Patients with Primary Immunodeficiency Disorders.

    Science.gov (United States)

    McLaughlin, Lauren P; Bollard, Catherine M; Keller, Michael

    2017-01-01

    Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens. Thus, the emergence of adoptive immunotherapy with virus-specific T lymphocytes (VSTs) is an attractive option for addressing the underlying impaired T cell immunity in many PID patients. VSTs have been utilized for PID patients following HSCT in many prior phase I trials, and may potentially be beneficial before HSCT in patients with chronic viral infections. We review the various methods of generating VSTs, clinical experience using VSTs for PID patients, and current limitations as well as potential ways to broaden the clinical applicability of adoptive immunotherapy for PID patients.

  11. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  12. Development of Functional Microfold (M Cells from Intestinal Stem Cells in Primary Human Enteroids.

    Directory of Open Access Journals (Sweden)

    Joshua D Rouch

    Full Text Available Intestinal microfold (M cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs, and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2 in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an

  13. Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.

    Science.gov (United States)

    Gil-Ibañez, Pilar; García-García, Francisco; Dopazo, Joaquín; Bernal, Juan; Morte, Beatriz

    2017-01-01

    Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Photoinduced Coherent Spin Fluctuation in Primary Dynamics of Insulator to Metal Transition in Perovskite Cobalt Oxide

    Directory of Open Access Journals (Sweden)

    Arima T.

    2013-03-01

    Full Text Available Coherent spin fluctuation was detected in the photoinduced Mott insulator-metal transition in perovskite cobalt oxide by using 3 optical-cycle infrared pulse. Such coherent spin fluctuation is driven by the perovskite distortion changing orbital gap.

  15. Primary mantle cell lymphoma of tonsil: Case report

    Directory of Open Access Journals (Sweden)

    Knežević Snežana B.

    2017-01-01

    Full Text Available Introduction: Mantle cell lymphoma is rare type of the mature B cell lymphoma. It includes 4% - 6% of all Non Hodgkin's Lymphomas. Compared to the other subtypes of lymphoma it develops more often in older men, and the median age of patients is 65 years. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies. Method: Data obtained from medical records of the patient. Objective: Emphasize the importance of early and accurate diagnosis and early treatment of malignant diseases. Case report: Patient RP, 63 years old, presents with difficult swallowing, hoarseness, enlarged tonsils, snoring. Left tonsil almost sets into the right tonsillar vine, displaces the uvula and covers the isthmus. Respiratory sound is normal, with rhythmic action of the heart and soft abdomen. Good general condition. Echo: enlarged and actively altered lymph glands of the middle right jugular chain, the largest 148x77 mm, on the left side lymph nodes are enlarged, the largest is 143x72 mm. Echo of the abdomen inconspicuous. Lab: WBC 5.9, RBC 5.2, Hb 152, Hct 0.44, SE 10, CK 129, LDH 331, CRP 4.6, ALP 61, fibrinogen 2.4, Ca2+ 2.3, phosphate 0.8; BK, HCV, HBsAg, EB, HIV negative. X-ray of the chest inconspicuous. Admitted to the hematology department of the General Hospital. PH: Immunoproliferative disease. Immunohistochemistry, at the institute of Pathology: IHH CK AE1-AE3, PAX5 +, CD20 +, CD3, bcl2 +, bcl6-, CyklinD1 +, CD23-, CD43 +, MUM1 - / +, Ki67 + in about 20% of the tumor cells. Morphological and immunohistochemical findings: Mantle cell lymphoma. MSCD of the neck, chest and upper abdomen: Left tonsil diameter is 28x32 mm and length is 36mm, with lobular contour and heterogeneous structure, asymmetrically narrowing lumen of the airways to 7 mm. pathologically enlarged submandibular and par jugular lymph nodes (10-15 mm diameter on the left. There were no pathological findings in the lung parenchyma. Abdominal and retroperitoneal lymph nodes

  16. Structural integrity assessment of steam generator tubes deteriorated through primary water stress corrosion cracking in transition region of tube expansion

    International Nuclear Information System (INIS)

    Silveira, Helvecio Carlos Klinke da

    2002-01-01

    In PWR plants, steam generator tube degradation has been one of the most important economical concerns, besides causing operational safety problems. In this work, a survey of steam generator tube degradation modes is done. Degradation mechanisms and influence factors are introduced and discussed. The importance of stress corrosion cracking, especially in transition region of tube expansion zone, is underlined. The actual steam generator tube plugging criteria are conservative. Proposed alternative criteria are introduced and discussed. Distinction is done to structural integrity assessment of defective tubes. Real data of tube defect indications of axial cracks in expansion transition zone due to primary water stress corrosion cracking are used in analysis. Results allow discussing application aspects of deterministic and probabilistic criteria on structural integrity assessment of tubes with defect indications. Applied models are specifics, but the application of concept may be extended to other steam generator tube degradation modes. (author)

  17. Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2012-01-01

    Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

  18. Synchronous sigmoid and caecal cancers together with a primary renal cell carcinoma.

    LENUS (Irish Health Repository)

    Bhargava, A

    2012-06-01

    Multiple primary neoplasms, a common clinical entity, can be classified as synchronous or metachronous. Renal cell carcinoma, in particular, is associated with a high rate of multiple primary neoplasms.

  19. Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Jignasa N. Bhalodia

    2011-01-01

    Full Text Available Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE.

  20. Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

    International Nuclear Information System (INIS)

    Vi, Linda; Feng, Lucy; Zhu, Rebecca D.; Wu, Yan; Satish, Latha; Gan, Bing Siang; O'Gorman, David B.

    2009-01-01

    Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, α smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

  1. Primary transitions between the yrast superdeformed band and low-lying normal deformed states in {sup 194}Pb

    Energy Technology Data Exchange (ETDEWEB)

    Hauschild, K.; Bernstein, L.A.; Becker, J.A. [Lawrence Livermore National Lab., CA (United States)] [and others

    1996-12-31

    The observation of one-step `primary` gamma-ray transitions directly linking the superdeformed (SD) states to the normal deformed (ND) low-lying states of known excitation energies (E{sub x}), spins and parities (J{sup {pi}}) is crucial to determining the E{sub x} and J{sup {pi}} of the SD states. With this knowledge one can begin to address some of the outstanding problems associated with SD nuclei, such as the identical band issue, and one can also place more stringent restrictions on theoretical calculations which predict SD states and their properties. Brinkman, et al., used the early implementation of the GAMMASPHERE spectrometer array (32 detectors) and proposed a single, candidate {gamma} ray linking the {sup 194}Pb yrast SD band to the low-lying ND states in {sup 194}Pb. Using 55 detectors in the GAMMASPHERE array Khoo, et al., observed multiple links between the yrast SD band in {sup 194}Hg and the low-lying level scheme and conclusively determined E{sub x} and J of the yrast SD states. Here the authors report on an experiment in which Gammasphere with 88 detectors was used and the E{sub x} and J{sup {pi}} values of the yrast SD states in {sup 194}Pb were uniquely determined. Twelve one-step linking transitions between the yrast SD band and low-lying states in {sup 194}Pb have been identified, including the transition proposed by Brinkman. These transitions have been placed in the level scheme of {sup 194}Pb using coincidence relationships and agreements between the energies of the primary transitions and the energy differences in level spacings. Furthermore, measurements of angular asymmetries have yielded the multipolarities of the primaries which have allowed J{sup {pi}} assignments of the {sup 194}Pb SD states to be unambiguously determined for the first time without a priori assumptions about the character of SD bands. A study performed in parallel to this work using the EUROGAM-II array reports similar, but somewhat less extensive, results.

  2. CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.

    Science.gov (United States)

    Lupia, Antonella; Peppicelli, Silvia; Witort, Ewa; Bianchini, Francesca; Carloni, Vinicio; Pimpinelli, Nicola; Urso, Carmelo; Borgognoni, Lorenzo; Capaccioli, Sergio; Calorini, Lido; Lulli, Matteo

    2014-12-01

    The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

  3. Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer

    International Nuclear Information System (INIS)

    Mego, M.; Cierna, Z.; Janega, P.; Karaba, M.; Minarik, G.; Benca, J.; Sedlácková, T.; Sieberova, G.; Gronesova, P.; Manasova, D.; Pindak, D.; Sufliarsky, J.; Danihel, L.; Reuben, JM; Mardiak, J.

    2015-01-01

    Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features

  4. The Mitotic and Metabolic Effects of Phosphatidic Acid in the Primary Muscle Cells of Turbot (Scophthalmus maximus

    Directory of Open Access Journals (Sweden)

    Tingting Wang

    2018-05-01

    Full Text Available Searching for nutraceuticals and understanding the underlying mechanism that promote fish growth is at high demand for aquaculture industry. In this study, the modulatory effects of soy phosphatidic acids (PA on cell proliferation, nutrient sensing, and metabolic pathways were systematically examined in primary muscle cells of turbot (Scophthalmus maximus. PA was found to stimulate cell proliferation and promote G1/S phase transition through activation of target of rapamycin signaling pathway. The expression of myogenic regulatory factors, including myoD and follistatin, was upregulated, while that of myogenin and myostatin was downregulated by PA. Furthermore, PA increased intracellular free amino acid levels and enhanced protein synthesis, lipogenesis, and glycolysis, while suppressed amino acid degradation and lipolysis. PA also was found to increased cellular energy production through stimulated tricarboxylic acid cycle and oxidative phosphorylation. Our results identified PA as a potential nutraceutical that stimulates muscle cell proliferation and anabolism in fish.

  5. A latent transition analysis of bullying and victimization in Chinese primary school students.

    Directory of Open Access Journals (Sweden)

    Yiqin Pan

    Full Text Available Bullying is a social phenomenon that impacts a large number of children and young people, worldwide. This study aimed to longitudinally examine the development of bullying and victimization in Chinese students in grades 4, 5, and 6. We used latent class analysis to empirically identify groups of youth with different bullying and victimization patterns, and then used latent transition analysis to explore the movement of children between these latent classes over time. Results showed that: (1 across the three time points, students could be classified into four classes: bullies, victims, bully-victims, and non-involved children; and (2 students in the non-involved class tended to remain in that class when moving to higher grades, students in the bully and victims classes tended to transition to the non-involved class, while students in the bully-victims class tended to transition to the bullies class. Thus, future intervention should be implemented to prevent bully-victims from bullying behaviors.

  6. Supporting and Stimulating the Learning of Socioeconomically Disadvantaged Children--Perspectives of Parents and Educators in the Transition from Preschool to Primary School

    Science.gov (United States)

    Arndt, Ann-Kathrin; Rothe, Antje; Urban, Michael; Werning, Rolf

    2013-01-01

    When children move from preschool to primary school in Germany, this involves a transition between two distinct systems with regard to political responsibility. Following Rimm-Kaufman and Pianta's (2000) ecological and dynamic model of transition, the research project focuses on the perspectives of parents and professionals on the learning…

  7. Imaging of transitional cell carcinomas of the urinary tracts

    International Nuclear Information System (INIS)

    Ozmen, M.

    2012-01-01

    Full text: Transitional cell carcinoma (TCC) is the most common urothelial neoplasm to involve the upper urinary tract and bladder. Prognosis significantly worsens with deeper invasion. The role of imaging is to detect the tiniest urothelial neoplasms while still potentially resectable and curable. In case of advance disease, imaging should identify the extent of disease. Intravenous or retrograde urography, ultrasonography, computed tomography or magnetic resonance imaging have been used for diagnosis of TCC. The diagnostic performances of these imaging modalities differ from each other. A recent review regarding imaging of TCC by Razavi et al states that the retrieved sensitivity/specificity for the detection of TCC of upper urinary tract for CT urography (CTU), MR urography, excretory urography, and retrograde urography were 96%/99%, 69%/97%, 80%/81%, and 96%/96%, respectively. For detecting bladder cancer, the retrieved sensitivity/specificity for CT cystography, MR cystography, and ultrasonography were 94%/98%, 91%/95%, and 78%/96%, respectively. They conclude that CT urography is the best imaging technique for confirming or excluding malignancy in the upper urinary tract, whereas CT cystography has the best diagnostic performance for diagnosing bladder cancer. While cystoscopy is still considered by most to be the gold-standard for evaluation of the urinary bladder, CTU is playing an increasing role in the detection of urinary bladder urothelial neoplasms. As with the upper urinary tract, bladder urothelial neoplasms typically present as a filling defect, a focal mass, or an area of abnormal focal wall thickening. Magnetic resonance imaging is superior for evaluation of the depth of tumour invasion into the bladder wall, but this knowledge may not ultimately affect treatment as feasibility for radical cystectomy depends on staging by a combination of clinical, histopathological and imaging findings. Radical cystectomy may include resection of adjacent organs

  8. Regulation of human renin expression in chorion cell primary cultures

    International Nuclear Information System (INIS)

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L.

    1990-01-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3 endash to 6 endash fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'endash flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'endash flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter

  9. Primary small cell carcinoma of the lesser omentum

    Directory of Open Access Journals (Sweden)

    Ji-Feng Feng

    2012-02-01

    Full Text Available Although pulmonary small cell carcinoma (SCC is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.

  10. Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

    Science.gov (United States)

    Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

    2008-02-01

    Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

  11. Parental education, children's performance and the transition to higher secondary education: trends in primary and secondary effects over five Dutch school cohorts (1965-99).

    Science.gov (United States)

    Kloosterman, Rianne; Ruiter, Stijn; de Graaf, Paul M; Kraaykamp, Gerbert

    2009-06-01

    According to Boudon, social background affects educational transitions as a result of differences in children's academic performance (primary effects) and differences in transition probabilities given children's level of academic performance (secondary effects). This study addresses historical changes in both primary and secondary effects on the educational transition from primary school to higher secondary education in The Netherlands. In addition, it considers changes over time in the relative importance of these effects. The study compares five cohorts of Dutch pupils, specifically those enrolling in secondary education in 1965, 1977, 1989, 1993 and 1999, and it employs counterfactual analyses. The main findings are that secondary effects have been stable and primary effects have fluctuated to some extent. As a result, the proportion of the total effect of social background accounted for by primary effects has increased somewhat, from 53 per cent to 58 per cent.

  12. Cell surface glycan alterations in epithelial mesenchymal transition process of Huh7 hepatocellular carcinoma cell.

    Directory of Open Access Journals (Sweden)

    Shan Li

    Full Text Available BACKGROUND AND OBJECTIVE: Due to recurrence and metastasis, the mortality of Hepatocellular carcinoma (HCC is high. It is well known that the epithelial mesenchymal transition (EMT and glycan of cell surface glycoproteins play pivotal roles in tumor metastasis. The goal of this study was to identify HCC metastasis related differential glycan pattern and their enzymatic basis using a HGF induced EMT model. METHODOLOGY: HGF was used to induce HCC EMT model. Lectin microarray was used to detect the expression of cell surface glycan and the difference was validated by lectin blot and fluorescence cell lectin-immunochemistry. The mRNA expression levels of glycotransferases were determined by qRT-PCR. RESULTS: After HGF treatment, the Huh7 cell lost epithelial characteristics and obtained mesenchymal markers. These changes demonstrated that HGF could induce a typical cell model of EMT. Lectin microarray analysis identified a decreased affinity in seven lectins ACL, BPL, JAC, MPL, PHA-E, SNA, and SBA to the glycan of cell surface glycoproteins. This implied that glycan containing T/Tn-antigen, NA2 and bisecting GlcNAc, Siaα2-6Gal/GalNAc, terminal α or βGalNAc structures were reduced. The binding ability of thirteen lectins, AAL, LCA, LTL, ConA, NML, NPL, DBA, HAL, PTL II, WFL, ECL, GSL II and PHA-L to glycan were elevated, and a definite indication that glycan containing terminal αFuc and ± Sia-Le, core fucose, α-man, gal-β(α GalNAc, β1,6 GlcNAc branching and tetraantennary complex oligosaccharides structures were increased. These results were further validated by lectin blot and fluorescence cell lectin-immunochemistry. Furthermore, the mRNA expression level of Mgat3 decreased while that of Mgat5, FucT8 and β3GalT5 increased. Therefore, cell surface glycan alterations in the EMT process may coincide with the expression of glycosyltransferase. CONCLUSIONS: The findings of this study systematically clarify the alterations of cell surface

  13. Predictive Power of Primary and Secondary School Success Criterion on Transition to Higher Education Examination Scores

    OpenAIRE

    Atilla ÖZDEMİR; Selahattin GELBAL

    2016-01-01

    It is seen that education has a significant effect that changes an individual’s life in our country in which education is a way of moving up the social ladder. In order to continue to a higher education program after graduating from high school, students have to succeed in transition to higher education examination. Thus, the entrance exam is an important factor to determine the future of the students. In our country, middle school grades and high school grade point average that is added to u...

  14. The Crisis of Disengagement: A discussion on motivation change and maintenance across the primary-secondary school transition

    Directory of Open Access Journals (Sweden)

    Cheng-Yu Hung

    2014-02-01

    Full Text Available The transition from primary to secondary education signals a process of developing and maturing physically and mentally, but this ‘rite of passage’ for some young adolescents is often associated with a drifting interest in school education. This phenomenon, caused by a decreased motivation for learning, has been observed by many relevant studies. This article adopts the psychological approach to study this long-lasting educational phenomenon while employing ‘intrinsic-extrinsic motivation theory’ and ‘goal theory’ to investigate the gap between primary and secondary schools as well as what possible pedagogies there are to maintain or stimulate the pupils’ motivation. An intrinsically motivated student acquires knowledge out of curiosity and interest, and they are willing to face the more difficult challenges that secondary education provides. As identified in the conclusion, the creation of a more integral educational system can alleviate the decrease in motivation while pupils undergo this period. A more amiable educational environment can be maintained that enhances the pupils’ self-concept, learning efficacy, and a sense of volition as well as self-determination to circumvent this transitional crisis.

  15. Research of TGF-beta1 Inducing Lung Adencarcinoma PC9 Cells to Mesenchymal Cells Transition

    Directory of Open Access Journals (Sweden)

    Xiaofeng CHEN

    2010-01-01

    Full Text Available Background and objective It has been proven that epithelial-mesenchymal transition (EMT not only correlated with embryonic development but also could promote tumor invasion and metastasis. Transforming growth factor beta-1 (TGF-β1 has been identified as the main inducer of tumor EMT. The aim of this study was to investigate the effects of TGF-β1 on EMT and PI3K/AKT signaling pathway in lung adencarcinoma PC9 cells. Methods Cultured PC9 cells were treated with different concentrations of TGF-β1 for 48 h. The morphological changes were observed under phase-contrast microscopy; EMT relative marker protein changes were assessed by Western blot and immunoflurescence staining. In addition, the expression of AKT and P-AKT were also measured by Western blot. Results The data showed that TGF-β1 could induce PC9 morphological alteration from epithelial to mesenchymal and upregulate the expression of mesenchymal maker protein Fibronectin. Obviously, the expression of P-AKT was downregulated by TGF-β1 treatment for 48 h. Conclusion TGF-β1 might induce EMT of PC9 cells , accompanied by the changes of PI3K/AKT signaling pathway.

  16. Wnt is necessary for mesenchymal to epithelial transition in colorectal cancer cells.

    Science.gov (United States)

    Schwab, Renate H M; Amin, Nancy; Flanagan, Dustin J; Johanson, Timothy M; Phesse, Toby J; Vincan, Elizabeth

    2018-03-01

    Metastasis underlies most colorectal cancer mortality. Cancer cells spread through the body as single cells or small clusters of cells that have an invasive, mesenchymal, nonproliferative phenotype. At the secondary site, they revert to a proliferative "tumor constructing" epithelial phenotype to rebuild a tumor. We previously developed a unique in vitro three-dimensional model, called LIM1863-Mph, which faithfully recapitulates these reversible transitions that underpin colorectal cancer metastasis. Wnt signaling plays a key role in these transitions and is initiated by the coupling of extracellular Wnt to Frizzled (FZD). Using the LIM1863-Mph model system we demonstrated that the Wnt receptor FZD7 is necessary for mesenchymal to epithelial transition (MET). Here we investigate the role of Wnt in MET. Wnt secretion is dependent on palmitoylation by Porcupine (PORC). A PORC inhibitor (IWP2) that prevents Wnt secretion, blocked the epithelial transition of mesenchymal LIM1863-Mph cells. Wnt gene array analysis identified several Wnts that are upregulated in epithelial compared with mesenchymal LIM1863-Mph cells, suggesting these ligands in MET. Wnt2B was the most abundant differentially expressed Wnt gene. Indeed, recombinant Wnt2B could overcome the IWP2-mediated block in epithelial transition of mesenchymal LIM1863-Mph cells. Wnt2B co-operates with Frizzled7 to mediate MET in colorectal cancer. Developmental Dynamics 247:521-530, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival.

    Science.gov (United States)

    Moreau, Aurélie; Blair, Paul A; Chai, Jian-Guo; Ratnasothy, Kulachelvy; Stolarczyk, Emilie; Alhabbab, Rowa; Rackham, Chloe L; Jones, Peter M; Smyth, Lesley; Elgueta, Raul; Howard, Jane K; Lechler, Robert I; Lombardi, Giovanna

    2015-03-01

    In humans, tolerance to renal transplants has been associated with alterations in B-cell gene transcription and maintenance of the numbers of circulating transitional B cells. Here, we use a mouse model of transplantation tolerance to investigate the contribution of B cells to allograft survival. We demonstrate that transfer of B cells from mice rendered tolerant to MHC class I mismatched skin grafts can prolong graft survival in a dose-dependent and antigen-specific manner to a degree similar to that afforded by graft-specific regulatory T (Treg) cells. Tolerance in this model was associated with an increase in transitional-2 (T2) B cells. Only T2 B cells from tolerized mice, not naïve T2 nor alloantigen experienced T2, were capable of prolonging skin allograft survival, and suppressing T-cell activation. Tolerized T2 B cells expressed lower levels of CD86, increased TIM-1, and demonstrated a preferential survival in vivo. Furthermore, we demonstrate a synergistic effect between tolerized B cells and graft-specific Treg cells. IL-10 production by T2 B cells did not contribute to tolerance, as shown by transfer of B cells from IL-10(-/-) mice. These results suggest that T2 B cells in tolerant patients may include a population of regulatory B cells that directly inhibit graft rejection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2011

    Science.gov (United States)

    2011-11-11

    his report is the fifth in a series of annual status reports that summarize the progress resulting from fuel cell transit bus demonstrations in the United States and provide a discussion of the achievements and challenges of fuel cell propulsion in t...

  19. Fuel Cell Buses in U.S. Transit Fleets : Current Status 2013

    Science.gov (United States)

    2013-12-01

    This report is the seventh in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. This r...

  20. Fuel Cell Buses in U.S. Transit Fleets : Current Status 2012

    Science.gov (United States)

    2012-11-12

    This report is the sixth in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The repo...

  1. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2012

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Chandler, Kevin [Battelle, Columbus, OH (United States); Gikakis, Christina [Federal Transit Administration, Washington, DC (United States)

    2012-11-01

    This report is the sixth in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results over the last year.

  2. Exclusive radiotherapy for primary squamous cell carcinoma of the vagina

    International Nuclear Information System (INIS)

    Crevoisier, Renaud de; Sanfilippo, Nicholas; Gerbaulet, Alain; Morice, Philippe; Pomel, Christophe; Castaigne, Damiene; Pautier, Patricia; Lhomme, Catherine; Duvillard, Pierre; Haie-meder, Christine

    2007-01-01

    Purpose: To retrospectively analyze results of external beam therapy (EBT) with brachytherapy (BT) for primary vaginal squamous cell carcinoma (PVSCC). Materials and methods: From 1970 to 2001, 91 patients were included. FIGO stages were: I (29%), II (38%), III (29%) and IVa (4%). EBT delivered a median total dose of 50 Gy to the pelvis. BT was performed with a customized intra-vaginal applicator and in 36% of applications combined endocavitary and interstitial BT. ICRU Report 38 parameters were reported. Results: The 5-year cause specific survival (CSS) rates were: 83% for stage I, 76% for stage II, 52% for stage III, and 2 of the 4 stage IVa patients died 9 and 36 months after treatment. The 5-year pelvis control rates were: 79% for stage I and II and 62% for stage III. Recurrences as a first event were local only in 68% of cases, nodal only in 10%, metastatic only in 13% and combined in 9%. In multivariate analysis: stage (I and II versus II and IV), response to EBT (evaluated at BT), and the number of BT applications were statistically significant for CSS. Grade 2-3 toxicities were as follows (Franco-Italian Glossary): rectum (n = 3), sigmoid colon and small bowel (n = 8), bladder (n = 5), ureter (n = 4) and vagina (n = 13). Anterior location of the tumor increased bladder toxicity (p = 0.01) and total reference air kerma was higher in patients who experienced grade 2-3 urinary or digestive toxicity (p = 0.03). Conclusion: EBT with BT is an effective treatment for patients with stage I-II PVSCC. The incidence and severity of late toxicity were relatively low. Recent advances in the treatment of cervix carcinoma emphasize the need for concomitant radio-chemotherapy in stages III-IV and the use of MRI for treatment planning

  3. Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT)

    International Nuclear Information System (INIS)

    Chen, Li-Mei; Verity, Nicole J; Chai, Karl X

    2009-01-01

    The glycosylphosphatidylinositol (GPI)-anchored epithelial extracellular membrane serine protease prostasin (PRSS8) is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC) of the human bladder and in human TCC cell lines. Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA) were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP). Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15) TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy

  4. Loss of prostasin (PRSS8 in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT

    Directory of Open Access Journals (Sweden)

    Chai Karl X

    2009-10-01

    Full Text Available Abstract Background The glycosylphosphatidylinositol (GPI-anchored epithelial extracellular membrane serine protease prostasin (PRSS8 is expressed abundantly in normal epithelia and essential for terminal epithelial differentiation, but down-regulated in human prostate, breast, and gastric cancers and invasive cancer cell lines. Prostasin is involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR and is an invasion suppressor. The aim of this study was to evaluate prostasin expression states in the transitional cell carcinomas (TCC of the human bladder and in human TCC cell lines. Methods Normal human bladder tissues and TCC on a bladder cancer tissue microarray (TMA were evaluated for prostasin expression by means of immunohistochemistry. A panel of 16 urothelial and TCC cell lines were evaluated for prostasin and E-cadherin expression by western blot and quantitative PCR, and for prostasin gene promoter region CpG methylation by methylation-specific PCR (MSP. Results Prostasin is expressed in the normal human urothelium and in a normal human urothelial cell line, but is significantly down-regulated in high-grade TCC and lost in 9 (of 15 TCC cell lines. Loss of prostasin expression in the TCC cell lines correlated with loss of or reduced E-cadherin expression, loss of epithelial morphology, and promoter DNA hypermethylation. Prostasin expression could be reactivated by demethylation or inhibition of histone deacetylase. Re-expression of prostasin or a serine protease-inactive variant resulted in transcriptional up-regulation of E-cadherin. Conclusion Loss of prostasin expression in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT, and may have functional implications in tumor invasion and resistance to chemotherapy.

  5. The impact of personal background and school contextual factors on academic competence and mental health functioning across the primary-secondary school transition.

    Science.gov (United States)

    Vaz, Sharmila; Parsons, Richard; Falkmer, Torbjörn; Passmore, Anne Elizabeth; Falkmer, Marita

    2014-01-01

    Students negotiate the transition to secondary school in different ways. While some thrive on the opportunity, others are challenged. A prospective longitudinal design was used to determine the contribution of personal background and school contextual factors on academic competence (AC) and mental health functioning (MHF) of 266 students, 6-months before and after the transition to secondary school. Data from 197 typically developing students and 69 students with a disability were analysed using hierarchical linear regression modelling. Both in primary and secondary school, students with a disability and from socially disadvantaged backgrounds gained poorer scores for AC and MHF than their typically developing and more affluent counterparts. Students who attended independent and mid-range sized primary schools had the highest concurrent AC. Those from independent primary schools had the lowest MHF. The primary school organisational model significantly influenced post-transition AC scores; with students from Kindergarten--Year 7 schools reporting the lowest scores, while those from the Kindergarten--Year 12 structure without middle school having the highest scores. Attending a school which used the Kindergarten--Year 12 with middle school structure was associated with a reduction in AC scores across the transition. Personal background factors accounted for the majority of the variability in post-transition AC and MHF. The contribution of school contextual factors was relatively minor. There is a potential opportunity for schools to provide support to disadvantaged students before the transition to secondary school, as they continue to be at a disadvantage after the transition.

  6. The impact of personal background and school contextual factors on academic competence and mental health functioning across the primary-secondary school transition.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available Students negotiate the transition to secondary school in different ways. While some thrive on the opportunity, others are challenged. A prospective longitudinal design was used to determine the contribution of personal background and school contextual factors on academic competence (AC and mental health functioning (MHF of 266 students, 6-months before and after the transition to secondary school. Data from 197 typically developing students and 69 students with a disability were analysed using hierarchical linear regression modelling. Both in primary and secondary school, students with a disability and from socially disadvantaged backgrounds gained poorer scores for AC and MHF than their typically developing and more affluent counterparts. Students who attended independent and mid-range sized primary schools had the highest concurrent AC. Those from independent primary schools had the lowest MHF. The primary school organisational model significantly influenced post-transition AC scores; with students from Kindergarten--Year 7 schools reporting the lowest scores, while those from the Kindergarten--Year 12 structure without middle school having the highest scores. Attending a school which used the Kindergarten--Year 12 with middle school structure was associated with a reduction in AC scores across the transition. Personal background factors accounted for the majority of the variability in post-transition AC and MHF. The contribution of school contextual factors was relatively minor. There is a potential opportunity for schools to provide support to disadvantaged students before the transition to secondary school, as they continue to be at a disadvantage after the transition.

