WorldWideScience

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  1. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Catherine Oakman

    2010-06-01

    Full Text Available Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC in the bone marrow and circulating tumor cells (CTC from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer.

  2. In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2015-12-01

    determine the tumor cell of origin [KrasG12D L/-/ /Sftpc- creER or KrasG12D L/-/ / p53 L/L /Sftpc-creER], or the contribution of alveolar type II cells in...cancer have advanced disease at the time of presentation, a finding that may be consistent with early spread. Even when lung cancer is diagnosed and...identify early stage patients at high risk of recurrence or metastatic disease as well as to develop more effective therapies for NSCLC. 7 The studies

  3. Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern

    NARCIS (Netherlands)

    Effenberger, Katharina E.; Borgen, Elin; Eulenburg, Christine Zu; Bartkowiak, Kai; Grosser, Andrea; Synnestvedt, Marit; Kaaresen, Rolf; Brandt, Burkhard; Nesland, Jahn M.; Pantel, Klaus; Naume, Bjorn

    2011-01-01

    The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two antibodies frequently used for DTC detection. Reactivities of antibodies A45-B/B3 (A45) and AE1/AE3 (AE) fo

  4. In Vivo Tagging of Lung Epithelial Cells to Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2014-10-01

    derived lung cells, only the epithelium will be tagged by this method. Prior to using these animals for our studies, we will ensure that lineage labeled...1 AWARD NUMBER: W81XWH-13-1-0184 TITLE: In Vivo Tagging of Lung Epithelial Cells To Define...REPORT TYPE Annual 3. DATES COVERED 15Sep2013-14Sep2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER In Vivo Tagging of Lung

  5. Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor Initiating Cells

    Science.gov (United States)

    2013-06-01

    redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples...collagenase (300 U/ml)/hyaluronidase (100 U/ml) solution followed by sequential filtration . Single cell suspensions were cultured on ultra low attachment...Curriculum Vitae Carolyn Marsden 6 Assistant Professor Research Associate Professor Department of Pharmacology Department of Microbiology and

  6. Macrophage Function in Early Dissemination and Dormancy of Breast Cancer

    Science.gov (United States)

    2015-09-01

    of Oncological Sciences, The Immunology Institute, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY, USA 3Department of...cell 13, 58-68. Joyce, J. A., and Pollard, J. W. (2009). Microenvironmental regulation of metastasis. Nature reviews Cancer 9, 239-252. Kaplan, R. N...AWARD NUMBER: W81XWH-14-1-0365 TITLE: Macrophage Functions in Early Dissemination and Dormancy of Breast Cancer PRINCIPAL INVESTIGATOR: Nina

  7. Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX(®), clinicopathological markers and tumor cell dissemination in the blood and bone marrow.

    Science.gov (United States)

    Aktas, Bahriye; Bankfalvi, Agnes; Heubner, Martin; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2013-11-01

    The Oncotype DX(®) assay is a validated genomic test that predicts the likelihood of breast cancer recurrence, patient survival within ten years of diagnosis and the benefit of chemotherapy in early-stage, node-negative, estrogen receptor-positive breast cancer. Further markers of recurrence include disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood, particularly stemness-like tumor cells (slCTCs). In this study, Oncotype DX, DTCs, CTCs and slCTCs were used to evaluate the risk of recurrence in 68 patients with human epidermal growth factor receptor 2-negative, early-stage breast cancer. Formalin-fixed, paraffin-embedded tissue sections were analyzed for the expression of 16 cancer genes and 5 reference genes by Oncotype DX, yielding a recurrence score (RS). G2 tumors were evaluated for urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor type 1 (PAI1) and Ki-67. Two BM aspirates were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. CTCs and slCTCs in the blood were detected using the AdnaTest BreastCancer, AdnaTest EMT and the AdnaTest TumorStemCell. Oncotype DX was performed in 68 cases, yielding a low RS in 30/68 patients (44%), an intermediate RS in 29/68 patients (43%) and a high RS in 9/68 patients (13%). DTCs were detected in 19/68 patients (28%), CTCs in 13/68 patients (19%) and slCTCs in 26/68 (38%) patients. Moreover, 8/68 patients (12%) with G2 tumors were positive for uPA, 6/68 (9%) for PAI1 and 21/68 (31%) for Ki-67. Ki-67, progesterone receptor (PR) and G3 tumors were significantly correlated with RS (P<0.001; P=0.006; and P=0,002, respectively), whereas no correlation was identified between DTCs, CTCs, slCTCs and RS. Ki-67 may support therapeutic decisions in cases where Oncotype DX is not feasible. Larger patient cohorts are required to estimate the additional detection of DTCs and CTCs for the determination of risk recurrence.

  8. Dissemination of a highly virulent pathogen: tracking the early events that define infection.

    Directory of Open Access Journals (Sweden)

    Rodrigo J Gonzalez

    2015-01-01

    Full Text Available The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of Yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1 do the bacteria encounter barriers in disseminating to draining lymph nodes (LN, and (2 what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by Y. pestis to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response

  9. Study of Disseminating Landslide Early Warning Information in Malaysia

    Science.gov (United States)

    Koay, Swee Peng; Lateh, Habibah; Tien Tay, Lea; Ahamd, Jamilah; Chan, Huah Yong; Sakai, Naoki; Jamaludin, Suhaimi

    2015-04-01

    In Malaysia, rain induced landslides are occurring more often than before. The Malaysian Government allocates millions of Malaysian Ringgit for slope monitoring and slope failure remedial measures in the budget every year. In rural areas, local authorities also play a major role in monitoring the slope to prevent casualty by giving information to the residents who are staying near to the slopes. However, there are thousands of slopes which are classified as high risk slopes in Malaysia. Implementing site monitoring system in these slopes to monitor the movement of the soil in the slopes, predicting the occurrence of slopes failure and establishing early warning system are too costly and almost impossible. In our study, we propose Accumulated Rainfall vs. Rainfall Intensity prediction method to predict the slope failure by referring to the predicted rainfall data from radar and the rain volume from rain gauges. The critical line which determines if the slope is in danger, is generated by simulator with well-surveyed the soil property in the slope and compared with historical data. By establishing such predicting system, the slope failure warning information can be obtained and disseminated to the surroundings via SMS, internet and siren. However, establishing the early warning dissemination system is not enough in disaster prevention, educating school children and the community by giving knowledge on landslides, such as landslide's definition, how and why does the slope failure happen and when will it fail, to raise the risk awareness on landslides will reduce landslides casualty, especially in rural area. Moreover, showing video on the risk and symptom of landslides in school will also help the school children gaining the knowledge of landslides. Generating hazard map and landslides historical data provides further information on the occurrence of the slope failure. In future, further study on fine tuning of landslides prediction method, applying IT technology to

  10. Breast Fibroblasts Modulate Early Dissemination, Tumorigenesis, and Metastasis through Alteration of Extracellular Matrix Characteristics

    Directory of Open Access Journals (Sweden)

    Nancy Dumont

    2013-03-01

    Full Text Available A wealth of evidence has now demonstrated that the microenvironment in which a tumorigenic cell evolves is as critical to its evolution as the genetic mutations it accrues. However, there is still relatively little known about how signals from the microenvironment contribute to the early events in the progression to malignancy. To address this question, we used a premalignant mammary model to examine how fibroblasts, and the extracellular matrix (ECM proteins they secrete, influence progression to malignancy. Their effect on metastatic malignant cells was also assessed for comparison. We found that carcinoma-associated fibroblasts, and the distinct aligned ECM they deposit, can cause both premalignant and malignant mammary epithelial cells to assume a mesenchymal morphology that is associated with increased dissemination and metastasis, while benign reduction mammoplasty fibroblasts favor the maintenance of an epithelial morphology and constrain early dissemination, tumor growth, and metastasis. Our results suggest that normalizing the organization of the ECM could be effective in limiting systemic dissemination and tumor growth.

  11. Early diagnosis and successful treatment of disseminated toxoplasmosis after cord blood transplantation.

    Science.gov (United States)

    Kurihara, Taro; Sumi, Masahiko; Kaiume, Hiroko; Takeda, Wataru; Kirihara, Takehiko; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Ueno, Mayumi; Ichikawa, Naoaki; Kaneko, Yumi; Hikosaka, Kenji; Norose, Kazumi; Kobayashi, Hikaru

    2016-06-01

    A 66-year-old woman with refractory angioimmunoblastic T-cell lymphoma underwent cord blood transplantation. Prior to transplantation, a serological test for Toxoplasma gondii-specific IgG antibodies was positive. On day 96, she exhibited fever and dry cough. Chest CT showed diffuse centrilobular ground glass opacities in both lungs. The reactivation of T. gondii was identified by the presence of parasite DNA in peripheral blood and bronchoalveolar lavage fluid. Moreover, brain MRI revealed a space occupying lesion in the right occipital lobe. Therefore, disseminated toxoplasmosis was diagnosed. She received pyrimethamine and sulfadiazine from day 99. The lung and brain lesions both showed improvement but the PCR assay for T. gondii DNA in peripheral blood was positive on day 133. On day 146, she developed blurred vision and reduced visual acuity, and a tentative diagnosis of toxoplasmic retinochoroiditis was made based on ophthalmic examination results. As agranulocytosis developed on day 158, we decided to discontinue pyrimethamine and sulfadiazine and the treatment was thus switched to atovaquone. Moreover, we added spiramycin to atovaquone therapy from day 174, and her ocular condition gradually improved. In general, the prognosis of disseminated toxoplasmosis after hematopoietic stem cell transplantation (HSCT) is extremely poor. However, early diagnosis and treatment may contribute to improvement of the fundamentally dismal prognosis of disseminated toxoplasmosis after HSCT.

  12. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2015-09-01

    metastases (overt and micrometastases) (Fig. 1E- F). Macro-metastases originating from early cancer cell mammospheres displayed a glandular phenotype but...whether a HER2+/P-p38lo profile was linked to the partial or total activation of an epithelium to mesenchyme transition program 19. Treatment of MCF10A...metastasis found in nude mice injected with MMTV-HER2 mammospheres (upper left). Upper right, shows differentiated glandular ductal structures found within

  13. Disseminated Acanthamoeba sinusitis in a patient with AIDS: a possible role for early antiretroviral therapy.

    Science.gov (United States)

    Carter, Wendy W; Gompf, Sandra G; Toney, John F; Greene, John N; Cutolo, Edward P

    2004-01-01

    Acanthamoeba, a free-living ameba, has been reported to infect humans with subacute encephalitis, sinusitis, or keratitis. Multiple cases of Acanthamoeba sinusitis with dissemination have been reported in association with AIDS, with high mortality. We report successful treatment of a 35-year-old woman who presented with sinusitis that progressed to disseminated acanthamebiasis as her initial manifestation of AIDS. To our knowledge, our patient was one of the few and longest-lived survivors of disseminated Acanthamoeba infection with AIDS. As with other opportunistic infections, early aggressive therapy including HAART may alter the outcome in this almost uniformly fatal disease.

  14. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Sorensen, Anne Marie; Perner, Anders;

    2011-01-01

    ABSTRACT: INTRODUCTION: It is debated whether the early trauma induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated...... the prevalence of overt DIC and ACoTS in trauma patients and characterized these conditions based on their biomarker profiles. METHODS: Observational study at a single Level I Trauma Centre. Inclusion of 80 adult trauma patients ([greater than or equal to]18 years) who met criteria for full trauma team...... activation and had an arterial cannula inserted. Blood was sampled a median of 68 min (IQR 48-88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone...

  15. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Sorensen, Anne Marie; Perner, Anders;

    2011-01-01

    ABSTRACT: INTRODUCTION: It is debated whether the early trauma induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated...... activation and had an arterial cannula inserted. Blood was sampled a median of 68 min (IQR 48-88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone......-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption...

  16. Lung Dendritic Cells Facilitate Extrapulmonary Bacterial Dissemination during Pneumococcal Pneumonia

    Directory of Open Access Journals (Sweden)

    Alva eRosendahl

    2013-06-01

    Full Text Available Streptococcus pneumoniae is a leading cause of bacterial pneumonia worldwide. Given the critical role of dendritic cells (DCs in regulating and modulating the immune response to pathogens, we investigated here the role of DCs in S. pneumoniae lung infections. Using a well-established transgenic mouse line which allows the conditional transient depletion of DCs, we showed that ablation of DCs resulted in enhanced resistance to intranasal challenge with S. pneumoniae. DC-depleted mice exhibited delayed bacterial systemic dissemination, significantly reduced bacterial loads in the infected organs and lower levels of serum inflammatory mediators than non-depleted animals. The increased resistance of DC-depleted mice to S. pneumoniae was associated with a better capacity to restrict pneumococci extrapulmonary dissemination. Furthermore, we demonstrated that S. pneumoniae disseminated from the lungs into the regional lymph nodes in a cell-independent manner and that this direct way of dissemination was much more efficient in the presence of DCs. We also provide evidence that S. pneumoniae induces expression and activation of matrix metalloproteinase-9 (MMP-9 in cultured bone marrow-derived DCs. MMP-9 is a protease involved in the breakdown of extracellular matrix proteins and is critical for DC trafficking across extracellular matrix and basement membranes during the migration from the periphery to the lymph nodes. MMP-9 was also significantly up-regulated in the lungs of mice after intranasal infection with S. pneumoniae. Notably, the expression levels of MMP-9 in the infected lungs were significantly decreased after depletion of DCs suggesting the involvement of DCs in MMP-9 production during pneumococcal pneumonia. Thus, we propose that S. pneumoniae can exploit the DC-derived proteolysis to open tissue barriers thereby facilitating its own dissemination from the local site of infection.

  17. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2015-09-01

    This could contribute silently to therapy resistance and late metastatic relapse. Unfortunately, these events have remained understudied because...cells expressing sFRP were generated using sFRP lentiviral vectors. Wnt3a and DKK1 conditioned media was prepared from Wnt3a expressing L-cells and Dkk1...expressing 293T cells. Vectors and sFRP plasmids were a kind gift from Dr. Stuart Aaronson, ISMMS, New York, NY. Conditioned media was prepared

  18. Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model.

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    Christian Franci

    Full Text Available Cancer metastases arise in part from disseminated tumor cells originating from the primary tumor and from residual disease persisting after therapy. The identification of biomarkers on micro-metastases, disseminated tumors, and residual disease may yield novel tools for early detection and treatment of these disease states prior to their development into metastases and recurrent tumors. Here we describe the molecular profiling of disseminated tumor cells in lungs, lung metastases, and residual tumor cells in the MMTV-PyMT breast cancer model. MMTV-PyMT mice were bred with actin-GFP mice, and focal hyperplastic lesions from pubertal MMTV-PyMT;actin-GFP mice were orthotopically transplanted into FVB/n mice to track single tumor foci. Tumor-bearing mice were treated with TAC chemotherapy (docetaxel, doxorubicin, cyclophosphamide, and residual and relapsed tumor cells were sorted and profiled by mRNA microarray analysis. Data analysis revealed enrichment of the Jak/Stat pathway, Notch pathway, and epigenetic regulators in residual tumors. Stat1 was significantly up-regulated in a DNA-damage-resistant population of residual tumor cells, and a pre-existing Stat1 sub-population was identified in untreated tumors. Tumor cells from adenomas, carcinomas, lung disseminated tumor cells, and lung metastases were also sorted from MMTV-PyMT transplant mice and profiled by mRNA microarray. Whereas disseminated tumors cells appeared similar to carcinoma cells at the mRNA level, lung metastases were genotypically very different from disseminated cells and primary tumors. Lung metastases were enriched for a number of chromatin-modifying genes and stem cell-associated genes. Histone analysis of H3K4 and H3K9 suggested that lung metastases had been reprogrammed during malignant progression. These data identify novel biomarkers of residual tumor cells and disseminated tumor cells and implicate pathways that may mediate metastasis formation and tumor relapse after

  19. An Intelligent Broadcasting Algorithm for Early Warning Message Dissemination in VANETs

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    Ihn-Han Bae

    2015-01-01

    Full Text Available Vehicular ad hoc network (VANET has gained much attention recently to improve road safety, reduce traffic congestion, and enable efficient traffic management because of its many important applications in transportation. In this paper, an early warning intelligence broadcasting algorithm is proposed, EW-ICAST, to disseminate a safety message for VANETs. The proposed EW-ICAST uses not only the early warning system on the basis of time to collision (TTC but also the intelligent broadcasting algorithm on the basis of fuzzy logic. Thus, the EW-ICAST resolves effectively broadcast storm problem and meets time-critical requirement. The performance of EW-ICAST is evaluated through simulation and compared with that of other alert message dissemination algorithms. From the simulation results, we know that EW-ICAST is superior to Simple, P-persistence, and EDB algorithms.

  20. Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report

    OpenAIRE

    2007-01-01

    Abstract Early disseminated Lyme disease can have a myriad of central nervous system manifestations. These run the gamut from meningitis to radiculopathy and cranial neuropathy. Here we present a case that manifested with only acute mental status change in the setting of central nervous system involvement with Lyme disease. A paucity of other central nervous system manifestations is rare, especially with positive serum and cerebrospinal fluid markers. This article underscores the importance o...

  1. Review: Biological relevance of disseminated tumor cells in cancer patients.

    Science.gov (United States)

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus

    2008-11-01

    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  2. Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report

    Science.gov (United States)

    Chabria, Shiven B; Lawrason, Jock

    2007-01-01

    Early disseminated Lyme disease can have a myriad of central nervous system manifestations. These run the gamut from meningitis to radiculopathy and cranial neuropathy. Here we present a case that manifested with only acute mental status change in the setting of central nervous system involvement with Lyme disease. A paucity of other central nervous system manifestations is rare, especially with positive serum and cerebrospinal fluid markers. This article underscores the importance of a high index of clinical suspicion in detection of Lyme disease related manifestations in endemic areas. PMID:17688693

  3. Altered mental status, an unusual manifestation of early disseminated Lyme disease: A case report

    Directory of Open Access Journals (Sweden)

    Chabria Shiven B

    2007-08-01

    Full Text Available Abstract Early disseminated Lyme disease can have a myriad of central nervous system manifestations. These run the gamut from meningitis to radiculopathy and cranial neuropathy. Here we present a case that manifested with only acute mental status change in the setting of central nervous system involvement with Lyme disease. A paucity of other central nervous system manifestations is rare, especially with positive serum and cerebrospinal fluid markers. This article underscores the importance of a high index of clinical suspicion in detection of Lyme disease related manifestations in endemic areas.

  4. Disseminated Langerhans' cell histiocytosis and massive protein-losing enteropathy

    Directory of Open Access Journals (Sweden)

    Santos-Machado T.M.

    1999-01-01

    Full Text Available Symptomatic involvement of the gastrointestinal (GI tract as a prominent symptom in Langerhans' cell histiocytosis (LCH is uncommon, occurring in less than 1 to 5% of all cases, even when the disease is in its disseminated form. Up to now, there have been reports of 18 cases of LCH with GI manifestations, including our 2 cases, with diarrhea (77.7%, protein-losing enteropathy (33.3% and bloody stool being the most frequent findings. The authors present two patients with severe diarrhea and refractory hypoalbuminemia, and with the protein-losing enteropathy documented by Cr51-labeled albumin studies. A review of the literature indicated that the presence of GI symptoms is often associated with systemic disease as well as with poor prognosis, mainly under 2 years of age. Radioisotopes are useful for documenting protein loss in several diseases with high specificity and sensitivity, and their utilization in the cases reviewed here permitted diagnoses in 6 children, as well as improved therapeutic management.

  5. Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination

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    Eliah R. Shamir

    2016-09-01

    Full Text Available Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+ epithelium displayed extensive intercellular junctions, and Twist1– luminal epithelial cells could still adhere to disseminating Twist1+ cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+ cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate.

  6. Human Cytomegalovirus US28 Facilitates Cell-to-Cell Viral Dissemination

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    Vanessa M. Noriega

    2014-03-01

    Full Text Available Human cytomegalovirus (HCMV encodes a number of viral proteins with homology to cellular G protein-coupled receptors (GPCRs. These viral GPCRs, including US27, US28, UL33, and UL78, have been ascribed numerous functions during infection, including activating diverse cellular pathways, binding to immunomodulatory chemokines, and impacting virus dissemination. To investigate the role of US28 during virus infection, two variants of the clinical isolate TB40/E were generated: TB40/E-US28YFP expressing a C-terminal yellow fluorescent protein tag, and TB40/E-FLAGYFP in which a FLAG-YFP cassette replaces the US28 coding region. The TB40/E-US28YFP protein localized as large perinuclear fluorescent structures at late times post-infection in fibroblasts, endothelial, and epithelial cells. Interestingly, US28YFP is a non-glycosylated membrane protein throughout the course of infection. US28 appears to impact cell-to-cell spread of virus, as the DUS28 virus (TB40/E-FLAGYFP generated a log-greater yield of extracellular progeny whose spread could be significantly neutralized in fibroblasts. Most strikingly, in epithelial cells, where dissemination of virus occurs exclusively by the cell-to-cell route, TB40/E-FLAGYFP (DUS28 displayed a significant growth defect. The data demonstrates that HCMV US28 may contribute at a late stage of the viral life cycle to cell-to-cell dissemination of virus.

  7. Efficacy of a Hypotonic Treatment for Peritoneal Dissemination from Gastric Cancer Cells: An In Vivo Evaluation

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    Atsushi Shiozaki

    2014-01-01

    Full Text Available The aim of the present study was to determine the efficacy of a hypotonic treatment for peritoneal dissemination from gastric cancer cells using an in vivo model. We firstly evaluated the toxicity of a peritoneal injection of distilled water (DW (2 mL for 3 days in mice. Macroscopic and microscopic examinations revealed that the peritoneal injection of DW did not severely damage the abdominal organs of these mice. MKN45 gastric cancer cells preincubated with NaCl buffer or DW for 20 minutes in vitro were then intraperitoneally injected into nude mice, and the development of dissemination nodules was analyzed. The total number, weight, and volume of the dissemination nodules were significantly decreased by the DW preincubation. We then determined whether the peritoneal injection of DW inhibited the establishment of peritoneal dissemination. After a peritoneal injection of MKN45 cells into nude mice, NaCl buffer or DW was injected into the abdominal cavity for 3 days. The total volume of dissemination nodules was significantly lower in DW-injected mice than in NaCl-injected mice. In conclusion, we demonstrated the safeness of a peritoneal injection of DW. Furthermore, the development of dissemination nodules from gastric cancer cells was prevented by a preincubation with or peritoneal injection of DW.

  8. Activation of Pro-uPA is Critical for Initial Escape from the Primary Tumor and Hematogenous Dissemination of Human Carcinoma Cells

    DEFF Research Database (Denmark)

    Bekes, Erin; Deryugina, Elena; Kuprianova, Tatyana;

    2011-01-01

    Urokinase-type plasminogen activator (uPA) and plasmin have long been implicated in cancer progression. However, the precise contributions of the uPA/plasmin system to specific steps involved in cancer cell dissemination have not been fully established. Herein, we have employed a highly...... disseminating variant of the human PC-3 prostate carcinoma cell line, PC-hi/diss, as a prototype of aggressive carcinomas to investigate the mechanisms whereby pro-uPA activation and uPA-generated plasmin functionally contribute to specific stages of metastasis. The PC-hi/diss cells secrete and activate....... To mechanistically examine the uPA/plasmin-mediated aspects of tumor cell dissemination, the anti pro-uPA mAb-112 and the potent serine protease inhibitor, aprotinin, were utilized in parallel in a number of in vivo assays modeling various rate-limiting steps in early metastatic spread. Our findings demonstrate...