  7. Pre-Service Primary Science Teachers' Understandings of the Effect of Temperature and Pressure on Solid-Liquid Phase Transition of Water

    Science.gov (United States)

    Yalcin, Fatma Aggul

    2012-01-01

    The aim of this study was to explore pre-service primary teachers' understandings of the effect of temperature and pressure on the solid-liquid phase transition of water. In the study a survey approach was used, and the sample consisted of one-hundred and three, third year pre-service primary science teachers. As a tool for data collection, a test…

  8. Prospective capillaroscopy-based study on transition from primary to secondary Raynaud’s phenomenon: preliminary results

    Directory of Open Access Journals (Sweden)

    E. Bernero

    2013-10-01

    Full Text Available The objective of this prospective study was to investigate the transition from primary (PRP to secondary (SRP Raynaud’s phenomenon (RP, in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC. Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late. NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years. Sixty-eight patients (16% achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases, Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01. This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

  9. Role of videocapillaroscopy in early detection of transition from primary to secondary Raynaud’s fenomenon in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    B. Seriolo

    2011-09-01

    Full Text Available Patients initially diagnosed as having primary Raynaud’s phenomenon (PRP may shift to secondary (SRP during the follow-up. Nailfold videocapillaroscopy (NVC is a tool that allows to distinguish between PRP and SRP through the identification of the “early” scleroderma-pattern of microangiopathy. The aim of this study was to evaluate the transition from PRP to SRP in an Italian cohort of patients during their follow-up. 129 patients with PRP were identified and followed-up for 2721 months. The diagnosis of PRP was achieved as suggested by LeRoy. The NVC diagnosis of scleroderma-pattern was based on the presence of specific “early” capillary abnormalities (i.e. giant capillaries, microhaemorrhages, and/or slight reduction of capillary density. Based on the identification of the “early” scleroderma-pattern by NVC, 14% of patients changed from PRP to SRP during the follow-up. Interestingly, 4.6% of these patients showed at baseline a fully normal NVC pattern (transition from normal to scleroderma NVC pattern in 3427 months, and 10% showed slight and not-specific nailfold capillary abnormalities (i.e. dystrophic capillaries and/or enlarged capillaries at baseline (transition to scleroderma NVC pattern in 2515 months. Following a careful NVC analysis, we showed the progression from PRP to SRP in 14% of the analyzed patients. We suggest the capillaroscopic analysis twice a year in presence of PRP, in order to early detect the transition to SRP in patients showing at the beginning a normal pattern or not-specific nailfold capillary abnormalities, as assessed by NVC.

  10. On the transition to sustainability: an analysis of the costs of school feeding compared with the costs of primary education.

    Science.gov (United States)

    Bundy, Donald; Burbano, Carmen; Gelli, Aulo; Risley, Claire; Neeser, Kristie

    2011-09-01

    The current food, fuel, and financial crises have highlighted the importance of school feeding programs both as a social safety net for children living in poverty and food insecurity, and as part of national educational policies and plans. To examine the costs of school feeding, in terms of both the absolute cost per child and the cost per child relative to overall education expenditure and gross domestic product (GDP) in low-, middle-, and high-income countries. Data on the costs of school feeding in different countries were collected from multiple sources, including World Food Programme project data, reports from government ministries, and, where such searches failed, newspaper articles and other literature obtained from internet searches. Regression models were then used to analyze the relationships between school feeding costs, the per capita costs of primary education and GDP per capita. School feeding programs in low-income countries exhibit large variations in cost, with concomitant opportunities for cost containment. As countries get richer, however, school feeding costs become a much smaller proportion of the investment in education. The per capita costs of feeding relative to education decline nonlinearly with increasing GDP. These analyses suggest that the main reason for this decline in the relative cost of school feeding versus primary education is a greatly increased investment per child in primary education as GDP rises, but a fairly flat investment in food. The analyses also show that there appears to be a transitional discontinuity at the interface between the lower- and middle-income countries, which tends to coincide with changes in the capacity of governments to take over the management and funding of programs. Further analysis is required to define these relationships, but an initial conclusion is that supporting countries to maintain an investment in school feeding through this transition may emerge as a key role for development partners.

  11. Neuroglobin overexpression inhibits oxygen-glucose deprivation-induced mitochondrial permeability transition pore opening in primary cultured mouse cortical neurons.

    Science.gov (United States)

    Yu, Zhanyang; Liu, Ning; Li, Yadan; Xu, Jianfeng; Wang, Xiaoying

    2013-08-01

    Neuroglobin (Ngb) is an endogenous neuroprotective molecule against hypoxic/ischemic brain injury, but the underlying mechanisms remain largely undefined. Our recent study revealed that Ngb can bind to voltage-dependent anion channel (VDAC), a regulator of mitochondria permeability transition (MPT). In this study we examined the role of Ngb in MPT pore (mPTP) opening following oxygen-glucose deprivation (OGD) in primary cultured mouse cortical neurons. Co-immunoprecipitation (Co-IP) and immunocytochemistry showed that the binding between Ngb and VDAC was increased after OGD compared to normoxia, indicating the OGD-enhanced Ngb-VDAC interaction. Ngb overexpression protected primary mouse cortical neurons from OGD-induced neuronal death, to an extent comparable to mPTP opening inhibitor, cyclosporine A (CsA) pretreatment. We further measured the role of Ngb in OGD-induced mPTP opening using Ngb overexpression and knockdown approaches in primary cultured neurons, and recombinant Ngb exposure to isolated mitochondria. Same as CsA pretreatment, Ngb overexpression significantly reduced OGD-induced mPTP opening markers including mitochondria swelling, mitochondrial NAD(+) release, and cytochrome c (Cyt c) release in primary cultured neurons. Recombinant Ngb incubation significantly reduced OGD-induced NAD(+) release and Cyt c release from isolated mitochondria. In contrast, Ngb knockdown significantly increased OGD-induced neuron death, and increased OGD-induced mitochondrial NAD(+) release and Cyt c release as well, and these outcomes could be rescued by CsA pretreatment. In summary, our results demonstrated that Ngb overexpression can inhibit OGD-induced mPTP opening in primary cultured mouse cortical neurons, which may be one of the molecular mechanisms of Ngb's neuroprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer

    International Nuclear Information System (INIS)

    Karamitopoulou, Eva

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial–mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

  13. Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

    Science.gov (United States)

    Karamitopoulou, Eva

    2012-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

  14. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  15. Primary central nervous system B-cell lymphoma in a young dog

    Science.gov (United States)

    Kim, Na-Hyun; Ciesielski, Thomas; Kim, Jung H.; Yhee, Ji-Young; Im, Keum-Soon; Nam, Hae-Mi; Kim, Il-Hwan; Kim, Jong-Hyuk; Sur, Jung-Hyang

    2012-01-01

    This report describes a primary central nervous system B-cell lymphoma in a 3-year-old intact female Maltese dog. Canine primary central nervous system lymphomas constitute about 4% of all intracranial primary neoplasms, but comprehensive histopathologic classifications have rarely been carried out. This is the first report of this disease in a young adult dog. PMID:23115372

  16. Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells.

    Science.gov (United States)

    Shan, Xiaoyin; Roberts, Cleresa; Kim, Eun Ji; Brenner, Ariana; Grant, Gregory; Percec, Ivona

    2017-05-01

    Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASCs), is increasingly recognized, the study of chronological aging in ASCs is technically difficult and remains poorly understood. Here, we use our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase. Our results reveal novel chronological aging mechanisms in ASCs that are inherently different from differentiated cells and that may reflect an organismal attempt to meet the increased demands of tissue and organ homeostasis during aging. Stem Cells 2017;35:1392-1401. © 2017 AlphaMed Press.

  17. Hypermethylation Is A Key Feature of the Transition of Multiple Myeloma to Plasma Cell Leukemia

    DEFF Research Database (Denmark)

    Walker, Brian A.; Wardell, Christopher P.; Boyd, Kevin D.

    2010-01-01

    in the transition of MM to PCL can be classified as either tumor suppressor genes, genes involved in cell-cell signaling, or as cell adhesion molecules. The further analysis of these genes will allow us to identify genes which are down-regulated through methylation and mediate the progression of MM to PCL allowing...... to malignant plasma cells and little is known about the genetic mechanisms mediating the final stages of this pathway. The methylation status of genes in myeloma can change as the malignancy progresses and as such identifying genes deregulated by methylation that mediate the progression of MM to PCL may offer...... the various cytogenetic subgroups of MM and in mediating the transition to PCL. Hypermethylation affects genes and pathways important in retaining plasma cells in the bone marrow as well as in their growth factor independent growth in the absence of stromal cell support. DisclosuresNo relevant conflicts...

  18. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    International Nuclear Information System (INIS)

    Dvorak, J; Kasaova, L; Filip, S; Petera, J; Sitorova, V; Nikolov, D Hadzi; Ryska, A; Mokry, J; Richter, I

    2011-01-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G 1 (G 0 ) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  19. Primary cilium - antenna-like structure on the surface of most mammalian cell types

    Science.gov (United States)

    Dvorak, J.; Sitorova, V.; Hadzi Nikolov, D.; Mokry, J.; Richter, I.; Kasaova, L.; Filip, S.; Ryska, A.; Petera, J.

    2011-12-01

    The primary cilium is a sensory solitary non-motile microtubule-based organelle protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including embryonic cells, stem cells and stromal cells of malignant tumors. The presence of a primary cilium on the surface of a cell is transient, limited to the quiescent G1(G0) phase and the beginning of the S phase of the cell cycle. The primary cilium is formed from the mother centriole. Primary cilia are key coordinators of signaling pathways during development and tissue homeostasis and, when deffective, they are a major cause of human diseases and developmental disorders, now commonly referred to as ciliopathies. Most cancer cells do not possess a primary cilium. The loss of the primary cilium is a regular feature of neoplastic transformation in the majority of solid tumors. The primary cilium could serve as a tumor suppressor organelle. The aim of this paper was to provide a review of the current knowledge of the primary cilium.

  20. Cell type and transfection reagent-dependent effects on viability, cell content, cell cycle and inflammation of RNAi in human primary mesenchymal cells

    DEFF Research Database (Denmark)

    Yang, Hsiao Yin; Vonk, Lucienne A.; Licht, Ruud

    2014-01-01

    % amidation), for siRNA delivery into primary mesenchymal cells including nucleus pulposus cells, articular chondrocytes and mesenchymal stem cells (MSCs). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an endogenous model gene to evaluate the extent of silencing by 20 nM or 200 nM siRNA at day...

  1. Supporting Transition

    Science.gov (United States)

    Qureshi, Asima; Petrucco, James

    2018-01-01

    Meadowbrook Primary School has explored the use of The Teacher Assessment in Primary Science (TAPS) to support transition, initially for transfer to secondary school and now for transition from Early Years Foundation Stage (EYFS) into Key Stage 1 (ages 5-7). This article will consider an example of a secondary transition project and discuss the…

  2. The increase of microRNA-21 during lung fibrosis and its contribution to epithelial-mesenchymal transition in pulmonary epithelial cells.

    Science.gov (United States)

    Yamada, Mitsuhiro; Kubo, Hiroshi; Ota, Chiharu; Takahashi, Toru; Tando, Yukiko; Suzuki, Takaya; Fujino, Naoya; Makiguchi, Tomonori; Takagi, Kiyoshi; Suzuki, Takashi; Ichinose, Masakazu

    2013-09-24

    cells during bleomycin-induced lung fibrosis and human idiopathic pulmonary fibrosis. MicroRNA-21 was also upregulated in the cultured alveolar epithelial cells under the conditions that enhance epithelial-mesenchymal transition. Exogenous administration of a microRNA-21 inhibitor prevented the increased expression of vimentin and alpha-smooth muscle actin in cultured primary mouse alveolar type II cells under culture conditions that induce epithelial-mesenchymal transition. Our experiments demonstrate that microRNA-21 is increased in lung epithelial cells during lung fibrosis and that it promotes epithelial-mesenchymal transition.

  3. Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Meng Hang

    2015-06-01

    Full Text Available The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

  4. Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Jan Pavel Kucera

    2015-09-01

    Full Text Available Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs. However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands.CV was significantly lower in strands composed purely of SCMs (5.5±1.5 cm/s, n=11 as compared to PCMs (34.9±2.9 cm/s, n=21 at similar refractoriness (100% SCMs: 122±25 ms, n=9; 100% PCMs: 139±67 ms, n=14. In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV.These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.

  5. Multiple primary cancers: Simultaneously occurring prostate cancer ...

    African Journals Online (AJOL)

    We also reviewed the existing literatures for possible biologic links between prostatic carcinoma and other primary tumors. ... The primary tumors co-existing with prostate cancer were colonic adenocarcinoma, rectal adenocarcinoma, urinary bladder transitional cell carcinoma, primary liver cell carcinoma, and thyroid ...

  6. Staphylococcus aureus Lpl Lipoproteins Delay G2/M Phase Transition in HeLa Cells.

    Science.gov (United States)

    Nguyen, Minh-Thu; Deplanche, Martine; Nega, Mulugeta; Le Loir, Yves; Peisl, Loulou; Götz, Friedrich; Berkova, Nadia

    2016-01-01

    The cell cycle is an ordered set of events, leading to cell growth and division into two daughter cells. The eukaryotic cell cycle consists of interphase (G 1 , S, and G 2 phases), followed by the mitotic phase and G 0 phase. Many bacterial pathogens secrete cyclomodulins that interfere with the host cell cycle. In Staphylococcus aureus four cyclomodulins have been described so far that all represent toxins and are secreted into the culture supernatant. Here we show that the membrane-anchored lipoprotein-like proteins (Lpl), encoded on a genomic island called νSaα, interact with the cell cycle of HeLa cells. By comparing wild type and lpl deletion mutant it turned out that the lpl cluster is causative for the G2/M phase transition delay and also contributes to increased invasion frequency. The lipoprotein Lpl1, a representative of the lpl cluster, also caused G2/M phase transition delay. Interestingly, the lipid modification, which is essential for TLR2 signaling and activation of the immune system, is not necessary for cyclomodulin activity. Unlike the other staphylococcal cyclomodulins Lpl1 shows no cytotoxicity even at high concentrations. As all Lpl proteins are highly conserved there might be a common function that is accentuated by their multiplicity in a tandem gene cluster. The cell surface localized Lpls' suggests a correlation between G2/M phase transition delay and host cell invasion.

  7. Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

    Science.gov (United States)

    Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

    2018-05-01

    The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

  8. Prognostic relevance of epithelial-mesenchymal transition and proliferation in surgically treated primary parotid gland cancer.

    Science.gov (United States)

    Busch, Alina; Bauer, Larissa; Wardelmann, Eva; Rudack, Claudia; Grünewald, Inga; Stenner, Markus

    2017-05-01

    Cancer of the major salivary glands comprises a morphologically diverse group of rare tumours of largely unknown cause. Epithelial-mesenchymal transition (EMT) has been shown to play a significant prognostic role in various human cancers. The aim was to assess the expression of EMT markers in different histological subtypes of parotid gland cancer (PGC) and analyse their prognostic value. We examined 94 PGC samples (13 histological subtypes) for the expression of MIB-1, epithelial cadherin (E-cadherin), β-catenin, vimentin and cytokeratin 8/18 (CK8/18) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. We detected all analysed EMT and proliferation markers in specifically different constellations within the examined histological subtypes of PGC. We found high epithelial marker expressions (CK8/18, E-cadherin, membranous β-catenin) only in a distinct variety of carcinomas. A high proliferation rate (high MIB-1 expression) as well as a combination of high CK8/18 and low vimentin expression was associated with a significantly worse survival. Our findings indicate that activation of the EMT pathway is a relevant explanation for tumour progression in individual histological subtypes of malignant parotid gland lesions, but by far not in all. Evidence of EMT activation in PGC cannot be seen as an isolated prognostic factor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells During Prostate Cancer Metastasis

    Science.gov (United States)

    Ruscetti, Marcus; Quach, Bill; Dadashian, Eman L.; Mulholland, David J.; Wu, Hong

    2015-01-01

    The epithelial-mesenchymal transition (EMT) has been postulated as a mechanism by which cancer cells acquire the invasive and stem-like traits necessary for distant metastasis. However, direct in vivo evidence for the role of EMT in the formation of cancer stem-like cells (CSC) and the metastatic cascade remains lacking. Here we report the first isolation and characterization of mesenchymal and EMT tumor cells, which harbor both epithelial and mesenchymal characteristics, in an autochthonous murine model of prostate cancer. By crossing the established Pb-Cre+/−;PtenL/L;KrasG12D/+ prostate cancer model with a vimentin-GFP reporter strain, generating CPKV mice, we were able to isolate epithelial, EMT and mesenchymal cancer cells based on expression of vimentin and EpCAM. CPKV mice (but not mice with Pten deletion alone) exhibited expansion of cells with EMT (EpCAM+/Vim-GFP+) and mesenchymal (EpCAM−/Vim-GFP+) characteristics at the primary tumor site and in circulation. These EMT and mesenchymal tumor cells displayed enhanced stemness and invasive character compared to epithelial tumor cells. Moreover, they displayed an enriched tumor-initiating capacity and could regenerate epithelial glandular structures in vivo, indicative of epithelia-mesenchyme plasticity. Interestingly, while mesenchymal tumor cells could persist in circulation and survive in the lung following intravenous injection, only epithelial and EMT tumor cells could form macrometastases. Our work extends the evidence that mesenchymal and epithelial states in cancer cells contribute differentially to their capacities for tumor initiation and metastatic seeding, respectively, and that EMT tumor cells exist with plasticity that can contribute to multiple stages of the metastatic cascade. PMID:25948589

  10. Regulation of Pituitary Stem Cells by Epithelial to Mesenchymal Transition Events and Signaling Pathways

    Science.gov (United States)

    Cheung, Leonard Y. M.; Davis, Shannon W.; Brinkmeier, Michelle L.; Camper, Sally A.; Pérez-Millán, María Inés

    2017-01-01

    The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. The adult anterior pituitary responds to physiological challenge by mobilizing the SOX2-expressing progenitor pool and producing additional hormone-producing cells. Knowledge of the role of signaling pathways and extracellular matrix components in these processes may lead to improvements in the efficiency of differentiation of embryonic stem cells or induced pluripotent stem cells into hormone producing cells in vitro. Advances in our basic understanding of pituitary stem cell regulation and differentiation may lead to improved diagnosis and treatment for patients with hypopituitarism. PMID:27650955

  11. Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation.

    Science.gov (United States)

    Chen, Zhong-Shu; Ling, Dong-Jin; Zhang, Yang-De; Feng, Jian-Xiong; Zhang, Xue-Yu; Shi, Tian-Sheng

    2015-03-01

    Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial‑mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the β‑catenin/E‑cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N‑cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting β‑catenin/E‑cadherin complex degradation and regulating nuclear localization of β‑catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the β‑catenin/E‑cadherin complex was regulated by Oct4 during the process of EMT.

  12. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Fourth Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2013-01-01

    SunLine Transit Agency, which provides public transit services to the Coachella Valley area of California, has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technology (AT) fuel cell bus with a hybrid electric propulsion system, fuel cell power system, and lithium-based hybrid batteries. This report describes operations at SunLine for the AT fuel cell bus and five compressed natural gas buses. The U.S. Department of Energy's National Renewable Energy Laboratory (NREL) is working with SunLine to evaluate the bus in real-world service to document the results and help determine the progress toward technology readiness. NREL has previously published three reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from February 2012 through November 2012.

  13. The application of transition metal ion chromatography to the determination of elemental and radiochemical species in PWR primary coolant

    International Nuclear Information System (INIS)

    Bridle, D.A.; Brown, G.R.; Johnson, P.A.V.

    1992-01-01

    The accurate determination of both elemental and radiochemical transition metal corrosion products, particularly cobalt and nickel, in PWR coolants is necessary if the transport mechanisms and their role in the development of out-of-core radiation fields are to be fully understood. AEA Technology, Winfrith, has collaborated for several years with a number of PWR utilities in Europe, developing advanced sampling and analytical techniques for the determination of both soluble and insoluble corrosion products in primary coolant. The design and installation of continuously flowing isokinetic capillary modifications to the existing sampling systems has been shown to be an effective method of providing a low, but representative, sample flow from high pressure systems for on-line determination of corrosion product species. Transition metal ion chromatography coupled with gamma-spectrometry has been used to determine both insoluble and soluble elemental and radiochemical species in reactor coolant, with particular attention being given to the determination of soluble elemental cobalt at levels as low as 1 ng per kg. Soluble species were determined directly following their concentration from up to 1 litre of coolant. Insoluble species collected on 0.45 micron filter membranes, following filtration of up to 1500 litres of coolant, were solubilised by fusion with potassium hydrogen sulphate before the application of ion chromatography. In each case the eluant from the chromatographic column was collected and the radionuclides determined by gamma-spectrometry

  14. Potential of primary kidney cells for somatic cell nuclear transfer mediated transgenesis in pig

    Directory of Open Access Journals (Sweden)

    Richter Anne

    2012-11-01

    Full Text Available Abstract Background Somatic cell nuclear transfer (SCNT is currently the most efficient and precise method to generate genetically tailored pig models for biomedical research. However, the efficiency of this approach is crucially dependent on the source of nuclear donor cells. In this study, we evaluate the potential of primary porcine kidney cells (PKCs as cell source for SCNT, including their proliferation capacity, transfection efficiency, and capacity to support full term development of SCNT embryos after additive gene transfer or homologous recombination. Results PKCs could be maintained in culture with stable karyotype for up to 71 passages, whereas porcine fetal fibroblasts (PFFs and porcine ear fibroblasts (PEFs could be hardly passaged more than 20 times. Compared with PFFs and PEFs, PKCs exhibited a higher proliferation rate and resulted in a 2-fold higher blastocyst rate after SCNT and in vitro cultivation. Among the four transfection methods tested with a GFP expression plasmid, best results were obtained with the NucleofectorTM technology, resulting in transfection efficiencies of 70% to 89% with high fluorescence intensity, low cytotoxicity, good cell proliferation, and almost no morphological signs of cell stress. Usage of genetically modified PKCs in SCNT resulted in approximately 150 piglets carrying at least one of 18 different transgenes. Several of those pigs originated from PKCs that underwent homologous recombination and antibiotic selection before SCNT. Conclusion The high proliferation capacity of PKCs facilitates the introduction of precise and complex genetic modifications in vitro. PKCs are thus a valuable cell source for the generation of porcine biomedical models by SCNT.

  15. Cell-surface proteoglycan in sea urchin primary mesenchyme cell migration

    International Nuclear Information System (INIS)

    Lane, M.C.

    1989-01-01

    Early in the development of the sea urchin embryo, the primary mesenchyme cells (PMC) migrate along the basal lamina of the blastocoel. Migration is inhibited in L. pictus embryos cultured in sulfate-free seawater and in S. purpuratus embryos exposed to exogenous β-D-xylosides. An in vitro assay was developed to test the migratory capacity of normal PMC on normal and treated blastocoelic matrix. Sulfate deprivation and exposure to exogenous xyloside render PMC nonmotile on either matrix. Materials removed from the surface of normal PMC by treatment with 1 M urea restored migratory ability to defective cells, whereas a similar preparation isolated from the surface of epithelial cells at the same stage did not. Migration also resumed when cells were removed from the xyloside or returned to normal seawater. The urea extract was partially purified and characterized by radiolabeling, gel electrophoresis, fluorography, ion exchange chromatography, and western blotting. The PMC synthesize a large chondroitin sulfate/dermatan sulfate proteoglycan that is present in an active fraction isolated by chromatography. Chondroitinase ABC digestion of live cells blocked migration reversibly, further supporting the identification of the chondroitin sulfate/dermatan sulfate proteoglycan as the active component in the urea extract. Much of the incorporated sulfate was distributed along the filopodia in 35 SO 4 -labelled PMC by autoradiography. The morphology of normal and treated S. purpuratus PMC was examined by scanning electron microscopy, and differences in spreading, particularly of the extensive filopodia present on the cells, was observed. A model for the role of the chondroitin sulfate/dermatan sulfate proteoglycan in cell detachment during migration is proposed

  16. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Cui, Ju; Jin, Guoxiang; Yu, Bin; Wang, Zai; Lin, Raozhou; Huang, Jian-Dong

    2015-01-01

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown

  17. Stable knockdown of Kif5b in MDCK cells leads to epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing (China); Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Jin, Guoxiang; Yu, Bin [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Wang, Zai [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Lin, Raozhou [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR (China); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China)

    2015-07-17

    Polarization of epithelial cells requires vectorial sorting and transport of polarity proteins to apical or basolateral domains. Kif5b is the mouse homologue of the human ubiquitous Kinesin Heavy Chain (uKHC). To investigate the function of Kif5b in epithelial cells, we examined the phenotypes of Kif5b-deficient MDCK cells. Stable knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate, profound changes in cell morphology, loss of epithelial cell marker, and gain of mesenchymal marker, as well as increased cell migration, invasion, and tumorigenesis abilities. E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells, and their expression levels were decreased in Kif5b-deficient MDCK cells. Overexpression of E-cadherin and NMMIIA in Kif5b depleted MDCK cells could decrease mesenchymal marker expression and cell migration ability. These results indicate that stable knockdown of Kif5b in MDCK cells can lead to epithelial–mesenchymal transition, which is mediated by defective E-cadherin and NMMIIA expression. - Highlights: • Knockdown of Kif5b in MDCK cells resulted in reduced cell proliferation rate. • Kif5b deficient MDCK cells underwent epithelial–mesenchymal transition. • E-cadherin and NMMIIA could interact with Kif5b in polarized MDCK cells. • Decreased E-cadherin and NMMIIA levels mediate EMT in Kif5b deficient MDCK cells. • Overexpression of E-cadherin and NMMIIA reverse the effects of Kif5b knockdown.

  18. Primary intraosseous squamous cell carcinoma of the mandible arising de novo.

    Science.gov (United States)

    Shamim, Thorakkal

    2009-07-01

    Primary intraosseous squamous cell carcinoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th to 7th decades of life. The tumour is characterized by progressive swelling of the jaw, pain and loosening of teeth. Microscopically, the lesion is showing foci of keratinising cells separated by collagenous connective tissue stroma. A case of primary intraosseous squamous cell carcinoma of mandible arising de novo in a 40-year-old man is reported.

  19. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

    OpenAIRE

    Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring...

  20. Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

    Directory of Open Access Journals (Sweden)

    Sarah Phillips

    2014-05-01

    Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

  1. Rapid Fatal Outcome from Pulmonary Arteries Compression in Transitional Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ioannis A. Voutsadakis

    2009-01-01

    Full Text Available Transitional cell carcinoma of the urinary bladder is a malignancy that metastasizes frequently to lymph nodes including the mediastinal lymph nodes. This occurrence may produce symptoms due to compression of adjacent structures such as the superior vena cava syndrome or dysphagia from esophageal compression. We report the case of a 59-year-old man with metastatic transitional cell carcinoma for whom mediastinal lymphadenopathy led to pulmonary artery compression and a rapidly fatal outcome. This rare occurrence has to be distinguished from pulmonary embolism, a much more frequent event in cancer patients, in order that proper and prompt treatment be initiated.

  2. Primary cell culture and morphological characterization of canine dermal papilla cells and dermal fibroblasts.

    Science.gov (United States)

    Bratka-Robia, Christine B; Mitteregger, Gerda; Aichinger, Amanda; Egerbacher, Monika; Helmreich, Magdalena; Bamberg, Elmar

    2002-02-01

    Skin biopsies were taken from female dogs, the primary hair follicles isolated and the dermal papilla dissected. After incubation in supplemented Amniomax complete C100 medium in 24-well culture plates, the dermal papilla cells (DPC) grew to confluence within 3 weeks. Thereafter, they were subcultivated every 7 days. Dermal fibroblast (DFB) cultures were established by explant culture of interfollicular dermis in serum-free medium, where they reached confluence in 10 days. They were subcultivated every 5 days. For immunohistochemistry, cells were grown on cover slips for 24 h, fixed and stained with antibodies against collagen IV and laminin. DPC showed an aggregative growth pattern and formation of pseudopapillae. Intensive staining for collagen IV and laminin could be observed until the sixth passage. DFB grew as branching, parallel lines and showed only weak staining for collagen IV and laminin.

  3. Origin of the Hawaiian rainforest and its transition states in long-term primary succession

    Science.gov (United States)

    Mueller-Dombois, D.; Boehmer, H. J.