  9. A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model.

    Science.gov (United States)

    Msaki, Aichi; Pastò, Anna; Curtarello, Matteo; Arigoni, Maddalena; Barutello, Giuseppina; Calogero, Raffaele Adolfo; Macagno, Marco; Cavallo, Federica; Amadori, Alberto; Indraccolo, Stefano

    2016-05-31

    Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment.

  10. Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Fouad Mona N

    2011-08-01

    Full Text Available Abstract Background We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment. Methods We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US. Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression. Results Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026. Patients ≥ 75 years were less likely to receive bevacizumab than patients Conclusions One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.

  11. Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease.

    Science.gov (United States)

    Jones, Kathryn L; Glickstein, Lisa J; Damle, Nitin; Sikand, Vijay K; McHugh, Gail; Steere, Allen C

    2006-12-01

    Three genetic markers of Borrelia burgdorferi have been associated with disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type (RST), and vlsE. Here, we modified previous methods so as to identify the three markers by PCR and restriction fragment length polymorphism in parallel, analyzed B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients, and correlated the results with evidence of dissemination. OspC type A was found approximately twice as frequently in patients with disseminated disease, whereas type K was identified approximately twice as often in those without evidence of dissemination, but these trends were not statistically significant. The remaining seven types identified were found nearly equally in patients with or without evidence of dissemination. RST 1 strains were significantly associated with dissemination (P=0.03), whereas RST 2 and RST 3 strains tended to have an inverse association with this outcome. The vlsE gene was identified in all 91 cases, using primer sets specific for an N-terminal sequence of B. burgdorferi strain B31 (vlsEB31) or strain 297 (vlsE297), but neither marker was associated with dissemination. Specific combinations of the three genetic markers usually occurred together. OspC type A was always found with RST 1 and vlsEB31, type K was always identified with RST 2 and more often with vlsE297, and types E and I were almost always found with RST 3 and equally often with vlsEB31 and vlsE297. We conclude that B. burgdorferi strains vary in their capacity to disseminate, but almost all strains isolated from EM lesions sometimes caused disseminated disease.

  12. Borrelia burgdorferi Genetic Markers and Disseminated Disease in Patients with Early Lyme Disease▿

    Science.gov (United States)

    Jones, Kathryn L.; Glickstein, Lisa J.; Damle, Nitin; Sikand, Vijay K.; McHugh, Gail; Steere, Allen C.

    2006-01-01

    Three genetic markers of Borrelia burgdorferi have been associated with disseminated disease: the OspC type, the 16S-23S rRNA intergenic spacer type (RST), and vlsE. Here, we modified previous methods so as to identify the three markers by PCR and restriction fragment length polymorphism in parallel, analyzed B. burgdorferi isolates from erythema migrans (EM) skin lesions in 91 patients, and correlated the results with evidence of dissemination. OspC type A was found approximately twice as frequently in patients with disseminated disease, whereas type K was identified approximately twice as often in those without evidence of dissemination, but these trends were not statistically significant. The remaining seven types identified were found nearly equally in patients with or without evidence of dissemination. RST 1 strains were significantly associated with dissemination (P = 0.03), whereas RST 2 and RST 3 strains tended to have an inverse association with this outcome. The vlsE gene was identified in all 91 cases, using primer sets specific for an N-terminal sequence of B. burgdorferi strain B31 (vlsEB31) or strain 297 (vlsE297), but neither marker was associated with dissemination. Specific combinations of the three genetic markers usually occurred together. OspC type A was always found with RST 1 and vlsEB31, type K was always identified with RST 2 and more often with vlsE297, and types E and I were almost always found with RST 3 and equally often with vlsEB31 and vlsE297. We conclude that B. burgdorferi strains vary in their capacity to disseminate, but almost all strains isolated from EM lesions sometimes caused disseminated disease. PMID:17035489

  13. Low-grade Schwann cell neoplasms with leptomeningeal dissemination: clinicopathologic and autopsy findings.

    Science.gov (United States)

    Rodriguez, Erika F; Blakeley, Jaishri; Langmead, Shannon; Olivi, Alessandro; Tufaro, Anthony; Tabbarah, Abeer; Berkenblit, Gail; Sacks, Justin M; Newsome, Scott D; Montgomery, Elizabeth; Rodriguez, Fausto J

    2017-02-01

    Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patient's death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed.

  14. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Banys, Malgorzata, E-mail: maggybanys@yahoo.de [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany); Department of Obstetrics and Gynecology, Marienkrankenhaus Hamburg, Hamburg D-22087 (Germany); Krawczyk, Natalia; Fehm, Tanja [Department of Obstetrics and Gynecology, University of Duesseldorf, Duesseldorf D-40225 (Germany)

    2014-01-15

    Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs) in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  15. The Role and Clinical Relevance of Disseminated Tumor Cells in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Malgorzata Banys

    2014-01-01

    Full Text Available Tumor cell dissemination is a common phenomenon observed in most cancers of epithelial origin. One-third of breast cancer patients present with disseminated tumor cells (DTCs in bone marrow at time of diagnosis; these patients, as well as patients with persistent DTCs, have significantly worse clinical outcome than DTC-negative patients. Since DTC phenotype may differ from the primary tumor with regard to ER and HER2 status, reevaluation of predictive markers on DTCs may optimize treatment choices. In the present review, we report on the clinical relevance of DTC detection in breast cancer.

  16. Necessary and sufficient role for T helper cells to prevent fungal dissemination in allergic lung disease.

    Science.gov (United States)

    Porter, Paul C; Roberts, Luz; Fields, Anna; Knight, Morgan; Qian, Yuping; Delclos, George L; Han, Shuhua; Kheradmand, Farrah; Corry, David B

    2011-11-01

    Mucosal immune responses to fungal infection range from T helper type 2 (Th2) cell-directed allergic inflammation to Th1-predominant neutrophilic inflammation, but the mechanisms directing these divergent mucosal immune outcomes and the role of T cells in host defense against mucosal fungal infections are not known. Here we examined the mouse mucosal immune responses to 12 filamentous environmental fungal species over a broad range of exposure doses and determined the requirement of T cells for host defense. For all tested fungi, low-grade conidium exposures induced Th2- and eosinophil-predominant allergic lung disease, whereas higher exposures led to rapid conversion to neutrophil- and Th1 cell-predominant inflammation, a phenomenon we term immune phenotype switching. All fungal exposure doses were further linked to the secretion of interleukin-17A (IL-17A). Fungal infections with Curvularia lunata and Aspergillus fumigatus were typically confined to the airway during allergic inflammation but became locally invasive and disseminated to the brain at higher conidium challenge doses, in association with predominant Th1 responses. Fungal dissemination occurred at relatively low challenge doses with the conidia of Aspergillus fumigatus administered to recombinase activating gene 1 (Rag-1)-deficient mice, which lack B and T cells, but B cell-deficient μMT mice and T helper cell-reconstituted Rag-1-deficient mice were comparable to wild-type mice in preventing fungal dissemination. Our findings demonstrate that Th2 cell-predominant allergic responses followed by immune phenotype switching and fungal dissemination are highly predictable outcomes with progressive fungal infectious burdens and that T helper cell responses are protective against lethal fungal dissemination.

  17. Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog.

    Science.gov (United States)

    Beltran, Elsa; de Stefani, Alberta; Stewart, Jennifer; De Risio, Luisa; Johnson, Victoria

    2010-05-01

    Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6-year-old male neutered Greyhound presented with a 3-day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo-oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2-weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.

  18. T Cell Gene Therapy to Eradicate Disseminated Breast Cancers

    Science.gov (United States)

    2012-05-01

    Cells. In this project I found DC maturation stimuli lead to caspase-1 activation in human monocyte-derived DCs. RNAi mediated inhibition of the...inflammasome component ASC shows marked inhibition of the capacity of lipopolysachharide (LPS)-matured DCs to stimulate antigen specific T cells. RNAi ...proteins in insect cell expression system for testing their effectiveness in inhibiting tick feeding by using them as vaccines to immunize the host

  19. Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barré syndrome.

    Science.gov (United States)

    Jiang, Qin Li; Pytel, Peter; Rowin, Julie

    2010-07-01

    We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement.

  20. PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2.

    Science.gov (United States)

    Daulat, Avais M; Bertucci, François; Audebert, Stéphane; Sergé, Arnauld; Finetti, Pascal; Josselin, Emmanuelle; Castellano, Rémy; Birnbaum, Daniel; Angers, Stéphane; Borg, Jean-Paul

    2016-05-23

    Components of the evolutionarily conserved developmental planar cell polarity (PCP) pathway were recently described to play a prominent role in cancer cell dissemination. However, the molecular mechanisms by which PCP molecules drive the spread of cancer cells remain largely unknown. PRICKLE1 encodes a PCP protein bound to the promigratory serine/threonine kinase MINK1. We identify RICTOR, a member of the mTORC2 complex, as a PRICKLE1-binding partner and show that the integrity of the PRICKLE1-MINK1-RICTOR complex is required for activation of AKT, regulation of focal adhesions, and cancer cell migration. Disruption of the PRICKLE1-RICTOR interaction results in a strong impairment of breast cancer cell dissemination in xenograft assays. Finally, we show that upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival.

  1. T-Cell Gene Therapy to Eradicate Disseminated Breast Cancers

    Science.gov (United States)

    2011-05-01

    Barr virus+ Hodgkin’s disease. J Exp Med. 2004;200(12):1623-1633. 6. Grimm EA, Robb RJ, Roth JA, et al. Lymphokine-activated killer cell phenomenon...Roger Williams Medical Center on June 13, 2011. bloodjournal.hematologylibrary.orgFrom 29 99. Sanderson K, Scotland R, Lee P, et al. Autoimmunity

  2. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    Science.gov (United States)

    Loizides, Anthony M.; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  3. Case of early-disseminated Rhizopus microsporus var. microsporus mucormycosis in a renal transplant patient

    Directory of Open Access Journals (Sweden)

    Sharma D

    2016-06-01

    Full Text Available Dikshya Sharma,1 Kumud Dahal,2 Bandana Pathak,3 Udip Dahal4 1Staten Island University Hospital, Staten Island, NY, 2University of Illinois College of Medicine, 3OSF Saint Francis Medical Center, Peoria, IL, 4University of Utah, Salt Lake City, UT, USA Abstract: Mucormycosis is a rare infection caused by the ubiquitous filamentous fungi of the order Mucorales and class Zygomycetes. These species are vasotropic, causing rapid onset of tissue infarctions and necrosis and subsequent thrombosis by invading vascular bed. The disease spectrum ranges from involvement of skin, sinuses, lung, and brain to disseminated and mostly fatal infections, especially in immunocompromised hosts. Here, we present a case of a fatal disseminated mucormycosis in a 56-year-old female who had deceased donor renal allograft transplantation ~2 weeks prior to presentation. She presented with shortness of breath and dry cough. Despite being on broad-spectrum antibiotics/antifungals and proper management by transplant, infectious disease, and primary team, she died within 3 weeks of admission. Autopsy showed disseminated mucormycosis of lungs and thyroid. Disseminated infection within 2 weeks of solid organ transplantation in this patient was one of the rare features of mucormycosis. Keywords: Zygomycetes, immunocompromised, transplant

  4. Media Analysis of Early Dissemination of Canadian Child Maltreatment Surveillance Data

    Science.gov (United States)

    Tonmyr, Lil; Jack, Susan

    2010-01-01

    A media strategy was developed to disseminate Canadian child maltreatment surveillance data. Print media were systematically searched and 29 articles reporting on the data were retrieved. Using content analysis, the articles were analyzed to assess informational accuracy and to understand how the media framed the issue of maltreatment. This…

  5. Vaginal immunization to elicit primary T-cell activation and dissemination.

    Directory of Open Access Journals (Sweden)

    Elena Pettini

    Full Text Available Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4(+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4(+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.

  6. Primary rectal signet ring cell carcinoma with peritoneal dissemination and gastric secondaries

    Institute of Scientific and Technical Information of China (English)

    Hsien-Lin Sim; Kok-Yang Tan; Pak-Leng Poon; Anton Cheng

    2008-01-01

    Disseminated signet ring cell carcinomas frequently arise from the stomach. However, primaries in the colon and rectum have also been reported. We present a 68 year old lady who presented with a change in her bowel habit. Colonoscopy showed a stenosing rectal tumour at 7 cm to 8 cm from the anal verge. Multiple scattered ulcers were also noted along the entire length of the colon. Biopsy of the lesions revealed signet ring cell adenocarcinoma. Gastroscopy showed multiple nodules with ulceration over several areas of the stomach which were similar in appearance to the colonic lesions. However, no primary tumour of the stomach was seen. Biopsy of the gastric lesions also showed signet ring cell adenocarcinoma. Computed tomography scan of the abdomen and pelvis revealed circumferential tumour at the rectosigmoid junction with possible invasion into the left ischiorectal fossa. The overall picture was that of a primary rectal signet ring cell carcinoma with peritoneal dissemination. The patient was referred for palliative chemotherapy in view of the disseminated disease. In the present report, we discuss this interesting pathological entity and review the role of various histolological techniques in helping to identify the primary tumor.

  7. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

    Science.gov (United States)

    Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

    2016-08-01

    Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs.

  8. International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥ 6: a new predictor of hemorrhagic early death in acute promyelocytic leukemia.

    Science.gov (United States)

    Mitrovic, Mirjana; Suvajdzic, Nada; Bogdanovic, Andrija; Kurtovic, Nada Kraguljac; Sretenovic, Aleksandra; Elezovic, Ivo; Tomin, Dragica

    2013-03-01

    High-hemorrhagic early death (ED) rate is a major impediment in the managing of acute promyelocytic leukemia (APL). In our group of 56 newly diagnosed APL patients, ED occurred in 12 subjects, due to endocranial bleeding (8/12), differentiation syndrome (2/12), or infection (2/12). Predictors of hemorrhagic ED were as follows: white blood cells count ≥ 20 × 10(9)/L (P = 0.002337), Eastern cooperative oncology group performance status ≥ 3 (P = 0.00173), fibrinogen level disseminated intravascular coagulation (ISTH DIC score) ≥ 6 (P = 0.00741). Multivariate analysis indicated ISTH DIC score ≥ 6 to be the most significant predictor for hemorrhagic ED (P = 0.008). The main finding of this study is that simple coagulation-related tests, performed on hospital admission and combined in the ISTH DIC score, might help to identify patients at high risk for fatal bleeding needing more aggressive supportive measures.

  9. The potential role of cell phones in dissemination of bacteria in a healthcare sett

    Directory of Open Access Journals (Sweden)

    Mateusz P. Kister

    2016-04-01

    Full Text Available The mobile phone is an indispensible accessory, both from a social and a professional point of view, which is being used in a variety of environments, including those with high bacteria levels. Medical personnel, patients or even people simply passing by the healthcare facilities, having and using their mobile phones are likely to transmit bacteria, thus it might be suspected that mobile phones are to some extent a link in the cross-contamination. The purpose of this work was to collect information concerning the potential role of cell phones in a dissemination of bacteria based on available research data.

  10. Transgenic mice overexpressing arginase 1 in monocytic cell lineage are affected by lympho-myeloproliferative disorders and disseminated intravascular coagulation.

    Science.gov (United States)

    Astigiano, Simonetta; Morini, Monica; Damonte, Patrizia; Fraternali Orcioni, Giulio; Cassanello, Michela; Puglisi, Andrea; Noonan, Douglas M; Bronte, Vincenzo; Barbieri, Ottavia

    2015-11-01

    Arginase (ARG) is a metabolic enzyme present in two isoforms that hydrolyze l-arginine to urea and ornithine. In humans, ARG isoform 1 is also expressed in cells of the myeloid lineage. ARG activity promotes tumour growth and inhibits T lymphocyte activation. However, the two ARG transgenic mouse lines produced so far failed to show such effects. We have generated, in two different genetic backgrounds, transgenic mice constitutively expressing ARG1 under the control of the CD68 promoter in macrophages and monocytes. Both heterozygous and homozygous transgenic mice showed a relevant increase in mortality at early age, compared with wild-type siblings (67/267 and 48/181 versus 8/149, respectively, both P < 0.005). This increase was due to high incidence of haematologic malignancies, in particular myeloid leukaemia, myeloid dysplasia, lymphomas and disseminated intravascular coagulation (DIC), diseases that were absent in wild-type mice. Atrophy of lymphoid organs due to reduction in T-cell compartment was also detected. Our results indicate that ARG activity may participate in the pathogenesis of lymphoproliferative and myeloproliferative disorders, suggest the involvement of alterations of L-arginine metabolism in the onset of DIC and confirm a role for the enzyme in regulating T-cell homeostasis.

  11. A Fatal Case of Congenital Langerhans Cell Histiocytosis with Disseminated Cutaneous Lesions in a Premature Neonate

    Directory of Open Access Journals (Sweden)

    Michio Inoue

    2016-01-01

    Full Text Available Background. The outcome of neonates with congenital cutaneous Langerhans cell histiocytosis (LCH is variable. Observations. We report a case of LCH in a female premature neonate born at 33-week gestation. She had disseminated cutaneous lesions, which consisted of hemorrhagic papules and vesicles, with sparse healthy skin areas, and the hands and feet were contracted with scarring and blackened. She was in respiratory failure although no apparent pulmonary or bone lesions on X-rays were noted. Skin biopsy confirmed a diagnosis of LCH due to observation of CD1a+ Langerhans cells, which lacked expression of E-cadherin and CD56. The patient died 57 hours after birth. Conclusions. Based on this case and the literature survey, the outcome of premature babies with congenital cutaneous LCH lesions is noted to be unfavorable, with the majority of such cases suffering from multisystem disease.

  12. Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient.

    Science.gov (United States)

    Osthoff, M; Chew, E; Bajel, A; Kelsey, G; Panek-Hudson, Y; Mason, K; Szer, J; Ritchie, D; Slavin, M

    2013-02-01

    Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.

  13. Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination

    Institute of Scientific and Technical Information of China (English)

    Dan Huang; Xiang Du

    2008-01-01

    Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous p-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway.

  14. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  15. Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence.

    Science.gov (United States)

    Bifulco, Katia; Votta, Giuseppina; Ingangi, Vincenzo; Di Carluccio, Gioconda; Rea, Domenica; Losito, Simona; Montuori, Nunzia; Ragno, Pia; Stoppelli, Maria Patrizia; Arra, Claudio; Carriero, Maria Vincenza

    2014-06-30

    The clinical relevance of the urokinase receptor (uPAR) as a prognostic marker in ovarian cancer is well documented. We had shown that the uPAR sequence corresponding to 84-95 residues, linking D1 and D2 domains (uPAR84-95), drives cell migration and angiogenesis in a protease-independent manner. This study was aimed at defining the contribution of uPAR84-95 sequence to invasion of ovarian cancer cells. Now, we provide evidence that the ability of uPAR-expressing ovarian cancer cells to cross extra-cellular matrix and mesothelial monolayers is prevented by specific inhibitors of the uPAR84-95 sequence. To specifically investigate uPAR84-95 function, uPAR-negative CHO-K1 cells were stably transfected with cDNAs coding for uPAR D2 and D3 regions exposing (uPARD2D3) or lacking (uPAR∆D2D3) the 84-95 sequence. CHO-K1/D2D3 cells were able to cross matrigel, mesothelial and endothelial monolayers more efficiently than CHO-K1/∆D2D3 cells, which behave as CHO-K1 control cells. When orthotopically implanted in nude mice, tumor nodules generated by CHO-K1/D2D3 cells spreading to peritoneal cavity were more numerous as compared to CHO-K1/∆D2D3 cells. Ovarian tumor size and intra-tumoral microvessel density were significantly reduced in the absence of uPAR84-95. Our results indicate that cell associated uPAR promotes growth and abdominal dissemination of ovarian cancer cells mainly through its uPAR84-95 sequence.

  16. Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

    Directory of Open Access Journals (Sweden)

    Dayana Santos Mendes

    2013-02-01

    Full Text Available Disseminated leishmaniasis (DL differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics. Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.

  17. Different prognostic value of circulating and disseminated tumor cells in primary breast cancer: Influence of bisphosphonate intake?

    Science.gov (United States)

    Kasimir-Bauer, Sabine; Reiter, Katharina; Aktas, Bahriye; Bittner, Ann-Kathrin; Weber, Stephan; Keller, Thomas; Kimmig, Rainer; Hoffmann, Oliver

    2016-01-01

    Disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood of breast cancer patients (pts) are known to correlate with worse outcome. Here we demonstrate a different prognostic value of DTCs and CTCs and explain these findings by early clodronate intake. CTCs (n = 376 pts) were determined using the AdnaTest BreastCancer (Qiagen Hannover GmbH, Germany) and DTCs (n = 525 pts) were analyzed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Clodronate intake was recommended in case of DTC-positivity. CTCs were detected in 22% and DTCs in 40% of the pts, respectively. DTCs were significantly associated with nodal status (p = 0.03), grading (p = 0.01), lymphangiosis (p = 0.03), PR status (p = 0.02) and clodronate intake (p < 0.0001), no significant associations were demonstrated for CTCs. CTCs significantly correlated with reduced PFS (p = 0.0227) and negative prognostic relevance was predominantly related to G2 tumors (p = 0.044), the lobular (p = 0.024) and the triple-negative subtype (p = 0.005), HR-negative pts (p = 0.001), postmenopausal women (p = 0.013) and patients who had received radiation therapy (p = 0.018). No prognostic significance was found for DTCs. Therefore early clodronate intake can improve prognosis of breast cancer patients and CTCs might be a high risk indicator for the onset of metastasis not limited to bone metastasis. PMID:27212060

  18. Different prognostic value of circulating and disseminated tumor cells in primary breast cancer: Influence of bisphosphonate intake?

    Science.gov (United States)

    Kasimir-Bauer, Sabine; Reiter, Katharina; Aktas, Bahriye; Bittner, Ann-Kathrin; Weber, Stephan; Keller, Thomas; Kimmig, Rainer; Hoffmann, Oliver

    2016-05-23

    Disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in blood of breast cancer patients (pts) are known to correlate with worse outcome. Here we demonstrate a different prognostic value of DTCs and CTCs and explain these findings by early clodronate intake. CTCs (n = 376 pts) were determined using the AdnaTest BreastCancer (Qiagen Hannover GmbH, Germany) and DTCs (n = 525 pts) were analyzed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Clodronate intake was recommended in case of DTC-positivity. CTCs were detected in 22% and DTCs in 40% of the pts, respectively. DTCs were significantly associated with nodal status (p = 0.03), grading (p = 0.01), lymphangiosis (p = 0.03), PR status (p = 0.02) and clodronate intake (p < 0.0001), no significant associations were demonstrated for CTCs. CTCs significantly correlated with reduced PFS (p = 0.0227) and negative prognostic relevance was predominantly related to G2 tumors (p = 0.044), the lobular (p = 0.024) and the triple-negative subtype (p = 0.005), HR-negative pts (p = 0.001), postmenopausal women (p = 0.013) and patients who had received radiation therapy (p = 0.018). No prognostic significance was found for DTCs. Therefore early clodronate intake can improve prognosis of breast cancer patients and CTCs might be a high risk indicator for the onset of metastasis not limited to bone metastasis.