    2013-07-01

    This paper addresses the question of transition states in the Hawaiian rainforest ecosystem with emphasis on their initial developments. Born among volcanoes in the north central Pacific about 4 million years ago, the Hawaiian rainforest became assembled from spores of algae, fungi, lichens, bryophytes, ferns and from seeds of about 275 flowering plants that over the millennia evolved into ca. 1000 endemic species. Outstanding among the forest builders were the tree ferns (Cibotium spp.) and the 'ōhi'a lehua trees (Metrosideros spp.), which still dominate the Hawaiian rainforest ecosystem today. The structure of this forest is simple. The canopy in closed mature rainforests is dominated by cohorts of Metrosideros polymorpha and the undergrowth by tree fern species of Cibotium. When a new lava flow cuts through this forest, kipuka are formed, i.e., islands of remnant vegetation. On the new volcanic substrate, the assemblage of plant life forms is similar to the assemblage during the evolution of this system. In open juvenile forests, a mat-forming fern, the uluhe fern (Dicranopteris linearis), becomes established. It inhibits further regeneration of the dominant 'ōhi'a tree, thereby reinforcing the cohort structure of the canopy guild. In the later part of its life cycle, the canopy guild breaks down often in synchrony. The trigger is hypothesized to be a climatic perturbation. After the disturbance, the forest becomes reestablished in about 30-40 yr. As the volcanic surfaces age, they go from a mesotrophic to a eutrophic phase, reaching a biophilic nutrient climax by about 1-25 K yr. Thereafter, a regressive oligotrophic phase follows; the soils become exhausted of nutrients. The shield volcanoes break down. Marginally, forest habitats change into bogs and stream ecosystems. The broader 'ōhi'a rainforest redeveloping in the more dissected landscapes of the older islands loses stature, often forming large gaps that are invaded by the aluminum tolerant uluhe fern

  4. Origin of the Hawaiian rainforest and its transition states in long-term primary succession

    Directory of Open Access Journals (Sweden)

    D. Mueller-Dombois

    2013-07-01

    Full Text Available This paper addresses the question of transition states in the Hawaiian rainforest ecosystem with emphasis on their initial developments. Born among volcanoes in the north central Pacific about 4 million years ago, the Hawaiian rainforest became assembled from spores of algae, fungi, lichens, bryophytes, ferns and from seeds of about 275 flowering plants that over the millennia evolved into ca. 1000 endemic species. Outstanding among the forest builders were the tree ferns (Cibotium spp. and the 'ōhi'a lehua trees (Metrosideros spp., which still dominate the Hawaiian rainforest ecosystem today. The structure of this forest is simple. The canopy in closed mature rainforests is dominated by cohorts of Metrosideros polymorpha and the undergrowth by tree fern species of Cibotium. When a new lava flow cuts through this forest, kipuka are formed, i.e., islands of remnant vegetation. On the new volcanic substrate, the assemblage of plant life forms is similar to the assemblage during the evolution of this system. In open juvenile forests, a mat-forming fern, the uluhe fern (Dicranopteris linearis, becomes established. It inhibits further regeneration of the dominant 'ōhi'a tree, thereby reinforcing the cohort structure of the canopy guild. In the later part of its life cycle, the canopy guild breaks down often in synchrony. The trigger is hypothesized to be a climatic perturbation. After the disturbance, the forest becomes reestablished in about 30–40 yr. As the volcanic surfaces age, they go from a mesotrophic to a eutrophic phase, reaching a biophilic nutrient climax by about 1–25 K yr. Thereafter, a regressive oligotrophic phase follows; the soils become exhausted of nutrients. The shield volcanoes break down. Marginally, forest habitats change into bogs and stream ecosystems. The broader 'ōhi'a rainforest redeveloping in the more dissected landscapes of the older islands loses stature, often forming large gaps that are invaded by the aluminum

  5. Identification of differences in gene expression in primary cell cultures of human endometrial epithelial cells and trophoblast cells following their interaction

    DEFF Research Database (Denmark)

    Høgh, Mette; Islin, Henrik; Møller, Charlotte

    2006-01-01

    The interaction between the cell types was simulated in vitro by growing primary cell cultures of human endometrial epithelial cells and trophoblast cells together (co-culture) and separately (control cultures). Gene expression in the cell cultures was compared using the Differential Display method and confirmed...

  6. Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes

    International Nuclear Information System (INIS)

    Kadohira, Ikuko; Abe, Yoichiro; Nuriya, Mutsuo; Sano, Kazumi; Tsuji, Shoji; Arimitsu, Takeshi; Yoshimura, Yasunori; Yasui, Masato

    2008-01-01

    Aquaporin-4 (AQP4) is expressed in the perivascular and subpial astrocytes end-feet in mammalian brain, and plays a critical component of an integrated water and potassium homeostasis. Here we examine whether AQP4 is phosphorylated in primary cultured mouse astrocytes. Astrocytes were metabolically labeled with [ 32 P]phosphoric acid, then AQP4 was immunoprecipitated with anti-AQP4 antibody. We observed that AQP4 was constitutively phosphorylated, which is reduced by treatment with protein kinase CK2 inhibitors. To elucidate the phosphorylation of AQP4 by CK2, myc-tagged wild-type or mutant AQP4 was transiently transfected in primary cultured astrocytes. Substitution of Ala residues for four putative CK2 phosphorylation sites in the C terminus abolished the phosphorylation of AQP4. Immunofluorescent microscopy revealed that the quadruple mutant was localized in the Golgi apparatus. These observations indicate that the C-terminal domain of AQP4 is constitutively phosphorylated at least in part by protein kinase CK2 and it is required for Golgi transition.

  7. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available Lung cancer (LC with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC, large cell carcinoma (LCC, squamous cell carcinoma (SCC and adenocarcinoma (AC. We identified a small population of cells strongly positive for CD44 (CD44(high and a main population which was either weakly positive or negative for CD44 (CD44(low/-. Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(highCD90(+ sub-population. Moreover, these CD44(highCD90(+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(highCD90(+ population a good candidate for the lung CSCs. Both CD44(highCD90(+ and CD44(highCD90(- cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/- cells were lacking this potential. These results indicate that CD44(highCD90(+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high sub-population.

  8. Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

    Science.gov (United States)

    Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

    2013-01-01

    Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

  9. Effects of Tyrosine Kinase inhibitor Imatinib (Glivec) on PDGFR-positive primary and metastatic melanoma cells

    International Nuclear Information System (INIS)

    Straface, E.; Gambardella, L.; Vona, R.

    2009-01-01

    In summary these preliminary results indicate that Imatinib is able to induce apoptosis in metastatic cells and to sensitize these cells to pro-apoptotic agents commonly used in melanoma therapy, e.g. radiation or Cisplatin. Conversely, primary melanoma cells seem to be intrinsically resistant either to Imatinib given alone or in combination with Cisplatin or radiation. By contrast, these cells underwent autophagy and replicative senescence boostering their survival. Interestingly, the use of Imatinib in combination with anti-CD95/Fas antibodies sensitizes primary melanoma cells to apoptosis

  10. Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

    Science.gov (United States)

    Fernández-Guarino, M; Ortiz-Romero, P L; Fernández-Misa, R; Montalbán, C

    2014-06-01

    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  11. Transition of care: experiences and preferences of patients across the primary/secondary interface – a qualitative study

    Directory of Open Access Journals (Sweden)

    Dekker Janny H

    2009-04-01

    Full Text Available Abstract Background Coordination between care providers of different disciplines is essential to improve the quality of care, in particular for patients with chronic diseases. The way in which general practitioners (GP's and medical specialists interact has important implications for any healthcare system in which the GP plays the role of gatekeeper to specialist care. Patient experiences and preferences have proven to be increasingly important in discussing healthcare policy. The Dutch government initiated the development of a special website with information for patients on performance indicators of hospitals as well as information on illness or treatment. In the present study we focus on the transition of care at the primary – secondary interface with reference to the impact of patients' ability to make choices about their secondary care providers. The purpose of this study is to (a explore experiences and preferences of patients regarding the transition between primary and secondary care, (b study informational resources on illness/treatment desired by patients and (c determine how information supplied could make it easier for the patient to choose between different options for care (hospital or specialist. Methods We conducted a qualitative study using semi-structured focus group interviews among 71 patients referred for various indications in the north and west of The Netherlands. Results Patients find it important that they do not have to wait, that they are taken seriously, and receive adequate and individually relevant information. A lack of continuity from secondary to primary care was experienced. The patient's desire for free choice of type of care did not arise in any of the focus groups. Conclusion Hospital discharge information needs to be improved. The interval between discharge from specialist care and the report of the specialist to the GP might be a suitable performance indicator in healthcare. Patients want to receive

  12. Posttransplantation primary cutaneous CD30 (Ki-1)-positive large-cell lymphoma.

    Science.gov (United States)

    Seçkin, D; Demirhan, B; Oğuz Güleç, T; Arikan, U; Haberal, M

    2001-12-01

    We describe the case of a 51-year-old female renal transplant recipient with primary cutaneous CD30-positive large-cell lymphoma of T-cell origin. Cutaneous T-cell lymphomas are rarely reported in organ transplant recipients, and we believe they should be considered in the differential diagnosis of cutaneous neoplastic and infectious diseases affecting this patient group.

  13. Primary clear cell sarcoma of bone: a unique site of origin

    International Nuclear Information System (INIS)

    Gelczer, R.K.; Wenger, D.E.; Wold, L.E.

    1999-01-01

    Clear cell sarcoma is a rare soft tissue neoplasm, accounting for less than 1% of soft tissue sarcomas. We are presenting a case of a clear cell sarcoma of bone which, to our knowledge, is the only report of a primary clear cell sarcoma of bone. (orig.)

  14. Pediatric to Adult Care Transition: Perspectives of Young Adults With Sickle Cell Disease.

    Science.gov (United States)

    Porter, Jerlym S; Wesley, Kimberly M; Zhao, Mimi S; Rupff, Rebecca J; Hankins, Jane S

    2017-10-01

    The aim of this study was to explore perspectives of transition and transition readiness of young adult patients (YAs) with sickle cell disease (SCD) who have transitioned to adult health care. In all, 19 YAs with SCD (ages 18-30 years) participated in one of three focus groups and completed a brief questionnaire about transition topics. Transcripts were coded and emergent themes were examined using the social-ecological model of adolescent and young adult readiness for transition (SMART). Themes were consistent with most SMART components. Adult provider relationships and negative medical experiences emerged as salient factors. YAs ranked choosing an adult provider, seeking emergency care, understanding medications/medication adherence, knowing SCD complications, and being aware of the impact of health behaviors as the most important topics to include in transition programming. The unique perspectives of YAs can inform the development and evaluation of SCD transition programming by incorporating the identified themes. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  15. The nature and dynamic of phase transitions during cooling - warming of garlic cell sap

    Directory of Open Access Journals (Sweden)

    А. Т. Ходько

    2015-04-01

    Full Text Available To identify the type of phase transition during cooling-warming in the garlic cell sap by cryomicroscopy of samples in transmitted light phenomenon of critical opalescence was recorded. Critical state is peculiar only for phase transitions between the isotropic mediums. This fact gives grounds to include phase transition in the investigated system to liquid-liquid type, which proceeds according to spinodal mechanism and nucleus growth mechanism. During rapid cooling cracking of the samples due to high internal stresses (in contrast to the slow cooling was observed. After the phase transition during cooling rouglydispersed system – highly concentrated emulsion-gel was formed. Signs of crystallization in the system under the studied conditions were not found.

  16. Investigation of microwave transitions and nonlinear magneto-optical rotation in anti-relaxation-coated cells

    International Nuclear Information System (INIS)

    Budker, D.; Hollberg, L.; Kimball, D.F.; Kitching, J.; Pustclny, S.; Robinson, H.G.; Yashchuk, V.V.

    2004-01-01

    Using laser optical pumping, widths and frequency shifts are determined for microwave transitions between the components of the ground-state hyperfine structure for 85 Rb and 87 Rb atoms contained in vapor cells with alkane anti-relaxation coatings. The results are compared with data on Zeeman relaxation obtained in nonlinear magneto-optical rotation (NMOR) experiments, a comparison important for quantitative understanding of spin-relaxation mechanisms in coated cells. By comparing cells manufactured over a forty-year period we demonstrate the long-term stability of coated cells, which may be useful for atomic clocks and magnetometers

  17. Investigation of microwave transitions and nonlinear magneto-optical rotation in anti-relaxation-coated cells

    International Nuclear Information System (INIS)

    Budker, Dmitry; Hollberg, Leo; Kimball, Derek F.; Kitching, J.; Pustelny, Szymon; Yashchuk, Valeriy V.

    2004-01-01

    Using laser optical pumping, widths and frequency shifts are determined for microwave transitions between ground-state hyperfine components of 85 Rb and 87 Rb atoms contained in vapor cells with alkane anti-relaxation coatings. The results are compared with data on Zeeman relaxation obtained in nonlinear magneto-optical rotation (NMOR) experiments, a comparison important for quantitative understanding of spin-relaxation mechanisms in coated cells. By comparing cells manufactured over a forty-year period we demonstrate the long-term stability of coated cells, an important property for atomic clocks and magnetometers

  18. Impact of primary metastatic bone disease in germ cell tumors

    DEFF Research Database (Denmark)

    Oing, C; Oechsle, K; Necchi, A

    2017-01-01

    (multivariate Cox regression; HR, 0.32; P=0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for non-seminoma patients. Conclusions: Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected...

  19. Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells

    Directory of Open Access Journals (Sweden)

    Rattner Jerome B

    2009-12-01

    Full Text Available Abstract Background Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. Methods Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. Results We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. Conclusions The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first

  20. A case with primary signet ring cell adenocarcinoma of the prostate and review of the literature

    Directory of Open Access Journals (Sweden)

    Orcun Celik

    2014-06-01

    Full Text Available Primary signet cell carcinoma of the prostate is a rare histological variant of prostate malignancies. It is commonly originated from the stomach, colon, pancreas, and less commonly in the bladder. Prognosis of the classical type is worse than the adenocarcinoma of the prostate. Primary signet cell adenocarcinoma is diagnosed by eliminating the adenocarcinomas of other organs such as gastrointestinal tract organs. In this case report, we present a case with primary signet cell adenocarcinoma of the prostate who received docetaxel chemotherapy because of short prostate specific antigen doubling time.

  1. Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines

    Czech Academy of Sciences Publication Activity Database

    Skalníková, Helena; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2011-01-01

    Roč. 11, - (2011), s. 691-708 ISSN 1615-9853 R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) ME10044 Institutional research plan: CEZ:AV0Z50450515 Keywords : cell biology * conditioned media * cytokine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.505, year: 2011

  2. Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency.

    Science.gov (United States)

    Leng, Lizhi; Tan, Yueqiu; Gong, Fei; Hu, Liang; Ouyang, Qi; Zhao, Yan; Lu, Guangxiu; Lin, Ge

    2015-03-01

    Can the induced pluripotent stem cells (iPSCs) derived from women with primary ovarian insufficiency (POI) differentiate into germ cells for potential disease modeling in vitro? The iPSC lines derived from POI patients with 46, X, del(X)(q26) or 46, X, del(X)(q26)9qh+ could differentiate into germ cells and expressed lower levels of genes in the deletion region of the X chromosome. iPSC technology has been envisioned as an approach for generating patient-specific stem cells for disease modeling and for developing novel therapies. It has also been confirmed that iPSCs differentiate into germ cells. We compared the differentiation ability of germ cells and the gene expression level of germ cell-related genes in the X chromosome deletion region of iPSC lines derived from POI patients (n = 2) with an iPSC line derived from normal fibroblasts (n = 1). We established three iPSC lines from two patients with partial Xq deletion-induced POI and normal fibroblasts by overexpressing four factors: octamer-binding transcription factor 4 (OCT4), sex-determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and lin-28 homolog (LIN28), using lentiviral vectors. We then generated stable-transfected fluorescent reporter cell lines under the control of the Asp-Glu-Ala-Asp box polypeptide 4 (DDX4, also called VASA) promoter, and selected clonal derived sublines. We induced subline differentiation into germ cells by adding Wnt3a (30 ng/ml) and bone morphogenetic protein 4 (100 ng/ml). After 12 days of differentiation, green fluorescent protein (GFP)-positive and GFP-negative cells were isolated via fluorescence-activated cell sorting and analyzed for endogenous VASA protein (immunostaining) and for germ cell markers and genes expressed in the deleted region of the X chromosome (quantitative RT-PCR). The POI- and normal fibroblast-derived iPSCs had typical self-renewal and pluripotency characteristics. After stable transfection with the VASA-GFP construct, the sublines POI1-iPS-V.1

  3. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2010

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.; Gigakis, C.

    2010-11-01

    This status report, fourth in a series of annual status reports from the U.S. Department of Energy's National Renewable Energy Laboratory, summarizes progress and accomplishments from demonstrations of fuel cell transit buses in the United States. This year's assessment report provides the results from the fifth year of operation of five Van Hool, ISE, and UTC Power fuel cell buses operating at AC Transit, SunLine, and CTTRANSIT. The achievements and challenges of this bus design, implementation, and operating are presented, with a focus on the next steps for implementing larger numbers and new and different designs of fuel cell buses. The major positive result from nearly five years of operation is the dramatic increase in reliability experienced for the fuel cell power system.

  4. Osteo-/odontogenic differentiation of induced mesenchymal stem cells generated through epithelial-mesenchyme transition of cultured human keratinocytes.

    Science.gov (United States)

    Yi, Jin-Kyu; Mehrazarin, Shebli; Oh, Ju-Eun; Bhalla, Anu; Oo, Jenessa; Chen, Wei; Lee, Min; Kim, Reuben H; Shin, Ki-Hyuk; Park, No-Hee; Kang, Mo K

    2014-11-01

    Revascularization of necrotic pulp has been successful in the resolution of periradicular inflammation; yet, several case studies suggest the need for cell-based therapies using mesenchymal stem cells (MSCs) as an alternative for de novo pulp regeneration. Because the availability of MSCs may be limited, especially in an aged population, the current study reports an alternative approach in generating MSCs from epidermal keratinocytes through a process called epithelial-mesenchymal transition (EMT). We induced EMT in primary normal human epidermal keratinocytes (NHEKs) by transient transfection of small interfering RNA targeting the p63 gene. The resulting cells were assayed for their mesenchymal marker expression, proliferation capacities as a monolayer and in a 3-dimensional collagen scaffold, and differentiation capacities. Transient transfection of p63 small-interfering RNA successfully abolished the expression of endogenous p63 in NHEKs and induced the expression of mesenchymal markers (eg, vimentin and fibronectin), whereas epithelial markers (eg, E-cadherin and involucrin) were lost. The NHEKs exhibiting the EMT phenotype acquired extended replicative potential and an increased telomere length compared with the control cells. Similar to the established MSCs, the NHEKs with p63 knockdown showed attachment onto the 3-dimensional collagen scaffold and underwent progressive proliferation and differentiation. Upon differentiation, these EMT cells expressed alkaline phosphatase activity, osteocalcin, and osteonectin and readily formed mineralized nodules detected by alizarin S red staining, showing osteo-/odontogenic differentiation. The induction of EMT in primary NHEKs by means of transient p63 knockdown allows the generation of induced MSCs from autologous sources. These cells may be used for tissues engineering purposes, including that of dental pulp. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Effects of calcitriol, seocalcitol, and medium-chain triglyceride on a canine transitional cell carcinoma cell line

    DEFF Research Database (Denmark)

    Kaewsakhorn, T.; Kisseberth, W.C.; Capen, C.C.

    2005-01-01

    Background: Transitional cell carcinoma (TCC) in dogs is associated with high morbidity and mortality. Calcitriol and its analog seocalcitol, combined with medium-chain triglyceride (MCT), have potential for the treatment of this disease. Materials and Methods: TCC cells were treated with calcitr...... inhibited TCC cell growth via induction of cell cycle arrest and MCT enhanced this effect. Therefore, calcitriol and seocalcitol with MCT may have therapeutic potential for canine bladder cancer....... with calcitriol or seocalcitol, alone or combined with MCT. Cell growth, cell cycle kinetics, vitamin D receptor (VDR) localization and expression, and Bcl-2 expression were measured. Results: Canine TCC expresses high levels of nuclear VDR. Furthermore, calcitriol and seocalcitol significantly inhibited cell...

  6. Dual-axis vapor cell for simultaneous laser frequency stabilization on disparate optical transitions

    Science.gov (United States)

    Jayakumar, Anupriya; Plotkin-Swing, Benjamin; Jamison, Alan O.; Gupta, Subhadeep

    2015-07-01

    We have developed a dual-axis ytterbium (Yb) vapor cell and used it to simultaneously address the two laser cooling transitions in Yb at wavelengths 399 nm and 556 nm, featuring the disparate linewidths of 2π × 29 MHz and 2π × 182 KHz, respectively. By utilizing different optical paths for the two wavelengths, we simultaneously obtain comparable optical densities suitable for saturated absorption spectroscopy for both the transitions and keep both the lasers frequency stabilized over several hours. We demonstrate that by appropriate control of the cell temperature profile, two atomic transitions differing in relative strength across a large range of over three orders of magnitude can be simultaneously addressed, making the device adaptable to a variety of spectroscopic needs. We also show that our observations can be understood with a simple theoretical model of the Yb vapor.

  7. Dual-axis vapor cell for simultaneous laser frequency stabilization on disparate optical transitions

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Anupriya, E-mail: anupriya@uw.edu; Plotkin-Swing, Benjamin; Jamison, Alan O.; Gupta, Subhadeep [Department of Physics, University of Washington, P.O. Box 351560, Seattle, Washington 98195-1560 (United States)

    2015-07-15

    We have developed a dual-axis ytterbium (Yb) vapor cell and used it to simultaneously address the two laser cooling transitions in Yb at wavelengths 399 nm and 556 nm, featuring the disparate linewidths of 2π × 29 MHz and 2π × 182 KHz, respectively. By utilizing different optical paths for the two wavelengths, we simultaneously obtain comparable optical densities suitable for saturated absorption spectroscopy for both the transitions and keep both the lasers frequency stabilized over several hours. We demonstrate that by appropriate control of the cell temperature profile, two atomic transitions differing in relative strength across a large range of over three orders of magnitude can be simultaneously addressed, making the device adaptable to a variety of spectroscopic needs. We also show that our observations can be understood with a simple theoretical model of the Yb vapor.

  8. Considerations for the transition from fuel cell R ampersand D to manufacturing

    International Nuclear Information System (INIS)

    Cobb, M.A.

    1992-01-01

    There are a growing number of contractors within the present fuel cell community who have the potential of becoming high volume manufacturers of fuel cell power plants or components. Many are transitioning from basic research operations to manufacturing for the first time. Moving a product from the R ampersand D stage to a viable commercial product depends upon many factors. Some companies are more successful at it than others. We believe there is an underlying transition process from invention to market that is much the same for large, well established firms, as it is for start-ups. How well the process is understood and executed often determines the winners and losers in product commercialization. This paper presents a viewpoint on considerations for transitioning a new technology into commercial production and discusses some affects on organizational development

  9. Fuel Cell Buses in U.S. Transit Fleets: Current Status 2012

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chander, K.; Gikakis, C.

    2012-11-01

    This report is the sixth in an annual series of reports that summarize the progress of fuel cell electric bus (FCEB) development in the United States and discuss the achievements and challenges of introducing fuel cell propulsion in transit. The report also provides a snapshot of current FCEB performance results over the last year. There are 25 active FCEBs in demonstrations this year at eight locations.

  10. Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes

    Science.gov (United States)

    Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Petzold-Quinque, Stefanie; Damm, Georg; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2014-01-01

    Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells. PMID:24603648

  11. Resveratrol differentially regulates NAMPT and SIRT1 in Hepatocarcinoma cells and primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Susanne Schuster

    Full Text Available Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382. Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells.

  12. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    Casado, L.; Mansilla, F.; Mansilla, M.D.; Marin, A.

    1998-01-01

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

  13. Cutaneous features seen in primary liver cell (Hepatocellular ...

    African Journals Online (AJOL)

    kemrilib

    features associated with the entity as a possible aid to diagnosis cutaneous features being considered a cheap tool that can help ... liver cell cancer (PLCC) and cancer of the breast and ... laboratory based -abdominal ultrasonography, liver.

  14. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

  15. Primary pleuro-pulmonary malignant germ cell tumours.

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2002-01-01

    Full Text Available Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

  16. Precise Temporal Profiling of Signaling Complexes in Primary Cells Using SWATH Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Etienne Caron

    2017-03-01

    Full Text Available Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primarycells, using the scaffold protein GRB2 as a model. The workflow also provided a sufficient level of robustness to pinpoint differential interaction dynamics between two similar, but functionally distinct, primarycell populations. Altogether, we demonstrated that precise and reproducible quantitative measurements of protein interaction dynamics can be achieved in primary cells isolated from mammalian tissues, allowing resolution of the tissue-specific context of cell-signaling events.

  17. Preprocessing with Photoshop Software on Microscopic Images of A549 Cells in Epithelial-Mesenchymal Transition.

    Science.gov (United States)

    Ren, Zhou-Xin; Yu, Hai-Bin; Shen, Jun-Ling; Li, Ya; Li, Jian-Sheng

    2015-06-01

    To establish a preprocessing method for cell morphometry in microscopic images of A549 cells in epithelial-mesenchymal transition (EMT). Adobe Photoshop CS2 (Adobe Systems, Inc.) was used for preprocessing the images. First, all images were processed for size uniformity and high distinguishability between the cell and background area. Then, a blank image with the same size and grids was established and cross points of the grids were added into a distinct color. The blank image was merged into a processed image. In the merged images, the cells with 1 or more cross points were chosen, and then the cell areas were enclosed and were replaced in a distinct color. Except for chosen cellular areas, all areas were changed into a unique hue. Three observers quantified roundness of cells in images with the image preprocess (IPP) or without the method (Controls), respectively. Furthermore, 1 observer measured the roundness 3 times with the 2 methods, respectively. The results between IPPs and Controls were compared for repeatability and reproducibility. As compared with the Control method, among 3 observers, use of the IPP method resulted in a higher number and a higher percentage of same-chosen cells in an image. The relative average deviation values of roundness, either for 3 observers or 1 observer, were significantly higher in Controls than in IPPs (p Photoshop, a chosen cell from an image was more objective, regular, and accurate, creating an increase of reproducibility and repeatability on morphometry of A549 cells in epithelial to mesenchymal transition.

  18. Real world data on primary treatment for mantle cell lymphoma

    DEFF Research Database (Denmark)

    Abrahamsson, Anna; Albertsson-Lindblad, Alexandra; Brown, Peter N

    2014-01-01

    to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000 to 2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased...... analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice....

  19. TGF-β signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: A study on human primary cell cultures.

    Directory of Open Access Journals (Sweden)

    Anna Maria Lustri

    Full Text Available Cholangiocarcinoma (CCA and its subtypes (mucin- and mixed-CCA arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i CX-4945, a casein kinase-2 (CK2 inhibitor that blocks TGF-β1-induced EMT; and (ii LY2157299, a TGF-β receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay.at a dose of 10 μM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30μM. At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA. Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks foci, suggesting the active role of CK2 as

  20. Gene transfer to primary corneal epithelial cells with an integrating lentiviral vector

    Directory of Open Access Journals (Sweden)

    Lauro Augusto de Oliveira

    2010-10-01

    Full Text Available PURPOSE: To evaluate the transfer of heterologous genes carrying a Green Fluorescent Protein (GFP reporter cassette to primary corneal epithelial cells ex vivo. METHODS: Freshly enucleated rabbit corneoscleral tissue was used to obtain corneal epithelial cell suspension via enzymatic digestion. Cells were plated at a density of 5×10³ cells/cm² and allowed to grow for 5 days (to 70-80% confluency prior to transduction. Gene transfer was monitored using fluorescence microscopy and fluorescence activated cell sorter (FACS. We evaluated the transduction efficiency (TE over time and the dose-response effect of different lentiviral particles. One set of cells were dual sorted by fluorescence activated cell sorter for green fluorescent protein expression as well as Hoechst dye exclusion to evaluate the transduction of potentially corneal epithelial stem cells (side-population phenotypic cells. RESULTS: Green fluorescent protein expressing lentiviral vectors were able to effectively transduce rabbit primary epithelial cells cultured ex vivo. Live cell imaging post-transduction demonstrated GFP-positive cells with normal epithelial cell morphology and growth. The transduction efficiency over time was higher at the 5th post-transduction day (14.1% and tended to stabilize after the 8th day. The number of transduced cells was dose-dependent, and at the highest lentivirus concentrations approached 7%. When double sorted by fluorescence activated cell sorter to isolate both green fluorescent protein positive and side population cells, transduced side population cells were identified. CONCLUSIONS: Lentiviral vectors can effectively transfer heterologous genes to primary corneal epithelial cells expanded ex vivo. Genes were stably expressed over time, transferred in a dose-dependence fashion, and could be transferred to mature corneal cells as well as presumable putative stem cells.

  1. Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

    Science.gov (United States)

    Carney, Colleen M.; Muszynski, Jessica L.; Strotman, Lindsay N.; Lewis, Samantha R.; O'Connell, Rachel L.; Beebe, David J.; Theberge, Ashleigh B.; Jorgensen, Joan S.

    2014-01-01

    ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture. PMID:25143354

  2. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  3. Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT)-Phenotypic Cells: Are They Cousins or Twins?

    International Nuclear Information System (INIS)

    Kong, Dejuan; Li, Yiwei; Wang, Zhiwei; Sarkar, Fazlul H.

    2011-01-01

    Cancer stem cells (CSCs) are cells within a tumor that possess the capacity to self-renew and maintain tumor-initiating capacity through differentiation into the heterogeneous lineages of cancer cells that comprise the whole tumor. These tumor-initiating cells could provide a resource for cells that cause tumor recurrence after therapy. Although the cell origin of CSCs remains to be fully elucidated, mounting evidence has demonstrated that Epithelial-to-Mesenchymal Transition (EMT), induced by different factors, is associated with tumor aggressiveness and metastasis and these cells share molecular characteristics with CSCs, and thus are often called cancer stem-like cells or tumor-initiating cells. The acquisition of an EMT phenotype is a critical process for switching early stage carcinomas into invasive malignancies, which is often associated with the loss of epithelial differentiation and gain of mesenchymal phenotype. Recent studies have demonstrated that EMT plays a critical role not only in tumor metastasis but also in tumor recurrence and that it is tightly linked with the biology of cancer stem-like cells or cancer-initiating cells. Here we will succinctly summarize the state-of-our-knowledge regarding the molecular similarities between cancer stem-like cells or CSCs and EMT-phenotypic cells that are associated with tumor aggressiveness focusing on solid tumors

  4. Change in cell shape is required for matrix metalloproteinase-induced epithelial-mesenchymal transition of mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Celeste M.; Khauv, Davitte; Bissell, Mina J.; Radisky, Derek C.