  19. Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

    Science.gov (United States)

    Miki, T; Yano, S; Hanibuchi, M; Sone, S

    2000-01-01

    Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer

  20. Molecular characteristics of KPC-producing Enterobacteriaceae at the early stage of their dissemination in Poland, 2008-2009.

    Science.gov (United States)

    Baraniak, Anna; Grabowska, Anna; Izdebski, Radosław; Fiett, Janusz; Herda, Małgorzata; Bojarska, Katarzyna; Żabicka, Dorota; Kania-Pudło, Marta; Młynarczyk, Grazyna; Żak-Puławska, Zofia; Hryniewicz, Waleria; Gniadkowski, Marek

    2011-12-01

    After the first report in May 2008, the National Reference Center for Susceptibility Testing confirmed 113 cases of infection or colonization by KPC-producing members of the family Enterobacteriaceae in Poland by the end of 2009. The vast majority of patients were found in 18 hospitals; three patients were diagnosed at outpatient clinics. Most of the institutions were in the Warsaw area, including three hospitals with the highest numbers of cases. When available, the data on previous hospitalizations often indicated that these hospitals were the probable acquisition sites; one patient arrived from New York. The group of 119 unique isolates consisted of Klebsiella pneumoniae (n = 114), followed by Klebsiella oxytoca (n = 3), and Escherichia coli (n = 2). The K. pneumoniae isolates were dominated by the clone sequence type 258 (ST258) (n = 111); others were ST11 and ST23. The ST258 group was heterogeneous, with 28 pulsed-field gel electrophoresis (PFGE) subtypes, ∼25 plasmid profiles, and nine β-lactamase patterns differing by KPC variants (KPC-2 mainly), and SHV-12, CTX-M-3, and TEM-1-like enzymes. Plasmids carrying bla(KPC) genes varied in size (~48 to 250 kb), structure, and conjugation potential. Transferable IncFII(K) plasmids of ~110 to 160 kb, probably pKpQIL or its derivatives, were observed in all K. pneumoniae clones and in K. oxytoca. Also prevalent were nontypeable pETKp50-like plasmids of ~50 kb, found in K. pneumoniae ST258 and E. coli isolates (ST93 and ST224). Two K. pneumoniae-E. coli pairs from single patients might represent the in vivo transfer of such plasmids. The striking diversity of KPC producers at the early stage of dissemination could result from several introductions of these bacteria into the country, their multidirectional evolution during clonal spread, and transfer of the plasmids.

  1. Disseminated sporotrichosis.

    Science.gov (United States)

    Romero-Cabello, Raúl; Bonifaz, Alexandro; Romero-Feregrino, Raúl; Sánchez, Carlos Javier; Linares, Yancy; Zavala, Jorge Tay; Romero, Leticia Calderón; Romero-Feregrino, Rodrigo; Vega, José T Sánchez

    2011-03-25

    Sporotrichosis is a subacute or chronic infection caused by Sporothrix schenckii. It is a primary cutaneous infection and it has different clinical forms: disseminated by lymphatic vessels (75%), localised cutaneous form (20%), disseminated cutaneous and extracuteus rarely. The systemic disseminated sporotrichosis is considered a severe opportunistic infection. The best diagnostic test is the culture. The authors report a case of a 36-year-old man, originally from Puebla, Mexico, with a diagnosis of disseminated sporotrichosis. Differential diagnosis with other pathologies includes leishmaniasis, chromoblastomycosis, tuberculosis verrucose and lymphangitis. The development of unusual presentations in immunocompromised patients has been reported.

  2. Disseminated sporotrichosis

    Science.gov (United States)

    Romero-Cabello, Raúl; Bonifaz, Alexandro; Romero-Feregrino, Raúl; Sánchez, Carlos Javier; Linares, Yancy; Zavala, Jorge Tay; Romero, Leticia Calderón; Romero-Feregrino, Rodrigo; Vega, José T Sánchez

    2011-01-01

    Sporotrichosis is a subacute or chronic infection caused by Sporothrix schenckii. It is a primary cutaneous infection and it has different clinical forms: disseminated by lymphatic vessels (75%), localised cutaneous form (20%), disseminated cutaneous and extracuteus rarely. The systemic disseminated sporotrichosis is considered a severe opportunistic infection. The best diagnostic test is the culture. The authors report a case of a 36-year-old man, originally from Puebla, Mexico, with a diagnosis of disseminated sporotrichosis. Differential diagnosis with other pathologies includes leishmaniasis, chromoblastomycosis, tuberculosis verrucose and lymphangitis. The development of unusual presentations in immunocompromised patients has been reported. PMID:22700076

  3. Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation.

    Science.gov (United States)

    Iwen, P C; Rupp, M E; Bishop, M R; Rinaldi, M G; Sutton, D A; Tarantolo, S; Hinrichs, S H

    1998-12-01

    The first case of disseminated aspergillosis caused by Aspergillus ustus in an allogeneic peripheral stem cell transplant patient is described. The patient, a 46-year-old female with a history of myelodysplastic syndrome, underwent high-dose chemotherapy and total body irradiation prior to transplantation. She was released from the hospital 49 days posttransplant (p.t.) in a stable condition with an absolute neutrophil count (ANC) of 2,700 cells per microl. Multiple antimicrobial agents, including itraconazole (ITR), were prescribed during hospitalization and at the time of discharge. Three days after discharge, the patient was readmitted with hemorrhagic cystitis, persistent thrombocytopenia, and bilateral pulmonary consolidation, although no fever was present. The ANC at the time of readmission was 3,500. Upon detection of a pulmonary nodule (day 67 p.t.), a bronchoalveolar lavage was performed; the lavage fluid was positive for both cytomegalovirus and parainfluenza virus and negative for fungus. The patient was placed on ganciclovir. A biopsy specimen from a leg lesion also noted on day 67 p.t. revealed septate hyphae consistent with Aspergillus species, and a culture subsequently yielded Aspergillus ustus. Confirmation detection of A. ustus was made by demonstration of characteristic reproductive structures with the presence of Hülle cells. On day 67 p.t., ITR was discontinued and liposomal amphotericin B (AMB) was initiated. The patient's condition worsened, and she died 79 days p.t. At the time of autopsy, septate hyphae were present in heart, thyroid, and lung tissues, with lung tissue culture positive for A. ustus. In vitro susceptibility testing indicated probable resistance to AMB but not to ITR. This case supports the need for the development of rapid methods to determine antifungal susceptibility.

  4. Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

    Science.gov (United States)

    Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

    1991-02-01

    Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

  5. B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

    Directory of Open Access Journals (Sweden)

    MGS Vieira

    2002-10-01

    Full Text Available Biopsies from human localized cutaneous lesions (LCL n = 7 or disseminated lesions (DL n = 8 cases were characterized according to cellular infiltration,frequency of cytokine (IFN-g, TNF-alpha or iNOS enzyme producing cells. LCL, the most usual form of the disease with usually one or two lesions, exhibits extensive tissue damage. DL is a rare form with widespread lesions throughout the body; exhibiting poor parasite containment but less tissue damage. We demonstrated that LCL lesions exhibit higher frequency of B lymphocytes and a higher intensity of IFN-gamma expression. In both forms of the disease CD8+ were found in higher frequency than CD4+ T cells. Frequency of TNF-alpha and iNOS producing cells, as well as the frequency of CD68+ macrophages, did not differ between LCL and DL. Our findings reinforce the link between an efficient control of parasite and tissue damage, implicating higher frequency of IFN-gamma producing cells, as well as its possible counteraction by infiltrated B cells and hence possible humoral immune response in situ.

  6. Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.

    Directory of Open Access Journals (Sweden)

    Benjamin Davido

    Full Text Available In bone and joint infections (BJIs, bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL expression leads to severe local damage, including bone distortion and abscesses, while α-hemolysin (Hla production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA strain USA300 (LAC WT were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated.We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαβhld using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney, lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D 14.Severe sepsis-related mortality tended to be lower for Δpsm derivatives (Kaplan-Meier curves, P = .06. Non-survivors' bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04 or -Δpsmαβhld (6.86 log10 CFUs/g of bone, P = .014 densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone. Conversely, lung Δpsmαβhld CFUs were significantly lower than LAC WT (P = .04. LAC Δpsmα, Δpsmαβhld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone. Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Δpsmα- and Δpsmαβhld-infected rabbits compared to LAC WT (P = .04 and .01, respectively but with comparable lung bacterial densities.Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early

  7. Myxoma Virus Sensitizes Cancer Cells to Gemcitabine and Is an Effective Oncolytic Virotherapeutic in Models of Disseminated Pancreatic Cancer

    OpenAIRE

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M.; Mona, Mahmoud; McFadden, Grant

    2012-01-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and comb...

  8. Heterogeneity of Mesenchymal Markers Expression—Molecular Profiles of Cancer Cells Disseminated by Lymphatic and Hematogenous Routes in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Markiewicz, Aleksandra [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland); Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw 02-091 (Poland); Książkiewicz, Magdalena [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland); Seroczyńska, Barbara [Bank of Frozen Tissues and Genetic Specimens, Department of Medical Laboratory Diagnostics, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Skokowski, Jarosław [Bank of Frozen Tissues and Genetic Specimens, Department of Medical Laboratory Diagnostics, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk 80-214 (Poland); Szade, Jolanta [Department of Pathomorphology, Medical University of Gdańsk, Gdańsk 80-214 (Poland); Wełnicka-Jaśkiewicz, Marzena [Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Zaczek, Anna J., E-mail: azaczek@gumed.edu.pl [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland)

    2013-11-08

    Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination.

  9. B cells enhance antigen-specific CD4 T cell priming and prevent bacteria dissemination following Chlamydia muridarum genital tract infection.

    Science.gov (United States)

    Li, Lin-Xi; McSorley, Stephen J

    2013-10-01

    B cells can contribute to acquired immunity against intracellular bacteria, but do not usually participate in primary clearance. Here, we examined the endogenous CD4 T cell response to genital infection with Chlamydia muridarum using MHC class-II tetramers. Chlamydia-specific CD4 T cells expanded rapidly and persisted as a stable memory pool for several months after infection. While most lymph node Chlamydia-specific CD4 T cells expressed T-bet, a small percentage co-expressed Foxp3, and RORγt-expressing T cells were enriched within the reproductive tract. Local Chlamydia-specific CD4 T cell priming was markedly reduced in mice lacking B cells, and bacteria were able to disseminate to the peritoneal cavity, initiating a cellular infiltrate and ascites. However, bacterial dissemination also coincided with elevated systemic Chlamydia-specific CD4 T cell responses and resolution of primary infection. Together, these data reveal heterogeneity in pathogen-specific CD4 T cell responses within the genital tract and an unexpected requirement for B cells in regulating local T cell activation and bacterial dissemination during genital infection.

  10. Expression of β-globin by cancer cells promotes cell survival during blood-borne dissemination

    Science.gov (United States)

    Zheng, Yu; Miyamoto, David T.; Wittner, Ben S.; Sullivan, James P.; Aceto, Nicola; Jordan, Nicole Vincent; Yu, Min; Karabacak, Nezihi Murat; Comaills, Valentine; Morris, Robert; Desai, Rushil; Desai, Niyati; Emmons, Erin; Milner, John D.; Lee, Richard J.; Wu, Chin-Lee; Sequist, Lecia V.; Haas, Wilhelm; Ting, David T.; Toner, Mehmet; Ramaswamy, Sridhar; Maheswaran, Shyamala; Haber, Daniel A.

    2017-01-01

    Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that β-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis. PMID:28181495

  11. Renal small B-cell lymphoma with plasmacytic differentiation presenting with monoclonal gammopathy and disseminated intravascular coagulation syndrome

    Directory of Open Access Journals (Sweden)

    Paula de Oliveira Pádua Prestes

    2013-10-01

    Full Text Available Primary renal lymphomas are very rare. However, the kidney may be a site of metastasis, usually from a disseminated aggressive lymphoma. A 58-year-old woman was brought to the medical facility due to acute mental confusion, severe hypotension, septic shock, and signs of disseminated intravascular coagulation. Laboratory tests showed severe leukopenia, renal failure, altered liver function, and elevated serum lactate dehydrogenase levels. Protein electrophoresis revealed hypergammaglobulinemia with a monoclonal peak of IgG lambda. The clinical outcome was fulminant and the patient died less than 24 hours after admission. Autopsy revealed an indolent B-cell lymphoma with extensive plasmacytic differentiation infiltrating the right renal sinus and involving the submandibular and sublingual glands, cervical and peri-aortic lymph nodes, multiple microscopic foci in pituitary and adrenal glands, lung, breast, liver, thyroid, and bone marrow. Numerous IgG4-positive plasma cells were detected by immunohistochemistry although other histological features of IgG4-related disease were missing. There was also extensive hemorrhagic necrosis of the adrenal glands and purulent cystitis, which was probably responsible for the septic shock. The authors concluded that the kidney was most likely the primary site of the indolent lymphoma, as that was the site with the largest tumor mass. Infiltration of other organs was considered as dissemination of the disease. The differential diagnosis with mucosa-associated lymphoid tissue and lymphoplasmacytic lymphoma is discussed.

  12. OPERATIONAL REMOTE SENSING SERVICES IN NORTH EASTERN REGION OF INDIA FOR NATURAL RESOURCES MANAGEMENT, EARLY WARNING FOR DISASTER RISK REDUCTION AND DISSEMINATION OF INFORMATION AND SERVICES

    Directory of Open Access Journals (Sweden)

    P. L. N. Raju

    2016-06-01

    Full Text Available North Eastern Region (NER of India comprising of eight states considered to be most unique and one of the most challenging regions to govern due to its unique physiographic condition, rich biodiversity, disaster prone and diverse socio-economic characteristics. Operational Remote Sensing services increased manifolds in the region with the establishment of North Eastern Space Applications Centre (NESAC in the year 2000. Since inception, NESAC has been providing remote sensing services in generating inventory, planning and developmental activities, and management of natural resources, disasters and dissemination of information and services through geo-web services for NER. The operational remote sensing services provided by NESAC can be broadly divided into three categories viz. natural resource planning and developmental services, disaster risk reduction and early warning services and information dissemination through geo-portal services. As a apart of natural resources planning and developmental services NESAC supports the state forest departments in preparing the forest working plans by providing geospatial inputs covering entire NER, identifying the suitable culturable wastelands for cultivation of silkworm food plants, mapping of natural resources such as land use/land cover, wastelands, land degradation etc. on temporal basis. In the area of disaster risk reduction, NESAC has initiated operational services for early warning and post disaster assessment inputs for flood early warning system (FLEWS using satellite remote sensing, numerical weather prediction, hydrological modeling etc.; forest fire alert system with actionable attribute information; Japanese Encephalitis Early Warning System (JEWS based on mosquito vector abundance, pig population and historical disease intensity and agriculture drought monitoring for the region. The large volumes of geo-spatial databases generated as part of operational services are made available to the

  13. Operational Remote Sensing Services in North Eastern Region of India for Natural Resources Management, Early Warning for Disaster Risk Reduction and Dissemination of Information and Services

    Science.gov (United States)

    Raju, P. L. N.; Sarma, K. K.; Barman, D.; Handique, B. K.; Chutia, D.; Kundu, S. S.; Das, R. Kr.; Chakraborty, K.; Das, R.; Goswami, J.; Das, P.; Devi, H. S.; Nongkynrih, J. M.; Bhusan, K.; Singh, M. S.; Singh, P. S.; Saikhom, V.; Goswami, C.; Pebam, R.; Borgohain, A.; Gogoi, R. B.; Singh, N. R.; Bharali, A.; Sarma, D.; Lyngdoh, R. B.; Mandal, P. P.; Chabukdhara, M.

    2016-06-01

    North Eastern Region (NER) of India comprising of eight states considered to be most unique and one of the most challenging regions to govern due to its unique physiographic condition, rich biodiversity, disaster prone and diverse socio-economic characteristics. Operational Remote Sensing services increased manifolds in the region with the establishment of North Eastern Space Applications Centre (NESAC) in the year 2000. Since inception, NESAC has been providing remote sensing services in generating inventory, planning and developmental activities, and management of natural resources, disasters and dissemination of information and services through geo-web services for NER. The operational remote sensing services provided by NESAC can be broadly divided into three categories viz. natural resource planning and developmental services, disaster risk reduction and early warning services and information dissemination through geo-portal services. As a apart of natural resources planning and developmental services NESAC supports the state forest departments in preparing the forest working plans by providing geospatial inputs covering entire NER, identifying the suitable culturable wastelands for cultivation of silkworm food plants, mapping of natural resources such as land use/land cover, wastelands, land degradation etc. on temporal basis. In the area of disaster risk reduction, NESAC has initiated operational services for early warning and post disaster assessment inputs for flood early warning system (FLEWS) using satellite remote sensing, numerical weather prediction, hydrological modeling etc.; forest fire alert system with actionable attribute information; Japanese Encephalitis Early Warning System (JEWS) based on mosquito vector abundance, pig population and historical disease intensity and agriculture drought monitoring for the region. The large volumes of geo-spatial databases generated as part of operational services are made available to the administrators and

  14. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    María Laura Chiribao

    2014-01-01

    Full Text Available Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response, a great number of transcription factors (including the majority of NFκB family members, and host metabolism (cholesterol, fatty acids, and phospholipids. These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination.

  15. Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization.

    Science.gov (United States)

    Riethdorf, Sabine; Pantel, Klaus

    2008-01-01

    Despite the progress resulting from early detection and improved adjuvant therapy, the prognosis of breast cancer patients is still limited by the occurrence of distant metastases largely due to clinically occult micrometastases that remain undetected at primary diagnosis even by high-resolution imaging approaches. Recent research efforts have concentrated on the identification of additional parameters allowing individual risk assessment and stratification of patients for targeted therapies, since traditional prognostic factors are not sufficient to predict metastatic relapse and treatment decisions are still mainly based on statistical risk parameters. Highly sensitive and specific immunocytochemical and molecular assays now enable the detection and characterization of disseminated and circulating tumor cells (DTCs and CTCs, respectively) at the single cell level in bone marrow (BM) and peripheral blood, providing insights into the first crucial steps of the metastatic cascade. However, because of the still high variability of results in DTC/CTC detection, the necessity of standardized approaches will be discussed. A large number of studies showed that the presence of DTCs in BM has prognostic impact for primary breast cancer patients. DTCs are likely to escape from chemotherapy by maintaining a dormant nonproliferating state. There is also evidence for a stem cell-like phenotype of DTCs, probably contributing to the opportunity to escape from dormancy control and to start expansion to manifest metastases. Blood would also be an ideal source for the detection and monitoring of CTCs because of an easy noninvasive sampling procedure enabling repeated analyses. While prognostic significance of CTCs could be reliably demonstrated for metastatic breast cancer, studies to analyze the impact of CTCs in primary breast cancer patients and the potential to replace or supplement BM analysis are still ongoing. Furthermore, molecular characterization of CTCs might contribute

  16. Infected Dendritic Cells Facilitate Systemic Dissemination and Transplacental Passage of the Obligate Intracellular Parasite Neospora caninum in Mice

    Science.gov (United States)

    Collantes-Fernandez, Esther; Arrighi, Romanico B. G.; Álvarez-García, Gema; Weidner, Jessica M.; Regidor-Cerrillo, Javier; Boothroyd, John C.; Ortega-Mora, Luis M.; Barragan, Antonio

    2012-01-01

    The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9) was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC) by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites. PMID:22403627

  17. Infected dendritic cells facilitate systemic dissemination and transplacental passage of the obligate intracellular parasite Neospora caninum in mice.

    Directory of Open Access Journals (Sweden)

    Esther Collantes-Fernandez

    Full Text Available The obligate intracellular parasite Neospora caninum disseminates across the placenta and the blood-brain barrier, to reach sites where it causes severe pathology or establishes chronic persistent infections. The mechanisms used by N. caninum to breach restrictive biological barriers remain elusive. To examine the cellular basis of these processes, migration of different N. caninum isolates (Nc-1, Nc-Liverpool, Nc-SweB1 and the Spanish isolates: Nc-Spain 3H, Nc-Spain 4H, Nc-Spain 6, Nc-Spain 7 and Nc-Spain 9 was studied in an in vitro model based on a placental trophoblast-derived BeWo cell line. Here, we describe that infection of dendritic cells (DC by N. caninum tachyzoites potentiated translocation of parasites across polarized cellular monolayers. In addition, powered by the parasite's own gliding motility, extracellular N. caninum tachyzoites were able to transmigrate across cellular monolayers. Altogether, the presented data provides evidence of two putative complementary pathways utilized by N. caninum, in an isolate-specific fashion, for passage of restrictive cellular barriers. Interestingly, adoptive transfer of tachyzoite-infected DC in mice resulted in increased parasitic loads in various organs, e.g. the central nervous system, compared to infections with free parasites. Inoculation of pregnant mice with infected DC resulted in an accentuated vertical transmission to the offspring with increased parasitic loads and neonatal mortality. These findings reveal that N. caninum exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. The findings are indicative of conserved dissemination strategies among coccidian apicomplexan parasites.

  18. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  19. Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis.

    Science.gov (United States)

    Cleary, Ian A; Reinhard, Sara M; Lazzell, Anna L; Monteagudo, Carlos; Thomas, Derek P; Lopez-Ribot, Jose L; Saville, Stephen P

    2016-03-01

    The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health. Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we used strains in which the morphological transition could be externally manipulated through controlled expression of NRG1 or TUP1. Remarkably, hyphal form inocula retain the capacity to cause disease. Whilst induction of a pseudohyphal morphology through depletion of TUP1 did result in attenuated virulence, this was not due to a defect in the ability to escape the bloodstream. Instead, we observed that pseudohyphal cells are cleared from tissues much more efficiently than either hyphal (virulent) or yeast form (avirulent) cells, indicating that different C. albicans morphologies have distinct interactions with host cells during an infection.

  20. Survival and Toxicity in Patients With Disseminated Germ CellCancer Aged 40 Years and Older

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Bandak, Mikkel; Thomsen, Maria F

    2014-01-01

    , treatment related toxicity and survival in patients aged ≥40 years treated with standard chemotherapy for GCC compared with a younger control group that received similar treatment during the same period. METHODS: From 1984 to 2011, 135 patients aged ≥40 years with disseminated GCC treated with bleomycin...... followed until death or October 1, 2011. RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged ≥40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P = 0.03). No differences between...

  1. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  2. New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line.

    Science.gov (United States)

    Terawaki, Kiyoshi; Sawada, Yumi; Kashiwase, Yohei; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Suzuki, Masami; Miyano, Kanako; Sudo, Yuka; Shiraishi, Seiji; Higami, Yoshikazu; Yanagihara, Kazuyoshi; Kase, Yoshio; Ueta, Yoichi; Uezono, Yasuhito

    2014-02-15

    Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

  3. Disseminated breast cancer cells acquire a highly malignant and aggressive metastatic phenotype during metastatic latency in the bone.

    Directory of Open Access Journals (Sweden)

    Carolyn G Marsden

    Full Text Available BACKGROUND: Disseminated tumor cells (DTCs in the bone marrow may exist in a dormant state for extended periods of time, maintaining the ability to proliferate upon activation, engraft at new sites, and form detectable metastases. However, understanding of the behavior and biology of dormant breast cancer cells in the bone marrow niche remains limited, as well as their potential involvement in tumor recurrence and metastasis. Therefore, the purpose of this study was to investigate the tumorigenicity and metastatic potential of dormant disseminated breast cancer cells (prior to activation in the bone marrow. METHODOLOGY/PRINCIPAL FINDINGS: Total bone marrow, isolated from mice previously injected with tumorspheres into the mammary fat pad, was injected into the mammary fat pad of NUDE mice. As a negative control, bone marrow isolated from non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were analyzed by H+E staining to detect metastases. The injection of bone marrow isolated from mice previously injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-injection. However, the injection of bone marrow isolated from non-injected mice did not result in tumor formation in the mammary fat pad. The DTC-derived tumors exhibited accelerated development of metastatic lesions within the lung, liver and kidney. The resultant tumors and the majority of metastatic lesions within the lung and liver exhibited a mesenchymal-like phenotype. CONCLUSIONS/SIGNIFICANCE: Dormant DTCs within the bone marrow are highly malignant upon injection into the mammary fat pad, with the accelerated development of metastatic lesions within the lung, liver and kidney. These results suggest the acquisition of a more aggressive phenotype of DTCs during

  4. Therapeutic effect of human iPS-cell-derived myeloid cells expressing IFN-β against peritoneally disseminated cancer in xenograft models.

    Science.gov (United States)

    Koba, Chihiro; Haruta, Miwa; Matsunaga, Yusuke; Matsumura, Keiko; Haga, Eriko; Sasaki, Yuko; Ikeda, Tokunori; Takamatsu, Koutaro; Nishimura, Yasuharu; Senju, Satoru

    2013-01-01

    We recently developed a method to generate myeloid cells with proliferation capacity from human iPS cells. iPS-ML (iPS-cell-derived myeloid/macrophage line), generated by introducing proliferation and anti-senescence factors into iPS-cell-derived myeloid cells, grew continuously in an M-CSF-dependent manner. A large number of cells exhibiting macrophage-like properties can be readily obtained by using this technology. In the current study, we evaluated the possible application of iPS-ML in anti-cancer therapy. We established a model of peritoneally disseminated gastric cancer by intraperitoneally injecting NUGC-4 human gastric cancer cells into SCID mice. When iPS-ML were injected intraperitoneally into the mice with pre-established peritoneal NUGC-4 tumors, iPS-ML massively accumulated and infiltrated into the tumor tissues. iPS-ML expressing IFN-β (iPS-ML/IFN-β) significantly inhibited the intra-peritoneal growth of NUGC-4 cancer. Furthermore, iPS-ML/IFN-β also inhibited the growth of human pancreatic cancer MIAPaCa-2 in a similar model. iPS-ML are therefore a promising treatment agent for peritoneally disseminated cancers, for which no standard treatment is currently available.

  5. Dissemination profile of perioperative tumor cells in peripheral blood of colorectal cancer patients detected by multiple marker genes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This work proposes a method to assess the molecular profile of perioperative circulating tumor cells in peripheral blood (PB) of colorectal cancer patients for differentiating the dissemination process of tumor cells. Two-point quantification of multiple marker genes was designed for describing the profile. The expression levels of cytokeratin 20 (CK20),carcino-embryonic antigen (CEA) and survivin mRNA in PB and tumor tissue samples in 37 colorectal cancer patients from 1 d pre-operation to 2 h postoperation were detected with real-time quantitative reverse transcription-polymerase chain reaction. β-Actin mRNA was used as internal control to standardize the results of different mRNA expression levels. The data analysis using Stata statistical packages,Chi-Square test and Mann-Whitney test indicated the expression level of CEA mRNA in PB increased significantly,while those of CK20 and survivin mRNA decreased significantly. Quantitative comparison with tumor tissues indicated that the increase of CEA mRNA level in PB coincided with the decrease of CK20 and survivin mRNA levels in different tumor cells. These results showed surgical manipulation caused tumor cells shedding into blood from primary tumor tissue and significant increase of CEA mRNA level,while occult tumor cells with high expression levels of CK20 and survivin mRNA before surgery decreased after surgery.

  6. Severe Periodontal Disease Manifested in Chronic Disseminated Type of Langerhans Cell Histiocytosis in a 3-Year Old Child

    Science.gov (United States)

    Srivastava, Vinay Kumar; Bansal, Rajesh; Gupta, Vineeta; Bansal, Manish; Patne, Shashikant

    2014-01-01

    ABSTRACT% Langerhans cell histiocytosis (LCH), previously known as histio-cytosis X, is a rare idiopathic disorder of reticulo-endothelial system with abnormal proliferation of bone marrow derived Langerhans cells along with a variable number of leukocytes, such as eosinophils, neutrophils, lymphocytes and plasma cells. Three years old male child presented with multifocal osteolytic lesions and papulosquamous skin lesions. Clinical and radio-graphic features, such as severe alveolar bone loss, mobility of teeth, precocious eruption of teeth, foating appearance of teeth in orthopantomogram (OPG), osteolytic lesion in skull and cutaneous lesions were highly suggestive of LCH disease. Skin biopsy confirmed a diagnosis of LCH. Induction chemotherapy with oral prednisolone and intravenous vinblastine was started. Child responded well to chemotherapy. The clinical significance of the presented case is to diagnose the case of LCH on the basis of the manifestation of severe periodontal disease as this can be first or only manifestation of LCH. A dentist plays a major role in the multidisciplinary treatment of LCH through routine examination and periodic follow-up. How to cite this article: Bansal M, Srivastava VK, Bansal R, Gupta V, Bansal M, Patne S. Severe Periodontal Disease Manifested in Chronic Disseminated Type of Langerhans Cell Histiocytosis in a 3-Year Old Child. Int J Clin Pediatr Dent 2014;7(3):217-219. PMID:25709306

  7. Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer.

    Science.gov (United States)

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M; Mona, Mahmoud; McFadden, Grant

    2012-04-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and combination therapy with gemcitabine was also evaluated. In cell culture, MYXV replication was robust in a broad range of pancreatic cancer cells and also showed increased oncolysis in combination with gemcitabine. In animal models, MYXV treatment conferred survival benefits over control or gemcitabine-treated cohorts regardless of the cell line or animal model used. MYXV monotherapy was most effective in an immunocompetent IPD model, and resulted in 60% long-term survivors. In Pan02 engrafted immunocompetent IPD models, sequential treatment in which MYXV was administered first, followed by gemcitabine, was the most effective and resulted in 100% long-term survivors. MYXV is an effective oncolytic virus for pancreatic cancer and can be combined with gemcitabine to enhance survival, particularly in the presence of an intact host immune system.

  8. Effectiveness and Cost-effectiveness of School-based Dissemination Strategies of an Internet-based Program for the Prevention and Early Intervention in Eating Disorders: A Randomized Trial.

    Science.gov (United States)

    Moessner, Markus; Minarik, Carla; Ozer, Fikret; Bauer, Stephanie

    2016-04-01

    Only little is known about costs and effects (i.e., success) of dissemination strategies, although cost-effective dissemination strategies are crucial for the transfer of interventions into routine care. This study investigates the effects and cost-effectiveness of five school-based dissemination strategies for an Internet-based intervention for the prevention and early intervention of eating disorders. Three-hundred ninety-five schools were randomly assigned to one of five dissemination strategies. Strategies varied with respect to intensity from only sending advertisement materials and asking the school to distribute them among students to organizing presentations and workshops at schools. Effects were defined as the number of page visits, the number of screenings conducted, and the number of registrations to the Internet-based intervention. More expensive strategies proved to be more cost-effective. Cost per page visit ranged from 2.83€ (introductory presentation plus workshop) to 20.37€ (dissemination by student representatives/peers). Costs per screening ranged from 3.30€ (introductory presentation plus workshop) to 75.66€ (dissemination by student representatives/peers), and costs per registration ranged from 6.86€ (introductory presentation plus workshop) to 431.10€ (advertisement materials only). Dissemination of an Internet-based intervention for prevention and early intervention is challenging and expensive. More intense, expensive strategies with personal contact proved to be more cost-effective. The combination of an introductory presentation on eating disorders and a workshop in the high school was most effective and had the best cost-effectiveness ratio. The sole distribution of advertisement materials attracted hardly any participants to the Internet-based program.

  9. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    DEFF Research Database (Denmark)

    Brokken, Leon J S; Lundberg-Giwercman, Yvonne; Rajpert-De Meyts, Ewa

    2013-01-01

    In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing...

  10. Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Specht, L; Larsen, S K; Hansen, H S

    2000-01-01

    Results with docetaxel as single drug in squamous-cell head and neck cancer have been encouraging. The purpose of the present phase II study is to evaluate the antitumour efficacy and toxicity of the combination of docetaxel and cisplatin in patients with recurrent or disseminated squamous...

  11. Disseminated T-cell lymphoma in a Brazilian porcupine (Coendou prehensilis).

    Science.gov (United States)

    de Araújo, Marina Rios; Luppi, Marcela Miranda; Malta, Marcelo de Campos Cordeiro; Assumpção, Anna Luiza Facchetti Vinhaes; Langohr, Ingeborg Maria; Ecco, Roselene

    2011-01-01

    The current study describes the clinical, gross, histopathologic, and immunohistochemical findings of a T-cell lymphoma in a captive porcupine (Coendou prehensilis), a species typically seen in the tropical forests of Brazil. At necropsy, extensive neoplastic involvement was observed in the cervical lymph nodes, with extension into the salivary gland. The spleen was mildly enlarged, and neoplastic nodules were grossly evident in the liver and right kidney. Histologically, sheets of large and markedly pleomorphic round cells were observed in the cervical lymph nodes, lung, liver, spleen, and kidney. The neoplastic cells were positive for cluster of differentiation (CD)3 and negative for CD79a by immunohistochemistry.

  12. Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of pancreatic carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Katrin Hoffmann; Christiane Kerner; Wolfgang Wilfert; Marc Mueller; Joachim Thiery; Johann Hauss; Helmut Witzigmann

    2007-01-01

    AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas.METHODS: Sixty-eight patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non-pancreatic benign surgical diseases (n = 15, control group)were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR.RESULTS: CK-19 mRNA expression was increased in 24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the patients with pancreatic cancer.In 15 (40%) of the patients with pancreatic cancer,disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3). Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis.CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.

  13. Early restriction of alphavirus replication and dissemination contributes to age-dependent attenuation of systemic hyperinflammatory disease.

    Science.gov (United States)

    Ryman, Kate D; Gardner, Christina L; Meier, Kathryn C; Biron, Christine A; Johnston, Robert E; Klimstra, William B

    2007-02-01

    Severity of alphavirus infection in humans tends to be strongly age-dependent and several studies using laboratory-adapted Sindbis virus (SB) AR339 strains have indicated that SB-induced disease in mice is similarly contingent upon host developmental status. In the current studies, the consensus wild-type SB, TR339, and in vivo imaging technology have been utilized to examine virus replication and disease manifestations in mice infected subcutaneously at 5 days of age (5D) vs 11D. Initial virulence studies with TR339 indicated that this age range is coincident with rapid transition from fatal to non-fatal outcome. Fatal infection of 5D mice is characterized by high-titre serum viraemia, extensive virus replication in skin, fibroblast connective tissue, muscle and brain, and hyperinflammatory cytokine induction. In contrast, 11D-infected mice experience more limited virus replication and tissue damage and develop mild, immune-mediated pathologies including encephalitis. These results further establish the linkage between hyperinflammatory cytokine induction and fatal outcome of infection. In vivo imaging using luciferase-expressing viruses and non-propagative replicons revealed that host development results in a restriction of virus replication within individual infected cells that is manifested as a delay in reduction of virus replication in the younger mice. Thus, an important contributing factor in age-dependent resistance to alphavirus infection is restriction of replication within first infected cells in peripheral tissues, which may augment other developmentally regulated attenuating effects, such as increasing neuronal resistance to virus infection and apoptotic death.

  14. Moving Away from Dogmatic Knowledge Dissemination in a Cell Biology Module: Examples from Singapore

    Science.gov (United States)

    Yeong, Foong May

    2012-01-01

    A surge in the amount of information in the discipline of Cell Biology presents a problem to the teaching of undergraduates under time constraints. In most textbooks and during lectures, students in Singapore are often taught in a dogmatic manner where concepts and ideas are expounded to them. The students in turn passively receive the materials…

  15. THE RESPONSE OF DISSEMINATED RETICULUM CELL SARCOMA TO THE INTRAVENOUS INJECTION OF COLLOIDAL RADIOACTIVE GOLD

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Levitt, Seymour H.

    1963-06-15

    Case histories of two patients treated with colloidal radiogold for diffuse reticulum cell sarcoma are presented. Further analysis of the method is suggested by the unusually long survival time of one of the patients. It was concluded that, although external radiotherapy remains the treatment of choice in localized reticulum cell sarcoma, intravenous colloidal radiogold may be a useful agent in lymphosarcomas with diffuse minute neoplastic liver and spleen involvements. Intravenous colloidal radiogold can produce bone marrow depression and thrombocytopenia which can lead to death. This factor tends to argue against therapeutic use of the agent. It is suggested that no more than 50 mC Au/sup 198/ intravenously should be used for treatment of this disease. (R.M.G.)

  16. T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma

    OpenAIRE

    Singh, Nathan; Kulikovskaya, Irina; Barrett, David M.; Binder-Scholl, Gwendolyn; Jakobsen, Bent; Martinez, Daniel; Pawel, Bruce; June, Carl H.; Kalos, Michael D.; Grupp, Stephan A.

    2015-01-01

    The cancer-testis antigen NY-ESO-1 is expressed by many solid tumors and has limited expression by mature somatic tissues, making it a highly attractive target for tumor immunotherapy. Targeting NY-ESO-1 using engineered T cells has demonstrated clinical efficacy in the treatment of some adult tumors. Neuroblastoma is a significant cause of cancer mortality in children, and is a tumor type shown to be responsive to immunotherapies. We evaluated a large panel of primarily resected neuroblastom...

  17. Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YUAN Guang-jin; KE Qin-hua; XU Xi-ming; YANG Ji-yuan; SU Xiao-yan

    2010-01-01

    @@ In February 2005, Gefitinib (Iressa), a small-molecular epidermal growth factor receptor and tyrosine kinase inhibitor, was approved in China as an anticancer agent for patients with advanced (local or metastatic) non-small cell lung cancer (NSCLC), who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.~1

  18. Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Larissa Bubnovskaya

    2014-01-01

    Full Text Available Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs in bone marrow (BM of patients with gastric cancer (GC and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1 expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P<0.024. DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (P<0.0248. Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (P<0.05. Overall survival (OS of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only (P=0.0497. Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.

  19. Cardiac metastasis of squamous cell carcinoma of the thyroid gland with severe disseminated intravascular coagulation: A case report.

    Science.gov (United States)

    Yoshihiro, Tomoyasu; Tsuchihashi, Kenji; Kusaba, Hitoshi; Nakashima, Torahiko; Obara, Teppei; Nio, Kenta; Takayoshi, Kotoe; Kodama, Hiroyuki; Tsuruta, Nobuhiro; Kiyohara, Hideyuki; Asai, Kaori; Harada, Eiji; Kamezaki, Kenjiro; Arita, Takeshi; Sato, Masanobu; Yamamoto, Hidetaka; Arita, Shuji; Ariyama, Hiroshi; Odashiro, Keita; Oda, Yoshinao; Akashi, Koichi; Baba, Eishi

    2017-01-01

    Distant metastasis of primary squamous cell carcinoma (SCC) of the thyroid gland is rare and, to the best of our knowledge, cardiac metastasis has not been reported to date. A 57-year-old man underwent surgery and adjuvant chemoradiotherapy for stage IVA SCC of the thyroid gland. After 3 months, the patient was admitted to the Kyushu University Hospital (Fukuoka, Japan) with subcutaneous hematomas of the left thigh and lower leg, and he was diagnosed with cardiac and mediastinal lymph node metastases of SCC of the thyroid gland with severe disseminated intravascular coagulation (DIC). Echocardiography revealed a mass, 52 mm in greatest diameter, protruding from the interventricular septum towards the right ventricle. Weekly administration of paclitaxel and concurrent irradiation of the cardiac and lymph node metastases were performed. Eighteen days after the initiation of chemoradiotherapy, the DIC and hematomas had significantly improved, and the cardiac metastasis was stable. However, 2 months after admission, the patient developed dyspnea and multiple nodular shadows appeared to be spreading in the subpleura of the lungs bilaterally, which were initially suspected to be pulmonary tumor embolisms. Prednisolone and subsequent administration of lenvatinib were not effective and the patient succumbed to respiratory failure. Severe DIC caused by extremely rare cardiac metastasis of SCC of the thyroid gland was effectively controlled by chemoradiotherapy. However, intensive local control appears to be required for this condition.

  20. Cell fate regulation in early mammalian development

    Science.gov (United States)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  1. Non-native scientists, research dissemination and English neologisms: What happens in the early stages of reception and re-production?

    Directory of Open Access Journals (Sweden)

    Daniel Linder

    2016-11-01

    Full Text Available That the English language is the prevailing language in international scientific discourse is an undeniable fact for research professionals who are non-native speakers of English (NNSE. An exploratory, survey-based study of scientists in the experimental disciplines of neuroscience and medicine seeks to reveal, on the one hand, the habits of scientists who in their research practice come across neologisms in English and need to use them in oral and written scientific discourse in their own languages, and, on the other hand, their attitudes towards these neologisms and towards English as the language of international science. We found that all scientists write and publish their research articles (RAs in English and most submit them unrevised by native speakers of English. When first encountering a neologism in English, scientists tend to pay close attention to these new concepts, ideas or terms and very early in the reception process attempt to coin acceptable, natural-sounding Spanish equivalents for use in the laboratory and in their Spanish texts. In conjunction with the naturalized Spanish term, they often use the English neologism verbatim in a coexistent bilingual form, but they avoid using only the English term and very literal translations. These behaviors show an ambivalent attitude towards English (the language of both new knowledge reception and dissemination of their RAs and Spanish (used for local professional purposes and for popularization: while accepting to write in their acquired non-native language, they simultaneously recognize that their native language needs to preserve its specificity as a language of science.

  2. Complete sequencing of an IncX3 plasmid carrying blaNDM-5 allele reveals an early stage in the dissemination of the blaNDM gene

    Directory of Open Access Journals (Sweden)

    M Krishnaraju

    2015-01-01

    Full Text Available Purpose: The aim of the present study was to perform molecular characterisation of the blaNDM plasmids and to understand the mechanism of its spread among pathogenic bacteria. Materials and Methods: Seventy-six non-repetitive carbapenem-resistant isolates which were collected during Nov 2011 to April 2013 from four hospitals in Chennai were analyzed for the presence of the blaNDM gene by PCR. Further, the genetic context of the blaNDM gene was analyzed by PCR specific to ISAba125 and bleMBL gene. One of the blaNDM plasmid was completely sequenced in the Illumina HiSeq platform. Results: Twenty-three isolates consisting of 8 Escherichia coli, 8 Klebsiella pneumoniae, 3 Klebsiella oxytoca, 3 Acinetobacter baumanii and 1 Pseudomonas aeruginosa were found to carry the blaNDM gene. In 18 isolates the blaNDM gene was associated with a bleMBL gene and the ISAba125 element. The complete sequencing of pNDM-MGR194 revealed an IncX3 replication type plasmid, with a length of 46,253 bp, an average GC content of 47% and 59 putative ORFs. The iteron region contained the blaNDM5 gene and the bleMBL , trpF and dsbC genes downstream and an IS5 inserted within the ISAba125 element upstream. Conclusion: This is the first report where the blaNDM gene insertion in a plasmid is not accompanied by other resistance gene determinants. These observations suggest that the IncX3 plasmid pNDM-MGR194 is an early stage in the dissemination of the blaNDM .

  3. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London Univ. (United Kingdom)

    2010-11-15

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. {sup 211}At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (author)

  4. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London University (United Kingdom)

    2010-07-01

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. {sup 211}At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)

  5. Maternity Disseminated Intravascular Coagulation Early Diagnosis of Clinical Curative Effect Analysis%产科弥漫性血管内凝血早期诊治的临床疗效探析

    Institute of Scientific and Technical Information of China (English)

    陆玲军; 苏敏君

    2013-01-01

    目的:分析探讨产科弥漫性血管内凝血早期诊治的临床效果。方法:选取本院收治的共28例弥漫性血管内凝血患者,根据患者早期诊断标准不同得出的诊断结果分为两组,其中根据一般弥漫性血管内凝血诊断标准诊断出的7例为A组,根据早期弥漫性血管内凝血标准诊断出的21例为B组,根据患者的病情严重性给予相应的治疗,比较两组患者临床效果。结果:A组治愈率为28.57%,B组的治愈率为80.95%,两组相比有明显的差异,B组的治愈率远远高于A组(P<0.05)。结论:根据早期弥漫性血管内凝血标准诊断出的患者可以及时得到治疗,提高治愈率,有效保障患者生命安全。%Objective:To analyze the obstetric disseminated intravascular coagulation of early diagnosis and clinical effect. Methods: Select treated at our hospital, A total of 28 patients with disseminated intravascular coagulation,according to different patients early diagnosis standard of diagnosis is divided into two groups, which according to the general diagnostic criteria diagnosis of disseminated intravascular coagulation of 7 cases of group A, according to the early diagnosis of disseminated intravascular coagulation standard 21 cases in group B, according to the patient's illness severity give corresponding treatment, compared two groups of patients clinical effect. Results:The cure rate of group A was 28.57%, the cure rate of group B was 80.95%, compared two groups have significant difference, the cure rate of group B is higher than group A (P<0.05).Conclusion:According to the early diagnosis of disseminated intravascular coagulation standard patients can receive timely treatment, improve the cure rate, effective guarantee patient safety.

  6. Targeting Tumor Cell Invasion and Dissemination In Vivo by an Aptamer That Inhibits Urokinase-type Plasminogen Activator through a Novel Multifunctional Mechanism

    DEFF Research Database (Denmark)

    Botkjaer, Kenneth A; Deryugina, Elena I; Dupont, Daniel M

    2012-01-01

    , because the topology of the proteases' active sites are highly similar. In an effort to generate highly specific uPA inhibitors with new inhibitory modalities, we isolated uPA-binding RNA aptamers by screening a library of 35 nucleotides long 2'-fluoro-pyrimidine RNA molecules using a version of human pro...... in the chick embryo assay of cell escape from microtumors. Finally, upanap-126 significantly reduced the levels of tumor cell intravasation and dissemination in the chick embryo model of spontaneous metastasis. Together, our findings show that usage of upanap-126 represents a novel multifunctional mechanistic...

  7. Disseminated histoplasmosis (image)

    Science.gov (United States)

    Histoplasmosis is a fungal infection caused by inhaling dust from spore-infected bird droppings. In the disseminated ... fairly high for people with untreated widespread (disseminated) histoplasmosis, but is reduced significantly with treatment.

  8. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  9. Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings

    Directory of Open Access Journals (Sweden)

    Chiofalo Maria

    2012-02-01

    Full Text Available Abstract Background Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis. Case presentation Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml. Discussion and Conclusion Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.