    2008-06-26

    Cell morphology dictates response to a wide variety of stimuli, controlling cell metabolism, differentiation, proliferation, and death. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells acquire migratory characteristics, and in the process convert from a 'cuboidal' epithelial structure into an elongated mesenchymal shape. We had shown previously that matrix metalloproteinase-3 (MMP3) can stimulate EMT of cultured mouse mammary epithelial cells through a process that involves increased expression of Rac1b, a protein that stimulates alterations in cytoskeletal structure. We show here that cells treated with MMP-3 or induced to express Rac1b spread to cover a larger surface, and that this induction of cell spreading is a requirement of MMP-3/Rac1b-induced EMT. We find that limiting cell spreading, either by increasing cell density or by culturing cells on precisely defined micropatterned substrata, blocks expression of characteristic markers of EMT in cells treated with MMP-3. These effects are not caused by general disruptions in cell signaling pathways, as TGF-{beta}-induced EMT is not affected by similar limitations on cell spreading. Our data reveal a previously unanticipated cell shape-dependent mechanism that controls this key phenotypic alteration and provide insight into the distinct mechanisms activated by different EMT-inducing agents.

  5. Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT-Phenotypic Cells: Are They Cousins or Twins?

    Directory of Open Access Journals (Sweden)

    Fazlul H. Sarkar

    2011-02-01

    Full Text Available Cancer stem cells (CSCs are cells within a tumor that possess the capacity to self-renew and maintain tumor-initiating capacity through differentiation into the heterogeneous lineages of cancer cells that comprise the whole tumor. These tumor-initiating cells could provide a resource for cells that cause tumor recurrence after therapy. Although the cell origin of CSCs remains to be fully elucidated, mounting evidence has demonstrated that Epithelial-to-Mesenchymal Transition (EMT, induced by different factors, is associated with tumor aggressiveness and metastasis and these cells share molecular characteristics with CSCs, and thus are often called cancer stem-like cells or tumor-initiating cells. The acquisition of an EMT phenotype is a critical process for switching early stage carcinomas into invasive malignancies, which is often associated with the loss of epithelial differentiation and gain of mesenchymal phenotype. Recent studies have demonstrated that EMT plays a critical role not only in tumor metastasis but also in tumor recurrence and that it is tightly linked with the biology of cancer stem-like cells or cancer-initiating cells. Here we will succinctly summarize the state-of-our-knowledge regarding the molecular similarities between cancer stem-like cells or CSCs and EMT-phenotypic cells that are associated with tumor aggressiveness focusing on solid tumors.

  6. Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

    Science.gov (United States)

    Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

    2010-02-01

    The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

  7. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    Science.gov (United States)

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

  8. Systematic analysis of protein turnover in primary cells.

    Science.gov (United States)

    Mathieson, Toby; Franken, Holger; Kosinski, Jan; Kurzawa, Nils; Zinn, Nico; Sweetman, Gavain; Poeckel, Daniel; Ratnu, Vikram S; Schramm, Maike; Becher, Isabelle; Steidel, Michael; Noh, Kyung-Min; Bergamini, Giovanna; Beck, Martin; Bantscheff, Marcus; Savitski, Mikhail M

    2018-02-15

    A better understanding of proteostasis in health and disease requires robust methods to determine protein half-lives. Here we improve the precision and accuracy of peptide ion intensity-based quantification, enabling more accurate protein turnover determination in non-dividing cells by dynamic SILAC-based proteomics. This approach allows exact determination of protein half-lives ranging from 10 to >1000 h. We identified 4000-6000 proteins in several non-dividing cell types, corresponding to 9699 unique protein identifications over the entire data set. We observed similar protein half-lives in B-cells, natural killer cells and monocytes, whereas hepatocytes and mouse embryonic neurons show substantial differences. Our data set extends and statistically validates the previous observation that subunits of protein complexes tend to have coherent turnover. Moreover, analysis of different proteasome and nuclear pore complex assemblies suggests that their turnover rate is architecture dependent. These results illustrate that our approach allows investigating protein turnover and its implications in various cell types.

  9. Analysis of T Cell Subsets in Adult Primary/Idiopathic Minimal Change Disease: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Francisco Salcido-Ochoa

    2017-01-01

    Full Text Available Aim. To characterise infiltrating T cells in kidneys and circulating lymphocyte subsets of adult patients with primary/idiopathic minimal change disease. Methods. In a cohort of 9 adult patients with primary/idiopathic minimal change recruited consecutively at disease onset, we characterized (1 infiltrating immune cells in the kidneys using immunohistochemistry and (2 circulating lymphocyte subsets using flow cytometry. As an exploratory analysis, association of the numbers and percentages of both kidney-infiltrating immune cells and the circulating lymphocyte subsets with kidney outcomes including deterioration of kidney function and proteinuria, as well as time to complete clinical remission up to 48 months of follow-up, was investigated. Results. In the recruited patients with primary/idiopathic minimal change disease, we observed (a a dominance of infiltrating T helper 17 cells and cytotoxic cells, comprising cytotoxic T cells and natural killer cells, over Foxp3+ Treg cells in the renal interstitium; (b an increase in the circulating total CD8+ T cells in peripheral blood; and (c an association of some of these parameters with kidney function and proteinuria. Conclusions. In primary/idiopathic minimal change disease, a relative numerical dominance of effector over regulatory T cells can be observed in kidney tissue and peripheral blood. However, larger confirmatory studies are necessary.

  10. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    Borowski, J.; Jokoniuk, P.

    1977-01-01

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  11. Primary leiomyoma of ureter coexisting with renal cell carcinoma: A case report

    International Nuclear Information System (INIS)

    Baek, Seung Hwan; Kim, Hee Jin; Han, Hyun Young

    2014-01-01

    Mesenchymal origin of ureter tumors account for less than 3 percent of all primary ureteral tumors. Among mesenchymal tumors, primary leiomyoma of ureter is extremely rare. Here, we present a case of primary leiomyoma of ureter coexisting with renal cell carcinoma. When encountering well-defined homogeneously enhanced mass of ureter on computed tomography, radiologist should keep in mind that ureteral leiomyoma should be considered as differential diagnosis.

  12. Primary leiomyoma of ureter coexisting with renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Seung Hwan; Kim, Hee Jin; Han, Hyun Young [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

    2014-12-15

    Mesenchymal origin of ureter tumors account for less than 3 percent of all primary ureteral tumors. Among mesenchymal tumors, primary leiomyoma of ureter is extremely rare. Here, we present a case of primary leiomyoma of ureter coexisting with renal cell carcinoma. When encountering well-defined homogeneously enhanced mass of ureter on computed tomography, radiologist should keep in mind that ureteral leiomyoma should be considered as differential diagnosis.

  13. Hyperplasia of epithelium adjacent to transitional cell carcinoma can be induced by growth factors through paracrine pathways

    NARCIS (Netherlands)

    W.I. de Boer (Pim); J.M.J. Rebel (Annemarie); C.D.E.M. Thijssen (C. D E M); M. Vermey; Th.H. van der Kwast (Theo); A.J.M. van den Eijnden-van Raaij (Janny)

    1994-01-01

    textabstractHyperplasia of transitional cell epithelium adjacent to human transitional cell carcinomas (TCC) is a common finding in pathology. This hyperplasia may be a precancerous aberration. Alternatively, it has been suggested that the hyperplasia is due to paracrine action of tumour-derived

  14. Establishment of primary cell culture from the temperate symbiotic cnidarian, Anemonia viridis.

    Science.gov (United States)

    Barnay-Verdier, Stéphanie; Dall'osso, Diane; Joli, Nathalie; Olivré, Juliette; Priouzeau, Fabrice; Zamoum, Thamilla; Merle, Pierre-Laurent; Furla, Paola

    2013-10-01

    The temperate symbiotic sea anemone Anemonia viridis, a member of the Cnidaria phylum, is a relevant experimental model to investigate the molecular and cellular events involved in the preservation or in the rupture of the symbiosis between the animal cells and their symbiotic microalgae, commonly named zooxanthellae. In order to increase research tools for this model, we developed a primary culture from A. viridis animal cells. By adapting enzymatic dissociation protocols, we isolated animal host cells from a whole tentacle in regeneration state. Each plating resulted in a heterogeneous primary culture consisted of free zooxanthellae and many regular, small rounded and adherent cells (of 3-5 μm diameter). Molecular analyses conducted on primary cultures, maintained for 2 weeks, confirmed a specific signature of A. viridis cells. Further serial dilutions and micromanipulation allowed us to obtain homogenous primary cultures of the small rounded cells, corresponding to A. viridis "epithelial-like cells". The maintenance and the propagation over a 4 weeks period of primary cells provide, for in vitro cnidarian studies, a preliminary step for further investigations on cnidarian cellular pathways notably in regard to symbiosis interactions.

  15. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    -brain barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  16. Primary endometrial squamous cell carcinoma with extensive squamous metaplasia and dysplasia

    Directory of Open Access Journals (Sweden)

    Bagga Permeet

    2008-04-01

    Full Text Available Primary squamous cell carcinoma of endometrium is a rare entity. Only 64 cases have been documented in the literature. We report a case of 60-year-old postmenopausal woman who presented with abdominal distention and blood-stained vaginal discharge for 6-7 months. Clinically, chronic pyometra was considered. Total abdominal hysterectomy was performed and histopathologically, it was diagnosed as a case of primary squamous cell carcinoma of endometrium with extensive squamous metaplasia and dysplasia.

  17. A novel retinoic acid chalcone reverses epithelial‑mesenchymal transition in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Jian Zhong

    2015-06-01

    Full Text Available The present study was performed to investigate the effect of retinoic acid fluoro chalcone (RAFC on lipopolysaccharide (LPS induced epithelial-mesenchymal transition (EMT in PC3 and CWR22rv1 prostate cell lines. Lipo-polysaccharide (LPS was used to induce epithelial-mesenchymal transition in prostate carcinoma cell lines. The results revealed that treatment of PC3 and CWR22rv1 cells with LPS resulted in significant changes in the morphological features of the EMT. The mesenchymal marker, vimentin expression was significantly increased whereas the expression level of E‑cadherin was markedly decreased after the treatment. We also observed increased cell motility and higher level of transcription factor glioma‑associated oncogene homolog 1 (Gli1 expression on LPS treatment. Treatment of prostate cells with RAFC reversed the morphological changes induced by LPS in prostate cells. RAFC also reduced the expression of EMT markers induced by LPS and suppressed the Gli1 expression. The resultant effect of these changes was the suppression of motility and invasiveness of the prostrate cells. Thus, RAFC exhibited anti‑invasive effect on prostrate cells by inhibition of the EMT process via Hedgehog signaling pathway.

  18. Cellular lead toxicity and metabolism in primary and clonal osteoblastic bone cells

    International Nuclear Information System (INIS)

    Long, G.J.; Rosen, J.F.; Pounds, J.G.

    1990-01-01

    A knowledge of bone lead metabolism is critical for understanding the toxicological importance of bone lead, as a toxicant both to bone cells and to soft tissues of the body, as lead is mobilized from large reservoirs in hard tissues. To further understand the processes that mediate metabolism of lead in bone, it is necessary to determine lead metabolism at the cellular level. Experiments were conducted to determine the intracellular steady-state 210 Pb kinetics in cultures of primary and clonal osteoblastic bone cells. Osteoblastic bone cells obtained by sequential collagenase digestion of mouse calvaria or rat osteosarcoma (ROS 17/2.8) cells were labeled with 210 Pb as 5 microM lead acetate for 20 hr, and kinetic parameters were determined by measuring the efflux of 210 Pb from the cells over a 210 -min period. The intracellular metabolism of 210 Pb was characterized by three kinetic pools of 210 Pb in both cell types. Although the values of these parameters differed between the primary osteoblastic cells and ROS cells, the profile of 210 Pb was remarkably similar in both cell types. Both types exhibited one large, slowly exchanging pool (S3), indicative of mitochondrial lead. These data show that primary osteoblastic bone cells and ROS cells exhibit similar steady-state lead kinetics, and intracellular lead distribution. These data also establish a working model of lead kinetics in osteoblastic bone cells and now permit an integrated view of lead kinetics in bone

  19. miR-32 inhibits proliferation, epithelial–mesenchymal transition, and metastasis by targeting TWIST1 in non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Li L

    2016-03-01

    Full Text Available Lei Li,1,* Dapeng Wu2,* 1Department of Pneumology, 2Department of Radiotherapy, Huaihe Hospital of Henan University, Kaifeng, Henan, People’s Republic of China *These authors contributed equally to this work Background: By analyzing published microRNA microarray studies, miR-32 was found to be markedly reduced in non-small-cell lung cancer (NSCLC tissues compared with that in nontumor tissues. However, little is known about its role and molecular mechanism involved in NSCLC development and progression. Here, we report the effect of miR-32 on NSCLC cell proliferation, epithelial–mesenchymal transition (EMT, and metastasis. Methods: Quantitative real-time PCR was performed to detect the expression level of miR-32 in primary NSCLC cases and cell lines. miR-32-overexpressing H1299 and A549 cells were constructed by lipofection transfection. MTT, transwell chamber, and Western blot assays were used to assess the effect of miR-32 on proliferation, EMT, and metastasis of NSCLC cells, respectively. Target prediction and luciferase reporter assays were performed to investigate the targets of miR-32. Tumor formation assay in vivo was performed to investigate the antitumor effect of miR-32. Results: An inverse correlation existed between miR-32 expression level and NSCLC cell proliferation, EMT, and metastasis, and upregulation of miR-32 repressed NSCLC cell proliferation, EMT, and metastasis. Moreover, we identified and validated that TWIST1 was a direct target of miR-32, and miR-32 regulated NSCLC cell proliferation, EMT, and metastasis, at least in part via modulation of TWIST1. The animal experiments showed that overexpression of miR-32 inhibited the growth of NSCLC tumors in vivo. Keywords: non-small-cell lung cancer, miR-32, TWIST1, proliferation, EMT, nude mice

  20. Primary culture of glial cells from mouse sympathetic cervical ganglion: a valuable tool for studying glial cell biology.

    Science.gov (United States)

    de Almeida-Leite, Camila Megale; Arantes, Rosa Maria Esteves

    2010-12-15

    Central nervous system glial cells as astrocytes and microglia have been investigated in vitro and many intracellular pathways have been clarified upon various stimuli. Peripheral glial cells, however, are not as deeply investigated in vitro despite its importance role in inflammatory and neurodegenerative diseases. Based on our previous experience of culturing neuronal cells, our objective was to standardize and morphologically characterize a primary culture of mouse superior cervical ganglion glial cells in order to obtain a useful tool to study peripheral glial cell biology. Superior cervical ganglia from neonatal C57BL6 mice were enzymatically and mechanically dissociated and cells were plated on diluted Matrigel coated wells in a final concentration of 10,000cells/well. Five to 8 days post plating, glial cell cultures were fixed for morphological and immunocytochemical characterization. Glial cells showed a flat and irregular shape, two or three long cytoplasm processes, and round, oval or long shaped nuclei, with regular outline. Cell proliferation and mitosis were detected both qualitative and quantitatively. Glial cells were able to maintain their phenotype in our culture model including immunoreactivity against glial cell marker GFAP. This is the first description of immunocytochemical characterization of mouse sympathetic cervical ganglion glial cells in primary culture. This work discusses the uses and limitations of our model as a tool to study many aspects of peripheral glial cell biology. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Dedifferentiation of Human Primary Thyrocytes into Multilineage Progenitor Cells without Gene Introduction

    Science.gov (United States)

    Saenko, Vladimir; Suzuki, Masatoshi; Matsuse, Michiko; Ohtsuru, Akira; Kumagai, Atsushi; Uga, Tatsuya; Yano, Hiroshi; Nagayama, Yuji; Yamashita, Shunichi

    2011-01-01

    While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases. PMID:21556376

  2. Transitional Cell Carcinoma of the Upper Ureter Metastatic to the Thoracic Spine Presenting as a Spinal Cord Compression

    Directory of Open Access Journals (Sweden)

    J. O. Larkin

    2008-01-01

    Full Text Available We performed a left nephroureterectomy for a gentleman with transitional cell carcinoma of the upper ureter. Histological analysis revealed it to be a T1 lesion, but to be highly mitotically active. The gentleman defaulted on adjuvant therapy and defaulted on follow-up. He represented with symptoms of acute spinal cord compression and magnetic resonance imaging demonstrated a lesion at T6/7. Neurosurgical resection of the lesion showed it to be a metastatic deposit from the ureteric primary. Despite surgical debulking and subsequent radiotherapy to the lesion, the patient died secondary to metastatic complications. This case report is of interest to the surgeon as it demonstrates both the high metastatic potential of upper tract carcinomas and educates the surgeon on the presentation of acute spinal cord compression.

  3. A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

    Science.gov (United States)

    Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

    2017-11-01

    Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

  4. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: First Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2011-03-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. This report provides the early data results and implementation experience of the AT fuel cell bus since it was placed in service.

  5. Endothelin-1 promotes epithelial–mesenchymal transition in human chondrosarcoma cells by repressing miR-300

    Science.gov (United States)

    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-01-01

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis. PMID:27602960

  6. Endothelin-1 promotes epithelial-mesenchymal transition in human chondrosarcoma cells by repressing miR-300.

    Science.gov (United States)

    Wu, Min-Huan; Huang, Pei-Han; Hsieh, Mingli; Tsai, Chun-Hao; Chen, Hsien-Te; Tang, Chih-Hsin

    2016-10-25

    Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial-mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

  7. Global investigation of interleukin-1β signaling in primary β-cells using quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Engholm-Keller, Kasper; Størling, Joachim; Pociot, Flemming

    in β-cells by which this cytokine can modulate cell-matrix interactions during inflammation, a regulation shown in other cell types. Further data analysis is currently ongoing, and the collective results of the experiments will hopefully facilitate additional insights into the effect of IL-1β......Novel Aspect: Global phosphoproteomic analysis of cytokine signaling in primary β-cells Introduction The insulin-producing β-cells of the pancreatic islets of Langerhans are targeted by aberrant immune system responses in diabetes mellitus involving cytokines, especially interleukin-1β (IL-1 β......), which initiate apoptosis of the β-cells. As only limited amounts of primary β-cells can be isolated from model organisms like mouse and rat, global phosphoproteomic analysis of these signaling events by mass spectrometry has generally been unfeasible. We have therefore developed a strategy...

  8. Transition from an asylum seeker-specific health service to mainstream primary care for community-based asylum seekers: a qualitative interview study.

    Science.gov (United States)

    Fair, Genevieve L; Harris, Mark F; Smith, Mitchell M

    2018-03-15

    Transition of asylum seekers from special-purpose health services to mainstream primary care is both necessary and difficult. This study explores the issues encountered by asylum seekers undergoing this transition in Sydney, Australia. Qualitative semistructured interviews were conducted with nine asylum seeker patients and nine staff working in the sector. Asylum seekers faced significant challenges in the transition to mainstream primary care. Contributing factors included the complexity of health and immigration systems, the way in which asylum seeker-specific services provide care, lack of understanding and accommodation by mainstream general practioner (GP) services, asylum seekers' own lack of understanding of the health system, mental illness, and social and financial pressures. There is a need for better preparation of asylum seekers for the transition to mainstream primary care. Mainstream GPs and other providers need more education and support so that they can better accommodate the needs of asylum seeker patients. This is an important role for Australia's refugee health services and Primary Health Networks.

  9. Transition from an asylum seeker–specific health service to mainstream primary care for community-based asylum seekers: a qualitative interview study

    Directory of Open Access Journals (Sweden)

    Genevieve L Fair

    2018-03-01

    Full Text Available Background and aim: Transition of asylum seekers from special-purpose health services to mainstream primary care is both necessary and difficult. This study explores the issues encountered by asylum seekers undergoing this transition in Sydney, Australia. Methods: Qualitative semistructured interviews were conducted with nine asylum seeker patients and nine staff working in the sector. Results: Asylum seekers faced significant challenges in the transition to mainstream primary care. Contributing factors included the complexity of health and immigration systems, the way in which asylum seeker–specific services provide care, lack of understanding and accommodation by mainstream general practioner (GP services, asylum seekers’ own lack of understanding of the health system, mental illness, and social and financial pressures. Conclusions: There is a need for better preparation of asylum seekers for the transition to mainstream primary care. Mainstream GPs and other providers need more education and support so that they can better accommodate the needs of asylum seeker patients. This is an important role for Australia’s refugee health services and Primary Health Networks.

  10. A Challenge of Living? Understanding the Psycho-Social Processes of the Child during Primary-Secondary Transition through Resilience and Self-Esteem Theories

    Science.gov (United States)

    Jindal-Snape, D.; Miller, D. J.

    2008-01-01

    The transition from primary to secondary school can be a period of anxiety for many children. Although most schools have developed systems to ease this process, it has been argued that the emphasis is often on administrative and organisational procedures. In contrast, children and parents are typically more concerned with personal and social…

  11. An intensive primary-literature-based teaching program directly benefits undergraduate science majors and facilitates their transition to doctoral programs.

    Science.gov (United States)

    Kozeracki, Carol A; Carey, Michael F; Colicelli, John; Levis-Fitzgerald, Marc; Grossel, Martha

    2006-01-01

    UCLA's Howard Hughes Undergraduate Research Program (HHURP), a collaboration between the College of Letters and Science and the School of Medicine, trains a group of highly motivated undergraduates through mentored research enhanced by a rigorous seminar course. The course is centered on the presentation and critical analysis of scientific journal articles as well as the students' own research. This article describes the components and objectives of the HHURP and discusses the results of three program assessments: annual student evaluations, interviews with UCLA professors who served as research advisors for HHURP scholars, and a survey of program alumni. Students indicate that the program increased their ability to read and present primary scientific research and to present their own research and enhanced their research experience at UCLA. After graduating, they find their involvement in the HHURP helped them in securing admission to the graduate program of their choice and provided them with an advantage over their peers in the interactive seminars that are the foundation of graduate education. On the basis of the assessment of the program from 1998-1999 to 2004-2005, we conclude that an intensive literature-based training program increases student confidence and scientific literacy during their undergraduate years and facilitates their transition to postgraduate study.

  12. Primary and secondary kinetic deuterium isotope effects and transition-state structures for benzylic chlorination and bromination of toluene

    International Nuclear Information System (INIS)

    Hanzlik, R.P.; Schaefer, A.R.; Moon, J.B.; Judson, C.M.

    1987-01-01

    As a chemical model for benzylic hydroxylation effects by cytochrome P-450 enzymes, the chlorination of PhCH 3 , PhCH 2 D, PhCHD 2 , and PhCD 3 in a two-phase system of hypochlorite/CH 2 Cl 2 with a phase-transfer catalyst has been investigated. On the basis of the deuterium content of the product benzyl chlorides, relative rate constants were deduced for all possible H- and D-abstractions with these substrates. From this the primary (P) and secondary (S) KDIEs were found to be 5.90 +/- 0.41 and 1.03 +/- 0.02, respectively, and the rule of the geometric mean was found to be closely obeyed. For the analogous bromination of toluene by N-bromosuccinimide in CCl 4 , P and S were 6.37 +/- 0.43 and 1.05 +/- 0.01. The transition states of these processes must therefore involve extensive C-H bond breaking but relatively little rehybridization toward planarity at the reacting carbon

  13. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  14. Assembly and enlargement of the primary cell wall in plants

    Science.gov (United States)

    Cosgrove, D. J.

    1997-01-01

    Growing plant cells are shaped by an extensible wall that is a complex amalgam of cellulose microfibrils bonded noncovalently to a matrix of hemicelluloses, pectins, and structural proteins. Cellulose is synthesized by complexes in the plasma membrane and is extruded as a self-assembling microfibril, whereas the matrix polymers are secreted by the Golgi apparatus and become integrated into the wall network by poorly understood mechanisms. The growing wall is under high tensile stress from cell turgor and is able to enlarge by a combination of stress relaxation and polymer creep. A pH-dependent mechanism of wall loosening, known as acid growth, is characteristic of growing walls and is mediated by a group of unusual wall proteins called expansins. Expansins appear to disrupt the noncovalent bonding of matrix hemicelluloses to the microfibril, thereby allowing the wall to yield to the mechanical forces generated by cell turgor. Other wall enzymes, such as (1-->4) beta-glucanases and pectinases, may make the wall more responsive to expansin-mediated wall creep whereas pectin methylesterases and peroxidases may alter the wall so as to make it resistant to expansin-mediated creep.

  15. Proliferation and mineralization ability of dental pulp cells derived from primary and permanent teeth

    Directory of Open Access Journals (Sweden)

    Suttatip Kamolmatyakul

    2011-04-01

    Full Text Available The aims of this study were to compare the proliferation and mineralization ability of CFU-F selected dental pulp cellsderived from primary and permanent teeth. Those cells were isolated by enzyme digestion and analyzed for their colonyformingcapacity. The cell proliferation was measured by the MTT assay on day 1, day 7, and day14. Alizarin Red S stainingwas used to detect mineralized nodule formation of the cells on day 7, 14, 21, and 28. Proliferation of CFU-F selected pulpcells from primary teeth was significantly higher than that of CFU-F selected pulp cells from permanent teeth in all periods ofthe experiment. Upon cultured cells in mineralization inducing media, the mineralized nodules appeared as early as day 14 inCFU-F selected pulp cells from primary teeth and MG-63, whereas those of CFU-F selected pulp cells from permanent teethcan be found at day 21. On day 21 and day 28, the mineralized nodules of the CFU-F selected pulp cells from the primaryteeth group were more than those in the CFU-F selected pulp cells from the permanent teeth group. Mineralized noduleformation in the CFU-F selected pulp cells from the permanent teeth group appeared later and were less than those ofCFU-F selected pulp cells from primary teeth. However, mineralized nodules in CFU-F selected pulp cells from the permanentteeth group increased very fast after their appearance. Those results suggest that CFU-F selected pulp cells from primaryteeth had a higher proliferation rate and mineralization rate when compared to CFU-F selected pulp cells from permanentteeth.

  16. Increasing the solar cell power output by coating with transition metal-oxide nanorods

    International Nuclear Information System (INIS)

    Kuznetsov, I.A.; Greenfield, M.J.; Mehta, Y.U.; Merchan-Merchan, W.; Salkar, G.; Saveliev, A.V.

    2011-01-01

    Highlights: → Nanoparticles enhance solar cell efficiency. → Solar cell power increase by nanorod coating. → Metal-oxide nanorods are prepared in flames. → Molybdenum oxide nanorods effectively scatter light on solar cell surface. → Scattering efficiency depends on coating density. -- Abstract: Photovoltaic cells produce electric current through interactions among photons from an ambient light source and electrons in the semiconductor layer of the cell. However, much of the light incident on the panel is reflected or absorbed without inducing the photovoltaic effect. Transition metal-oxide nanoparticles, an inexpensive product of a process called flame synthesis, can cause scattering of light. Scattering can redirect photon flux, increasing the fraction of light absorbed in the thin active layer of silicon solar cells. This research aims to demonstrate that the application of transition metal-oxide nanorods to the surface of silicon solar panels can enhance the power output of the panels. Several solar panels were coated with a nanoparticle-methanol suspension, and the power outputs of the panels before and after the treatment were compared. The results demonstrate an increase in power output of up to 5% after the treatment. The presence of metal-oxide nanorods on the surface of the coated solar cells is confirmed by electron microscopy.

  17. Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Shuai Yang

    Full Text Available To study the role of long non-coding RNA (lncRNA MALAT1 in transforming growth factor beta 1 (TGF-β1-induced epithelial-mesenchymal transition (EMT of retinal pigment epithelial (RPE cells.ARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1 at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA. The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR vitreous samples.The expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples.LncRNA MALAT1 is involved in TGFβ1-induced EMT of human RPE cells and provides new understandings for the pathogenesis of PVR.

  18. Treatment results and prognostic analysis of 47 patients with urethral transitional cell carcinoma treated with post-operative adjuvant radiotherapy

    International Nuclear Information System (INIS)

    He Ke; Hou Xiaorong; Shen Jie; Lian Xin; Sun Shuai; Zhang Fuquan

    2010-01-01

    Objective: To evaluate treatment results and prognostic factors of 47 patients with primary urethral transitional cell carcinoma treated with post-operative adjuvant radiotherapy. Methods: From October 1998 to October 2008, 47 patients with primary urethral transitional cell carcinoma received postoperative adjuvant radiotherapy. Thirty-one patients had stage T 3 /T 4 disease, 7 had lymph node metastasis. Thirty-nine patients had G3 tumor, 13 had stump-positive. The median radiotherapy dose was 60 Gy (36-64 Gy). 81% patients (38/47) were treated with regional irradiation. Results: The median follow-up time was 21 months (6 -88 months). The follow-up rate was 92%. The median overall survival time was 35 months (5 -88 months). The 2-and 5-year overall survival rates were 57% and 49%, respectively. In univariate analysis, the median overall survival time was better in patients with stage T 1 or T 2 compared with stage T 3 or T 4 tumor (42 months vs. 19 months, χ 2 =7.28, P=0.007), with age of ≤65 years compared with >65 years (28 mouths vs 18 months,χ 2 =8.23, P =0.004). There was no significant difference in the long term survival in patients with non-radical surgery compared with radical mastectomy (21 months vs. 20 months, χ 2 = 0.90, P = 0.344). In multivariate analysis, the stage T 3 or T 4 (χ 2 = 7.89, P =0.005), >65 years old (χ 2 = 4.85, P = 0.028), renal pelvis involvement (χ 2 = 5.65, P = 0.018), and tumor located in the mid or inferior segment (χ 2 =6.08,P =0.014) were factors associated with poorer prognosis. Conclusions: Postoperative adjuvant radiotherapy can improve the efficacy of patients with locally advanced urethral transitional cell carcinoma. Advanced T stage and > 65 years age are associated with poorer prognosis. (authors)

  19. Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

    Science.gov (United States)

    McMurray, R. J.; Wann, A. K. T.; Thompson, C. L.; Connelly, J. T.; Knight, M. M.