  10. A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

    Directory of Open Access Journals (Sweden)

    Rusudan Okujava

    2014-06-01

    Full Text Available Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs infected with a ΔbepE mutant of B. henselae (Bhe displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID domain of BepEBhe (BID2.EBhe. Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d. model for B. tribocorum (Btr infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we

  11. A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

    Science.gov (United States)

    Okujava, Rusudan; Guye, Patrick; Lu, Yun-Yueh; Mistl, Claudia; Polus, Florine; Vayssier-Taussat, Muriel; Halin, Cornelia; Rolink, Antonius G; Dehio, Christoph

    2014-06-01

    Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps) into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs) infected with a ΔbepE mutant of B. henselae (Bhe) displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID) domain of BepEBhe (BID2.EBhe). Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d.) model for B. tribocorum (Btr) infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we propose that

  12. New mechanism for neural stem cell maintenance in early embryos

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Teamning up with co-workers from Japan, UK and US,CAS biochemists have revealed a novel mechanism for maintaining neural stem cells in early embryos. Their work was published on the 6 August issue of Cell Development.

  13. Data Analysis for ARRA Early Fuel Cell Market Demonstrations (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, J.; Wipke, K.; Sprik, S.; Ramsden, T.

    2010-05-01

    Presentation about ARRA Early Fuel Cell Market Demonstrations, including an overview of the ARRE Fuel Cell Project, the National Renewable Energy Laboratory's data analysis objectives, deployment composite data products, and planned analyses.

  14. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

    Directory of Open Access Journals (Sweden)

    Paola Secchiero

    Full Text Available BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL, significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM mesenchymal stem cells (MSC on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(- Burkitt-type BJAB, median survival = 46 days and an aggressive (EBV(+ B lymphoblastoid SKW6.4, median survival = 27 days behavior in nude-SCID mice. Intra-peritoneal (i.p. injection of MSC (4 days after i.p. injection of lymphoma cells significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days. Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

  15. Myeloma multiplex with pulmonary dissemination

    OpenAIRE

    Terzić Brankica; Maksić Đoko; Škuletić Vesna; Pilčević Dejan; Mijušković Mirjana; Čukić Zoran; Obrenčević Katarina; Petrović Marijana; Tadić-Pilčević Jelena; Petrović Milica

    2014-01-01

    Introduction. Multiple myeloma is a hemathological malignancy characterized by the clonal proliferation of plasma cells in the bone the marrow. Extramedullary dissemination of multiple myeloma is uncommon. In several cases only, the multiple myeloma malignant plasma cells had diseminated to the lung parenchyma. Case report. We presented a case of multiple myeloma with lung plasmacytoma, in a 79-year-old patient, hospitalized for febrility and infiltrative m...

  16. Metronomic chemotherapy following the maximum tolerated dose is an effective anti-tumour therapy affecting angiogenesis, tumour dissemination and cancer stem cells.

    Science.gov (United States)

    Vives, Marta; Ginestà, Mireia M; Gracova, Kristina; Graupera, Mariona; Casanovas, Oriol; Capellà, Gabriel; Serrano, Teresa; Laquente, Berta; Viñals, Francesc

    2013-11-15

    In this article, the effectiveness of a multi-targeted chemo-switch (C-S) schedule that combines metronomic chemotherapy (MET) after treatment with the maximum tolerated dose (MTD) is reported. This schedule was tested with gemcitabine in two distinct human pancreatic adenocarcinoma orthotopic models and with cyclophosphamide in an orthotopic ovarian cancer model. In both models, the C-S schedule had the most favourable effect, achieving at least 80% tumour growth inhibition without increased toxicity. Moreover, in the pancreatic cancer model, although peritoneal metastases were observed in control and MTD groups, no dissemination was observed in the MET and C-S groups. C-S treatment caused a decrease in angiogenesis, and its effect on tumour growth was similar to that produced by the MTD followed by anti-angiogenic DC101 treatment. C-S treatment combined an increase in thrombospondin-1 expression with a decrease in the number of CD133+ cancer cells and triple-positive CD133+/CD44+/CD24+ cancer stem cells (CSCs). These findings confirm that the C-S schedule is a challenging clinical strategy with demonstrable inhibitory effects on tumour dissemination, angiogenesis and CSCs.

  17. Dissemination Strategy Report

    DEFF Research Database (Denmark)

    Badger, Merete; Kjems, Jørgen; Farinetti, Laura;

    This report describes the dissemination and exploitation strategy for project Virtual Campus Hub (EU FP7 contract RI-283746). The project duration is October 2011-13 and the dissemination and exploitation plan will be revised continuously during the project’s lifecycle.......This report describes the dissemination and exploitation strategy for project Virtual Campus Hub (EU FP7 contract RI-283746). The project duration is October 2011-13 and the dissemination and exploitation plan will be revised continuously during the project’s lifecycle....

  18. Disseminated Herpes Zoster in Association with HIV

    Directory of Open Access Journals (Sweden)

    Kuchabal D

    2000-01-01

    Full Text Available HIV infected individuals are susceptible to a wide variety of skin manifestations due to profound defect in cell-mediated immunity. We describe 2 patients with Disseminated Herpes Zoster, both the patients has associated HIV infection.

  19. The early history of B cells.

    Science.gov (United States)

    Cooper, Max D

    2015-03-01

    The separate development of functionally intertwined lineages of lymphocytes known as B cells and T cells is now recognized as a fundamental organizing principle of the adaptive immune system in all vertebrates. Immunologists strive to define the different sublineages of the clonally diverse B cells and T cells, how they interact with each other and how they interact with innate lymphoid cells and other elements of the innate immune system to counter infections, cancer and the development of autoimmune and inflammatory diseases. On the 50th anniversary of the recognition of B cells as a discrete cell lineage, this Timeline article recounts some of the milestones marking the development of the concept that B cells are a functionally and developmentally distinct arm of the adaptive immune system.

  20. DNA breaks early in replication in B cell cancers

    Science.gov (United States)

    Research by scientists at the NCI has identified a new class of DNA sites in cells that break early in the replication process. They found that these break sites correlate with damage often seen in B cell cancers, such as diffuse large B cell lymphoma.

  1. Intracranial germinoma with ventricular system dissemination

    Directory of Open Access Journals (Sweden)

    Shi-yun CHEN

    2014-05-01

    Full Text Available Objective To study the clinical, neuroimaging and histopathological features of intracranial germinoma.  Methods One case of intracranial germinoma with ventricular system dissemination was reported, and related literatures were reviewed.  Results A 34-year-old male complained of progressive dizziness for 30 d and manifested unsteady gait for 45 d. Radiological examinations revealed low signal intensity on T1WI and hyperintense on T2WI in the corpus callosum, left cerebellum, around the fourth ventricle, aqueduct mesencephalon, the ventral pons and pineal region, with even or uneven enhancement after contrast. The clinical initial diagnosis was "intracranial multiple focal lesions and high possibility of multiple sclerosis". After well response to glucocorticoid impact and dehydration, the patient stopped taking drugs but presented relapse and exacerbation. Later, he underwent biopsy on pineal region and was diagnosed as intracranial germinoma. Microscopically, the big germ cells and lymphocytes coexisted. Tumor cells were epithelioid cells with transparent cytoplasm, prominent nuclei and mitotic activity. Lymphocytes were distributed along interstitial substance of vessel and fiber, and individual syncytiotrophoblasts were sprasely distributed. Immunohistochemical staining showed tumor cells were positive for CD117 and OCT3/4, and the syncytiotrophoblasts were positive for β-human chorionic gonadotropin ( β-hCG. The clinical symptoms were completely alleviated after radiotherapy and chemotherapy.  Conclusions Because of the sensitivity for radiotherapy and chemotherapy, intracranial germinoma can be diagnosed and treated early to improve its prognosis. However, it is very easy to disseminate along with ventricular system and form multiple lesions, leading to atypical clinical and imaging manifestations, which is a big challenge for clinical diagnosis. doi: 10.3969/j.issn.1672-6731.2014.05.010

  2. Oxidative stress tolerance of early stage diabetic endothelial progenitor cell

    Directory of Open Access Journals (Sweden)

    Dewi Sukmawati

    2015-06-01

    Conclusions: Primitive BM-EPCs showed vasculogenic dysfunction in early diabetes. However the oxidative stress is not denoted as the major initiating factor of its cause. Our results suggest that primitive BM-KSL cell has the ability to compensate oxidative stress levels in early diabetes by increasing the expression of anti-oxidative enzymes.

  3. Hippocampal granule cells opt for early retirement.

    Science.gov (United States)

    Alme, C B; Buzzetti, R A; Marrone, D F; Leutgeb, J K; Chawla, M K; Schaner, M J; Bohanick, J D; Khoboko, T; Leutgeb, S; Moser, E I; Moser, M-B; McNaughton, B L; Barnes, C A

    2010-10-01

    Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of

  4. A prominent role for DC-SIGN+ dendritic cells in initiation and dissemination of measles virus infection in non-human primates.

    Directory of Open Access Journals (Sweden)

    Annelies W Mesman

    Full Text Available Measles virus (MV is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150(+ T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGN(hi DCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGN(hi cells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection.

  5. Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Specht, L; Larsen, S K; Hansen, H S

    2000-01-01

    BACKGROUND: Results with docetaxel as single drug in squamous-cell head and neck cancer have been encouraging. The purpose of the present phase II study is to evaluate the antitumour efficacy and toxicity of the combination of docetaxel and cisplatin in patients with recurrent or disseminated......; no previous systemic chemotherapy (prior radiotherapy and/or surgery were allowed), no other previous or concurrent malignancy; no peripheral neuropathy. Treatment consisted of docetaxel 75 mg/m2 in a one-hour infusion after pre-treatment with prednisolone, followed by cisplatin 75 mg/m2 in a half...... but one patient. Grade 3 neuropathy occurred in one patient, none had grade 4. Grade 3 oral mucositis occurred in three patients, none had grade 4. Grade 2-3 hypomagnesaemia occurred in 10 patients requiring magnesium infusion. CONCLUSIONS: Docetaxel and cisplatin is an active combination in patients...

  6. Early cell death detection with digital holographic microscopy.

    Directory of Open Access Journals (Sweden)

    Nicolas Pavillon

    Full Text Available BACKGROUND: Digital holography provides a non-invasive measurement of the quantitative phase shifts induced by cells in culture, which can be related to cell volume changes. It has been shown previously that regulation of cell volume, in particular as it relates to ionic homeostasis, is crucially involved in the activation/inactivation of the cell death processes. We thus present here an application of digital holographic microscopy (DHM dedicated to early and label-free detection of cell death. METHODS AND FINDINGS: We provide quantitative measurements of phase signal obtained on mouse cortical neurons, and caused by early neuronal cell volume regulation triggered by excitotoxic concentrations of L-glutamate. We show that the efficiency of this early regulation of cell volume detected by DHM, is correlated with the occurrence of subsequent neuronal death assessed with the widely accepted trypan blue method for detection of cell viability. CONCLUSIONS: The determination of the phase signal by DHM provides a simple and rapid optical method for the early detection of cell death.

  7. Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC® is a predictor for relapse: A preliminary report

    Directory of Open Access Journals (Sweden)

    Höffken Klaus

    2005-03-01

    Full Text Available Abstract Background Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery. Methods 30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT chemotherapy (CT or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC® for quantification of these cells. Results In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21 whereas pneumonectomy led to a decrease (5/8 of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase. In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia

  8. CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

    Directory of Open Access Journals (Sweden)

    Dmitry Osinsky

    2015-01-01

    Full Text Available Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC and bone marrow (BM with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (P<0.05, VEGF expression (P<0.01, and gelatinases activity (P<0.05. CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs. Overall survival (OS of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (P=0.037. The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (P<0.05. CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with M0 category and with both CXCR4-positive BM and DTCs (P=0.03. Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs.

  9. A new approach to the pathomechanism of amniotic fluid embolism:unknown role of amniotic cells in the induction of disseminated intravascular coagulation

    Institute of Scientific and Technical Information of China (English)

    Mieczyslaw Uszyński; Waldemar Uszyński

    2012-01-01

    There are four concepts (theories) of amniotic fluid embolism (AFE). The aim of the study was to perform their critical review and to popularize a novel integrated concept. We searched Medline (from its inception to 2011), using key words:amniotic fluid embolism, amniotic cells, tissue factor, leukotriene and microparticles. Articles most eligible for the study of etiopathomechanism of AFE were chosen by title and/or abstract contents. The analysis of the publications revealed that:(i) the integrated concept of AFE is an adequate tool to interpret the complication, being particularly useful for taking direct therapeutic decisions; (ii) disseminated intravascular coagulation (DIC) in this complication is induced not by tissue factor (TF) of amniotic origin but by spectacular procoagulant activity of apoptosis-affected amniotic cells. Descriptions of molecular processes were provided. In clonclusioin, there are two independent pathways of AFE-the DIC pathway and the leukotriene pathway. It is not the TF but the apoptosis-affected amniotic cells that are responsible for the process of DIC in AFE. 3. One of the therapeutic conclusions of the new approach to the concept of AFE indicates that attempts to use heparin in AFE are justified (at the onset of the complication).

  10. Circumventing Therapeutic Resistance and the Emergence of Disseminated Breast Cancer Cells Through Non-Invasive Optical Imaging

    Science.gov (United States)

    2015-06-01

    has previously used FNB-based chemistry to successfully functionalize NIREPs with the cell-penetrating Tat peptide for tracking dendritic cells...chromophore absorbs at 428 nm (Scheme 1).19 Presence of the peptide did not adversely affect the resulting polymersome morphology. We have adapted this...will delay or halt the development of drug resistance, drastically improving patient survival and remission rates. Importantly, we expect this

  11. Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.

    Directory of Open Access Journals (Sweden)

    Alyssa D Flora

    Full Text Available Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.

  12. Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.

    Science.gov (United States)

    Flora, Alyssa D; Teel, Louise D; Smith, Mark A; Sinclair, James F; Melton-Celsa, Angela R; O'Brien, Alison D

    2013-01-01

    Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.

  13. A color discriminating broad range cell staining technology for early detection of cell transformation

    Directory of Open Access Journals (Sweden)

    Sagiv Idit

    2009-01-01

    Full Text Available Background: Advanced diagnostic tools stand today at the heart of successful cancer treatment. CellDetect® is a new histochemical staining technology that enables color discrimination between normal cells and a wide variety of neoplastic tissues. Using this technology, normal cells are colored blue/green, while neoplastic cells color red. This tinctorial difference coincides with clear morphological visualization properties, mainly in tissue samples. Here we show that the CellDetect® technology can be deployed to distinguish normal cells from transformed cells and most significantly detect cells in their early pre-cancerous transformed state. Materials and Methods: In tissue culture, we studied the ability of the CellDetect® technology to color discriminate foci in a number of two stage transformation systems as well as in a well defined cellular model for cervical cancer development, using HPV16 transformed keratinocytes. Results: In all these cellular systems, the CellDetect® technology was able to sensitively show that all transformed cells, including pre-cancerous HPV 16 transformed cells, are colored red, whereas normal cells are colored blue/green. The staining technology was able to pick up: (i early transformation events in the form of small type 1 foci (non-invasive, not piled up small, with parallel alignment of cells, and (ii early HPV16 transformed cells, even prior to their ability to form colonies in soft agar. The study shows the utility of the CellDetect® technology in early detection of transformation events.

  14. Critical early events in hematopoietic cell seeding and engraftment.

    OpenAIRE

    Jerry Stein; Isaac Yaniv; Nadir Askenasy

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic ce...

  15. Hydrolyzed infant formula and early β-cell autoimmunity

    DEFF Research Database (Denmark)

    Knip, Mikael; Åkerblom, Hans K; Becker, Dorothy

    2014-01-01

    IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain ...

  16. Dissemination and Exploitation Strategy

    DEFF Research Database (Denmark)

    Badger, Merete; Monaco, Lucio; Fransson, Torsten

    of Technology in Sweden, Politecnico di Torino in Italy, and Eindhoven University of Technology in the Netherlands. The project is partially funded by the European Commission under the 7th Framework Programme (project no. RI-283746). This report describes the final dissemination and exploitation strategy...

  17. The Effects of Microwave Ablation and Surgical Resection on Hematogenous Dissemination of Cancer Cells in Treating Patients with Small Primary Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chaoyang Wen; Baowei Dong; Ping Liang; Xiaoling Yu; Li Su; Dejiang Yu; Hongtian Xia

    2006-01-01

    OBJECTIVE To conduct a comparative study of the effects of treatment using microwave ablation versus surgical resection on hematogenous dissemination of cancer cells, and on the level of immune cells of the peripheral blood in patients with small primary hepatocellular carcinoma (PHC, ≤5 cm).METHODS Forty patients with small PHC (maximal diameter ≤5 cm) were divided into a microwave group (19 cases) and a surgical operation group (21 cases). A real-time (RT) quantitative nested RT-PCR examination was performed for peripheral blood alpha-fetoprotein (AFP) mRNA. Studies were conducted to determine the level of CD3, CD4, CD8 and CD4/CD8 cells and for liver function at 30 min before, and 30 min,1 day and 3 days after the treatment.RESULTS Compared to the value before ablation, no obvious changes of CD3, CD4, CD8 and CD4/CD8 cells were found in patients of the microwave group within 7 days after ablation, but CD3, CD4 and CD4/CD8 cells in the operation group were lower compared to that before operatioh. The copy number of AFP mRNA in the peripheral blood samples of the patients of the 2 groups before operation was determined in 67.5% of the patients (27/40). There was an rise in the expression after treatment but no statistical difference was found in comparing the 2 groups. Follow-up of the patients was conducted for 1 to 16 months. For patients with continuous expression of peripheral blood AFP mRNA, the possibility of relapse and metastasis was increased.CONCLUSION Surgical resection or microwave ablation can cause more exfoliation of hepatoma carcinoma cells in the peripheral blood of patients with small PHC. The immune function of peripheral blood cells decreased in the patients after surgical resection, however, the immune function was better protected following microwave ablation. Microwave ablation causes minor reduction in liver function, and the treatment method presents a definite value for PHC therapy.

  18. Critical early events in hematopoietic cell seeding and engraftment.

    Directory of Open Access Journals (Sweden)

    Jerry Stein

    2005-12-01

    Full Text Available Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  19. Critical early events in hematopoietic cell seeding and engraftment.

    Science.gov (United States)

    Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  20. Endemicity and phylogeny of the human T cell lymphotropic virus type II subtype A from the Kayapo Indians of Brazil: evidence for limited regional dissemination.

    Science.gov (United States)

    Switzer, W M; Black, F L; Pieniazek, D; Biggar, R J; Lal, R B; Heneine, W

    1996-05-01

    Long terminal repeat (LTR)-based restriction fragment length polymorphism (RFLP) analysis of human T cell lymphotropic virus type II (HTLV-II) from 17 seropositive Kayapo Indians from Brazil showed that all 17 samples contained a unique HTLV-IIa subtype (A-II). Additional RFLP screening demonstrated the presence of this subtype in two of three Brazilian blood donors and a Mexican prostitute and her child. In contrast, 129 samples from blood donors and intravenous drug users (IDUs) from the United States, two Pueblo Indian samples, five samples from Norwegian IDUs, and two samples from blood donors from Denmark were all found to be a different HTLV-IIa subtype (A-III). Phylogenetic analysis of two Kayapo and one Mexican LTR sequences showed that they cluster with a subtype A-II sequence from a Brazilian blood donor and with sequences from two prostitutes from Ghana and Cameroon. These results demonstrate that infection with the A-II subtype is endemic among the Kayapo Amerindians, has disseminated to non-Indian populations in Brazil, and is also present in Mexico. Furthermore, the A-II subtype does not appear to represent an origin for the HTLV-IIa infection in urban areas of the United States and Europe. This study provides evidence that HTLV-IIa may be a Paleo-Indian subtype as previously suggested for HTLV-IIb.

  1. TGFβ2 dictates disseminated tumour cell fate in target organs through TGFβ-RIII and p38α/β signalling

    Science.gov (United States)

    Bragado, Paloma; Estrada, Yeriel; Parikh, Falguni; Krause, Sarah; Capobianco, Carla; Farina, Hernan G.; Schewe, Denis M; Aguirre-Ghiso, Julio A.

    2013-01-01

    In patients non-proliferative disseminated tumour cells (DTCs) can persist in the bone marrow (BM) while other organs (i.e. lung) present growing metastasis. This suggested that the BM might be a metastasis “restrictive soil” by encoding dormancy-inducing cues in DTCs. Here we show in a HNSCC model that strong and specific TGFβ2 signalling in the BM activates p38α/β, inducing a [ERK/p38]low signalling ratio. This results in induction of DEC2/SHARP1 and p27, downregulation of CDK4 and dormancy of malignant DTCs. TGFβ2-induced dormancy required TGFβ-receptor-I, TGFβ-receptor-III and SMAD1/5 activation to induce p27. In lungs, a metastasis “permissive soil” with low TGFβ2 levels, DTC dormancy was short lived and followed by metastatic growth. Importantly, systemic inhibition of TGFβ-receptor-I or p38α/β activities awakened dormant DTCs fueling multi-organ metastasis. Our work reveals a “seed and soil” mechanism where TGFβ2 and TGFβRIII signalling through p38α/β regulates DTC dormancy and defines restrictive (BM) and -permissive (lung) microenvironments for HNSCC metastasis. PMID:24161934

  2. A naturally occurring single nucleotide polymorphism in the Salmonella SPI-2 type III effector srfH/sseI controls early extraintestinal dissemination.

    Directory of Open Access Journals (Sweden)

    Joshua M Thornbrough

    Full Text Available CD18 expressing phagocytes associated with the gastro-intestinal (GI epithelium can shuttle Salmonella directly into the bloodstream within a few minutes following microbial ingestion. We have previously demonstrated that Salmonella controls the CD18 pathway to deeper tissue, manipulating the migratory properties of infected cells as an unappreciated component of its pathogenesis. We have observed that one type III effector, SrfH (also called SseI that Salmonella secretes into infected phagocytes manipulates the host protein TRIP6 to stimulate their migration. Paradoxically, SrfH was shown in another study to subvert a different host protein, IQGAP1, in a manner that inhibits the productive motility of such cells, perhaps to avoid interactions with T cells. Here, we resolve the discrepancy. We report that one naturally occurring allele of srfH promotes the migration of infected phagocytes into the bloodstream, while another naturally occurring allele that differs by only a single nucleotide polymorphism (SNP does not. This SNP determines if the protein contains an aspartic acid or a glycine residue at position 103 and may determine if SrfH binds TRIP6. SrfH Gly103 is a rare allele, but is present in the highly invasive strain Salmonella enterica serovar Typhimurium UK-1 (stands for universal killer. It is also present in the genome of the only sequenced strain belonging to the emerging pandemic Salmonella enterica serovar 4, [5],12,i:-, which is frequently associated with septicemia. Finally, we present evidence that suggests that Gifsy-2, the bacteriophage upon which srfH resides, is present in a clinical isolate of the human-specific pathogen, Salmonella enterica serovar Typhi. These observations may have interesting implications for our understanding of Salmonella pathogenesis.

  3. Dataset of transcriptional landscape of B cell early activation

    Directory of Open Access Journals (Sweden)

    Alexander S. Garruss

    2015-09-01

    Full Text Available Signaling via B cell receptors (BCR and Toll-like receptors (TLRs result in activation of B cells with distinct physiological outcomes, but transcriptional regulatory mechanisms that drive activation and distinguish these pathways remain unknown. At early time points after BCR and TLR ligand exposure, 0.5 and 2 h, RNA-seq was performed allowing observations on rapid transcriptional changes. At 2 h, ChIP-seq was performed to allow observations on important regulatory mechanisms potentially driving transcriptional change. The dataset includes RNA-seq, ChIP-seq of control (Input, RNA Pol II, H3K4me3, H3K27me3, and a separate RNA-seq for miRNA expression, which can be found at Gene Expression Omnibus Dataset GSE61608. Here, we provide details on the experimental and analysis methods used to obtain and analyze this dataset and to examine the transcriptional landscape of B cell early activation.

  4. Early specification of dopaminergic phenotype during ES cell differentiation

    Directory of Open Access Journals (Sweden)

    Li Meng

    2007-07-01

    Full Text Available Abstract Background Understanding how lineage choices are made during embryonic stem (ES cell differentiation is critical for harnessing strategies for controlled production of therapeutic somatic cell types for cell transplantation and pharmaceutical drug screens. The in vitro generation of dopaminergic neurons, the type of cells lost in Parkinson's disease patients' brains, requires the inductive molecules sonic hedgehog and FGF8, or an unknown stromal cell derived inducing activity (SDIA. However, the exact identity of the responding cells and the timing of inductive activity that specify a dopaminergic fate in neural stem/progenitors still remain elusive. Results Using ES cells carrying a neuroepithelial cell specific vital reporter (Sox1-GFP and FACS purification of Sox1-GFP neural progenitors, we have investigated the temporal aspect of SDIA mediated dopaminergic neuron specification during ES cell differentiation. Our results establish that SDIA induces a dopaminergic neuron fate in nascent neural stem or progenitor cells at, or prior to, Sox1 expression and does not appear to have further instructive role or neurotrophic activity during late neuronal differentiation of neural precursors. Furthermore, we show that dopaminergic neurons could be produced efficiently in a monolayer differentiation paradigm independent of SDIA activity or exogenous signalling molecules. In this case, the competence for dopaminergic neuron differentiation is also established at the level of Sox1 expression. Conclusion Dopaminergic neurons are specified early during mouse ES cell differentiation. The subtype specification seems to be tightly linked with the acquisition of a pan neuroectoderm fate.

  5. Myeloma multiplex with pulmonary dissemination

    Directory of Open Access Journals (Sweden)

    Terzić Brankica

    2014-01-01

    Full Text Available Introduction. Multiple myeloma is a hemathological malignancy characterized by the clonal proliferation of plasma cells in the bone the marrow. Extramedullary dissemination of multiple myeloma is uncommon. In several cases only, the multiple myeloma malignant plasma cells had diseminated to the lung parenchyma. Case report. We presented a case of multiple myeloma with lung plasmacytoma, in a 79-year-old patient, hospitalized for febrility and infiltrative mass in the right lung. Two months before the patient was admitted, because of developing terminal renal failure, hemodialysis treatment had started three times a week. Since then, the patient was oliguric, but because of febrility and hemoptysis that appeared, at first he was treated with dual antibiotic therapy which resulted in temporary improvement of his general condition, but pleural effusion remained. After thoracocentesis, followed by myelogram, the multiple myeloma diagnosis was established. Conclusion. In patients of middle and older age, with general weakness, exhaustion, loss of weight, renal failure which progresses to the end stage rapidly, if symptoms of respiratory tract occur, consider this uncommon disease - extramedullary dissemination of multiple myeloma.

  6. Obstetrical disseminated intravascular coagulation score.

    Science.gov (United States)

    Kobayashi, Takao

    2014-06-01

    Obstetrical disseminated intravascular coagulation (DIC) is usually a very acute, serious complication of pregnancy. The obstetrical DIC score helps with making a prompt diagnosis and starting treatment early. This DIC score, in which higher scores are given for clinical parameters rather than for laboratory parameters, has three components: (i) the underlying diseases; (ii) the clinical symptoms; and (iii) the laboratory findings (coagulation tests). It is justifiably appropriate to initiate therapy for DIC when the obstetrical DIC score reaches 8 points or more before obtaining the results of coagulation tests. Improvement of blood coagulation tests and clinical symptoms are essential to the efficacy evaluation for treatment after a diagnosis of obstetrical DIC. Therefore, the efficacy evaluation criteria for obstetrical DIC are also defined to enable follow-up of the clinical efficacy of DIC therapy.

  7. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.

    OpenAIRE

    Nagy, A.; Rossant, J.; Nagy, R.; Abramow-Newerly, W; Roder, J C

    1993-01-01

    Several newly generated mouse embryonic stem (ES) cell lines were tested for their ability to produce completely ES cell-derived mice at early passage numbers by ES cell tetraploid embryo aggregation. One line, designated R1, produced live offspring which were completely ES cell-derived as judged by isoenzyme analysis and coat color. These cell culture-derived animals were normal, viable, and fertile. However, prolonged in vitro culture negatively affected this initial totipotency of R1, and...

  8. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  9. Developing an Effective Dissemination Plan.

    Science.gov (United States)

    Southwest Educational Development Laboratory, Austin, TX. National Center for the Dissemination of Disability Research.

    This booklet offers guidelines for the development of dissemination strategies, especially those concerned with research and programs. Individual sections address: the importance of including sound dissemination plans in grant proposals, factors found to be closely related to information utilization in the dissemination process, a philosophical…

  10. Disseminating Service Registry Records

    OpenAIRE

    A. Apps

    2006-01-01

    The JISC Information Environment Service Registry (IESR) contains descriptions of collections of resources available to researchers, learners and teachers in the UK, along with technical service access details. This paper describes the data model and metadata description schema of IESR, and the services IESR provides to disseminate its records. There is a particular focus on the Open Archives Initiative Protocol for Metadata Harvesting (OAI-PMH) interface, including a possible use scenario. I...

  11. Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model

    Institute of Scientific and Technical Information of China (English)

    WANG Biao; WU Shu-ming; WANG Tao; LIU Kai; ZHANG Gong; ZHANG Xi-quan; YU Jian-hua; LIU Chuan-zhen; FANG Chang-cun

    2012-01-01

    Background Bacterial lipopolysaccharide (LPS) can activate immunological cells to secrete various proinflammatory cytokines involved in the pathophysiological process of disseminated intravascular coagulation (DIC) during infection.In recent years,it has been found that bone marrow-derived mesenchymal stem cells (BMSCs) can affect the activity of these immune cells and regulate the secretion of proinflammatory cytokines.Here,we report the possible protective effect of BMSCs pre-treatment in LPS-induced DIC rat model and the mechanism.Methods Forty-eight adult male rats were divided into five experimental groups and one control group with eight animals in each group.In the treatment groups,0,1×106,2×106,3×106,and 5×106 of BMSCs were injected intravenously for 3 days before LPS injection,while the control group was treated with pure cell culture medium injection.Then,the LPS (3 mg/kg) was injected via the tail vein in the treatment groups,while the control group received 0.9% NaCl.Blood was withdrawn before and 4 and 8 hours after LPS administration.The following parameters were monitored:platelets (PLT),fibrinogen (Fib),D-dimer (D-D),activated partial thromboplastin time (APTT),prothrombin time (PT),tumor necrosis factor-o (TNF-α),interferon-γ (IFN-γ),interleukin-1β (IL-1β),creatinine (Cr),alanine aminotransferase (ALT),creatinine kinase-MB (CK-MB),and endothelin (ET).Results Compared with the control group,a significant change of coagulation parameters were found in the experimental groups.The plasma level of the inflammatory mediator (TNF-α,IFN-γ,IL-1β),organ indicator (Cr,ALT,and CK-MB),and ET in the experimental groups were much lower (P <0.05) than that in the control group.Furthermore,some of these effects were dose-dependent; the statistical comparison of the plasma levels between the groups (from group 2 to group 5) showed a significant difference (P<0.05),except the ALT and CK-MB levels (P>0.05).Conclusion Pre-treatment with BMSCs can

  12. Adenocarcinoma ex-goblet cell carcinoid (appendiceal-type crypt cell adenocarcinoma) is a morphologically distinct entity with highly aggressive behavior and frequent association with peritoneal/intra-abdominal dissemination: an analysis of 77 cases.

    Science.gov (United States)

    Reid, Michelle D; Basturk, Olca; Shaib, Walid L; Xue, Yue; Balci, Serdar; Choi, Hye-Jeong; Akkas, Gizem; Memis, Bahar; Robinson, Brian S; El-Rayes, Bassel F; Staley, Charles A; Staley, Christopher A; Winer, Joshua H; Russell, Maria C; Knight, Jessica H; Goodman, Michael; Krasinskas, Alyssa M; Adsay, Volkan

    2016-10-01

    High-grade versions of appendiceal goblet cell carcinoids ('adenocarcinoma ex-goblet cell carcinoids') are poorly characterized. We herein document 77 examples. Tumors occurred predominantly in females (74%), mean age 55 years (29-84), most with disseminated abdominal (77% peritoneal, 58% gynecologic tract involvement) and stage IV (65%) disease. Many presented to gynecologic oncologists, and nine had a working diagnosis of ovarian carcinoma. Metastases to liver (n=3) and lung (n=1) were uncommon and none arose in adenomatous lesions. Tumors had various histologic patterns, in variable combinations, most of which were fairly specific, making them recognizable as appendiceal in origin, even at metastatic sites: I: Ordinary goblet cell carcinoid/crypt pattern (rounded, non-luminal acini with well-oriented goblet cells), in variable amounts in all cases. II: Poorly cohesive goblet cell pattern (diffusely infiltrative cords/single files of signet ring-like/goblet cells). III: Poorly cohesive non-mucinous cell (diffuse-infiltrative growth of non-mucinous cells). IV: Microglandular (rosette-like glandular) pattern without goblet cells. V: Mixed 'other' carcinoma foci (including ordinary intestinal/mucinous). VI: goblet cell carcinoid pattern with high-grade morphology (marked nuclear atypia). VII: Solid sheet-like pattern punctuated by goblet cells/microglandular units. Ordinary nested/trabecular ('carcinoid pattern') was very uncommon. In total, 33(52%) died of disease, with median overall survival 38 months and 5-year survival 32%. On multivariate analysis perineural invasion and younger age (tumor progression. In conclusion, 'adenocarcinoma ex-goblet cell carcinoid' is an appendix-specific, high-grade malignant neoplasm with distinctive morphology that is recognizable at metastatic sites and recapitulates crypt cells (appendiceal crypt cell adenocarcinoma). Unlike intestinal-type adenocarcinoma, it occurs predominantly in women, is disguised as gynecologic malignancy

  13. [Progress in early pancreas development and reprogramming of terminally differentiated cells into β cells].

    Science.gov (United States)

    Mingjun, Cao; Huansheng, Dong; Qingjie, Pan; Hongjun, Wang; Xiao, Dong

    2014-06-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the immune system attacks insulin-secreting β cells, thus leading to an absolute deficiency of insulin. Patients must rely on exogenous insulin, which cannot effectively prevent diabetes complications. Generation of insulin-secreting cells by reprogramming of pluripotent stem cells or somatic cells is a potential approach for the treatment of T1DM. These cells can be used for cell therapy and drug screening, and may eventually provide a cure for the disease. Significant progress has been made in generating insulin-secreting cells through the expression of β cell specific transcription factors in stem cells or somatic cells. In this review, we summarize recent research progress in early pancreas development, β cell specific transcription factors and reprogramming of terminally differentiated cells into β cells.

  14. The molecular biology of rotaviruses X: intercellular dissemination of rotavirus NSP4 requires glycosylation and is mediated by direct cell-cell contact through cytoplasmic extrusions.

    Science.gov (United States)

    Yang, Weiming; McCrae, Malcolm A

    2012-02-01

    The effect of expressing the NSP4 protein of group A rotaviruses in cells has been studied. It led to the rapid appearance of long cytoplasmic extrusions, which, through site-directed mutagenesis of the N-linked glycosylation sites near the amino terminus of the protein, were shown to be dependent on its ability to become fully glycosylated. Real-time confocal microscopy was used to follow the appearance of similar cytoplasmic extrusions in virus-infected cells and revealed them to grow at a rate of ~2 microns/min to more than three cell diameters and to have a lifespan of 30-60 minutes. CellTracker dyes were used to label cell populations and facilitate the monitoring of the transfer of cytoplasm from virus-infected to surrounding uninfected cells through cytoplasmic extrusions that broke down to vesicles, seen both on the surface of and within uninfected cells in mixed cell populations. Staining of these tagged cell mixtures with monospecific antibody to NSP4 revealed the presence of the protein on uninfected cells, suggesting that the cytoplasmic extrusions formed by virus-infected cells facilitates the direct cell-cell spread of NSP4. This direct cell-cell transfer of infected cell material triggered by expression of glycosylated NSP4 in virus-infected cells may contribute to viral pathogenesis and facilitate host invasion by rotaviruses.

  15. Hydrogen Storage Needs for Early Motive Fuel Cell Markets

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, J.; Ainscough, C.; Simpson, L.; Caton, M.

    2012-11-01

    The National Renewable Energy Laboratory's (NREL) objective for this project is to identify performance needs for onboard energy storage of early motive fuel cell markets by working with end users, manufacturers, and experts. The performance needs analysis is combined with a hydrogen storage technology gap analysis to provide the U.S. Department of Energy (DOE) Fuel Cell Technologies Program with information about the needs and gaps that can be used to focus research and development activities that are capable of supporting market growth.

  16. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...... through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP...... family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study...

  17. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kwon Joong Yong

    2016-05-01

    Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

  18. Transcriptome analysis of mouse stem cells and early embryos.

    Directory of Open Access Journals (Sweden)

    Alexei A Sharov

    2003-12-01

    Full Text Available Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine.

  19. Transcriptome Analysis of Mouse Stem Cells and Early Embryos

    Science.gov (United States)

    Sharov, Alexei A; Piao, Yulan; Matoba, Ryo; Dudekula, Dawood B; Qian, Yong; VanBuren, Vincent; Falco, Geppino; Martin, Patrick R; Stagg, Carole A; Bassey, Uwem C; Wang, Yuxia; Carter, Mark G; Hamatani, Toshio; Aiba, Kazuhiro; Akutsu, Hidenori; Sharova, Lioudmila; Tanaka, Tetsuya S; Kimber, Wendy L; Yoshikawa, Toshiyuki; Jaradat, Saied A; Pantano, Serafino; Nagaraja, Ramaiah; Boheler, Kenneth R; Taub, Dennis; Hodes, Richard J; Longo, Dan L; Schlessinger, David; Keller, Jonathan; Klotz, Emily; Kelsoe, Garnett; Umezawa, Akihiro; Vescovi, Angelo L; Rossant, Janet; Kunath, Tilo; Hogan, Brigid L. M; Curci, Anna; D'Urso, Michele; Kelso, Janet; Hide, Winston

    2003-01-01

    Understanding and harnessing cellular potency are fundamental in biology and are also critical to the future therapeutic use of stem cells. Transcriptome analysis of these pluripotent cells is a first step towards such goals. Starting with sources that include oocytes, blastocysts, and embryonic and adult stem cells, we obtained 249,200 high-quality EST sequences and clustered them with public sequences to produce an index of approximately 30,000 total mouse genes that includes 977 previously unidentified genes. Analysis of gene expression levels by EST frequency identifies genes that characterize preimplantation embryos, embryonic stem cells, and adult stem cells, thus providing potential markers as well as clues to the functional features of these cells. Principal component analysis identified a set of 88 genes whose average expression levels decrease from oocytes to blastocysts, stem cells, postimplantation embryos, and finally to newborn tissues. This can be a first step towards a possible definition of a molecular scale of cellular potency. The sequences and cDNA clones recovered in this work provide a comprehensive resource for genes functioning in early mouse embryos and stem cells. The nonrestricted community access to the resource can accelerate a wide range of research, particularly in reproductive and regenerative medicine. PMID:14691545

  20. Delusions of Disseminated Fungosis

    Directory of Open Access Journals (Sweden)

    Ian Gassiep

    2014-01-01

    Full Text Available Introduction. Delusional infestation is a rare monosymptomatic hypochondriacal psychosis according to The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013. It can be a primary disorder or associated with an underlying psychological or physical disorder. It commonly presents as delusional parasitosis, and less than 1% may be fungi related. We present this case as it is a rare presentation of a rare condition. Case Presentation. Our patient is a 60-year-old Caucasian man who presented with a 7-year history of delusional infestation manifested as a disseminated fungal infection. He had previously been reviewed by multiple physicians for the same with no systemic illness diagnosed. After multiple reviews and thorough investigation we diagnosed him with a likely delusional disorder. As is common with this patient cohort he refused psychiatric review or antipsychotic medication. Conclusion. A delusion of a disseminated fungal infestation is a rare condition. It is exceedingly difficult to treat as these patients often refuse to believe the investigation results and diagnosis. Furthermore, they either refuse or are noncompliant with treatment. Multidisciplinary outpatient evaluation may be the best way to allay patient fears and improve treatment compliance.

  1. Early gene regulation of osteogenesis in embryonic stem cells

    KAUST Repository

    Kirkham, Glen R.

    2012-01-01

    The early gene regulatory networks (GRNs) that mediate stem cell differentiation are complex, and the underlying regulatory associations can be difficult to map accurately. In this study, the expression profiles of the genes Dlx5, Msx2 and Runx2 in mouse embryonic stem cells were monitored over a 48 hour period after exposure to the growth factors BMP2 and TGFβ1. Candidate GRNs of early osteogenesis were constructed based on published experimental findings and simulation results of Boolean and ordinary differential equation models were compared with our experimental data in order to test the validity of these models. Three gene regulatory networks were found to be consistent with the data, one of these networks exhibited sustained oscillation, a behaviour which is consistent with the general view of embryonic stem cell plasticity. The work cycle presented in this paper illustrates how mathematical modelling can be used to elucidate from gene expression profiles GRNs that are consistent with experimental data. © 2012 The Royal Society of Chemistry.

  2. Phosphorylation site dynamics of early T-cell receptor signaling

    DEFF Research Database (Denmark)

    Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn;

    2014-01-01

    a systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found...... that diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites...

  3. PHENOTYPIC FEATURES OF T REGULATORY CELLS IN EARLY RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A. S. Avdeeva

    2016-01-01

    Full Text Available Objective: to investigate the count and characteristics of the phenotype of T regulatory cells (Treg in the peripheral blood of healthy donors and patients with early rheumatoid arthritis (RA, by using multicolor flow cytometry.Subjects and methods. The investigation enrolled 39 patients with early RA. The percentage and absolute count of Treg (FoxP3+CD25+, surface CD152+, intracellular CD152+, FoxP3+CD127, CD25+CD127, FoxP3+ICOS+, FoxP3+CD154+; and FoxP3+CD274+ was determined by multicolor flow-cytometry. A control group consisted of 20 healthy donors matched for sex and age with the examined patients.Results and discussion. In the patients included in the study, the median [25th; 75th percentiles] DAS28 was 5.01 [4.2; 5.8]; high, moderate, and low activity showed 22 (48.9%, 20 (44.4%, and 3 (6.7% patients, respectively. The patients with early RA had a lower percentage of FoxP3+CD25+ cells and a lower percentage and absolute count of FoxP3+ICOS+, FoxP3+CD154+, and FoxP3+CD274+ T cells than the healthy donors (p<0.05 in all cases. There was a negative correlation of the percentage of FoxP3+CD25+ cells with C-reactive protein (CRP (r = -0.4, that of intracellular CD152+ with DAS28 (r = -0.35, erythrocyte sedimentation rate (ESR (r = -0.46, and CRP (r=-0.54; that of FoxP3+CD127 with CRP (r = -0.42; that of CD25+CD127 with DAS28 (r = -0.38, Simplified Disease Activity Index (r = -0.41, Clinical Disease Activity Index (r = -0.36, ESR (r = -0.39, and CRP (r = -0.47 (p < 0.05 in all cases.Conclusion. The findings suggest that the functional activity of Treg is impaired in early RA, which has an impact on the activity of the inflammatory process.

  4. AIDS defining disease: Disseminated cryptococcosis

    Directory of Open Access Journals (Sweden)

    Roshan Anupama

    2006-01-01

    Full Text Available Disseminated cryptococcosis is one of the acquired immune deficiency syndrome defining criteria and the most common cause of life threatening meningitis. Disseminated lesions in the skin manifest as papules or nodules that mimic molluscum contagiosum (MC. We report here a human immunodeficiency virus positive patient who presented with MC like lesions. Disseminated cryptococcosis was confirmed by India ink preparation and histopathology. The condition of the patient improved with amphotercin B.

  5. Dissemination in athymic nude mice of lacZ transfected small cell lung cancer cells identified by X-gal staining

    DEFF Research Database (Denmark)

    Rømer, M U; Christiansen, J; Brünner, N;

    1995-01-01

    with the chromogenic substrate X-gal. lacZ expressing cells were investigated after subcutaneous (s.c.) inoculation and intravenous (i.v.) injection. The X-gal detection of beta-D-galactosidase activity proved to be a rapid and easy means for specific and highly sensitive identification of metastases. All primary s.......c. tumors stained by X-gal. The primary tumors of GLC-2 regularly demonstrated local invasive growth and produced multiple metastases in several organs. In contrast, primary DMS 456 tumors only occasionally demonstrated local invasion and very rarely generated secondary foci. No experimental metastases were......The small cell lung cancer cell lines GLC-2 and DMS 456 were genetically labeled with the lacZ gene and examined for invasive and metastatic potential in META/Bom nude mice. The lacZ gene encodes the enzyme beta-D- galactosidase, and cells expressing this enzyme were identified by staining...

  6. Nitric oxide coordinates cell proliferation and cell movements during early development of Xenopus.

    Science.gov (United States)

    Peunova, Natalia; Scheinker, Vladimir; Ravi, Kandasamy; Enikolopov, Grigori

    2007-12-15

    The establishment of a vertebrate body plan during embryogenesis is achieved through precise coordination of cell proliferation and morphogenetic cell movements. Here we show that nitric oxide (NO) suppresses cell division and facilitates cell movements during early development of Xenopus, such that inhibition of NO synthase (NOS) increases proliferation in the neuroectoderm and suppresses convergent extension in the axial mesoderm and neuroectoderm. NO controls cell division and cell movement through two separate signaling pathways. Both rely on RhoA-ROCK signaling but can be distinguished by the involvement of either guanylate cyclase or the planar cell polarity regulator Dishevelled. Through the cGMP-dependent pathway, NO suppresses cell division by negatively regulating RhoA and controlling the nuclear distribution of ROCK and p21WAF1. Through the cGMP-independent pathway, NO facilitates cell movement by regulating the intracellular distribution and level of Dishevelled and the activity of RhoA, thereby controlling the activity of ROCK and regulating actin cytoskeleton remodeling and cell polarization. Concurrent control by NO helps ensure that the crucial processes of cell proliferation and morphogenetic movements are coordinated during early development.