    2013-01-01

    The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation. PMID:24346024

  20. A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human Hepatocytes and Endothelial Cells.

    Science.gov (United States)

    Ware, Brenton R; Durham, Mitchell J; Monckton, Chase P; Khetani, Salman R

    2018-03-01

    Modeling interactions between primary human hepatocytes (PHHs) and primary human liver sinusoidal endothelial cells (LSECs) in vitro can help elucidate human-specific mechanisms underlying liver physiology/disease and drug responses; however, existing hepatocyte/endothelial coculture models are suboptimal because of their use of rodent cells, cancerous cell lines, and/or nonliver endothelial cells. Hence, we sought to develop a platform that could maintain the long-term phenotype of PHHs and primary human LSECs. Primary human LSECs or human umbilical vein endothelial cells as the nonliver control were cocultivated with micropatterned PHH colonies (to control homotypic interactions) followed by an assessment of PHH morphology and functions (albumin and urea secretion, and cytochrome P-450 2A6 and 3A4 enzyme activities) over 3 weeks. Endothelial phenotype was assessed via gene expression patterns and scanning electron microscopy to visualize fenestrations. Hepatic responses in PHH/endothelial cocultures were benchmarked against responses in previously developed PHH/3T3-J2 fibroblast cocultures. Finally, PHH/fibroblast/endothelial cell tricultures were created and characterized as described previously. LSECs, but not human umbilical vein endothelial cells, induced PHH albumin secretion for ∼11 days; however, neither endothelial cell type could maintain PHH morphology and functions to the same magnitude/longevity as the fibroblasts. In contrast, both PHHs and endothelial cells displayed stable phenotype for 3 weeks in PHH/fibroblast/endothelial cell tricultures; furthermore, layered tricultures in which PHHs and endothelial cells were separated by a protein gel to mimic the space of Disse displayed similar functional levels as the coplanar tricultures. PHH/fibroblast/endothelial tricultures constitute a robust platform to elucidate reciprocal interactions between PHHs and endothelial cells in physiology, disease, and after drug exposure.

  1. CT findings of primary squamous cell carcinoma of the stomach: a case report

    International Nuclear Information System (INIS)

    Kim, Kyoung Min; Lee, Chang Hee; Kim, Kyeong Ah; Park, Cheol Min

    2008-01-01

    Primary squamous cell carcinoma is a rare tumor of the stomach with an incidence ranging from 0.04% to 0.4% of all diagnosed gastric cancers. We report a case of squamous cell carcinoma in the stomach associated with hypertrophic gastropathy and observed as a huge mass and wall thickening on the greater curvature site by a multidetector CT

  2. Interactions of virulent and avirulent leptospires with primary cultures of renal epithelial cells

    DEFF Research Database (Denmark)

    Ballard, S A; Williamson, M; Adler, B

    1986-01-01

    A primary culture system for the cells of mouse renal-tubular epithelium was established and used to observe the adhesion of leptospires. Virulent strains of serovars copenhageni and ballum attached themselves to epithelial cells within 3 h of infection whereas an avirulent variant of serovar cop...

  3. Induced Pluripotent Stem Cells: A novel frontier in the study of human primary immunodeficiencies

    Science.gov (United States)

    Pessach, Itai M.; Ordovas-Montanes, Jose; Zhang, Shen-Ying; Casanova, Jean-Laurent; Giliani, Silvia; Gennery, Andrew R.; Al-Herz, Waleed; Manos, Philip D.; Schlaeger, Thorsten M.; Park, In-Hyun; Rucci, Francesca; Agarwal, Suneet; Mostoslavsky, Gustavo; Daley, George Q.; Notarangelo, Luigi D.

    2010-01-01

    Background The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells through the exogenous expression of transcription promises to revolutionize the study of human diseases. Objective Here we report on the generation of 25 induced pluripotent stem cell lines from 6 patients with various forms of Primary Immunodeficiencies, affecting adaptive and/or innate immunity. Methods Patients’ dermal fibroblasts were reprogrammed by expression of four transcription factors, OCT4, SOX2, KLF4, and c-MYC using a single excisable polycistronic lentiviral vector. Results Induced pluripotent stem cells derived from patients with primary immunodeficiencies show a stemness profile that is comparable to that observed in human embryonic stem cells. Following in vitro differentiation into embryoid bodies, pluripotency of the patient-derived indiced pluripotent stem cells lines was demonstrated by expression of genes characteristic of each of the three embryonic layers. We have confirmed the patient-specific origin of the induced pluripotent stem cell lines, and ascertained maintenance of karyotypic integrity. Conclusion By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of induced pluripotent stem cell lines from patients with primary immunodeficiencies represents a unique resource to investigate the pathophysiology of hematopoietic and extra-hematopoietic manifestations of these diseases, and may assist in the development of novel therapeutic approaches based on gene correction. PMID:21185069

  4. Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells

    International Nuclear Information System (INIS)

    Ray, Ratna B.; Basu, Arnab; Steele, Robert; Beyene, Aster; McHowat, Jane; Meyer, Keith; Ghosh, Asish K.; Ray, Ranjit

    2004-01-01

    Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing EGP (Ad-EGP). Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death. Transfer of conditioned medium from EGP-transduced HCMEC into naive cells did not induce loss of adhesion or cell death, suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect. Subsequent studies suggested that HCMEC death occurred through apoptosis. Results from this study shed light on the EGP-induced anoikis in primary human cardiac endothelial cells, which may have significant pathological consequences

  5. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    International Nuclear Information System (INIS)

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-01-01

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  6. Electromigration of cadmium in contaminated soils driven by single and multiple primary cells

    International Nuclear Information System (INIS)

    Yuan Songhu; Wu Chan; Wan Jinzhong; Lu Xiaohua

    2008-01-01

    This study tentatively used an iron (Fe) and carbon (C) primary cell, instead of dc electric power, to drive the electromigration of cadmium in contaminated soils. The addition of acid to C compartment increased the electric potential, while the addition of acid to Fe compartment had a slight influence on the potential. It was feasible using the primary cell to drive the electromigration of cadmium in kaolin. The electromigration efficiencies were highly related to the soil pH. Lower pH led to greater migration efficiency. The mechanisms involved the desorption of cadmium from soils to pore solution and the electromigration of cadmium in the pore solution. The desorption was critical to the electromigration process. The series of primary cells could expand the treatment area, but the electromigration efficiencies of cadmium in each cell were less than that achieved by single primary cell. Since the potential gradient produced by the primary cell was rather low, the electromigration rate of pollutants was very low and remediation duration was long. The application would be acceptable in some specific sites, such as acidic soils or artificially controlled acid conditions so that heavy metals have been desorbed from soils

  7. Quantitative analysis of rat adipose tissue cell recovery, and non-fat cell volume, in primary cell cultures

    Directory of Open Access Journals (Sweden)

    Floriana Rotondo

    2016-11-01

    Full Text Available Background White adipose tissue (WAT is a complex, diffuse, multifunctional organ which contains adipocytes, and a large proportion of fat, but also other cell types, active in defense, regeneration and signalling functions. Studies with adipocytes often require their isolation from WAT by breaking up the matrix of collagen fibres; however, it is unclear to what extent adipocyte number in primary cultures correlates with their number in intact WAT, since recovery and viability are often unknown. Experimental Design Epididymal WAT of four young adult rats was used to isolate adipocytes with collagenase. Careful recording of lipid content of tissue, and all fraction volumes and weights, allowed us to trace the amount of initial WAT fat remaining in the cell preparation. Functionality was estimated by incubation with glucose and measurement of glucose uptake and lactate, glycerol and NEFA excretion rates up to 48 h. Non-adipocyte cells were also recovered and their sizes (and those of adipocytes were measured. The presence of non-nucleated cells (erythrocytes was also estimated. Results Cell numbers and sizes were correlated from all fractions to intact WAT. Tracing the lipid content, the recovery of adipocytes in the final, metabolically active, preparation was in the range of 70–75%. Cells showed even higher metabolic activity in the second than in the first day of incubation. Adipocytes were 7%, erythrocytes 66% and other stromal (nucleated cells 27% of total WAT cells. However, their overall volumes were 90%, 0.05%, and 0.2% of WAT. Non-fat volume of adipocytes was 1.3% of WAT. Conclusions The methodology presented here allows for a direct quantitative reference to the original tissue of studies using isolated cells. We have also found that the “live cell mass” of adipose tissue is very small: about 13 µL/g for adipocytes and 2 µL/g stromal, plus about 1 µL/g blood (the rats were killed by exsanguination. These data translate (with

  8. Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells

    DEFF Research Database (Denmark)

    Billestrup, Nils; Mitchell, R L; Vale, W

    1987-01-01

    GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal...... induction of c-fos mRNA was observed 20-60 min after stimulation with 5 nM GRF, returning to basal levels after 2 h. Somatostatin-14 (5 nM) partially inhibited the GRF induced c-fos expression. Forskolin and phorbol 12, 13 dibutyrate induced c-fos gene in cultured primary pituitary cells with similar...

  9. A CASE REPORT OF MULTIPLE PRIMARY SQUAMOUS CELL CARCINOMAS OF THE OVARY AND SIGMOID COLON

    Directory of Open Access Journals (Sweden)

    A. B. Villert

    2016-01-01

    Full Text Available Squamous cell ovarian and sigmoid colon carcinomas are extremely rare malignancies. Because of their rarity, it is difficult to investigate the clinical characteristics and prognosis of patients with theses malignancies, and therefore, the increased interest in each clinical case report is highly relevant. Multiple primary squamous cell ovarian and sigmoid colon carcinomas are the subject of discussion and differential diagnosis of sigmoid colon cancer with secondary ovarian cancer. Histopathological and clinical characteristics of the tumors were present and evidences in favor of the multiple primary malignancies were given. The association of squamous cell ovarian and sigmoid colon carcinomas with human papilloma virus type 16 was shown.

  10. Effect of Topology Structures on Synchronization Transition in Coupled Neuron Cells System

    International Nuclear Information System (INIS)

    Liang Li-Si; Zhang Ji-Qian; Xu Gui-Xia; Liu Le-Zhu; Huang Shou-Fang

    2013-01-01

    In this paper, by the help of evolutionary algorithm and using Hindmarsh—Rose (HR) neuron model, we investigate the effect of topology structures on synchronization transition between different states in coupled neuron cells system. First, we build different coupling structure with N cells, and found the effect of synchronized transition contact not only closely with the topology of the system, but also with whether there exist the ring structures in the system. In particular, both the size and the number of rings have greater effects on such transition behavior. Secondly, we introduce synchronization error to qualitative analyze the effect of the topology structure. Furthermore, by fitting the simulation results, we find that with the increment of the neurons number, there always exist the optimization structures which have the minimum number of connecting edges in the coupling systems. Above results show that the topology structures have a very crucial role on synchronization transition in coupled neuron system. Biological system may gradually acquire such efficient topology structures through the long-term evolution, thus the systems' information process may be optimized by this scheme. (interdisciplinary physics and related areas of science and technology)

  11. Phosphoinositide-3-Kinase Signaling in Human Natural Killer Cells: New Insights from Primary Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Emily M. Mace

    2018-03-01

    Full Text Available Human natural killer (NK cells play a critical role in the control of viral infections and malignancy. Their importance in human health and disease is illustrated by severe viral infections in patients with primary immunodeficiencies that affect NK cell function and/or development. The recent identification of patients with phosphoinositide-3-kinase (PI3K-signaling pathway mutations that can cause primary immunodeficiency provides valuable insight into the role that PI3K signaling plays in human NK cell maturation and lytic function. There is a rich literature that demonstrates a requirement for PI3K in multiple key aspects of NK cell biology, including development/maturation, homing, priming, and function. Here, I briefly review these previous studies and place them in context with recent findings from the study of primary immunodeficiency patients, particularly those with hyperactivating mutations in PI3Kδ signaling.

  12. In wound repair vimentin mediates the transition of mesenchymal leader cells to a myofibroblast phenotype.

    Science.gov (United States)

    Walker, J L; Bleaken, B M; Romisher, A R; Alnwibit, A A; Menko, A S

    2018-05-02

    Following injury, mesenchymal repair cells are activated to function as leader cells that modulate wound healing. These cells have the potential to differentiate to myofibroblasts, resulting in fibrosis and scarring. The signals underlying these differing pathways are complex and incompletely understood. The ex vivo mock cataract surgery cultures are an attractive model with which to address this question. With this model we study, concurrently, the mechanisms that control mesenchymal leader cell function in injury repair within their native microenvironment, and the signals that induce this same cell population to acquire a myofibroblast phenotype when these cells encounter the environment of the adjacent tissue culture platform. Here, we show that upon injury, the cytoskeletal protein vimentin is released into the extracellular space, binds to the cell surface of the mesenchymal leader cells located at the wound edge in the native matrix environment, and supports wound closure. In pro-fibrotic environments, the extracellular vimentin pool also links specifically to the mesenchymal leader cells, and has an essential role in signaling their fate change to a myofibroblast. These findings suggest a novel role for extracellular, cell-surface-associated vimentin in mediating repair-cell function in wound repair and in transitioning these cells to a myofibroblast phenotype. Movie S1 Movie S1 Collective movement of mesenchymal leader and epithelial follower cells across the tissue culture substrate (ECZ) in response to injury was followed by time-lapse imaging from D0-D3. The mesenchymal cells at the leading edge were easily distinguished morphologically from the lens epithelial follower cells.

  13. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  14. Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

    Science.gov (United States)

    Desai, Shilpa J; Pruzan, Noelle L; Geske, Michael J; Jeng, Bennie H; Bloomer, Michele M; Vagefi, M Reza

    2016-04-06

    Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

  15. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    Directory of Open Access Journals (Sweden)

    Anupama Bains

    2016-01-01

    Full Text Available Primary cutaneous anaplastic large cell lymphoma (pcALCL forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary.

  16. Zeatin is indispensable for the G2-M transition in tobacco BY-2 cells.

    Science.gov (United States)

    Laureys, F; Dewitte, W; Witters, E; Van Montagu, M; Inzé, D; Van Onckelen, H

    1998-04-10

    The importance of N6-isoprenoid cytokinins in the G2-M transition of Nicotiana tabacum BY-2 cells was investigated. Both cytokinin biosynthesis and entry in mitosis were partially blocked by application at early or late G2 of lovastatin (10 microM), an inhibitor of mevalonic acid synthesis. LC-MS/MS quantification of endogenous cytokinins proved that lovastatin affects cytokinin biosynthesis by inhibiting HMG-CoA reductase. Out of eight different aminopurines and a synthetic auxin tested for their ability to override lovastatin inhibition of mitosis, only zeatin was active. Our data point to a key role for a well-defined cytokinin (here, zeatin) in the G2-M transition of tobacco BY-2 cells.

  17. Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

    Science.gov (United States)

    Karimpoor, Mahroo; Yebra-Fernandez, Eva; Parhizkar, Maryam; Orlu, Mine; Craig, Duncan; Khorashad, Jamshid S; Edirisinghe, Mohan

    2018-04-01

    The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells. © 2018 The Author(s).

  18. TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.

    Science.gov (United States)

    Wang, Qiang; Xu, Zhilin; An, Qun; Jiang, Dapeng; Wang, Long; Liang, Bingxue; Li, Zhaozhu

    2015-02-01

    Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes‑associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK‑N‑BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK‑N‑BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK‑N‑SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial‑mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF‑β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.

  19. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2017-01-01

    Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

  20. Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor

    Directory of Open Access Journals (Sweden)

    Luis M.M. Flórez

    Full Text Available Abstract: Immunochemistry with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3 and anti-CD79α antibodies has been used for characterization of primary cell culture in the transmissible venereal tumor (TVT. Samples for primary cell culture and immunohistochemistry assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To validate the immunochemical results in the primary cell culture of TVT, a chromosome count was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used. TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of 56 to 68. This is the first report on the use of immunocytochemical characterization in cell culture of TVT. Significant statistic difference between immunochemistry in tissue and culture cell was not established, what suggests that the use of this technique may provide greater certainty for the confirmation of tumors in the primary culture. This fact is particularly important because in vitro culture of tumor tissues has been increasingly used to provide quick access to drug efficacy and presents relevant information to identify potential response to anticancer medicine; so it is possible to understand the behavior of the tumor.

  1. Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Nadine Gillmaier

    Full Text Available The metabolic response of host cells, in particular of primary mammalian cells, to bacterial infections is poorly understood. Here, we compare the carbon metabolism of primary mouse macrophages and of established J774A.1 cells upon Listeria monocytogenes infection using (13C-labelled glucose or glutamine as carbon tracers. The (13C-profiles of protein-derived amino acids from labelled host cells and intracellular L. monocytogenes identified active metabolic pathways in the different cell types. In the primary cells, infection with live L. monocytogenes increased glycolytic activity and enhanced flux of pyruvate into the TCA cycle via pyruvate dehydrogenase and pyruvate carboxylase, while in J774A.1 cells the already high glycolytic and glutaminolytic activities hardly changed upon infection. The carbon metabolism of intracellular L. monocytogenes was similar in both host cells. Taken together, the data suggest that efficient listerial replication in the cytosol of the host cells mainly depends on the glycolytic activity of the hosts.

  2. Detection of Thyroid Metastasis pf Renal Transitional Cell Carcinoma Using FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Il; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. Bundang Hospital, Seoul (Korea, Republic of); Lee, Jong Jin [Univ. of Ulsan College of Medicine, Seoul (Korea, Republic of); Paik, Jin Ho [Seoul National Univ. Bundang Hospital, Seoul (Korea, Republic of)

    2011-06-15

    A 69 year old man who was diagnosed with renal transitional cell carcinoma (TCC) underwent F 18 fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) for detecting recurrence after chemotherapy. FDG PET/CT revealed multiple new hypermetabolic lesions in many places, including the right thyroid gland. Biopsy of the thyroid lesion was performed,and a diagnosis of metastatic TCC was made. We could detect thyroid metastasis of renal TCC by FDG PET/CT.

  3. Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

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    Paul M. Graham, DO

    2018-05-01

    Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

  4. A qualitative examination of factors related to the decrease in physical activity behavior in adolescent girls during the transition from primary to secondary school.

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    Knowles, Ann-Marie; Niven, Ailsa; Fawkner, Samantha

    2011-11-01

    Quantitative research has suggested that the decline in physical activity levels for adolescent girls is most marked during the transition from primary school to secondary school yet understanding the contributing factors for this decline may be advanced through qualitative research methods to gain an individual perspective of the girls' school transition experience. This study explored factors related to the decrease in physical activity behavior in 14 adolescent girls (mean age = 13.6 ± 0.3 years) during the transition between primary and secondary school through the use of narrative interviews and interpretative phenomenological analysis. The findings suggested that a change in the environment was central to understanding the decline in physical activity levels since primary school. During secondary school, a positive environment can be created by ensuring a choice of activities in Physical Education lessons; allowing a girls-only environment, to reduce the focus on competence and competition, and recognizing the importance of social support. These could enhance self-perceptions, reduce self-presentational concerns, increase enjoyment, and subsequently reduce the decrease in physical activity behavior during this key transitional period.

  5. Can widely used cell type markers predict the suitability of immortalized or primary mammary epithelial cell models?

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    Edgar Corneille Ontsouka

    Full Text Available BACKGROUND: Mammary cell cultures are convenient tools for in vitro studies of mammary gland biology. However, the heterogeneity of mammary cell types, e.g., glandular milk secretory epithelial or myoepithelial cells, often complicates the interpretation of cell-based data. The present study was undertaken to determine the relevance of bovine primary mammary epithelial cells isolated from American Holstein (bMEC US or Swiss Holstein-Friesian (bMEC CH cows, and of primary bovine mammary alveolar epithelial cells stably transfected with simian virus-40 (SV-40 large T-antigen (MAC-T for in vitro analyses. This was evaluated by testing their expression pattern of cytokeratin (CK 7, 18, 19, vimentin, and α-smooth muscle actin (α-SMA. RESULTS: The expression of the listed markers was assessed using real-time quantitative PCR, flow cytometry and immunofluorescence microscopy. Characteristic markers of the mesenchymal (vimentin, myoepithelial (α-SMA and glandular secretory cells (CKs showed differential expression among the studied cell cultures, partly depending on the analytical method used. The relative mRNA expression of vimentin, CK7 and CK19, respectively, was lower (P < 0.05 in immortalized than in primary mammary cell cultures. The stain index (based on flow cytometry of CK7 and CK19 protein was lower (P < 0.05 in MAC-T than in bMECs, while the expression of α-SMA and CK18 showed an inverse pattern. Immunofluorescence microscopy analysis mostly confirmed the mRNA data, while partly disagreed with flow cytometry data (e.g., vimentin level in MAC-T. The differential expression of CK7 and CK19 allowed discriminating between immortal and primary mammary cultures. CONCLUSIONS: The expression of the selected widely used cell type markers in primary and immortalized MEC cells did not allow a clear preference between these two cell models for in vitro analyses studying aspects of milk composition. All tested cell models exhibited to a variable

  6. A Case of Mature Natural Killer-Cell Neoplasm Manifesting Multiple Choroidal Lesions: Primary Intraocular Natural Killer-Cell Lymphoma

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    Yoshiaki Tagawa

    2015-11-01

    Full Text Available Purpose: Natural killer (NK cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.

  7. Laparoscopic-assisted nephroureterectomy after radical cystectomy for transitional cell carcinoma

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    Frederico R. Romero

    2006-12-01

    Full Text Available OBJECTIVE: To report our experience with laparoscopic-assisted nephroureterectomy for upper tract transitional cell carcinomas after radical cystectomy and urinary diversion. MATERIALS AND METHODS: Seven patients (53-72 years-old underwent laparoscopic-assisted nephroureterectomy 10 to 53 months after radical cystectomy for transitional cell carcinoma at our institution. Surgical technique, operative results, tumor features, and outcomes of all patients were retrospectively reviewed. RESULTS: Mean operative time was 305 minutes with a significant amount of time spent on the excision of the ureter from the urinary diversion. Estimate blood loss and length of hospital stay averaged 180 mL and 10.8 days, respectively. Intraoperative and postoperative complications occurred in two patients each. There was one conversion to open surgery. Pathology confirmed upper-tract transitional cell carcinoma in all cases. Metastatic disease occurred in two patients after a mean follow-up of 14.6 months. CONCLUSIONS: Nephrouretectomy following cystectomy is a complex procedure due to the altered anatomy and the presence of many adhesions. A laparoscopic-assisted approach can be performed safely in properly selected cases but does not yield the usual benefits seen with other laparoscopic renal procedures.

  8. Retrospective evaluation of doxorubicin-piroxicam combination for the treatment of transitional cell carcinoma in dogs.

    Science.gov (United States)

    Robat, C; Burton, J; Thamm, D; Vail, D

    2013-02-01

    To determine whether doxorubicin-piroxicam combination is safe and has activity against transitional cell carcinoma in dogs. Data was collected retrospectively from 34 dogs from two institutions over a 6-year period. Signalment, clinical presentation, treatment specifics, adverse events, response, progression-free survival and overall survival time were evaluated. Dogs received doxorubicin every 3 weeks and daily piroxicam; 17 dogs (50%) had surgery. Clinical presentations were those typically reported for transitional cell carcinoma. Mean number of doses administered was 3·5. Of the 23 dogs with measurable disease, 14 (60·5%) had stable disease, 7 (30·5%) had progressive disease and 2 (9%) a partial response. Adverse events were generally manageable, and gastrointestinal in origin; one dog died of treatment-related complications. Overall median progression-free survival and overall survival were 103 and 168 days, respectively. Cytoreductive surgery did not result in prolongation of progression-free survival, but significantly prolonged overall survival. All dogs but one died as a result of disease progression. Doxorubicin-piroxicam combination therapy is well-tolerated in dogs with transitional cell carcinoma although progression-free survival, overall survival and biological response rates appear modest. Combination with surgery appears to offer a survival advantage; however, this may reflect tumour location and volume. Prospective studies are necessary to compare activity of combination doxorubicin-piroxicam to currently applied therapies. © 2013 British Small Animal Veterinary Association.

  9. Thiol Redox Transitions in Cell Signaling: a Lesson from N-Acetylcysteine

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    Tiziana Parasassi

    2010-01-01

    Full Text Available The functional status of cells is under the control of external stimuli affecting the function of critical proteins and eventually gene expression. Signal sensing and transduction by messengers to specific effectors operate by post-translational modification of proteins, among which thiol redox switches play a fundamental role that is just beginning to be understood. The maintenance of the redox status is, indeed, crucial for cellular homeostasis and its dysregulation towards a more oxidized intracellular environment is associated with aberrant proliferation, ultimately related to diseases such as cancer, cardiovascular disease, and diabetes. Redox transitions occur in sensitive cysteine residues of regulatory proteins relevant to signaling, their evolution to metastable disulfides accounting for the functional redox switch. N-acetylcysteine (NAC is a thiol-containing compound that is able to interfere with redox transitions of thiols and, thus, in principle, able to modulate redox signaling. We here review the redox chemistry of NAC, then screen possible mechanisms to explain the effects observed in NAC-treated normal and cancer cells; such effects involve a modification of global gene expression, thus of functions and morphology, with a leitmotif of a switch from proliferation to terminal differentiation. The regulation of thiol redox transitions in cell signaling is, therefore, proposed as a new tool, holding promise not only for a deeper explanation of mechanisms, but indeed for innovative pharmacological interventions.

  10. Identification of genuine primary pulmonary NK cell lymphoma via clinicopathologic observation and clonality assay.

    Science.gov (United States)

    Gong, Li; Wei, Long-Xiao; Huang, Gao-Sheng; Zhang, Wen-Dong; Wang, Lu; Zhu, Shao-Jun; Han, Xiu-Juan; Yao, Li; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2013-08-19

    Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual reaction to treatment or an unusual prognosis, it is wise to differentiate NK from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and the clonal status was determined using female X-chromosomal inactivation mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion showed the typical histopathologic characteristics and immunohistochemical features of NK/T cell lymphoma. However, the sample was negative for TCR gene rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It is concluded that this is the first recorded case of genuine primary pulmonary NK cell lymphoma. The purpose of the present work is to recommend that pathologists carefully investigate the whole lesion to reduce the likelihood that primary pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In addition, TCR gene rearrangement and clonal analysis, which is based on female X-chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor (AR) loci, were found to play important roles in differentiating NK cell lymphoma from T cell lymphoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

  11. Cytological diagnosis of a rare case of cutaneous metastasis from transitional cell carcinoma, renal pelvis

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    Pragya Singh

    2017-12-01

    Full Text Available Transitional cell carcinoma (TCC arising from renal pelvis rarely gives rise to cutaneous metastasis. Due to the insufficient literature, the exact incidence is not known till date. Moreover, the diagnosis is confirmed on histopathological examination with the aid of immunohistochemistry wherever needed. We are presenting a case of a 70-year-old female with metastatic TCC from the renal pelvis to the abdominal skin, which was diagnosed on cytology alone along with the cell block preparation. We also highlight the important cytomorphological and immunohistochemical features noted, which need to be known to avoid any diagnostic delay.

  12. Cyclin D1 affects epithelial–mesenchymal transition in epithelial ovarian cancer stem cell-like cells

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    Jiao J

    2013-06-01

    Full Text Available Jie Jiao,1,4 Lu Huang,1 Feng Ye,1 MinFeng Shi,2 XiaoDong Cheng,3 XinYu Wang,3 DongXiao Hu,3 Xing Xie,3 WeiGuo Lu31Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 2Department of Gynaecology and Obstetrics, Changhai Hospital, the Second Military Medical University, Shanghai, 3Women's Reproductive Health Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 4Department of Gynaecology and Obstetrics, Hangzhou First People's Hospital, Hangzhou, People's Republic of ChinaBackground: The association of cancer stem cells with epithelial–mesenchymal transition (EMT is receiving attention. We found in our previous study that EMT existed from CD24- phenotype cells to their differentiated cells. It was shown that cyclin D1 functioned in sustaining self-renewal independent of CDK4/CDK6 activation, but its effect on the EMT mechanism in ovarian cancer stem cells is unclear.Methods: The anchorage-independent spheroids from ovarian adenocarcinoma cell line 3AO were formed in a serum-free medium. CD24- and CD24+ cells were isolated by fluorescence-activated cell sorting. Cell morphology, viability, apoptosis, and migratory ability were observed. Stem-related molecule Bmi-1, Oct-4 and EMT-related marker E-cadherin, and vimentin expressions were analyzed. Cyclin D1 expression in CD24- phenotype enriched spheroids was knocked down with small interfering RNA, and its effects on cell proliferation, apoptosis, migration ability, and EMT-related phenotype after transfection were observed. Results: In our study, CD24- cells presented stronger proliferative, anti-apoptosis capacity, and migratory ability, than CD24+ cells or parental cells. CD24- cells grew with a scattered spindle-shape within 3 days of culture and transformed into a cobblestone-like shape, identical to CD24+ cells or parental cells at 7

  13. Cysteine cathepsins B and X promote epithelial-mesenchymal transition of tumor cells.

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    Mitrović, Ana; Pečar Fonović, Urša; Kos, Janko

    2017-09-01

    Cathepsins B and X are lysosomal cysteine carboxypeptidases suggested as having a redundant role in cancer. They are involved in a number of processes leading to tumor progression but their role in the epithelial-mesenchymal transition (EMT) remains unknown. We have investigated the contribution of both cathepsins B and X in EMT using tumor cell lines differing in their expression of epithelial and mesenchymal markers and cell morphology. Higher levels of both cathepsins are shown to promote EMT and are associated with the mesenchymal-like cell phenotype. Moreover, simultaneous knockdown of the two peptidases triggers a reverse, mesenchymal to epithelial transition. Of the two cathepsins, cathepsin B appears to be the stronger promotor of EMT. Furthermore, we evaluated the involvement of cathepsin B and X in the transforming growth factor-β1 (TGF-β1) signaling pathway, one of the key signaling mechanisms triggering EMT in cancer. In MCF-7 cells the expression of cathepsin B was shown to depend on their activation with TGF-β1 while, for cathepsin X, a TGF-β1 independent mechanism of induction during EMT is indicated. EMT is thus shown to be another mechanism linking cathepsins B and X with tumor progression. With silencing of their expression or inhibition of enzymatic activity, the tumor cells could be reverted to less aggressive epithelial-like phenotype. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Controlled cell morphology and liver-specific function of engineered primary hepatocytes by fibroblast layer cell densities.

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    Sakai, Yusuke; Koike, Makiko; Kawahara, Daisuke; Hasegawa, Hideko; Murai, Tomomi; Yamanouchi, Kosho; Soyama, Akihiko; Hidaka, Masaaki; Takatsuki, Mitsuhisa; Fujita, Fumihiko; Kuroki, Tamotsu; Eguchi, Susumu

    2018-03-05

    Engineered primary hepatocytes, including co-cultured hepatocyte sheets, are an attractive to basic scientific and clinical researchers because they maintain liver-specific functions, have reconstructed cell polarity, and have high transplantation efficiency. However, co-culture conditions regarding engineered primary hepatocytes were suboptimal in promoting these advantages. Here we report that the hepatocyte morphology and liver-specific function levels are controlled by the normal human diploid fibroblast (TIG-118 cell) layer cell density. Primary rat hepatocytes were plated onto TIG-118 cells, previously plated 3 days before at 1.04, 5.21, and 26.1×10 3  cells/cm 2 . Hepatocytes plated onto lower TIG-118 cell densities expanded better during the early culture period. The hepatocytes gathered as colonies and only exhibited small adhesion areas because of the pushing force from proliferating TIG-118 cells. The smaller areas of each hepatocyte result in the development of bile canaliculi. The highest density of TIG-118 cells downregulated albumin synthesis activity of hepatocytes. The hepatocytes may have undergone apoptosis associated with high TGF-β1 concentration and necrosis due to a lack of oxygen. These occurrences were supported by apoptotic chromatin condensation and high expression of both proteins HIF-1a and HIF-1b. Three types of engineered hepatocyte/fibroblast sheets comprising different TIG-118 cell densities were harvested after 4 days of hepatocyte culture and showed a complete cell sheet format without any holes. Hepatocyte morphology and liver-specific function levels are controlled by TIG-118 cell density, which helps to design better engineered hepatocytes for future applications such as in vitro cell-based assays and transplantable hepatocyte tissues. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  15. A core invasiveness gene signature reflects epithelial-to-mesenchymal transition but not metastatic potential in breast cancer cell lines and tissue samples.

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    Melike Marsan

    Full Text Available INTRODUCTION: Metastases remain the primary cause of cancer-related death. The acquisition of invasive tumour cell behaviour is thought to be a cornerstone of the metastatic cascade. Therefore, gene signatures related to invasiveness could aid in stratifying patients according to their prognostic profile. In the present study we aimed at identifying an invasiveness gene signature and investigated its biological relevance in breast cancer. METHODS & RESULTS: We collected a set of published gene signatures related to cell motility and invasion. Using this collection, we identified 16 genes that were represented at a higher frequency than observed by coincidence, hereafter named the core invasiveness gene signature. Principal component analysis showed that these overrepresented genes were able to segregate invasive and non-invasive breast cancer cell lines, outperforming sets of 16 randomly selected genes (all P<0.001. When applied onto additional data sets, the expression of the core invasiveness gene signature was significantly elevated in cell lines forced to undergo epithelial-mesenchymal transition. The link between core invasiveness gene expression and epithelial-mesenchymal transition was also confirmed in a dataset consisting of 2420 human breast cancer samples. Univariate and multivariate Cox regression analysis demonstrated that CIG expression is not associated with a shorter distant metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186. DISCUSSION: These data demonstrate that we have identified a set of core invasiveness genes, the expression of which is associated with epithelial-mesenchymal transition in breast cancer cell lines and in human tissue samples. Despite the connection between epithelial-mesenchymal transition and invasive tumour cell behaviour, we were unable to demonstrate a link between the core invasiveness gene signature and enhanced metastatic potential.

  16. 27-hydroxycholesterol induces the transition of MCF7 cells into a mesenchymal phenotype.

    Science.gov (United States)

    Torres, Cristian G; Ramírez, María E; Cruz, Pamela; Epuñan, María J; Valladares, Luis E; Sierralta, Walter D

    2011-08-01

    A decrease in the expression of E-cadherin and β-catenin, paralleling the loss of adherens junction complex, was observed in MCF7 cells exposed for longer than 48 h to 2 µM 27-hydroxycholesterol (27OHC), indicating an epithelial-mesenchymal transition (EMT). Upon removal of 27OHC from the culture medium, the cells released by the exposure of 72 h to the oxysterol grew as loosely packed cell groups. In these cells, accumulation of E-cadherin and β-catenin in the cytoplasm and the prolonged expression of epidermal growth factor receptor 2 (EGFR2/neu) in the plasma membrane were observed, suggesting that the acquired phenotype was related to the expression of this tyrosine kinase-growth factor receptor. The results presented here are discussed on the basis of the claimed relationship between 27OHC, hypercholesterolemia, macrophage infiltration and therapy-resistant ERα+ breast cancer incidence.

  17. Primary Germ Cell Tumors of the Mediastinum: 10 Years of Experience in a Tertiary Teaching Hospital

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    Chih-Jen Yang

    2005-09-01

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

  18. Primary mucinous adenocarcinoma of the bladder with signet-ring cells: case report

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    Marcelo Lorenzi Marques

    Full Text Available CONTEXT: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma. CASE REPORT: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.

  19. Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

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    Kotteas, E A; Pavlidis, N

    2015-04-01

    Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Primary cutaneous marginal zone B-cell lymphoma: clinical and histological aspects.

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    Khaled, A; Sassi, S; Fazaa, B; Ben Hassouna, J; Ben Romdhane, K; Kamoun, M R

    2009-02-01

    According to the WHO-EORTC classification of cutaneous lymphomas, primary cutaneous marginal zone B-cell lymphoma are now well characterized. We report here a case of primary cutaneous marginal zone B-cell lymphoma in a 51 year-old man in which the diagnosis was made using both histology and immunopathology. The patient had no remarkable medical history, no history of either acute inflammation or insect bite, and presented with a 5 cm solitary asymptomatic erythematous firm, multinodular and infiltrated plaque on the back for 12 months. Histological examination and immunohistochemical study of a cutaneous biopsy provided a differential diagnosis between B cell lymphoma and lymphocytoma cutis. Full body work up revealed no signs of extracutaneous dissemination. The patient underwent surgical excision of the nodule. Histological examination showed a histological and immunophenotyping profile typical of primary cutaneous marginal zone B-cell lymphoma. The lesion was completely excised with clear margins and no recurrence occurred after a 12 month-follow-up period. Primary cutaneous marginal zone B-cell lymphoma are low-grade lymphomas that have an indolent course and a high tendency to recur. They should be differentiated from lymphocytoma cutis and from the other types of cutaneous B cell lymphomas that have a different course and prognosis.

  1. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells

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    Duncan, Henry F., E-mail: Hal.Duncan@dental.tcd.ie [Division of Restorative Dentistry and Periodontology, Dublin Dental University Hospital, Trinity College Dublin, Lincoln Place, Dublin 2 (Ireland); Smith, Anthony J. [Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham (United Kingdom); Fleming, Garry J.P. [Material Science Unit, Division of Oral Biosciences, Dublin Dental University Hospital, Trinity College Dublin, Dublin (Ireland); Cooper, Paul R. [Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham (United Kingdom)

    2013-06-10

    Application of histone deacetylase inhibitors (HDACi) to cells epigenetically alters their chromatin structure and induces transcriptional and cellular reparative events. This study investigated the application of two HDACi, valproic acid (VPA) and trichostatin A (TSA) on the induction of repair-associated responses in primary dental pulp cell (DPC) cultures. Flow cytometry demonstrated that TSA (100 nM, 400 nM) significantly increased cell viability. Neither HDACi was cytotoxic, although cell growth analysis revealed significant anti-proliferative effects at higher concentrations for VPA (>0.5 mM) and TSA (>50 nM). While high-content-analysis demonstrated that HDACi did not significantly induce caspase-3 or p21 activity, p53-expression was increased by VPA (3 mM, 5 mM) at 48 h. HDACi-exposure induced mineralization per cell dose-dependently to a plateau level (VPA-0.125 mM and TSA-25 nM) with accompanying increases in mineralization/dentinogenic-associated gene expression at 5 days (DMP-1, BMP-2/-4, Nestin) and 10 days (DSPP, BMP-2/-4). Both HDACis, at a range of concentrations, significantly stimulated osteopontin and BMP-2 protein expression at 10 and 14 days further supporting the ability of HDACi to promote differentiation. HDACi exert different effects on primary compared with transformed DPCs and promote mineralization and differentiation events without cytotoxic effects. These novel data now highlight the potential in restorative dentistry for applying low concentrations of HDACi in vital pulp treatment. -- Highlights: • Valproic acid and trichostatin A promoted mineralization in primary pulp cells. • Cell viability, apoptosis, caspase-3, p21 unaltered; p53 increased by valproic acid. • Trichostatin A increased cell viability at 24 h at selected concentrations. • Altered cell toxicity and differentiation between primary and transformed cells. • HDACi-induced the differentiation marker proteins osteopontin and BMP-2.

  2. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells

    International Nuclear Information System (INIS)

    Duncan, Henry F.; Smith, Anthony J.; Fleming, Garry J.P.; Cooper, Paul R.

    2013-01-01

    Application of histone deacetylase inhibitors (HDACi) to cells epigenetically alters their chromatin structure and induces transcriptional and cellular reparative events. This study investigated the application of two HDACi, valproic acid (VPA) and trichostatin A (TSA) on the induction of repair-associated responses in primary dental pulp cell (DPC) cultures. Flow cytometry demonstrated that TSA (100 nM, 400 nM) significantly increased cell viability. Neither HDACi was cytotoxic, although cell growth analysis revealed significant anti-proliferative effects at higher concentrations for VPA (>0.5 mM) and TSA (>50 nM). While high-content-analysis demonstrated that HDACi did not significantly induce caspase-3 or p21 activity, p53-expression was increased by VPA (3 mM, 5 mM) at 48 h. HDACi-exposure induced mineralization per cell dose-dependently to a plateau level (VPA-0.125 mM and TSA-25 nM) with accompanying increases in mineralization/dentinogenic-associated gene expression at 5 days (DMP-1, BMP-2/-4, Nestin) and 10 days (DSPP, BMP-2/-4). Both HDACis, at a range of concentrations, significantly stimulated osteopontin and BMP-2 protein expression at 10 and 14 days further supporting the ability of HDACi to promote differentiation. HDACi exert different effects on primary compared with transformed DPCs and promote mineralization and differentiation events without cytotoxic effects. These novel data now highlight the potential in restorative dentistry for applying low concentrations of HDACi in vital pulp treatment. -- Highlights: • Valproic acid and trichostatin A promoted mineralization in primary pulp cells. • Cell viability, apoptosis, caspase-3, p21 unaltered; p53 increased by valproic acid. • Trichostatin A increased cell viability at 24 h at selected concentrations. • Altered cell toxicity and differentiation between primary and transformed cells. • HDACi-induced the differentiation marker proteins osteopontin and BMP-2

  3. Self-renewing Monolayer of Primary Colonic or Rectal Epithelial CellsSummary

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    Yuli Wang

    2017-07-01

    Full Text Available Background & Aims: Three-dimensional organoid culture has fundamentally changed the in vitro study of intestinal biology enabling novel assays; however, its use is limited because of an inaccessible luminal compartment and challenges to data gathering in a three-dimensional hydrogel matrix. Long-lived, self-renewing 2-dimensional (2-D tissue cultured from primary colon cells has not been accomplished. Methods: The surface matrix and chemical factors that sustain 2-D mouse colonic and human rectal epithelial cell monolayers with cell repertoires comparable to that in vivo were identified. Results: The monolayers formed organoids or colonoids when placed in standard Matrigel culture. As with the colonoids, the monolayers exhibited compartmentalization of proliferative and differentiated cells, with proliferative cells located near the peripheral edges of growing monolayers and differentiated cells predominated in the central regions. Screening of 77 dietary compounds and metabolites revealed altered proliferation or differentiation of the murine colonic epithelium. When exposed to a subset of the compound library, murine organoids exhibited similar responses to that of the monolayer but with differences that were likely attributable to the inaccessible organoid lumen. The response of the human primary epithelium to a compound subset was distinct from that of both the murine primary epithelium and human tumor cells. Conclusions: This study demonstrates that a self-renewing 2-D murine and human monolayer derived from primary cells can serve as a physiologically relevant assay system for study of stem cell renewal and differentiation and for compound screening. The platform holds transformative potential for personalized and precision medicine and can be applied to emerging areas of disease modeling and microbiome studies. Keywords: Colonic Epithelial Cells, Monolayer, Organoids, Compound Screening

  4. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

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    González-Satué Carlos

    2012-01-01

    Full Text Available Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images.

  5. Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary

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    Dinesh Chandra Doval

    2009-03-01

    Full Text Available Metastasis to the breast from an extra-mammary primary is a rare phenomenon; metastasis from gastric carcinoma to the breast is extremely so. We report a case who initially presented as mucin-secreting and signet-ring cell tumor of the ovary, and after an interval of 8 months with breast and chest wall metastatic nodules. The covert gastric primary eluded the oncologists at both presentations.

  6. Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)

    International Nuclear Information System (INIS)

    Higashi, Kotaro; Takase, Shuko; Ohguchi, Manabu; Seki, Hiroyasu; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Rikimaru, Shigeho.

    1992-01-01

    This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r=-0.701, p<0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy. (author)

  7. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  8. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Directory of Open Access Journals (Sweden)

    Simon Heidegger

    Full Text Available Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  9. Variation in pestivirus growth in testicle primary cell culture is more dependent on the individual cell donor than cattle breed.

    Science.gov (United States)

    Weber, Matheus N; Bauermann, Fernando V; Gómez-Romero, Ninnet; Herring, Andy D; Canal, Cláudio W; Neill, John D; Ridpath, Julia F

    2017-03-01

    The causes of bovine respiratory disease complex (BRDC) are multifactorial and include infection with both viral and bacterial pathogens. Host factors are also involved as different breeds of cattle appear to have different susceptibilities to BRDC. Infection with bovine pestiviruses, including bovine viral diarrhea virus 1 (BVDV1), BVDV2 and 'HoBi'-like viruses, is linked to the development of BRDC. The aim of the present study was to compare the growth of different bovine pestiviruses in primary testicle cell cultures obtained from taurine, indicine and mixed taurine and indicine cattle breeds. Primary cells strains, derived from testicular tissue, were generated from three animals from each breed. Bovine pestivirus strains used were from BVDV-1a, BVDV-1b, BVDV-2a and 'HoBi'-like virus. Growth was compared by determining virus titers after one passage in primary cells. All tests were run in triplicate. Virus titers were determined by endpoint dilution and RT-qPCR. Statistical analysis was performed using one way analysis of variance (ANOVA) followed by the Tukey's Multiple Comparison Test (P˂0.05). Significant differences in virus growth did not correlate with cattle breed. However, significant differences were observed between cells derived from different individuals regardless of breed. Variation in the replication of virus in primary cell strains may reflect a genetic predisposition that favors virus replication.

  10. Distribution of Neuroendocrine Cells in the Transition Zone of the Prostate

    Directory of Open Access Journals (Sweden)

    Yuki Kyoda

    2017-01-01

    Full Text Available Objectives. To evaluate the distribution of neuroendocrine (NE cells which may influence the development of benign prostatic hyperplasia (BPH in the transition zone (TZ. Methods. We reviewed specimens from 80 patients who underwent radical prostatectomy in our institution and evaluated the density of NE cells in the TZ. They were histologically classified into 3 groups: those with no adenomatous nodule in the TZ (group A, those with small nodules with normal epithelium and stroma around them in the TZ (group B, and those with large nodules occupying the TZ (group C. In the patients of group B, intra-adenoma (adenomatous nodules and extra-adenoma (normal tissue NE cells in the TZ were separately counted. Results. There were 22, 23, and 35 patients in groups A, B, and C, respectively. The median density of NE cells in the TZ of group B patients, 2.80/mm2, was significantly higher than that of NE cells in group A, 1.43/mm2, and group C, 0.61/mm2 (p<0.001. In group B, the median density of extra-adenoma NE cells was significantly higher than that of intra-adenoma. Conclusions. Many NE cells exist around small adenoma in the TZ. NE cells may influence the initial growth of BPH in a paracrine fashion. Trial Registration. This study approved by our institutional review board was retrospectively registered (#272-14.

  11. Oxidative stress, mitochondrial permeability transition, and cell death in Cu-exposed trout hepatocytes

    International Nuclear Information System (INIS)

    Krumschnabel, Gerhard; Manzl, Claudia; Berger, Christian; Hofer, Bettina

    2005-01-01

    We have previously shown that, in trout hepatocytes, exposure to a high dose of copper (Cu) leads to disruption of Ca 2+ homeostasis and elevated formation of reactive oxygen species (ROS), with the latter ultimately causing cell death. In the present study, we aimed at identifying, using a lower Cu concentration, the role of mitochondria in this scenario, the potential involvement of the mitochondrial permeability transition (MPT), and the mode of cell death induced by the metal. Incubation with 10 μM Cu resulted in a strong stimulation of ROS formation, and after 2 h of exposure a significant increase of both apoptotic and necrotic cells was seen. Co-incubation of Cu-treated hepatocytes with the iron-chelator deferoxamine significantly inhibited ROS production and completely prevented cell death. The origin of the radicals generated was at least partly mitochondrial, as visualized by confocal laser scanning microscopy. Furthermore, ROS production was diminished by inhibition of mitochondrial respiration, but since this also aggravated the elevation of intracellular Ca 2+ induced by Cu, it did not preserve cell viability. In a sub-population of cells, Cu induced a decrease of mitochondrial membrane potential and occurrence of the MPT. Cyclosporin A, which did not inhibit ROS formation, prevented the onset of the MPT and inhibited apoptotic, but not necrotic, cell death. Cu-induced apoptosis therefore appears to be dependent on induction of the MPT, but the prominent contribution of mitochondria to ROS generation also suggests an important role of mitochondria in necrotic cell death

  12. Identification of cancer stem-like side population cells in purified primary cultured human laryngeal squamous cell carcinoma epithelia.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Wu

    Full Text Available Cancer stem-like side population (SP cells have been identified in many solid tumors; however, most of these investigations are performed using established cancer cell lines. Cancer cells in tumor tissue containing fibroblasts and many other types of cells are much more complex than any cancer cell line. Although SP cells were identified in the laryngeal squamous cell carcinoma (LSCC cell line Hep-2 in our pilot study, it is unknown whether the LSCC tissue contains SP cells. In this study, LSCC cells (LSCCs were primary cultured and purified from a surgically resected LSCC specimen derived from a well-differentiated epiglottic neoplasm of a Chinese male. This was followed by the verification of epithelium-specific characteristics, such as ultrastructure and biomarkers. A distinct SP subpopulation (4.45±1.07% was isolated by Hoechst 33342 efflux analysis from cultured LSCCs by using a flow cytometer. Cancer stem cell (CSC-associated assays, including expression of self-renewal and CSC marker genes, proliferation, differentiation, spheroid formation, chemotherapy resistance, and tumorigenicity were then conducted between SP and non-SP (NSP LSCCs. In vitro and in vivo assays revealed that SP cells manifested preferential expression of self-renewal and CSC marker genes, higher capacity for proliferation, differentiation, and spheroid formation; enhanced resistance to chemotherapy; and greater xenograft tumorigenicity in immunodeficient mice compared with NSP cells. These findings suggest that the primary cultured and purified LSCCs contain cancer stem-like SP cells, which may serve as a valuable model for CSC research in LSCC.

  13. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis.

    Science.gov (United States)

    Klettner, Alexa; Tahmaz, Nihat; Dithmer, Michaela; Richert, Elisabeth; Roider, Johann

    2014-10-01

    Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Primary RPE cells were prepared from freshly slaughtered pigs' eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2011-03-01

    Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

  15. Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

    Science.gov (United States)

    Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

    2013-10-01

    Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

  16. Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

    Science.gov (United States)

    Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

    2014-09-01

    Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

  17. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  18. Factors associated with a primary surgical approach for sinonasal squamous cell carcinoma.

    Science.gov (United States)

    Cracchiolo, Jennifer R; Patel, Krupa; Migliacci, Jocelyn C; Morris, Luc T; Ganly, Ian; Roman, Benjamin R; McBride, Sean M; Tabar, Viviane S; Cohen, Marc A

    2018-03-01

    Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS. © 2017 Wiley Periodicals, Inc.

  19. Primary diffuse large B cell lymphoma arising from a leiomyoma of the uterine corpus.

    Science.gov (United States)

    Zhao, Lianhua; Ma, Qiang; Wang, Qiushi; Zeng, Ying; Luo, Qingya; Xiao, Hualiang

    2016-01-20

    Primary diffuse large B cell lymphoma (DLBCL) of the uterus is rare, and primary DLBCL arising from a uterine leiomyoma (collision tumor) has not been reported in the literature. We describe the clinical, histological, immunohistochemical, and molecular features of primary DLBCL arising from a leiomyoma in the uterine corpus. A 73-year-old female patient had a uterine mass for 23 years. An ultrasound scan revealed marked enlargement of the uterus, measuring 18.2 × 13 × 16.3 cm, with a 17.6 × 10.9 × 11.6 cm hypoechoic mass in the uterine corpus. The tumors consisted of medium- to large-sized cells exhibiting a diffuse pattern of growth with a well-circumscribed leiomyoma. The neoplastic cells strongly expressed CD79α, CD20 and PAX5. Molecular analyses indicated clonal B-cell receptor gene rearrangement. To the best of our knowledge, no previous cases of primary DLBCL arising from a leiomyoma have been reported. It is necessary to differentiate a diagnosis of primary DLBCL arising from a leiomyoma from that of leiomyoma with florid reactive lymphocytic infiltration (lymphoma-like lesion). Careful analysis of clinical, histological, immunophenotypic, and genetic features is required to establish the correct diagnosis.

  20. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  1. Primary signet ring cell carcinoma of the appendix mimicking acute appendicitis

    Directory of Open Access Journals (Sweden)

    Mario Fusari

    2012-10-01

    Full Text Available Primary signet ring cell carcinoma of the appendix is a very rare neoplasm that usually presents with signs and symptoms of acute appendicitis and in particular with a right lower abdominal pain. Preoperative imaging detection of appendiceal adenocarcinoma has an important value because it may result in an appropriate surgical procedure. We report a rare case of primary signet ring cell carcinoma of the vermiform appendix in an 80-year-old man who was misdiagnosed on computed tomography (CT scan as acute appendicitis.

  2. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor

    DEFF Research Database (Denmark)

    Geisler, C; Pallesen, G; Platz, P

    1989-01-01

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor....... Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected...... deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue....

  3. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey

    Directory of Open Access Journals (Sweden)

    Alişan Yıldıran

    2017-12-01

    Full Text Available Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11, Chediak-Higashi syndrome (n=2, leukocyte adhesion deficiency (n=2, MHC class 2 deficiency (n=2, chronic granulomatous syndrome (n=2, hemophagocytic lymphohistiocytosis (n=1, Wiskott-Aldrich syndrome (n=1, and Omenn syndrome (n=1. Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

  4. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in the Black Sea Region of Turkey.

    Science.gov (United States)

    Yıldıran, Alişan; Çeliksoy, Mehmet Halil; Borte, Stephan; Güner, Şükrü Nail; Elli, Murat; Fışgın, Tunç; Özyürek, Emel; Sancak, Recep; Oğur, Gönül

    2017-12-01

    Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.

  5. Cell kinetics of irradiated experimental tumors: cell transition from the non-proliferating to the proliferating pool

    International Nuclear Information System (INIS)

    Potmesil, M.; Goldfeder, A.

    1980-01-01

    In murine mammary carcinomas, parenchymal tumor cells with dense nucleoli traverse the cell cycle and divide, thus constituting the proliferating pool. Cells with trabeculate or ring-shaped nucleoli either proceed slowly through G 1 phase or are arrested in it. The role of these non-proliferating, G 1 phase-confined cells in tumor regeneration was studied in vivo after a subcurative dose of X-irradiation in two transplantable tumor lines. Tumor-bearing mice were continuously injected with methyl[ 3 H]thymidine before and after irradiation. Finally, the labeling was discontinued, mice injected with vincristine sulfate and cells arrested in metaphase were accumulated over 10-hrs. Two clearly delineated groups of vincristine-arrested mitoses emerged in autoradiograms prepared from tumor tissue at the time of starting tumor regrowth: one group with the silver-grain counts corresponding to the background level, the other with heavily labeled mitoses. As the only source of unlabeled mitoses was unlabeled G 1 phase-confined cells persisting in the tumor, this indicated cell transition from the non-proliferating to the proliferating pool, which took place in the initial phase of the tumor regrowth. Unlabeled progenitors have apparently remained in G 1 phase for at least 5-12 days after irradiation. (author)

  6. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  7. Automated Expansion of Primary Human T Cells in Scalable and Cell-Friendly Hydrogel Microtubes for Adoptive Immunotherapy.

    Science.gov (United States)

    Lin, Haishuang; Li, Qiang; Wang, Ou; Rauch, Jack; Harm, Braden; Viljoen, Hendrik J; Zhang, Chi; Van Wyk, Erika; Zhang, Chi; Lei, Yuguo

    2018-05-11

    Adoptive immunotherapy is a highly effective strategy for treating many human cancers, such as melanoma, cervical cancer, lymphoma, and leukemia. Here, a novel cell culture technology is reported for expanding primary human T cells for adoptive immunotherapy. T cells are suspended and cultured in microscale alginate hydrogel tubes (AlgTubes) that are suspended in the cell culture medium in a culture vessel. The hydrogel tubes protect cells from hydrodynamic stresses and confine the cell mass less than 400 µm (in radial diameter) to ensure efficient mass transport, creating a cell-friendly microenvironment for growing T cells. This system is simple, scalable, highly efficient, defined, cost-effective, and compatible with current good manufacturing practices. Under optimized culture conditions, the AlgTubes enable culturing T cells with high cell viability, low DNA damage, high growth rate (≈320-fold expansion over 14 days), high purity (≈98% CD3+), and high yield (≈3.2 × 10 8 cells mL -1 hydrogel). All offer considerable advantages compared to current T cell culturing approaches. This new culture technology can significantly reduce the culture volume, time, and cost, while increasing the production. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  9. The role of primary health care services to better meet the needs of Aboriginal Australians transitioning from prison to the community

    OpenAIRE

    Lloyd, Jane E.; Delaney-Thiele, Dea; Abbott, Penny; Baldry, Eileen; McEntyre, Elizabeth; Reath, Jennifer; Indig, Devon; Sherwood, Juanita; Harris, Mark F.

    2015-01-01

    Background Aboriginal Australians are more likely than other Australians to cycle in and out of prison on remand or by serving multiple short sentences?a form of serial incarceration and institutionalisation. This cycle contributes to the over-representation of Aboriginal Australians in prison and higher rates of recidivism. Our research examined how primary health care can better meet the health care and social support needs of Aboriginal Australians transitioning from prison to the communit...

  10. Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing.

    Science.gov (United States)

    Nikolich-Žugich, J; Davies, J S

    2017-03-01

    Ageing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs. © 2017 British Society for Immunology.

  11. FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

    Science.gov (United States)

    Ogunbolude, Yetunde; Dai, Chenlu; Bagu, Edward T; Goel, Raghuveera Kumar; Miah, Sayem; MacAusland-Berg, Joshua; Ng, Chi Ying; Chibbar, Rajni; Napper, Scott; Raptis, Leda; Vizeacoumar, Frederick; Vizeacoumar, Franco; Bonham, Keith; Lukong, Kiven Erique

    2017-12-22

    The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.