  7. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Marquart, Hanne Vibeke; Friis, Lone Smidstrup

    2016-01-01

    Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate...... the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers...... on day 30 (NK30) > 150 cells/µL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/µL had significantly less transplant-related mortality (TRM), P = .01...

  8. Factors affecting daughter cells' arrangement during the early bacterial divisions.

    Directory of Open Access Journals (Sweden)

    Pin-Tzu Su

    Full Text Available On agar plates, daughter cells of Escherichia coli mutually slide and align side-by-side in parallel during the first round of binary fission. This phenomenon has been previously attributed to an elastic material that restricts apparently separated bacteria from being in string. We hypothesize that the interaction between bacteria and the underneath substratum may affect the arrangement of the daughter bacteria. To test this hypothesis, bacterial division on hyaluronic acid (HA gel, as an alternative substratum, was examined. Consistent with our proposition, the HA gel differs from agar by suppressing the typical side-by-side alignments to a rare population. Examination of bacterial surface molecules that may contribute to the daughter cells' arrangement yielded an observation that, with disrupted lpp, the E. coli daughter cells increasingly formed non-typical patterns, i.e. neither sliding side-by-side in parallel nor forming elongated strings. Therefore, our results suggest strongly that the early cell patterning is affected by multiple interaction factors. With oscillatory optical tweezers, we further demonstrated that the interaction force decreased in bacteria without Lpp, a result substantiating our notion that the side-by-side sliding phenomenon directly reflects the strength of in-situ interaction between bacteria and substratum.

  9. Osteoclast-like Cells in Early Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Faiza Sharif

    2014-06-01

    Full Text Available Objective: Genes involved in bone and tissue remodelling in the vertebrates include matrix metalloproteinase-9 (mmp-9, receptor activator of necrosis factor κ-β (rank, cathepsin-k (Ctsk and tartrate-resistant acid phosphatase (TRAcP. We examine whether these markers are expressed in cells of zebrafish embryos of 1-5 days post fertilization. We also examine adult scales, which are known to contain mature osteoclasts, for comparison. Materials and Methods: In this experimental study, in situ hybrdisation, histochemistry and serial plastic and paraffin sectioning were used to analyse marker expression. Results: We found that mmp-9 mRNA, TRAcP enzyme and Ctsk YFP protein were expressed in haematopoietic tissues and in the cells scattered sparsely in the embryo. Ctsk and rank mRNA were both expressed in the branchial skeleton and in the developing pectoral fin. In these skeletal structures, histology showed that the expressing cells were located around the developing cartilage elements, in the parachondral tissue. In a transgenic zebrafish line with YFP coupled to Ctsk promoter, Ctsk expressing cells were found around pharyngeal skeletal elements. To see whether we could activate osteoclasts, we exposed prim-6 zebrafish embryos to a mixture of 1 μM dexamethasone and 1 μM vitaminutes D3. These compounds, which are known to trigger osteoclastogenensis in cell cultures, lead to an increase in intensity of Ctsk YFP expression around the skeletal elements. Conclusion: Our findings show that cells expressing a range of osteoclast markers are present in early larvae and can be activated by the addition of osteoclastogenic compounds.

  10. DNA replication defects delay cell division and disrupt cell polarity in early Caenorhabditis elegans embryos.

    Science.gov (United States)

    Encalada, S E; Martin, P R; Phillips, J B; Lyczak, R; Hamill, D R; Swan, K A; Bowerman, B

    2000-12-15

    In early Caenorhabditis elegans embryos, asymmetric cell divisions produce descendants with asynchronous cell cycle times. To investigate the relationship between cell cycle regulation and pattern formation, we have identified a collection of embryonic-lethal mutants in which cell divisions are delayed and cell fate patterns are abnormal. In div (for division delayed) mutant embryos, embryonic cell divisions are delayed but remain asynchronous. Some div mutants produce well-differentiated cell types, but they frequently lack the endodermal and mesodermal cell fates normally specified by a transcriptional activator called SKN-1. We show that mislocalization of PIE-1, a negative regulator of SKN-1, prevents the specification of endoderm and mesoderm in div-1 mutant embryos. In addition to defects in the normally asymmetric distribution of PIE-1, div mutants also exhibit other losses of asymmetry during early embryonic cleavages. The daughters of normally asymmetric divisions are nearly equal in size, and cytoplasmic P-granules are not properly localized to germline precursors in div mutant embryos. Thus the proper timing of cell division appears to be important for multiple aspects of asymmetric cell division. One div gene, div-1, encodes the B subunit of the DNA polymerase alpha-primase complex. Reducing the function of other DNA replication genes also results in a delayed division phenotype and embryonic lethality. Thus the other div genes we have identified are likely to encode additional components of the DNA replication machinery in C. elegans.

  11. Selected Dissemination/Diffusion Strategies.

    Science.gov (United States)

    Schmitt, Marshall L.

    This analysis of selected diffusion and dissemination methods used by developer-demonstrator projects in the National Diffusion Network discusses strategies under the following headings: managing the project, developing materials, disseminating information, conducting awareness sessions, training personnel, using certified trainers, providing…

  12. Gene function in early mouse embryonic stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Campbell Pearl A

    2007-03-01

    Full Text Available Abstract Background Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5 undergoing undirected differentiation into embryoid bodies (EBs over a period of two weeks. Results We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1, our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2 that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. Conclusion Our analysis profiles for the first time gene expression at a very early stage of m

  13. Regulation of Arabidopsis Early Anther Development by Putative Cell-Cell Signaling Molecules and Transcriptional Regulators

    Institute of Scientific and Technical Information of China (English)

    Yu-Jin Sun; Carey LH Hord; Chang-Bin Chen; Hong Ma

    2007-01-01

    Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS (also called NOZZLE),to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 (DYT1) gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.

  14. Performativity: enrollments, contexts, dissemination

    Directory of Open Access Journals (Sweden)

    Miriam Soares Leite

    2014-04-01

    Full Text Available The term performativity and its inflexions have been applied to several concepts in the field of educational research. In this study, we trace the dissemination of the word performativity and its correlates, starting from the meanings attributed to the term by Stephen Ball, in his analysis of contemporary educational policies, but also using the theories of Jacques Derrida and Judith Butler, who used these terms to refer to social processes of signification and identification, and also references made to the term in studies of Anthropology, Arts, Political Science, Linguistics, Philosophy and Physics. On top of that, we researched studies in the field of academic education, examining articles from journals and other periodicals published over the last five years, in order to discuss the various meanings attributed to the term within the educational field. We present, in this paper, a synthesis of our investigations, highlighting the affirmations, negations and truth effects that can be construed from the use of these terms in educational research, in particular when approaching current educational policies.

  15. Circulating tumor cells in blood of primary breast cancer patients assessed by a novel RT-PCR test kit and comparison with status of bone marrow-disseminated tumor cells.

    Science.gov (United States)

    Schmitt, Manfred; Foekens, John A

    2009-01-01

    In breast cancer, circulating tumor cells (CTCs)/disseminated tumor cells (DTCs) may serve as independent adverse prognostic variables, to monitor the course of the disease and to predict response or failure to cancer therapy. Most of the techniques to enumerate DTCs in the bone marrow or CTCs in the bloodstream of breast cancer patients rely on a combination of an enrichment step and a detection step. A novel RT-PCR method, the AdnaTest BreastCancer kit, was developed for the enrichment of CTCs from peripheral blood of breast cancer patients followed by identification of CTC-associated marker transcripts by reverse transcription and PCR. Although this test has been demonstrated to identify breast cancer patients at risk, standardization of this technique and direct comparison with other established breast cancer CTC enrichment and detection techniques is still lacking, but highly needed. This is done best within prospective clinical trials, such as in the ongoing DETECT, SUCCESS, and BR-01-2004 trials.

  16. Early Onset Squamous Cell Carcinoma In A Case Of Lichen Planus

    Directory of Open Access Journals (Sweden)

    Singh Shri Nath

    1998-01-01

    Full Text Available Lichen planus, which is a very common condition, is being presented. However, the uncommon feature in this cases is its early onset and equally early development of squamous cell carcinoma on a lesion on the right thigh.

  17. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  18. How Is Disseminated Intravascular Coagulation Treated?

    Science.gov (United States)

    ... the NHLBI on Twitter. How Is Disseminated Intravascular Coagulation Treated? Treatment for disseminated intravascular coagulation (DIC) depends ... and treat the underlying cause. Acute Disseminated Intravascular Coagulation People who have acute DIC may have severe ...

  19. Herpes zoster (shingles) disseminated (image)

    Science.gov (United States)

    Herpes zoster (shingles) normally occurs in a limited area that follows a dermatome (see the "dermatome" picture). In individuals with damaged immune systems, herpes zoster may be widespread (disseminated), causing serious illness. Herpes ...

  20. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis

    Science.gov (United States)

    Mortilla, Marzia; Savelli, Sara; Grisotto, Laura; Di Giacomo, Gianpiero; Romano, Katiuscia; Fonda, Claudio; Biggeri, Annibale; Guerrini, Renzo; Aricò, Maurizio

    2015-01-01

    Background Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy. Methods We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI) (group 1) or specific risk factors for (diabetes insipidus, craniofacial bone lesions), but no evidence of, neurodegenerative MRI changes (group 2). All patients underwent clinical, neurophysiological and MRI studies. Results Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs), and five had abnormal brainstem auditory evoked potentials (BAEPs). MR spectroscopy (MRS) showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%), 100% (69.2%-100%), 100% (73.5%-100%), and 66.7% (38.4%-88.2%), respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient. Conclusion A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future

  1. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis.

    Directory of Open Access Journals (Sweden)

    Elena Sieni

    Full Text Available Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy.We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI (group 1 or specific risk factors for (diabetes insipidus, craniofacial bone lesions, but no evidence of, neurodegenerative MRI changes (group 2. All patients underwent clinical, neurophysiological and MRI studies.Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs, and five had abnormal brainstem auditory evoked potentials (BAEPs. MR spectroscopy (MRS showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%, 100% (69.2%-100%, 100% (73.5%-100%, and 66.7% (38.4%-88.2%, respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient.A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future therapeutic trials.

  2. Subcapsular sinus macrophages limit acute gammaherpesvirus dissemination.

    Science.gov (United States)

    Frederico, Bruno; Chao, Brittany; Lawler, Clara; May, Janet S; Stevenson, Philip G

    2015-08-01

    Lymphocyte proliferation, mobility and longevity make them prime targets for virus infection. Myeloid cells that process and present environmental antigens to lymphocytes are consequently an important line of defence. Subcapsular sinus macrophages (SSMs) filter the afferent lymph and communicate with B-cells. How they interact with B-cell-tropic viruses is unknown. We analysed their encounter with murid herpesvirus-4 (MuHV-4), an experimentally accessible gammaherpesvirus related to Kaposi's sarcoma-associated herpesvirus. MuHV-4 disseminated via lymph nodes, and intranasally or subcutaneously inoculated virions readily infected SSMs. However, this infection was poorly productive. SSM depletion with clodronate-loaded liposomes or with diphtheria toxin in CD169-diphtheria toxin receptor transgenic mice increased B-cell infection and hastened virus spread to the spleen. Dendritic cells provided the main route to B-cells, and SSMs slowed host colonization, apparently by absorbing virions non-productively from the afferent lymph.

  3. Profound peripheral T-lymphocyte depletion and activation in disseminated tuberculosis

    Directory of Open Access Journals (Sweden)

    Denise Silva Rodrigues

    2006-02-01

    Full Text Available Three HIV-1-seronegative patients with disseminated tuberculosis presented significant depletion of T-cell counts, in CD4+ and/or CD8+ cells, associated with increased expression of activation marker CD38 on CD8+ T-lymphocytes. This finding raises the question of potential mechanisms involved in the activation or loss of T-cells in disseminated tuberculosis.

  4. Radiofrequency Ablation Treatment for Renal Cell Carcinoma: Early Clinical Experience

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seong Hoon; Yoon, Seong Kuk; Cho, Jin Han; Oh, Jong Young; Nam, Kyung Jin; Kwon, Hee Jin; Kim, Su Yeon; Kang, Myong Jin; Choi, Sun Seob; Sung, Gyung Tak [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2008-08-15

    To evaluate the early clinical experience associated with radiofrequency (RF) ablation in patients with renal cell carcinoma (RCC). The RF ablation treatment was performed on 17 tumors from 16 patients (mean age, 60.5 years; range, 43 73 years) with RCC. The treatment indications were localized, solid renal mass, comorbidities, high operation risk, and refusal to perform surgery. All tumors were treated by a percutaneous CT (n = 10), followed by an US-guided (n = 2), laparoscopy-assisted US (n = 2), and an open (n = 2) RF ablation. Furthermore, patients underwent a follow- up CT at one day, one week, one month, three and six months, and then every six months from the onset of treatment. We evaluated the technical success, technical effectiveness, ablation zone, benign periablation enhancement, irregular peripheral enhancement, and complications. All 17 exophytic tumors (mean size, 2.2 cm; range, 1.1 5.0 cm) were completely ablated. Technical success and effectiveness was achieved in all cases and the mean follow-up period was 23.8 months (range, 17 33 months). A local recurrence was not detected in any of the cases; however, five patients developed complications as a result of treatment, including hematuria (n = 2), mild thermal injury of the psoas muscle (n = 1), mild hydronephrosis (n = 1), and fistula formation (n = 1). The RF ablation is an alternative treatment for exophytic RCCs and represents a promising treatment for some patients with small RCCs.

  5. Early death during chemotherapy in patients with small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Osterlind, K; Hirsch, F R

    1999-01-01

    Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were...

  6. Cell Attachment of Periodontal Ligament Cells on Commercially Pure Titanium at the Early Stage

    Institute of Scientific and Technical Information of China (English)

    周彬; 曹颖光; 吴丽娟; 袁艳祥; 曾引萍

    2004-01-01

    Summary: In order to study the character of periodontal ligament cells (PDLCs) attaching on commercially pure titanium (cpTi) by morphology and metrology on the early stage (24 h), 1×105/ml PDLCs in 2 ml culture medium were seeded on cpTi discs fixed in 24-well culture plates. Morphology of cell attachment was observed by contrast phase microscope, scanning electron microscope (SEM) and fluroscence microscopy. Cell adhesion was analyzed by MTT at 0.5, 1, 2, 4 h respectively. PDLCs could attach and spread on cpTi discs. SEM showed that PDLCs had pseudopod-like protuberance. PDLCs showed different attaching phases and reached saturation in cell number at 2 h. It was concluded that PDLCs had good biocompatibility with cpTi, and showed a regular and dynamic pattern in the process of attaching to cpTi.

  7. Interferon-γ Expression in Natural Killer Cells and Natural Killer T Cells Is Suppressed in Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yongyun Shi; Bin Ling; Ying Zhou; Ting Gao; Dingqing Feng; Min Xiao; Lin Feng

    2007-01-01

    Recent study has suggested that innate immune system might play an important role in pregnancy progression. In this study, to investigate whether NK cells and NKT cells, instead of T cells, are the dominant populations of peripheral blood in early pregnancy, flow cytometry was used to detect the percentage and intracellular cytokine expressions of T cells, NK cells, NKT cells in peripheral blood of non-pregnant women and early pregnant women.In our result, the percentages of NK cells and NKT cells were significantly increased in pregnancy compared to non-pregnancy. However, the percentage of T cells was not changed. We did not detect the Th2-dominance of total lymphocytes or T cells in peripheral blood of early pregnant women and there were also no significant changes of type 1 and type 2 cytokines in T cells, but IFN-γ production in both NK and NKT cells was decreased in early pregnancy. These results suggest that the innate immune system including NK cells and NKT cells should play a pivotal role in pregnancy progression. Type 1/type 2 shift mechanisms in innate immune system during the human early pregnancy should be paid more attention.

  8. A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases

    OpenAIRE

    Gustafsson, Mika; Gawel, Danuta; Alfredsson, Lars; Baranzini, Sergio; Bjorkander, Janne; Blomgran, Robert; Hellberg, Sandra; Eklund, Daniel; Ernerudh, Jan; KOCKUM, Ingrid; Konstantinell, Aelita; Lahesmaa, Riita; Lentini, Antonio; Liljenström, H. Robert I.; Mattson, Lina

    2015-01-01

    Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorph...

  9. Co-Culture of Early Embryo with Human Decidual Stromal Cells in vitro by Improvement of Early Embryo Development

    Institute of Scientific and Technical Information of China (English)

    YAN Jie; ZHU Guijin; LIU Jianxin; AI Jihui

    2000-01-01

    An early embryo co-culture system with human decidual stromal cells was established to study its effect on early embryonic cleavage and growth in vitro. Three hundred and eight 2-cell mouse embryos were co-cultured with human decidual stromal cell monolayer in MEM+0.4%bovine serum albumin (BSA) and 163 embryos cultured in MEM+15 % FCS alone as control. Among the mouse 2-cell embryos co-cultured with human decidual stromal cells, 72.73% developed to the morula stage and 67.21% cavitated to blastocysts with 59.74 % hatching, as compared with 61.34% to morula stage, 48.47% to blastocysts and none hatching in the controls,respectively. Co-cultured embryos cleaved slightly faster than controls and showed no or less fragmentation than those in the control. These results suggested that human decidual stromal cells can support early embryonic development and yield a reasonable number of embryos with good quality up to blastocyst stage.

  10. Interrogating a cell signalling network sensitively monitors cell fate transition during early differentiation of mouse embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU; Yi-Hsin; HO; Chih-ming

    2010-01-01

    The different cell types in an animal are often considered to be specified by combinations of transcription factors,and defined by marker gene expression.This paradigm is challenged,however,in stem cell research and application.Using a mouse embryonic stem cell(mESC) culture system,here we show that the expression level of many key stem cell marker genes/transcription factors such as Oct4,Sox2 and Nanog failed to monitor cell status transition during mESC differentiation.On the other hand,the response patterns of cell signalling network to external stimuli,as monitored by the dynamics of protein phosphorylation,changed dramatically.Our results also suggest that an irreversible alternation in the cell signalling network precedes the adjustment of transcription factor levels.This is consistent with the notion that signal transduction events regulate cell fate specification.We propose that interrogating a cell signalling network can assess the cell property more precisely,and provide a sensitive measurement for the early events in cell fate transition.We wish to bring attention to the potential problem of cell identification using a few marker genes,and suggest a novel methodology to address this issue.

  11. Cutaneous Manifestation of Underlying Disseminated Histoplasmosis in an Immunocompetent Host of Nonendemic Area with Reversible CD4 Cell Depletion and its Recovery on Antifungal Therapy.

    Science.gov (United States)

    Bharti, Praveen; Bala, Kiran; Gupta, Naresh

    2015-10-01

    We present the case of an 18-year-old male patient admitted with complaints of fever and rapid weight loss since 3 months. Patient had multiple umbilicated papular to nodular lesions over chin and forehead region. Complete blood count revealed bicytopenia. An excisional biopsy of the skin lesions had revealed cutaneous histoplasmosis. On further investigations for bicytopenia, histoplasmosis had been diagnosed on bone marrow trephine biopsy. For the immune status, patient's serology against HIV was negative and his CD4 lymphocyte counts were low at 161. Patient received antifungal therapy including amphotericin B and itraconazole. He showed remarkable improvement in his general condition and blood counts. A repeat CD4 count showed normal counts, and idiopathic CD4 lymphocytopenia was excluded. Disseminated histoplasmosis presenting as cutaneous lesions in an immunocompetent host is very rare, and we are not aware of any case report in the literature where there is reversible depletion of CD4 counts following antifungal treatment in an immunocompetent host of nonendemic area.

  12. Transcriptional regulation of early T-cell development in the thymus.

    Science.gov (United States)

    Seo, Wooseok; Taniuchi, Ichiro

    2016-03-01

    T-cell development occurs in multipotent progenitors arriving in the thymus, which provides a highly specialized microenvironment. Specification and sequential commitment processes to T cells begin in early thymic progenitors upon receiving thymus-specific environmental cues, resulting in the activation of the genetically programmed transcriptional cascade that includes turning on and off numerous transcription factors in a precise manner. Thus, early thymocyte differentiation has been an excellent model system to study cell differentiation processes. This review summarizes recent advances in our knowledge on thymic T-cell development from newly arrived multipotent T-cell progenitors to fully committed T-cell precursors, from the transcriptional regulation perspective.

  13. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Etienne Danis

    2016-03-01

    Full Text Available Earlycell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  14. Hypermutator Salmonella Heidelberg induces an early cell death in epithelial cells.

    Science.gov (United States)

    Le Gall-David, Sandrine; Zenbaa, Neila; Bouchard, Damien; Lavault, Marie-Thérèse; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne; Bousarghin, Latifa

    2015-10-22

    We have previously described that a strain of Salmonella Heidelberg with a hypermutator phenotype, B182, adhered strongly to HeLa cells. In this work, we showed that this hypermutator Salmonella strain invaded HeLa epithelial cells and induced cytoskeleton alteration. Those changes lead to HeLa cell death which was characteristic of apoptosis. For the first time, we showed that this hypermutator strain induced apoptosis associated with the activation of caspases 2, 9 and 3. Complementation of B182 strain showed a decrease in cells death induction. In the presence of other Salmonella Heidelberg with a normomutator phenotype, such as WT and SL486, cell death and caspase 3 were undetectable. These results suggested that early apoptosis and caspase 3 activation were specific to B182. Besides, B182 induced LDH release and caspase 3 activation in CaCo-2 and HCT116 cells. Heat-treated B182 and diffusible products failed to induce this phenotype. Epithelial cells treatment with cytochalasin D caused the inhibition of B182 internalisation and caspase 3 activation. These results showed that this cell death required active S. Heidelberg B182 protein synthesis and bacterial internalisation. However sipB and sopB, usually involved in apoptosis induced by Salmonella were not overexpressed in B182, contrary to fimA and fliC. Comparative genome analysis showed numerous mutations as in rpoS which would be more investigated. The role of the hypermutator phenotype might be suspected to be implicated in these specific features. This result expands our knowledge about strong mutators frequently found in bacterial organisms isolated from clinical specimens.

  15. Disseminating an Effective Educational Technology.

    Science.gov (United States)

    Axelrod, Saul

    1992-01-01

    Reasons for the failure to adopt behavior-analytic teaching strategies include the perception that behavior analysis is coercive and controlling, difficulties in implementation, university factors, and marketing problems. The goal of dissemination of these strategies could be met through creating motivational conditions and devising marketing…

  16. T-dependent B-cell activation is signalled by an early increase in potassium influx

    DEFF Research Database (Denmark)

    Owens, T; Kaplan, J G

    1982-01-01

    (previously demonstrated when B and T lymphocytes were separately stimulated) also occurs when B cells are stimulated through cooperation with mitogen-activated T cells, and is also detectable early in culture. T-dependent activation of B cells is therefore detectable considerably earlier than by conventional...

  17. Disseminated lupus vulgaris.

    Science.gov (United States)

    Garg, Taru; Ramchander; Shrihar, Rashmi; Gupta, Tanvi Pal; Aggarwal, Shilpi

    2011-01-01

    follicular plugging and multiple epithelioid cell granulomas, rimmed by lymphocytes in the deeper portion of the dermis, mainly peri-appendageal. Stain for acid-fast bacteria was negative. Cultures from the skin lesions were negative. The patient was diagnosed as having lupus vulgaris with multiple lesions of varying morphology at different sites with pulmonary tuberculosis and healed lymph node involvement.

  18. Endothelial cell promotion of early liver and pancreas development.

    Science.gov (United States)

    Freedman, Deborah A; Kashima, Yasushige; Zaret, Kenneth S

    2007-01-01

    Different steps of embryonic pancreas and liver development require inductive signals from endothelial cells. During liver development, interactions between newly specified hepatic endoderm cells and nascent endothelial cells are crucial for the endoderm's subsequent growth and morphogenesis into a liver bud. Reconstitution of endothelial cell stimulation of hepatic cell growth with embryonic tissue explants demonstrated that endothelial signalling occurs independent of the blood supply. During pancreas development, midgut endoderm interactions with aortic endothelial cells induce Ptf1a, a crucial pancreatic determinant. Endothelial cells also have a later effect on pancreas development, by promoting survival of the dorsal mesenchyme, which in turn produces factors supporting pancreatic endoderm. A major goal of our laboratory is to determine the endothelial-derived molecules involved in these inductive events. Our data show that cultured endothelial cells induce Ptf1a in dorsal endoderm explants lacking an endogenous vasculature. We are purifying endothelial cell line product(s) responsible for this effect. We are also identifying endothelial-responsive regulatory elements in genes such as Ptf1a by genetic mapping and chromatin-based assays. These latter approaches will allow us to track endothelial-responsive signal pathways from DNA targets within progenitor cells. The diversity of organogenic steps dependent upon endothelial cell signalling suggests that cross-regulation of tissue development with its vasculature is a general phenomenon.

  19. CD4+CD25+ and CD4+CD25high regulatory T cells in disseminated and localized forms of allergic contact dermatitis: relation to specific cytokines

    Directory of Open Access Journals (Sweden)

    Halina Laudańska

    2011-07-01

    Full Text Available The aim of this study was to evaluate regulatory T lymphocytes (Tregs in the course of allergic contact dermatitis (ACD and to elucidate the role of IL-10 and TGF-b in Tregs activity. Peripheral blood CD4+CD25+ and CD4+CD25high cells were determined by flow cytometry in patients with acute disseminated ACD (‘ad’, n = 36, acute localized ACD (‘al’, n = 26, and disseminated ACD during remission (‘rd’, n = 27 as well as in controls (n = 22. Serum levels of cytokines were measured using ELISA. The mean percentage of CD4+CD25+ and CD4+CD25high cells in patients with ad ACD was significantly higher than in controls (p < 0.01 and the remaining patients (p < 0.05. Both cell populations were significantly elevated in persons with widespread skin lesions (p < 0.05. In ad patients the CD4+CD25+ increased during three weeks of disease, although the significant increase of CD4+CD25high was noted only in the third week. Patients with ad ACD showed a significantly decreased serum level of TGF-b1 as compared with controls and the remaining ACD patients. IL-10 level did not differ between all groups. The elevated population of CD4+CD25high cells in ad ACD patients, and its dependence on the extension of skin lesions, suggest a role of Tregs in regulating the course of ACD. The growing Tregs percentages may indicate their peripheral generation during ACD. The development of lesions despite an increased population of Tregs suggests their functional defect. The role of TGF-b1 in the suppressive activity of Tregs cannot be excluded. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 255–262

  20. Quinine-Induced Disseminated Intravascular Coagulation

    Directory of Open Access Journals (Sweden)

    Firas Abed

    2016-01-01

    Full Text Available Every drug comes with some side effect. It is the benefit/risk ratio that determines the medical use of the drug. Quinine, a known antimalarial drug, has been used for nocturnal leg cramps since the 1930s; it is associated with severe life-threatening hematological and cardiovascular side effects. Disseminated intravascular coagulation (DIC, albeit rare, is a known coagulopathy associated with Quinine. It is imperative to inquire about the Quinine intake in medication history in patients with coagulopathy, as most patients still consider it a harmless home remedy for nocturnal leg cramps. In this report, we present a case of coagulopathy in a middle-aged woman, who gave a history of taking Quinine for nocturnal leg cramps, as her home remedy. Early identification of the offending agent led to the diagnosis, prompt discontinuation of the medication, and complete recovery and prevented the future possibility of recurrence.

  1. [Disseminated intravascular coagulation: clinical and biological diagnosis].

    Science.gov (United States)

    Touaoussa, Aziz; El Youssi, Hind; El Hassani, Imane; Hanouf, Daham; El Bergui, Imane; Zoulati, Ghizlane; Amrani Hassani, Moncef

    2015-01-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by the systemic activation of blood coagulation. Its pathophysiological mechanisms are complex and dependent on the underlying pathology, making the clinical and biological expression of quite variable DIC. Among the various biological parameters disrupted, most are not specific, and none of them allows in itself to make the diagnosis. All this does not facilitate the task of the practitioner for diagnosis of overt DIC, much less that of the non-overt DIC, early stage whose treatment would improve the prognosis. These considerations have led to develop scores, combining several parameters depending on their availability in daily practice, as well as their diagnostic relevance. Of all the scores, the ISTH (International society of thrombosis and hemostasis) remains the most used.

  2. Fuel cell added value for early market applications

    Science.gov (United States)

    Hardman, Scott; Chandan, Amrit; Steinberger-Wilckens, Robert

    2015-08-01

    Fuel Cells are often considered in the market place as just power providers. Whilst fuel cells do provide power, there are additional beneficial characteristics that should be highlighted to consumers. Due to the high price premiums associated with fuel cells, added value features need to be exploited in order to make them more appealing and increase unit sales and market penetration. This paper looks at the approach taken by two companies to sell high value fuel cells to niche markets. The first, SFC Energy, has a proven track record selling fuel cell power providers. The second, Bloom Energy, is making significant progress in the US by having sold its Energy Server to more than 40 corporations including Wal-Mart, Staples, Google, eBay and Apple. Further to these current markets, two prospective added value applications for fuel cells are discussed. These are fuel cells for aircraft APUs and fuel cells for fire prevention. These two existing markets and two future markets highlight that fuel cells are not just power providers. Rather, they can be used as solutions to many needs, thus being more cost effective by replacing a number of incumbent systems at the same time.

  3. Quantifying Epithelial Early Common Progenitors from Long-Term Primary or Cell Line Sphere Culture.

    Science.gov (United States)

    Clément, Flora; Zhu, Helen He; Gao, Wei-Qiang; Delay, Emmanuel; Maguer-Satta, Véronique

    2015-11-04

    Here, a protocol to quantify epithelial early common progenitor/stem cells grown as spheres in non-adherent culture conditions is described. This protocol is based on the combination of two functional tests: the sphere assay to maintain and enrich early progenitor/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated. Spheres are enzymatically and mechanically dissociated; the derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for further processing, as in the E-CFC assay. The principle of this assay is to quantify the number of epithelial colonies generated by cells present in the different sequential spheres. This assay has therefore been named the early common progenitor-derived colonies assay (ECP-DC).

  4. Acute disseminated histoplasmosis and endocarditis

    Directory of Open Access Journals (Sweden)

    SCAPELLATO Pablo G.

    1998-01-01

    Full Text Available Acute disseminated histoplasmosis is a frequent condition in HIV carriers. Thirty-five cases of endocarditis caused by Histoplasma capsulatum have been reported in international literature, and all these descriptions correspond to a context of subacute disseminated histoplasmosis. This paper presents the case of a HIV-positive patient with fever, dyspnea, weight loss, vomiting and polyadenopathies to whom histoplasmosis was diagnosed following blood-cultures and isolation of the agent responsible for cutaneous lesions, and in whom aortic-valve vegetations were found during an echocardiogram. The patient was treated with amphotericin B and had a good outcome; subsequent echocardiograms showed no vegetations. Literature on the subject is reviewed, with special emphasis on diagnosis and treatment of previously described cases.

  5. Knowledge dissemination: a core mission

    CERN Multimedia

    2011-01-01

    It’s been a year since the CERN Council approved our policy on intellectual property management, so I’d like to take a look at what we’ve achieved since then. In short, a great deal. We’ve moved away from a fairly unregulated approach towards a well balanced and clearly defined system built around sound intellectual property management designed to deliver maximum dissemination and benefit for society from CERN innovation. It’s a move that I celebrate and fully support.   In 2009, CERN signed two partnership agreements to develop CERN technologies, two commercial licenses and eleven R&D licenses. Last year, the figures were six partnership agreements, five commercial licenses and twenty R&D licenses, indicating a real increase in dissemination efforts. From 2009 to 2010, however, the number of new technologies that were identified and disclosed hardly changed: nine in 2009, ten in 2010. These numbers are good, but we must improve, particu...

  6. Disseminated sporotrichosis in an immunocompetent patient

    Science.gov (United States)

    Hassan, Kareem; Turker, Tolga; Zangeneh, Tirdad

    2016-01-01

    Abstract Sporothrix schenckii, the causative agent of sporotrichosis, is a relatively rare infection. Local infection usually occurs through direct inoculation of the organism through the skin; disseminated disease is rarely seen. This article describes a case of disseminated sporotrichosis in a middle-aged man without the commonly seen risk factors for dissemination. PMID:27583270

  7. MRI in acute disseminated encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Caldemeyer, K.S. (Div. of Neuroradiology, Dept. of Radiology, Indiana Univ. School of Medicine, Indianapolis, IN (United States)); Smith, R.R. (Div. of Neuroradiology, Dept. of Radiology, Indiana Univ. School of Medicine, Indianapolis, IN (United States)); Harris, T.M. (Div. of Neuroradiology, Dept. of Radiology, Indiana Univ. School of Medicine, Indianapolis, IN (United States)); Edwards, M.K. (Div. of Neuroradiology, Dept. of Radiology, Indiana Univ. School of Medicine, Indianapolis, IN (United States))

    1994-04-01

    A retrospective analysis of CT and MRI studies in 12 patients with a clinical diagnosis of acute disseminated encephalomyelitis (ADEM) was performed. MRI was the definitive modality for the assessment of the lesions of ADEM: all patients had abnormalities consistent with the clinical diagnosis. Ten had abnormalities in the brain, three spinal cord lesions, and three showed evidence of optic neuritis. CT was normal in 6 of the 7 patients in which it was performed. (orig.)

  8. Perforating Disseminated Necrobiosis Lipoidica Diabeticorum

    OpenAIRE

    Paula Lozanova; Lyubomir Dourmishev; Snejina Vassileva; Ljubka Miteva; Maria Balabanova

    2013-01-01

    Perforating necrobiosis lipoidica is a very rare clinical variant which consists of degeneration and transepidermal elimination of the collagen with few cases reported in the literature. In two-thirds of the patients it associates with diabetes, with no relation with the glucose control. We present a 42-year-old female patient with a 7-year history of diabetes on insulin therapy, referred to our clinic with a 3-year history of multiple asymptomatic firm plaques disseminated on the upper and l...

  9. Phosphorylation dynamics during early differentiation of human embryonic stem cells

    NARCIS (Netherlands)

    van Hoof, D.; Munoz, J.; Braam, S.R.; Pinkse, M.W.H.; Linding, R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2009-01-01

    Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during different

  10. Phosphorylation dynamics during early differentiation of human embryonic stem cells

    DEFF Research Database (Denmark)

    Van Hoof, Dennis; Muñoz, Javier; Braam, Stefan R

    2009-01-01

    Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during...

  11. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.

    Science.gov (United States)

    Martin, G R

    1981-12-01

    This report describes the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice. The pluripotency of these embryonic stem cells was demonstrated conclusively by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types. Such embryonic stem cells were isolated from inner cell masses of late blastocysts cultured in medium conditioned by an established teratocarcinoma stem cell line. This suggests that such conditioned medium might contain a growth factor that stimulates the proliferation or inhibits the differentiation of normal pluripotent embryonic cells, or both. This method of obtaining embryonic stem cells makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes. The availability of such cell lines should made possible new approaches to the study of early mammalian development.

  12. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  13. Association between PD-1/PD-L1 and T regulate cells in early recurrent miscarriage.

    Science.gov (United States)

    Li, Guiyu; Lu, Caixia; Gao, Jing; Wang, Xietong; Wu, Huanling; Lee, Chao; Xing, Baoxiang; Zhang, Qi

    2015-01-01

    In this study, we try to testify the relationship between the programmed cell death receptor-1 (PD-1)/programmed cell death ligand 1 (PD-L1) passway and Treg cells in maternal-fetal immune regulation through PD-1 blockade on lymphocytes of normal early pregnancy in vitro and investigation of the PD-1 and PD-L1 changes in early recurrent miscarriage patients. CD4+ CD25+ Treg cells and PD-1 (CD279) positive cell were detected in deciduas in early recurrent miscarriage patients by flow cytometry. And the normal early pregnant women were as controls. Meanwhile the mRNA level of PD-1 and molecular expression of PD-L1 in deciduas of early recurrent miscarriage patients were detected by real time RT-PCR test and Immunohistochemical staining respectively. Also through antibody blocking assay to block PD-1 on lymphocytes of normal early pregnancy in vitro further testify the relationship between PD-1/PD-L1 and Treg cells, the results were analyzed by flow cytometry. CD4+ CD25+ Treg cells decreased both in deciduas in RM (P 0.05). PD-L1 mRNA in deciduas decreased in RM (P 0.1). After PD-1 blockade there was no change in CD4+ CD25+ Treg cells percentage, while the CD4+ T cell percentage increased (P < 0.01), as well as the level of IFN-gamma in cells supernatant (P < 0.01). PD-1 blockade has a little influence on the number of Treg cells, and may lead to impaired Treg cells function, the decrease of PD-L1 may closely relates to the occurrence of early recurrent miscarriage and implies that Treg cells may through PD-1/PD-L1 pathway play a role of immunosuppression regulation, and the impairment of Treg cells function in recurrent early abortion cases may be due to PD-L1 decrease in deciduas or trophoblast cells rather than PD-1 change.

  14. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection.

    Science.gov (United States)

    Bacchus, Charline; Cheret, Antoine; Avettand-Fenoël, Véronique; Nembot, Georges; Mélard, Adeline; Blanc, Catherine; Lascoux-Combe, Caroline; Slama, Laurence; Allegre, Thierry; Allavena, Clotilde; Yazdanpanah, Yazdan; Duvivier, Claudine; Katlama, Christine; Goujard, Cécile; Seksik, Bao Chau Phung; Leplatois, Anne; Molina, Jean-Michel; Meyer, Laurence; Autran, Brigitte; Rouzioux, Christine

    2013-01-01

    Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3-CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that

  15. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection.

    Directory of Open Access Journals (Sweden)

    Charline Bacchus

    Full Text Available Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI. We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM] and short-lived (transitional-memory [TTM] and effector-memory cells [TEM] resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells, although 10-fold less (p = 0.0005 than in equally infected TCM (4.5, TTM (4.7 and TEM (4.6 cells. CD3-CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells, unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells. The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility

  16. Altered expression of heat shock proteins in embryonal carcinoma and mouse early embryonic cells.

    Science.gov (United States)

    Morange, M; Diu, A; Bensaude, O; Babinet, C

    1984-04-01

    In a previous paper, we have shown that in the absence of stress, mouse embryonal carcinoma cells, like mouse early embryo multipotent cells, synthesize high levels of 89- and 70-kilodalton heat shock proteins (HSP)(O. Bensaude and M. Morange, EMBO J. 2:173-177, 1983). We report here the pattern of proteins synthesized after a short period of hyperthermia in various mouse embryonal carcinoma cell lines and early mouse embryo cells. Among the various cell lines tested, two of them, PCC4-Aza R1 and PCC7-S-1009, showed an unusual response in that stimulation of HSP synthesis was not observed in these cells after hyperthermia. However, inducibility of 68- and 105-kilodalton HSP can be restored in PCC7-S-1009 cells after in vitro differentiation triggered by retinoic acid. Similarly, in the early mouse embryo, hyperthermia does not induce the synthesis of nonconstitutive HSP at the eight-cell stage, but induction of the 68-kilodalton HSP does occur at the blastocyst stage. Such a transition in the expression of HSP has already been described for Drosophila melanogaster and sea urchin embryos and recently for mouse embryos. It may be a general property of early embryonic cells.

  17. Clinical significance of T-cell clonality in mycosis fungoides and other cutaneous T-cell lymphomas

    NARCIS (Netherlands)

    Muche, Joachim Marcus

    2010-01-01

    The purpose of this thesis was to obtain more insight into T-cell clonality in blood of mycosis fungoides (MF) patients. Investigation of the frequency of blood T-cell clonality clearly indicated early dissemination of neoplastic T-cells into skin and blood as a sign of physiological recirculation.

  18. CT of disseminated plasmacytoma - in an AIDS patient

    Energy Technology Data Exchange (ETDEWEB)

    Leder, D.S.; Nazarian, L.N.; Burke, M. [Thomas Jefferson Univ., Philadelphia, PA (United States)

    1996-05-01

    It is well known that acquired immunodeficiency syndrome (AIDS) is associated with increased risk of neoplasms, particularly Kaposi sarcoma and non-Hodgkin lymphoma. There have been several recent reports in the literature describing plasma cell tumors in AIDS patients. We report the imaging findings in a case of widely disseminated plasmacytoma in a patient with known AIDS. 7 refs., 3 figs.

  19. Disseminated histoplasmosis in allogeneic bone marrow transplant: a diagnosis not to be missed.

    Science.gov (United States)

    Haydoura, S; Wallentine, J; Lopansri, B; Ford, C D; Saad, D; Burke, J P

    2014-10-01

    Immunosuppressed patients are at highest risk for disseminated histoplasmosis, but only a few cases have been reported in hematopoietic stem cell transplant recipients. We report a case of disseminated histoplasmosis in an allogeneic bone marrow transplant recipient residing in a non-endemic area. Diagnosis was first suspected based on a peripheral blood smear.

  20. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

    Science.gov (United States)

    2013-07-01

    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...DATES COVERED 1 July 2010 - 30 June 2013 4. TITLE AND SUBTITLE Targeting Cell Surface Proteins in Molecular 5a. CONTRACT NUMBER Photoacoustic ...upon request). Aim 2) Prioritize ovarian cancer-associated surface proteins for their utility as molecular photoacoustic imaging targets and

  1. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.

    Science.gov (United States)

    Gamal, Wesam; Treskes, Philipp; Samuel, Kay; Sullivan, Gareth J; Siller, Richard; Srsen, Vlastimil; Morgan, Katie; Bryans, Anna; Kozlowska, Ada; Koulovasilopoulos, Andreas; Underwood, Ian; Smith, Stewart; Del-Pozo, Jorge; Moss, Sharon; Thompson, Alexandra Inés; Henderson, Neil C; Hayes, Peter C; Plevris, John N; Bagnaninchi, Pierre-Olivier; Nelson, Leonard J

    2017-01-30

    Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.

  2. BLM has early and late functions in homologous recombination repair in mouse embryonic stem cells

    DEFF Research Database (Denmark)

    Chu, W K; Hanada, K; Kanaar, R;

    2010-01-01

    function of BLM remains unclear. Multiple roles have been proposed for BLM in the homologous recombination (HR) repair pathway, including 'early' functions, such as the stimulation of resection of DNA double-strand break ends or displacement of the invading strand of DNA displacement loops, and 'late...... in Rad54(-/-) cells rescued their mitomycin C (MMC) sensitivity, and decreased both the level of DNA damage and cell cycle perturbation induced by MMC, suggesting an early role for Blm. Our data are consistent with Blm having at least two roles in HR repair in mammalian cells....

  3. Ultrasound, CT and MRI of ruptured and disseminated hydatid cysts

    Energy Technology Data Exchange (ETDEWEB)

    Sinner, W.N. von (King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia). Department of Radiology)

    Three cases of echinococcus granulosus with rupture of hydatid cysts and widespread abdominal, pelvic of pleural dissemination are described. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) allowed recognition of ruptured hydatid cysts. This assisted to come to an appropriate therapy and exclusion or confirmation of hydatid cysts elsewhere in the body. Ultrasound, CT and MRI are also important for follow-up, evaluation of therapeutic response and/or early diagnosis of recurrence. (author). 22 refs.; 3 figs.

  4. Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript.

    Directory of Open Access Journals (Sweden)

    Maurice A Canham

    2010-05-01

    Full Text Available ES cells are defined as self-renewing, pluripotent cell lines derived from early embryos. Cultures of ES cells are also characterized by the expression of certain markers thought to represent the pluripotent state. However, despite the widespread expression of key markers such as Oct4 and the appearance of a characteristic undifferentiated morphology, functional ES cells may represent only a small fraction of the cultures grown under self-renewing conditions. Thus phenotypically "undifferentiated" cells may consist of a heterogeneous population of functionally distinct cell types. Here we use a transgenic allele designed to detect low level transcription in the primitive endoderm lineage as a tool to identify an immediate early endoderm-like ES cell state. This reporter employs a tandem array of internal ribosomal entry sites to drive translation of an enhanced Yellow Fluorescent Protein (Venus from the transcript that normally encodes for the early endodermal marker Hex. Expression of this Venus transgene reports on single cells with low Hex transcript levels and reveals the existence of distinct populations of Oct4 positive undifferentiated ES cells. One of these cells types, characterized by both the expression of the Venus transgene and the ES cells marker SSEA-1 (V(+S(+, appears to represent an early step in primitive endoderm specification. We show that the fraction of cells present within this state is influenced by factors that both promote and suppress primitive endoderm differentiation, but conditions that support ES cell self-renewal prevent their progression into differentiation and support an equilibrium between this state and at least one other that resembles the Nanog positive inner cell mass of the mammalian blastocysts. Interestingly, while these subpopulations are equivalently and clonally interconvertible under self-renewing conditions, when induced to differentiate both in vivo and in vitro they exhibit different behaviours

  5. Functional Heterogeneity of Embryonic Stem Cells Revealed through Translational Amplification of an Early Endodermal Transcript

    Science.gov (United States)

    Canham, Maurice A.; Sharov, Alexei A.; Ko, Minoru S. H.; Brickman, Joshua M.

    2010-01-01

    ES cells are defined as self-renewing, pluripotent cell lines derived from early embryos. Cultures of ES cells are also characterized by the expression of certain markers thought to represent the pluripotent state. However, despite the widespread expression of key markers such as Oct4 and the appearance of a characteristic undifferentiated morphology, functional ES cells may represent only a small fraction of the cultures grown under self-renewing conditions. Thus phenotypically “undifferentiated” cells may consist of a heterogeneous population of functionally distinct cell types. Here we use a transgenic allele designed to detect low level transcription in the primitive endoderm lineage as a tool to identify an immediate early endoderm-like ES cell state. This reporter employs a tandem array of internal ribosomal entry sites to drive translation of an enhanced Yellow Fluorescent Protein (Venus) from the transcript that normally encodes for the early endodermal marker Hex. Expression of this Venus transgene reports on single cells with low Hex transcript levels and reveals the existence of distinct populations of Oct4 positive undifferentiated ES cells. One of these cells types, characterized by both the expression of the Venus transgene and the ES cells marker SSEA-1 (V+S+), appears to represent an early step in primitive endoderm specification. We show that the fraction of cells present within this state is influenced by factors that both promote and suppress primitive endoderm differentiation, but conditions that support ES cell self-renewal prevent their progression into differentiation and support an equilibrium between this state and at least one other that resembles the Nanog positive inner cell mass