  12. Donor-derived stem-cells and epithelial mesenchymal transition in squamous cell carcinoma in transplant recipients.

    Science.gov (United States)

    Verneuil, Laurence; Leboeuf, Christophe; Bousquet, Guilhem; Brugiere, Charlotte; Elbouchtaoui, Morad; Plassa, Louis-François; Peraldi, Marie-Noelle; Lebbé, Celeste; Ratajczak, Philippe; Janin, Anne

    2015-12-08

    Skin squamous-cell-carcinoma (SCC), is the main complication in long-term kidney-transplant recipients, and it can include donor-derived cells. Preclinical models demonstrated the involvement of epithelial mesenchymal transition (EMT) in the progression of skin SCC, and the role of Snail, an EMT transcription factor, in cancer stem-cell survival and expansion.Here, we studied stem-cells and EMT expression in SCCs and concomitant actinic keratoses (AK) in kidney-transplant recipients. In SCC and AK in 3 female recipients of male kidney-transplants, donor-derived Y chromosome in epidermal stem cells was assessed using combined XY-FISH/CD133 immunostaining, and digital-droplet-PCR on laser-microdissected CD133 expressing epidermal cells.For EMT study, double immunostainings of CD133 with vimentin or snail and slug, electron microscopy and immunostainings of keratinocytes junctions were performed. Digital droplet PCR was used to check CDH1 (E-cadherin) expression level in laser-microdissected cells co-expressing CD133 and vimentin or snail and slug.The numbers of Y-chromosome were assessed using digital droplet PCR in laser-microdissected cells co-expressing CD133 and vimentin, or snail and slug, and in CD133 positive cells not expressing any EMT maker. We identified donor-derived stem-cells in basal layers and invasive areas in all skin SCCs and in concomitant AKs, but not in surrounding normal skin.The donor-derived stem-cells expressed the EMT markers, vimentin, snail and slug in SCCs but not in AKs. The expression of the EMT transcription factor, SNAI1, was higher in stem-cells when they expressed vimentin. They were located in invasive areas of SCCs. In these areas, the expressions of claudin-1 and desmoglein 1 were reduced or absent, and within the basal layer there were features of basal membrane disappearance.Donor-derived stem cells were in larger numbers in stem cells co-expressing vimentin or snail and slug than in stem cells not expressing any EMT marker

  13. Primary Endometrial Squamous Cell Carcinoma In Situ: Report of a rare disease.

    Science.gov (United States)

    Jetley, Sujata; Jairajpuri, Zeeba S; Hassan, Mohammad J; Madaan, Garima; Jain, Reena

    2015-11-01

    Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year's duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.

  14. Single to Two Cluster State Transition of Primary Motor Cortex 4-posterior (MI-4p Activities in Humans

    Directory of Open Access Journals (Sweden)

    Kazunori Nakada

    2015-11-01

    Full Text Available The human primary motor cortex has dual representation of the digits, namely, area 4 anterior (MI-4a and area 4 posterior (MI-4p. We have previously demonstrated that activation of these two functional subunits can be identified independently by functional magnetic resonance imaging (fMRI using independent component-cross correlation-sequential epoch (ICS analysis. Subsequent studies in patients with hemiparesis due to subcortical lesions and monoparesis due to peripheral nerve injury demonstrated that MI-4p represents the initiation area of activation, whereas MI-4a is the secondarily activated motor cortex requiring a “long-loop” feedback input from secondary motor systems, likely the cerebellum. A dynamic model of hand motion based on the limit cycle oscillator predicts that the specific pattern of entrainment of neural firing may occur by applying appropriate periodic stimuli. Under normal conditions, such entrainment introduces a single phase-cluster. Under pathological conditions where entrainment stimuli have insufficient strength, the phase cluster splits into two clusters. Observable physiological phenomena of this shift from single cluster to two clusters are: doubling of firing rate of output neurons; or decay in group firing density of the system due to dampening of odd harmonics components. While the former is not testable in humans, the latter can be tested by appropriately designed fMRI experiments, the quantitative index of which is believed to reflect group behavior of neurons functionally localized, e.g., firing density in the dynamic theory. Accordingly, we performed dynamic analysis of MI-4p activation in normal volunteers and paretic patients. The results clearly indicated that MI-4p exhibits a transition from a single to a two phase-cluster state which coincided with loss of MI-4a activation. The study demonstrated that motor dysfunction (hemiparesis in patients with a subcortical infarct is not simply due to afferent

  15. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Third Results Reports

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2012-05-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. NREL has previously published two reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from July 2011 through January 2012.

  16. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Second Results Report and Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2011-10-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. This is the second results report for the AT fuel cell bus since it was placed in service, and it focuses on the newest data analysis and lessons learned since the previous report. The appendices, referenced in the main report, provide the full background for the evaluation. They will be updated as new information is collected but will contain the original background material from the first report.

  17. Primary cutaneous peripheral T-cell lymphoma, unspecified with an indolent clinical course: a distinct peripheral T-cell lymphoma?

    LENUS (Irish Health Repository)

    Ryan, A J A

    2012-02-01

    Primary cutaneous peripheral T-cell lymphomas (PTL), unspecified, are rare lymphomas, with a poor prognosis. They grow and disseminate rapidly, leading to widespread disease. We report a case of PTL, unspecified occurring on the nose. Despite its aggressive histology, this tumour behaved indolently. It is remarkably similar, clinically and histologically, to four recently described cases that occurred on the ear.

  18. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  19. School Belongingness and Mental Health Functioning across the Primary-Secondary Transition in a Mainstream Sample: Multi-Group Cross-Lagged Analyses

    Science.gov (United States)

    Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

    2014-01-01

    The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students’ school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students. PMID:24967580

  20. School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

    Directory of Open Access Journals (Sweden)

    Sharmila Vaz

    Full Text Available The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

  1. Generation of iPSC lines from primary human chorionic villi cells

    Directory of Open Access Journals (Sweden)

    Björn Lichtner

    2015-11-01

    Full Text Available Primary human chorionic villi (CV cells were used to generate the iPSC line by retroviral transduction of the four Yamanaka-factors OCT4, SOX2, KLF4 and c-MYC. Pluripotency was confirmed both in vivo and in vitro. The transcriptomes of the CV-derived iPSC lines and the human embryonic stem cell lines—H1 and H9 have a Pearson correlation of 0.929 and 0.943 respectively.

  2. Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

    Science.gov (United States)

    2017-02-01

    a cell population particularly suitable for low serum propagation, provided that appropriate growth factors are available. A low serum medium...of MGK. 15. SUBJECT TERMS Cornea, chemical warfare agent, corneal endothelial cell, endothelium, growth , isolation, mouse, rabbit, porcine, in...with corneal SM exposure.2 A primary requirement in achieving this goal is to develop methods that enable the isolation of a pure CEC population and

  3. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    OpenAIRE

    Mansour Ansari; Hamid Nasrollahi; Majdaddin Rajaei; Maral Mokhtari; Seyed Hasan Hamedi; Mohammad Mohammadianpanah; Shapour Omidvari; Ahmad Mosalaei; Niloofar Ahmadloo

    2017-01-01

    Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymp...

  4. Adenoviral Gene Delivery to Primary Human Cutaneous Cells and Burn Wounds

    OpenAIRE

    Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

    2006-01-01

    The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determine...

  5. An optimized protocol for isolating primary epithelial cell chromatin for ChIP.

    Directory of Open Access Journals (Sweden)

    James A Browne

    Full Text Available A critical part of generating robust chromatin immunoprecipitation (ChIP data is the optimization of chromatin purification and size selection. This is particularly important when ChIP is combined with next-generation sequencing (ChIP-seq to identify targets of DNA-binding proteins, genome-wide. Current protocols refined by the ENCODE consortium generally use a two-step cell lysis procedure that is applicable to a wide variety of cell types. However, the isolation and size selection of chromatin from primary human epithelial cells may often be particularly challenging. These cells tend to form sheets of formaldehyde cross-linked material in which cells are resistant to membrane lysis, nuclei are not released and subsequent sonication produces extensive high molecular weight contamination. Here we describe an optimized protocol to prepare high quality ChIP-grade chromatin from primary human bronchial epithelial cells. The ENCODE protocol was used as a starting point to which we added the following key steps to separate the sheets of formaldehyde-fixed cells prior to lysis. (1 Incubation of the formaldehyde-fixed adherent cells in Trypsin-EDTA (0.25% room temperature for no longer than 5 min. (2 Equilibration of the fixed cells in detergent-free lysis buffers prior to each lysis step. (3 The addition of 0.5% Triton X-100 to the complete cell membrane lysis buffer. (4 Passing the cell suspension (in complete cell membrane lysis buffer through a 25-gauge needle followed by continuous agitation on ice for 35 min. Each step of the modified protocol was documented by light microscopy using the Methyl Green-Pyronin dual dye, which stains cytoplasm red (Pyronin and the nuclei grey-blue (Methyl green. This modified method is reproducibly effective at producing high quality sheared chromatin for ChIP and is equally applicable to other epithelial cell types.

  6. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  7. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  8. Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.

    Science.gov (United States)

    Komlósi, Zsolt I; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, György; Akdis, Cezmi A

    2017-09-20

    Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L + ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L + ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Chemosensitivity testing of primary human renal cell carcinoma by a tetrazolium based microculture assay (MTT).

    Science.gov (United States)

    Mickisch, G; Fajta, S; Keilhauer, G; Schlick, E; Tschada, R; Alken, P

    1990-01-01

    MTT staining procedures have been used in chemosensitivity testing of established cell lines of human and other sources as well as of human leukaemias, but only limited information on its application in primary solid human tumors is presently available. We have evaluated MTT staining in primary human Renal Cell Carcinomas (RCCs), studied various factors interfering with the optimal use, and finally applied it in subsequent chemosensitivity testing. The method depends on the conversion of a water-soluble tetrazolium salt (MTT) to a purple colored formazan precipitate, a reaction effected by enzymes active only in living cells. Single cell suspensions of RCCs were obtained either by enzymatic dispersion or by mechanical dissagregation, filtered through gauze, and purified by Ficoll density centrifugation. Tests were carried out in 96-well microculture plates. 10(4) viable tumor cells per well at 4 h incubation time with 20 micrograms MTT/100 microliters total medium volume yielded best results. Formazan crystals were dissolved with DMSO, and the plates were immediately measured on a microculture plate reader at 540 nm. Under these criteria, linearity of the system could be demonstrated. For chemosensitivity testing, cells were continuously exposed to a number of drugs prior to the MTT staining procedure. Reproducibility of results was assessed and confirmed by culturing RCCs in flasks additionally, resubmitting them after 1, 2, and 4 weeks to the MTT assay. We conclude that the semiautomated MTT assay offers a valid, rapid, reliable and simple method to determine the degree of chemoresistance in primary human RCCs.

  10. Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction.

    Science.gov (United States)

    Tan, Cong-Cong; Li, Gui-Xi; Tan, Li-Duan; Du, Xin; Li, Xiao-Qing; He, Rui; Wang, Qing-Shan; Feng, Yu-Mei

    2016-11-29

    Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-β/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance.

  11. Lifecycle cost assessment and carbon dioxide emissions of diesel, natural gas, hybrid electric, fuel cell hybrid and electric transit buses

    International Nuclear Information System (INIS)

    Lajunen, Antti; Lipman, Timothy

    2016-01-01

    This paper evaluates the lifecycle costs and carbon dioxide emissions of different types of city buses. The simulation models of the different powertrains were developed in the Autonomie vehicle simulation software. The carbon dioxide emissions were calculated both for the bus operation and for the fuel and energy pathways from well to tank. Two different operating environment case scenarios were used for the primary energy sources, which were Finland and California (USA). The fuel and energy pathways were selected appropriately in relation to the operating environment. The lifecycle costs take into account the purchase, operating, maintenance, and possible carbon emission costs. Based on the simulation results, the energy efficiency of city buses can be significantly improved by the alternative powertrain technologies. Hybrid buses have moderately lower carbon dioxide emissions during the service life than diesel buses whereas fully-electric buses have potential to significantly reduce carbon dioxide emissions, by up to 75%. The lifecycle cost analysis indicates that diesel hybrid buses are already competitive with diesel and natural gas buses. The high costs of fuel cell and battery systems are the major challenges for the fuel cell hybrid buses in order to reduce lifecycle costs to more competitive levels. - Highlights: • Alternative powertrains can significantly improve energy efficiency of transit buses. • Operating environment has an important impact on the lifecycle costs of buses. • Diesel hybrid buses are already cost effective solution for public transportation. • The cost of fuel cell technology is the major challenge for fuel cell hybrid buses. • Fully-electric buses have potential to significantly reduce carbon dioxide emissions.

  12. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyoshi, Ko, E-mail: miyoshi@cc.okayama-u.ac.jp [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan); Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato [Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558 (Japan)

    2009-10-30

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li{sub 2}CO{sub 3} were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  13. Lithium treatment elongates primary cilia in the mouse brain and in cultured cells

    International Nuclear Information System (INIS)

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Asanuma, Masato

    2009-01-01

    The molecular mechanisms underlying the therapeutic effects of lithium, a first-line antimanic mood stabilizer, have not yet been fully elucidated. Treatment of the algae Chlamydomonas reinhardtii with lithium has been shown to induce elongation of their flagella, which are analogous structures to vertebrate cilia. In the mouse brain, adenylyl cyclase 3 (AC3) and certain neuropeptide receptors colocalize to the primary cilium of neuronal cells, suggesting a chemosensory function for the primary cilium in the nervous system. Here we show that lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Brain sections from mice chronically fed with Li 2 CO 3 were subjected to immunofluorescence study. Primary cilia carrying both AC3 and the receptor for melanin-concentrating hormone (MCH) were elongated in the dorsal striatum and nucleus accumbens of lithium-fed mice, as compared to those of control animals. Moreover, lithium-treated NIH3T3 cells and cultured striatal neurons exhibited elongation of the primary cilia. The present results provide initial evidence that a psychotropic agent can affect ciliary length in the central nervous system, and furthermore suggest that lithium exerts its therapeutic effects via the upregulation of cilia-mediated MCH sensing. These findings thus contribute novel insights into the pathophysiology of bipolar mood disorder and other psychiatric diseases.

  14. Rat primary embryo fibroblast cells suppress transformation by the E6 and E7 genes of human papillomavirus type 16 in somatic hybrid cells.

    OpenAIRE

    Miyasaka, M; Takami, Y; Inoue, H; Hakura, A

    1991-01-01

    The E6 and E7 genes of human papillomavirus type 16 (HPV-16) transform established lines of rat cells but not rat cells in primary culture irrespective of the expression of the two genes. The reason for this difference between the susceptibilities of cell lines and primary cells was examined by using hybrid cells obtained by somatic cell fusion of rat cell lines transformed by the E6 and E7 genes of HPV-16 and freshly isolated rat embryo fibroblast cells. In these hybrid cells, transformed ph...

  15. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    2009-09-01

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  16. Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

    Science.gov (United States)

    Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

    2018-06-01

    Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

  17. Injectable scaffold materials differ in their cell instructive effects on primary human myoblasts

    DEFF Research Database (Denmark)

    Hejbøl, Eva Kildall; Sellathurai, Jeeva; Nair, Prabha Damodaran

    2017-01-01

    Scaffolds are materials used for delivery of cells for regeneration of tissues. They support three-dimensional organization and improve cell survival. For the repair of small skeletal muscles, injections of small volumes of cells are attractive, and injectable scaffolds for delivery of cells offer...... a minimally invasive technique. In this study, we examined in vitro the cell instructive effects of three types of injectable scaffolds, fibrin, alginate, and poly(lactic-co-glycolic acid)-based microparticles on primary human myoblasts. The myoblast morphology and progression in the myogenic program differed......, depending on the type of scaffold material. In alginate gel, the cells obtained a round morphology, they ceased to proliferate, and entered quiescence. In the fibrin gels, differentiation was promoted, and myotubes were observed within a few days in culture, while poly(lactic-co-glycolic acid...

  18. Edge Detection Based On the Characteristic of Primary Visual Cortex Cells

    Science.gov (United States)

    Zhu, M. M.; Xu, Y. L.; Ma, H. Q.

    2018-01-01

    Aiming at the problem that it is difficult to balance the accuracy of edge detection and anti-noise performance, and referring to the dynamic and static perceptions of the primary visual cortex (V1) cells, a V1 cell model is established to perform edge detection. A spatiotemporal filter is adopted to simulate the receptive field of V1 simple cells, the model V1 cell is obtained after integrating the responses of simple cells by half-wave rectification and normalization, Then the natural image edge is detected by using static perception of V1 cells. The simulation results show that, the V1 model can basically fit the biological data and has the universality of biology. What’s more, compared with other edge detection operators, the proposed model is more effective and has better robustness

  19. Alginate-Poly(ethylene glycol Hybrid Microspheres for Primary Cell Microencapsulation

    Directory of Open Access Journals (Sweden)

    Redouan Mahou

    2014-01-01

    Full Text Available The progress of medical therapies, which rely on the transplantation of microencapsulated living cells, depends on the quality of the encapsulating material. Such material has to be biocompatible, and the microencapsulation process must be simple and not harm the cells. Alginate-poly(ethylene glycol hybrid microspheres (alg-PEG-M were produced by combining ionotropic gelation of sodium alginate (Na-alg using calcium ions with covalent crosslinking of vinyl sulfone-terminated multi-arm poly(ethylene glycol (PEG-VS. In a one-step microsphere formation process, fast ionotropic gelation yields spherical calcium alginate gel beads, which serve as a matrix for simultaneously but slowly occurring covalent cross-linking of the PEG-VS molecules. The feasibility of cell microencapsulation was studied using primary human foreskin fibroblasts (EDX cells as a model. The use of cell culture media as polymer solvent, gelation bath, and storage medium did not negatively affect the alg-PEG-M properties. Microencapsulated EDX cells maintained their viability and proliferated. This study demonstrates the feasibility of primary cell microencapsulation within the novel microsphere type alg-PEG-M, serves as reference for future therapy development, and confirms the suitability of EDX cells as control model.

  20. Bufalin Inhibits the Differentiation and Proliferation of Cancer Stem Cells Derived from Primary Osteosarcoma Cells through Mir-148a.

    Science.gov (United States)

    Chang, Yuewen; Zhao, Yongfang; Gu, Wei; Cao, Yuelong; Wang, Shuqiang; Pang, Jian; Shi, Yinyu

    2015-01-01

    Osteosarcoma (OS) is the second leading cause of cancer-related death in children and young adults. Chemoresistance is the most important cause of treatment failure in OS, largely resulting from presence of cancer stem cells (CSCs). However, CSCs isolated from cancer cell lines do not necessarily represent those from primary human tumors due to accumulation of genetic aberrations that increase with passage number. Therefore, studies on CSCs from primary OS may be more important for understanding the mechanisms driving the chemoresistance of CSCs in OS. We established a primary culture of OS cells, known as C1OS, from freshly resected tumor tissue. We further isolated CSCs from C1OS cells (C1OS-CSCs). We analyzed the effects of bufalin, a traditional Chinese medicine, on the stemness of C1OS-CSCs. We also analyzed the microRNA (miR) targets of bufalin on the stemness of C1OS-CSCs. Moreover, we examined these findings in the OS specimen. Bufalin inhibited the stemness of C1OS-CSCs. Moreover, we found that miR-148a appeared to be a target of bufalin, and miR-148a further regulated DNMT1 and p27 to control the stemness of OS cells. This mechanism was further confirmed in OS specimen. Our data suggest that bufalin may be a promising treatment for OS, and its function may be conducted through regulation of miR-148a. © 2015 S. Karger AG, Basel.

  1. NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

    International Nuclear Information System (INIS)

    Bu, Youquan; Suenaga, Yusuke; Okoshi, Rintaro; Sang, Meixiang; Kubo, Natsumi; Song, Fangzhou; Nakagawara, Akira; Ozaki, Toshinori

    2010-01-01

    NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of γH2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.

  2. Academic success across the transition from primary to secondary schooling among lower-income adolescents: understanding the effects of family resources and gender.

    Science.gov (United States)

    Serbin, Lisa A; Stack, Dale M; Kingdon, Danielle

    2013-09-01

    Successful academic performance during adolescence is a key predictor of lifetime achievement, including occupational and social success. The present study investigated the important transition from primary to secondary schooling during early adolescence, when academic performance among youth often declines. The goal of the study was to understand how risk factors, specifically lower family resources and male gender, threaten academic success following this "critical transition" in schooling. The study involved a longitudinal examination of the predictors of academic performance in grades 7-8 among 127 (56 % girls) French-speaking Quebec (Canada) adolescents from lower-income backgrounds. As hypothesized based on transition theory, hierarchical regression analyses showed that supportive parenting and specific academic, social and behavioral competencies (including spelling ability, social skills, and lower levels of attention problems) predicted success across this transition among at-risk youth. Multiple-mediation procedures demonstrated that the set of compensatory factors fully mediated the negative impact of lower family resources on academic success in grades 7-8. Unique mediators (social skills, spelling ability, supportive parenting) also were identified. In addition, the "gender gap" in performance across the transition could be attributed statistically to differences between boys and girls in specific competencies observed prior to the transition, as well as differential parenting (i.e., support from mother) towards girls and boys. The present results contribute to our understanding of the processes by which established risk factors, such as low family income and gender impact development and academic performance during early adolescence. These "transitional" processes and subsequent academic performance may have consequences across adolescence and beyond, with an impact on lifetime patterns of achievement and occupational success.

  3. Andrographolide suppresses epithelial mesenchymal transition by inhibition of MAPK signalling pathway in lens epithelial cells.

    Science.gov (United States)

    Kayastha, Forum; Johar, Kaid; Gajjar, Devarshi; Arora, Anshul; Madhu, Hardik; Ganatra, Darshini; Vasavada, Abhay

    2015-06-01

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown. The purpose of this study is to evaluate the effect of andrographolide on EMT induced by growth factors in the fetal human lens epithelial cell line (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed that FHL 124 cells treated with growth factors had a significant decrease in protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After administering andrographolide, these levels significantly increased. It was noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly decreased after treatment with andrographolide when compared to the other group. Treatment with andrographolide significantly inhibited phosphorylation of ERK and JNK. Cell cycle analysis showed that andrographolide did not arrest cells at G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide helps sustain epithelial characteristics by modulating EMT markers and inhibiting the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it can prove to be useful in curbing EMT-mediated PCO.

  4. MiR-200c suppresses the migration of retinoblastoma cells by reversing epithelial mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xiao-Lei Shao

    2017-08-01

    Full Text Available AIM: To analyze the relationship between clinical features and epithelial mesenchymal transition (EMT in retinoblastoma (RB, further to investigate whether miR-200c regulates the EMT and migration of RB cells. METHODS: Expression of EMT-related markers and tumor-related factors were detected by immuno-histochemistry analysis in RB tissue from 29 cases. Correlations between their expression and clinical characteristics were analyzed. The regulation effects of miR-200c on EMT-related markers, tumor-related factors were observed in mRNA level and protein level by real-time polymerase chain reaction (PCR and Western blot, respectively, in Y79 and Weri-rb1 cells. Its effects on migration force of these RB cell lines were also detected with Transwell test. RESULTS: Lower expression of E-cadherin was present in the cases with malignant prognosis. MiR-200c promoted the expression of E-cadherin and decreased the expression of Vimentin and N-cadherin in Y79 and Weri-rb1 cells. Migration force of RB cells could be inhibited by miR-200c. CONCLUSION: EMT might be associated with bad prognosis in RB. MiR-200c suppresses the migration of retinoblastomatous cells by reverse EMT.

  5. Lentiviral Vector Mediated Claudin1 Silencing Inhibits Epithelial to Mesenchymal Transition in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xianqi Zhao

    2015-06-01

    Full Text Available Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human cancer, and have shown promising effects in controlling tumor development. Claudin1 (CLDN1 is a member of the tetraspan transmembrane protein family that plays a major role in tight junctions and is associated with tumor metastasis. However, the role of CLDN1 in breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two breast cancer (MDA-MB-231 and MCF7 cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (shRNA construct efficiently silenced CLDN1 expression in both breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT by upregulating the epithelial cell marker, E-cadherin, and downregulating mesenchymal markers, smooth muscle cell alpha-actin (SMA and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in breast cancer gene therapy by inhibiting EMT and controlling tumor cell growth.

  6. Electricity generation from fermented primary sludge using single-chamber air-cathode microbial fuel cells

    KAUST Repository

    Yang, Fei; Ren, Lijiao; Pu, Yuepu; Logan, Bruce E.

    2013-01-01

    Single-chamber air-cathode microbial fuel cells (MFCs) were used to generate electricity from fermented primary sludge. Fermentation (30°C, 9days) decreased total suspended solids (26.1-16.5g/L), volatile suspended solids (24.1-15.3g/L) and pH (5

  7. Primary thymic extranodal marginal zone B cell lymphoma as an incidental finding in a Caucasian woman

    DEFF Research Database (Denmark)

    Krogh Petersen, Jeanette; Larsen, Thomas Stauffer; Møller, Michael Boe

    2015-01-01

    Primary thymic extranodal marginal zone B cell lymphoma (TML) is an extremely rare lymphoma strongly associated with autoimmune disease. We report an exceedingly rare case of TML found in a non-Asian population. TML was found incidentally in a 60-year-old Caucasian woman with a short history...

  8. Primary temporal region squamous cell carcinoma diagnosed by a superficial temporal artery biopsy

    DEFF Research Database (Denmark)

    Andersen, S A W; Kiss, K

    2015-01-01

    artery biopsy was performed. The histopathology revealed perineural invasion of squamous cell carcinoma (SCC). A thorough investigation revealed no other primary site for the SCC and the patient was treated with surgical excision. CONCLUSION: Malignancy is rarely found in superficial temporal artery...

  9. Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery

    DEFF Research Database (Denmark)

    Kiprilov, Enko N; Awan, Aashir; Desprat, Romain

    2008-01-01

    Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC d...

  10. Primary cultures of glomerular parietal epithelial cells or podocytes with proven origin.

    NARCIS (Netherlands)

    Kabgani, N.; Grigoleit, T.; Schulte, K.; Sechi, A.; Sauer-Lehnen, S.; Tag, C.; Boor, P.; Kuppe, C.; Warsow, G.; Schordan, S.; Mostertz, J.; Chilukoti, R.K.; Homuth, G.; Endlich, N.; Tacke, F.; Weiskirchen, R.; Fuellen, G.; Endlich, K.; Floege, J.; Smeets, B.; Moeller, M.J.

    2012-01-01

    Parietal epithelial cells (PECs) are crucially involved in the pathogenesis of rapidly progressive glomerulonephritis (RPGN) as well as in focal and segmental glomerulosclerosis (FSGS). In this study, transgenic mouse lines were used to isolate pure, genetically tagged primary cultures of PECs or

  11. Interfacing polymeric scaffolds with primary pancreatic ductal adenocarcinoma cells to develop 3D cancer models

    NARCIS (Netherlands)

    Ricci, C.; Mota, C.M.; Moscato, S.; D' Alessandro, D.; Ugel, S.; Sartoris, S.; Bronte, V.; Boggi, U.; Campani, D.; Funel, N.; Moroni, Lorenzo; Danti, S.

    2014-01-01

    We analyzed the interactions between human primary cells from pancreatic ductal adenocarcinoma (PDAC) and polymeric scaffolds to develop 3D cancer models useful for mimicking the biology of this tumor. Three scaffold types based on two biocompatible polymeric formulations, such as poly(vinyl

  12. Infratemporal fossa extension of primary parotid squamous cell carcinoma: a rare entity with diagnosis dilemma

    International Nuclear Information System (INIS)

    Karaf, J.H.; Gendeh, B.S.; Yunus, M.R.M.

    2015-01-01

    Primary squamous cell carcinoma of parotid gland is rare but it is an aggressive neoplasm that can have extension into the infratemporal fossa. We report a 60-year-old female presenting with toothache over left lower molar causing a diagnostic dilemma. (author)

  13. Primary cutaneous large B-cell lymphoma of scalp: Case report of a rare variant

    Directory of Open Access Journals (Sweden)

    Yasmeen Khatib

    2017-01-01

    Full Text Available Primary cutaneous large B-cell lymphoma (Bcl is defined as a lymphoma composed of large cells constituting more than 80% of the infiltrate and absence of extracutaneous involvement after staging investigations. In the new World Health Organization/European Organization for Research and Treatment of Cancer classification, cutaneous Bcls with large cells are of three types - primary cutaneous large Bcl leg type (PCLBCLLT, primary cutaneous follicle center lymphoma diffuse type (PCFCLDT, and primary cutaneous large Bcls other (PCLBCLO. These three different types are distinct in terms of their clinicopathological features and survival. The PCLBCLO has intermediate features between those of PCLBCLLT and PCFCLDT. We present a case of PCLBCLO in a 57-year-old male who presented with a scalp swelling. Ultrasonography examination was suggestive of a sebaceous cyst. Computed tomography scan revealed the presence of an ill-defined hyperdense region in the soft tissue of the scalp region extending into the deeper layers of the scalp. Fine-needle aspiration cytology (FNAC revealed the presence of atypical lymphoid cells. Diagnosis was confirmed by biopsy and immunohistochemistry. Patient received rituximab combined with doxorubicin, vincristine, cyclophosphamide, and prednisolone regimen with complete resolution of the lesion. We present this case for its rarity, the utility of FNAC in early diagnosis, and to discuss the differential diagnosis.

  14. Regulation of proximal tubular cell differentiation and proliferation in primary culture by matrix stiffness and ECM components.

    Science.gov (United States)

    Chen, Wan-Chun; Lin, Hsi-Hui; Tang, Ming-Jer

    2014-09-15

    To explore whether matrix stiffness affects cell differentiation, proliferation, and transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in primary cultures of mouse proximal tubular epithelial cells (mPTECs), we used a soft matrix made from monomeric collagen type I-coated polyacrylamide gel or matrigel (MG). Both kinds of soft matrix benefited primary mPTECs to retain tubular-like morphology with differentiation and growth arrest and to evade TGF-β1-induced EMT. However, the potent effect of MG on mPTEC differentiation was suppressed by glutaraldehyde-induced cross-linking and subsequently stiffening MG or by an increasing ratio of collagen in the soft mixed gel. Culture media supplemented with MG also helped mPTECs to retain tubular-like morphology and a differentiated phenotype on stiff culture dishes as soft MG did. We further found that the protein level and activity of ERK were scaled with the matrix stiffness. U-0126, a MEK inhibitor, abolished the stiff matrix-induced dedifferentiation and proliferation. These data suggest that the ERK signaling pathway plays a vital role in matrix stiffness-regulated cell growth and differentiation. Taken together, both compliant property and specific MG signals from the matrix are required for the regulation of epithelial differentiation and proliferation. This study provides a basic understanding of how physical and chemical cues derived from the extracellular matrix regulate the physiological function of proximal tubules and the pathological development of renal fibrosis. Copyright © 2014 the American Physiological Society.

  15. Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

    Science.gov (United States)

    Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

    2015-01-01

    Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

  16. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

    2015-11-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

  17. Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

    International Nuclear Information System (INIS)

    Joo, Ijin; Kim, Haeryoung; Lee, Jeong Min

    2015-01-01

    There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients

  18. Chemo-radioresistance of small cell lung cancer cell lines derived from untreated primary tumors obtained by diagnostic bronchofiberscopy

    International Nuclear Information System (INIS)

    Tanio, Yoshiro; Watanabe, Masatoshi; Inoue, Tamotsu

    1990-01-01

    New cell lines of small cell lung cancer (SCLC) were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy. The advantage of this method was ease of obtaining specimens from lung tumors. Establishment of cell lines was successful with 4 of 13 specimens (30%). Clinical responses of the tumors showed considerable variation, but were well correlated with the in vitro sensitivity of the respective cell lines to chemotherapeutic drugs and irradiation. One of the cell lines was resistant to all drugs tested and irradiation, while another was sensitive to all of them. Although the acquired resistance of SCLC is the biggest problem in treatment, the natural resistance to therapy is another significant problem. Either acquired or natural, resistance mechanisms of SCLC may be elucidated by the use of such cell lines derived from untreated tumors. This method and these SCLC cell lines are expected to be useful for the serial study of biologic and genetic changes of untreated and pre-treated tumors, or primary and secondary tumors. (author)

  19. Overexpression of microRNA-194 suppresses the epithelial-mesenchymal transition in targeting stem cell transcription factor Sox3 in endometrial carcinoma stem cells.

    Science.gov (United States)

    Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi

    2017-06-01

    The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem

  20. Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wakao, Kazufumi [Department of Biotechnology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu-shi 400-8511 (Japan); Watanabe, Tadashi [Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichonocho 1, Yamashinaku, Kyoto 607-8412 (Japan); Takadama, Tadatoshi; Ui, Sadaharu [Department of Biotechnology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Kofu-shi 400-8511 (Japan); Shigemi, Zenpei; Kagawa, Hiroki [Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichonocho 1, Yamashinaku, Kyoto 607-8412 (Japan); Higashi, Chizuka; Ohga, Rie; Taira, Takahiro [Department of Molecular Cell Biology, Faculty of Medicine, University of Yamanashi, Chuoh-shi 409-3898 (Japan); Fujimuro, Masahiro, E-mail: fuji2@mb.kyoto-phu.ac.jp [Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichonocho 1, Yamashinaku, Kyoto 607-8412 (Japan)

    2014-02-07

    Highlights: • Sangivamycin induces the apoptosis of B cell lymphoma PEL cells. • Sangivamycin suppresses Erk signaling by inhibiting Erk phosphorylation in PEL cells. • The activation of Erk signaling is essential for PEL cell survival. • Sangivamycin induces the apoptosis of PEL cells without production of progeny virus. • Sangivamycin may serve as a novel drug for the treatment of PEL. - Abstract: Sangivamycin, a structural analog of adenosine and antibiotic exhibiting antitumor and antivirus activities, inhibits protein kinase C and the synthesis of both DNA and RNA. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients and HIV-infected homosexual males. PEL cells are derived from post-germinal center B cells, and are infected with KSHV. Herein, we asked if sangivamycin might be useful to treat PEL. We found that sangivamycin killed PEL cells, and we explored the underlying mechanism. Sangivamycin treatment drastically decreased the viability of PEL cell lines compared to KSHV-uninfected B lymphoma cell lines. Sangivamycin induced the apoptosis of PEL cells by activating caspase-7 and -9. Further, sangivamycin suppressed the phosphorylation of Erk1/2 and Akt, thus inhibiting activation of the proteins. Inhibitors of Akt and MEK suppressed the proliferation of PEL cells compared to KSHV-uninfected cells. It is known that activation of Erk and Akt signaling inhibits apoptosis and promotes proliferation in PEL cells. Our data therefore suggest that sangivamycin induces apoptosis by inhibiting Erk and Akt signaling in such cells. We next investigated whether sangivamycin, in combination with an HSP90 inhibitor geldanamycin (GA) or valproate (valproic acid), potentiated the cytotoxic effects of the latter drugs on PEL cells. Compared to treatment with GA or valproate alone, the addition of sangivamycin enhanced cytotoxic activity. Our data thus indicate that

  1. Sangivamycin induces apoptosis by suppressing Erk signaling in primary effusion lymphoma cells

    International Nuclear Information System (INIS)

    Wakao, Kazufumi; Watanabe, Tadashi; Takadama, Tadatoshi; Ui, Sadaharu; Shigemi, Zenpei; Kagawa, Hiroki; Higashi, Chizuka; Ohga, Rie; Taira, Takahiro; Fujimuro, Masahiro

    2014-01-01

    Highlights: • Sangivamycin induces the apoptosis of B cell lymphoma PEL cells. • Sangivamycin suppresses Erk signaling by inhibiting Erk phosphorylation in PEL cells. • The activation of Erk signaling is essential for PEL cell survival. • Sangivamycin induces the apoptosis of PEL cells without production of progeny virus. • Sangivamycin may serve as a novel drug for the treatment of PEL. - Abstract: Sangivamycin, a structural analog of adenosine and antibiotic exhibiting antitumor and antivirus activities, inhibits protein kinase C and the synthesis of both DNA and RNA. Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients and HIV-infected homosexual males. PEL cells are derived from post-germinal center B cells, and are infected with KSHV. Herein, we asked if sangivamycin might be useful to treat PEL. We found that sangivamycin killed PEL cells, and we explored the underlying mechanism. Sangivamycin treatment drastically decreased the viability of PEL cell lines compared to KSHV-uninfected B lymphoma cell lines. Sangivamycin induced the apoptosis of PEL cells by activating caspase-7 and -9. Further, sangivamycin suppressed the phosphorylation of Erk1/2 and Akt, thus inhibiting activation of the proteins. Inhibitors of Akt and MEK suppressed the proliferation of PEL cells compared to KSHV-uninfected cells. It is known that activation of Erk and Akt signaling inhibits apoptosis and promotes proliferation in PEL cells. Our data therefore suggest that sangivamycin induces apoptosis by inhibiting Erk and Akt signaling in such cells. We next investigated whether sangivamycin, in combination with an HSP90 inhibitor geldanamycin (GA) or valproate (valproic acid), potentiated the cytotoxic effects of the latter drugs on PEL cells. Compared to treatment with GA or valproate alone, the addition of sangivamycin enhanced cytotoxic activity. Our data thus indicate that

  2. Suitable parameter choice on quantitative morphology of A549 cell in epithelial–mesenchymal transition

    Science.gov (United States)

    Ren, Zhou-Xin; Yu, Hai-Bin; Li, Jian-Sheng; Shen, Jun-Ling; Du, Wen-Sen

    2015-01-01

    Evaluation of morphological changes in cells is an integral part of study on epithelial to mesenchymal transition (EMT), however, only a few papers reported the changes in quantitative parameters and no article compared different parameters for demanding better parameters. In the study, the purpose was to investigate suitable parameters for quantitative evaluation of EMT morphological changes. A549 human lung adenocarcinoma cell line was selected for the study. Some cells were stimulated by transforming growth factor-β1 (TGF-β1) for EMT, and other cells were as control without TGF-β1 stimulation. Subsequently, cells were placed in phase contrast microscope and three arbitrary fields were captured and saved with a personal computer. Using the tools of Photoshop software, some cells in an image were selected, segmented out and exchanged into unique hue, and other part in the image was shifted into another unique hue. The cells were calculated with 29 morphological parameters by Image Pro Plus software. A parameter between cells with or without TGF-β1 stimulation was compared statistically and nine parameters were significantly different between them. Receiver operating characteristic curve (ROC curve) of a parameter was described with SPSS software and F-test was used to compare two areas under the curves (AUCs) in Excel. Among them, roundness and radius ratio were the most AUCs and were significant higher than the other parameters. The results provided a new method with quantitative assessment of cell morphology during EMT, and found out two parameters, roundness and radius ratio, as suitable for quantification. PMID:26182364

  3. ZEB1 Promotes Oxaliplatin Resistance through the Induction of Epithelial - Mesenchymal Transition in Colon Cancer Cells.

    Science.gov (United States)

    Guo, Cao; Ma, Junli; Deng, Ganlu; Qu, Yanlin; Yin, Ling; Li, Yiyi; Han, Ying; Cai, Changjing; Shen, Hong; Zeng, Shan

    2017-01-01

    Background: Oxaliplatin (OXA) chemotherapy is widely used in the clinical treatment of colon cancer. However, chemo-resistance is still a barrier to effective chemotherapy in cases of colon cancer. Accumulated evidence suggests that the epithelial mesenchymal transition (EMT) may be a critical factor in chemo-sensitivity. The present study investigated the effects of Zinc finger E-box binding homeobox 1 (ZEB1) on OXA-sensitivity in colon cancer cells. Method: ZEB1expression and its correlation with clinicopathological characteristics were analyzed using tumor tissue from an independent cohort consisting of 118 colon cancer (CC) patients who receiving OXA-based chemotherapy. ZEB1 modulation of OXA-sensitivity in colon cancer cells was investigated in a OXA-resistant subline of HCT116/OXA cells and the parental colon cancer cell line: HCT116. A CCK8 assay was carried out to determine OXA-sensitivity. qRT-PCR, Western blot, Scratch wound healing and transwell assays were used to determine EMT phenotype of colon cells. ZEB1 knockdown using small interfering RNA (siRNA) was used to determine the ZEB1 contribution to OXA-sensitivity in vitro and in vivo (in a nude mice xenograft model). Result: ZEB1 expression was significantly increased in colon tumor tissue, and was correlated with lymph node metastasis and the depth of invasion. Compared with the parental colon cancer cells (HCT116), HCT116/OXA cells exhibited an EMT phenotype characterized by up-regulated expression of ZEB1, Vimentin, MMP2 and MMP9, but down-regulated expression of E-cadherin. Transfection of Si-ZEB1 into HCT116/OXA cells significantly reversed the EMT phenotype and enhanced OXA-sensitivity in vitro and in vivo . Conclusion: HCT116/OXA cells acquired an EMT phenotype. ZEB1 knockdown effectively restored OXA-sensitivity by reversing EMT. ZEB1 is a potential therapeutic target for the prevention of OXA-resistance in colon cancer.

  4. Inefficiency in macromolecular transport of SCS-based microcapsules affects viability of primary human mesenchymal stem cells but not of immortalized cells

    DEFF Research Database (Denmark)

    Sanz-Nogués, Clara; Horan, Jason; Thompson, Kerry

    2015-01-01

    mesenchymal stem cells (hMSCs). Human MSCs are of interest in regenerative medicine applications due to pro-angiogenic, anti-inflammatory and immunomodulatory properties, which result from paracrine effects of this cell type. In the present work we have encapsulated primary hMSCs and hMSC-TERT immortalized...... nutrients and had a more detrimental effect on the viability of primary cell cultures compared to cell lines and immortalized cells. This article is protected by copyright. All rights reserved....

  5. Heterostructures of phosphorene and transition metal dichalcogenides for excitonic solar cells: A first-principles study

    International Nuclear Information System (INIS)

    Ganesan, Vellayappan Dheivanayagam; Shen, Lei; Linghu, Jiajun; Zhang, Chun; Feng, Yuan Ping

    2016-01-01

    Using the many-body perturbation GW theory, we study the quasiparticle conduction-band offsets of phosphorene, a two-dimensional atomic layer of black phosphorus, and transition-metal dichalcogenides (TMDs). The calculated large exciton binding energies of phosphorene and TMDs indicate that their type-II heterostructures are suitable for excitonic thin-film solar cell applications. Our results show that these heterojunctions have a potential maximum power conversion efficiency of up to 12%, which can be further enhanced up to 20% by strain engineering.

  6. Heterostructures of phosphorene and transition metal dichalcogenides for excitonic solar cells: A first-principles study

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Vellayappan Dheivanayagam; Shen, Lei, E-mail: shenlei@nus.edu.sg [Engineering Science Programme, National University of Singapore, 9 Engineering Drive 1, Singapore 117575 (Singapore); Linghu, Jiajun; Zhang, Chun; Feng, Yuan Ping [Department of Physics, National University of Singapore, Singapore 117542 (Singapore)

    2016-03-21

    Using the many-body perturbation GW theory, we study the quasiparticle conduction-band offsets of phosphorene, a two-dimensional atomic layer of black phosphorus, and transition-metal dichalcogenides (TMDs). The calculated large exciton binding energies of phosphorene and TMDs indicate that their type-II heterostructures are suitable for excitonic thin-film solar cell applications. Our results show that these heterojunctions have a potential maximum power conversion efficiency of up to 12%, which can be further enhanced up to 20% by strain engineering.

  7. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

    DEFF Research Database (Denmark)

    Gui, Yaoting; Guo, Guangwu; Huang, Yi

    2011-01-01

    frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.......Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we...

  8. Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition

    OpenAIRE

    Kushiro, Kyoko; Chu, Randy A.; Verma, Akanksha; Núñez, Nomelí P.

    2011-01-01

    Metastatic melanoma is one of the most deadly and evasive types of cancer. On average, cancer patients with metastatic melanoma survive only 6–9 months after diagnosis. Epidemiological and animal studies suggest that obesity increases the metastatic ability of malignant melanoma, though the mechanism is not known. In the present studies, we assessed the ability of 3T3L1 adipocytes to modulate B16BL6 melanoma cell invasion and the Epithelial-to-Mesenchymal Transition (EMT). For this purpose, w...

  9. Primary pure squamous cell carcinoma of breast in a young female - a rare occurrence

    Directory of Open Access Journals (Sweden)

    P Raje

    2014-04-01

    Full Text Available Primary squamous cell carcinoma of breast is a rare disease. Incidence for primary SCC breast is 0.04-0.1 % of all malignancies of breast. A pure form of primary SCC breast is also described and its incidence is still less. Biologically it behaves differently and usually doesn’t metastasize to lymph nodes, though distant metastasis is more common. They occur usually in elderly women. Mean age of presentation is 54 years. We report the youngest patient so far - a 27 years old woman diagnosed initially as having fibrocystic disease and later as primary pure SCC breast. She did not have any other focus of malignancy in the body and is doing well 3-1/2 years post surgery and radiotherapy. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10322 Journal of Pathology of Nepal (2014 Vol. 4, 600-602

  10. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  11. Proteome-wide analysis of neural stem cell differentiation to facilitate transition to cell replacement therapies

    Czech Academy of Sciences Publication Activity Database

    Žižková, Martina; Suchá, Rita; Tylečková, Jiřina; Jarkovská, Karla; Mairychová, Kateřina; Kotrčová, Eva; Marsala, M.; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 12, č. 1 (2015), s. 83-95 ISSN 1478-9450 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : cell therapy * immunomodulation * neural stem cell differentiation * neural subpopulation * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.465, year: 2015

  12. Paeoniflorin prevents hypoxia-induced epithelial–mesenchymal transition in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Zhou Z

    2016-04-01

    Full Text Available Zhenyu Zhou,1,* Shunchang Wang,1,* Caijuan Song,2 Zhuang Hu11Department of Thyroid and Breast, Huaihe Hospital, Henan University, Kaifeng, 2Department of Immunization Program, Zhengzhou Center for Disease Control and Prevention, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Paeoniflorin (PF is a monoterpene glycoside extracted from the root of Paeonia lactiflora Pall. Previous studies have demonstrated that PF inhibits the growth, invasion, and metastasis of tumors in vivo and in vitro. However, the effect of PF on hypoxia-induced epithelial–mesenchymal transition (EMT in breast cancer cells remains unknown. Therefore, the objective of this study was to investigate the effect of PF on hypoxia-induced EMT in breast cancer cells, as well as characterize the underlying mechanism. The results presented in this study demonstrate that PF blocks the migration and invasion of breast cancer cells by repressing EMT under hypoxic conditions. PF also significantly attenuated the hypoxia-induced increase in HIF-1α level. Furthermore, PF prevented hypoxia-induced expression of phosphorylated PI3K and Akt in MDA-MB-231 cells. In conclusion, PF prevented hypoxia-induced EMT in breast cancer cells by inhibiting HIF-1α expression via modulation of PI3K/Akt signaling pathway. This finding provides evidence that PF can serve as a therapeutic agent for the treatment of breast cancer.Keywords: paeoniflorin, breast cancer, hypoxia, epithelial–mesenchymal transition, PI3K/Akt signaling pathway

  13. Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells

    DEFF Research Database (Denmark)

    Kostopoulou, Ourania N; Mohammad, Abdul-Aleem; Bartek, Jiri

    2018-01-01

    Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to therapy and can give rise to recurrent tumors. The identification of patient-related factors that support GSCs is thus necessary to design effective therapies for GBM patients. Glucocorticoids (GCs) are used to treat GBM......-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, which has been linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and GSCs. Here, we treated primary human GBM cells with dexamethasone and evaluated GC......-driven changes in cell morphology, proliferation, migration, gene expression, secretory activity and growth as neurospheres. Dexamethasone treatment of GBM cells appeared to promote the development of a GSC-like phenotype and conferred resistance to physiological stress and chemotherapy. We also analyzed...

  14. Primary B cell lymphoma of the tongue base: a case report

    Science.gov (United States)

    Bechir, Achour; Asma, Achour; Haifa, Regaieg; Nesrine, Abdessayed; Yosra, Ben Youssef; Badreddine, Sriha; Abderrahim, Khelif

    2016-01-01

    Primary non-Hodgkin’s lymphoma’s of the tongue is very rare and accounts for 1% of all malignant tumor of the oral cavity. Clinical features are non-specific ulcerative lesions that do not heal. In the literature, the majority of cases are diffuse large B cell type however, T cell phenotype also may occur. We describe a 77 years old man, who presented with an ulcerative mass in the left margin of the tongue the diagnosis diffuse large B cell lymphoma was confirmed. The patient is actually on treatment R-mini CEOP and has favorable evolution. PMID:28292136

  15. Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes

    Directory of Open Access Journals (Sweden)

    Higashi Richard M

    2008-10-01

    Full Text Available Abstract Background The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30 and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis. Results The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells. Conclusion The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells

  16. Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection.

    Directory of Open Access Journals (Sweden)

    Thavamalar Balakrishnan

    Full Text Available BACKGROUND: Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4-7 days after fever onset was more than 50% even after primary infection. CONCLUSIONS/SIGNIFICANCE: Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and "innate specificities" seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development.

  17. BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL.

    Science.gov (United States)

    Fu, Yao; Chang, Ye; Chen, Shuang; Li, Yuan; Chen, Yintao; Sun, Guozhe; Yu, Shasha; Ye, Ning; Li, Chao; Sun, Yingxian

    2018-05-01

    Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL

  18. Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

    Directory of Open Access Journals (Sweden)

    Milovanović Milena

    2017-06-01

    Full Text Available In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL, primary cutaneous follicle center lymphoma (PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT, and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O. The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP.

  19. MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Brian Shuch

    2015-01-01

    Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

  20. The role of primary health care services to better meet the needs of Aboriginal Australians transitioning from prison to the community.

    Science.gov (United States)

    Lloyd, Jane E; Delaney-Thiele, Dea; Abbott, Penny; Baldry, Eileen; McEntyre, Elizabeth; Reath, Jennifer; Indig, Devon; Sherwood, Juanita; Harris, Mark F

    2015-07-22

    Aboriginal Australians are more likely than other Australians to cycle in and out of prison on remand or by serving multiple short sentences-a form of serial incarceration and institutionalisation. This cycle contributes to the over-representation of Aboriginal Australians in prison and higher rates of recidivism. Our research examined how primary health care can better meet the health care and social support needs of Aboriginal Australians transitioning from prison to the community. Purposive sampling was used to identify 30 interviewees. Twelve interviews were with Aboriginal people who had been in prison; ten were with family members and eight with community service providers who worked with former inmates. Thematic analysis was conducted on the interviewees' description of their experience of services provided to prisoners both during incarceration and on transition to the community. Interviewees believed that effective access to primary health care on release and during transition was positively influenced by providing appropriate healthcare to inmates in custody and by properly planning for their release. Further, interviewees felt that poor communication between health care providers in custody and in the community prior to an inmate's release, contributed to a lack of comprehensive management of chronic conditions. System level barriers to timely communication between in-custody and community providers included inmates being placed on remand which contributed to uncertainty regarding release dates and therefore difficulties planning for release, cycling in and out of prison on short sentences and being released to freedom without access to support services. For Aboriginal former inmates and family members, release from prison was a period of significant emotional stress and commonly involved managing complex needs. To support their transition into the community, Aboriginal former inmates would benefit from immediate access to culturally- responsive

  1. CRISPR/Cas9-Mediated Correction of the FANCD1 Gene in Primary Patient Cells

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    Karolina Skvarova Kramarzova

    2017-06-01

    Full Text Available Fanconi anemia (FA is an inherited condition characterized by impaired DNA repair, physical anomalies, bone marrow failure, and increased incidence of malignancy. Gene editing holds great potential to precisely correct the underlying genetic cause such that gene expression remains under the endogenous control mechanisms. This has been accomplished to date only in transformed cells or their reprogrammed induced pluripotent stem cell counterparts; however, it has not yet been reported in primary patient cells. Here we show the ability to correct a mutation in Fanconi anemia D1 (FANCD1 primary patient fibroblasts. The clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 system was employed to target and correct a FANCD1 gene deletion. Homologous recombination using an oligonucleotide donor was achieved and a pure population of modified cells was obtained by using inhibitors of poly adenosine diphosphate-ribose polymerase (poly ADP-ribose polymerase. FANCD1 function was restored and we did not observe any promiscuous cutting of the CRISPR/Cas9 at off target sites. This consideration is crucial in the context of the pre-malignant FA phenotype. Altogether we show the ability to correct a patient mutation in primary FANCD1 cells in a precise manner. These proof of principle studies support expanded application of gene editing for FA.

  2. Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines.

    Science.gov (United States)

    Muñoz, Jorge; Lázcoz, Paula; Inda, María Mar; Nistal, Manuel; Pestaña, Angel; Encío, Ignacio J; Castresana, Javier S

    2004-05-01

    Neuroblastoma is the most common pediatric solid tumor. Although many allelic imbalances have been described, a bona fide tumor suppressor gene for this disease has not been found yet. In our study, we analyzed 2 genes, PTEN and DMBT1, mapping 10q23.31 and 10q25.3-26.1, respectively, which have been found frequently altered in other kinds of neoplasms. We screened both genes for homozygous deletions in 45 primary neuroblastic tumors and 12 neuroblastoma cell lines. Expression of these genes in cell lines was assessed by RT-PCR analysis. We could detect 2 of 41 (5%) primary tumors harboring PTEN homozygous deletions. Three of 41 (7%) primary tumors and 2 of 12 cell lines presented homozygous losses at the g14 STS on the DMBT1 locus. All cell lines analyzed expressed PTEN, but lack of DMBT1 mRNA expression was detected in 2 of them. We tried to see whether epigenetic mechanisms, such as aberrant promoter hypermethylation, had any role in DMBT1 silencing. The 2 cell lines lacking DMBT1 expression were treated with 5-aza-2'-deoxycytidine; DMBT1 expression was restored in only one of them (MC-IXC). From our work, we can conclude that PTEN and DMBT1 seem to contribute to the development of a small fraction of neuroblastomas, and that promoter hypermethylation might have a role in DMBT1 gene silencing. Copyright 2004 Wiley-Liss, Inc.

  3. A Case of Primary Gastric Small-Cell Carcinoma in an Elderly Patient

    Directory of Open Access Journals (Sweden)

    Fa-Chang Yu

    2012-03-01

    Full Text Available We report a case of primary small-cell carcinoma of the stomach in a 75-year-old man. The patient was admitted to our hospital with a 1-week history of intermittent tarry stool. An upper gastrointestinal examination revealed a large stage A2 ulcer in the greater curvature of the body of the stomach, and pathological findings from biopsy specimens revealed small-cell carcinoma. The tumor cells were small-sized, composed of hyperchromatic nuclei with scant cytoplasm, and stained positive for cytokeratin, synaptophysin, and chromogranin A. The patient was diagnosed with primary small-cell carcinoma of the stomach. He declined further evaluation and received palliative management. This is a rare carcinoma of the stomach, with aggressive manifestations and a poor prognosis. The mean survival of patients with primary gastric small-cell carcinoma is reported to be 7 months. The choice of treatment for this disease is still controversial. This rare gastric tumor should be listed in the differential diagnosis of gastric carcinoma in the elderly.

  4. Breast Carcinoma Cells in Primary Tumors and Effusions Have Different Gene Array Profiles

    Directory of Open Access Journals (Sweden)

    Sophya Konstantinovsky

    2010-01-01

    Full Text Available The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions included KRT8, BCAR1, CLDN4, VIL2, while DCN, CLDN19, ITGA7, and ITGA5 were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings for BCAR1, CLDN4, VIL2, and DCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities.

  5. HCMV Displays a Unique Transcriptome of Immunomodulatory Genes in Primary Monocyte-Derived Cell Types.

    Directory of Open Access Journals (Sweden)

    Ellen Van Damme

    Full Text Available Human cytomegalovirus (HCMV is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs. This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages. Consequently, it has been suggested that macrophages and dendritic cells contribute to viral spread in vivo. Thus far only limited knowledge is available on the expression of HCMV genes in terminally differentiated myeloid primary cells and whether or not the virus exhibits a different set of lytic genes in primary cells compared with lytic infection in NHDF fibroblasts. To address these questions, we used Illumina next generation sequencing to determine the HCMV transcriptome in macrophages and dendritic cells during lytic infection and compared it to the transcriptome in NHDF fibroblasts. Here, we demonstrate unique expression profiles in macrophages and dendritic cells which significantly differ from the transcriptome in fibroblasts mainly by modulating the expression of viral transcripts involved in immune modulation, cell tropism and viral spread. In a head to head comparison between macrophages and dendritic cells, we observed that factors involved in viral spread and virion composition are differentially regulated suggesting that the plasticity of the virion facilitates the infection of surrounding cells. Taken together, this study provides the full transcript expression analysis of lytic HCMV genes in monocyte-derived type 1 and type 2 macrophages as well as in monocyte-derived dendritic cells. Thereby

  6. Proliferation Rates of Bovine Primary Muscle Cells Relate to Liveweight and Carcase Weight in Cattle

    Science.gov (United States)

    Coles, Chantal A.; Wadeson, Jenny; Leyton, Carolina P.; Siddell, Jason P.; Greenwood, Paul L.; White, Jason D.; McDonagh, Matthew B.

    2015-01-01

    Muscling in cattle is largely influenced by genetic background, ultimately affecting beef yield and is of major interest to the beef industry. This investigation aimed to determine whether primary skeletal muscle cells isolated from different breeds of cattle with a varying genetic potential for muscling differ in their myogenic proliferative capacity. Primary skeletal muscle cells were isolated and cultured from the Longissimus muscle (LM) of 6 month old Angus, Hereford and Wagyu X Angus cattle. Cells were assessed for rate of proliferation and gene expression of PAX7, MYOD, MYF5, and MYOG. Proliferation rates were found to differ between breeds of cattle whereby myoblasts from Angus cattle were found to proliferate at a greater rate than those of Hereford and Wagyu X Angus during early stages of growth (5–20 hours in culture) in vitro (P cattle (P cattle (P cattle. PMID:25875203

  7. Alteration of UV primary fluorescence of vital tumor cells following irradiation with neutrons and gamma rays

    International Nuclear Information System (INIS)

    Merkle, K.

    1980-01-01

    The change of UV primary fluorescence intensity of vital unstained cells of Ehrlich ascites carcinoma after 60 Co-gamma and neutron irradiation was investigated. The mean neutron energy was 6.2 MeV. Fluorescence intensity was detected using impulse cytophotometry. The UV intensity of single cells was measured in the spectral range from 300-400 nm. An monotonous increase of dose-effect curves and a maximum at 3.5 Gy (neutrons) and 30 Gy (γ-rays) was obtained. The first relevant increase of fluorescence intensity was detected at 0.4 Gy (neutrons) and 0.75 Gy (γ-rays). Factors influencing the increase and decrease of primary fluorescence behavior of vital cells are discussed. (author)

  8. Primary candidiasis and squamous cell carcinoma of the larynx: report of a case.

    Science.gov (United States)

    Lee, Dong Hoon; Cho, Hyong Ho

    2013-02-01

    Primary candidiasis is rare and often confused with a pre-cancerous lesion, squamous cell carcinoma, or verrucous carcinoma. We report an extremely rare case of squamous cell carcinoma of the vocal cord following primary candidiasis. A 62-year-old man presented to our department reporting a 1-month history of hoarseness. He underwent laryngeal microscopic surgery for a presumptive diagnosis of glottic carcinoma. Histopathologic examination revealed candidiasis and scattered moderate dysplasia. He was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis. However, the 42-month follow-up examination revealed a focal whitish lesion on the right true vocal cord, and a repeat biopsy of this area revealed squamous cell carcinoma without evidence of candidiasis. The patient was treated with radiotherapy and remains well with no signs of tumor recurrence or candidiasis.

  9. Primary clear cell carcinoma of parotid gland: Case report and review of literature.

    Science.gov (United States)

    Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

    2013-01-01

    Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimension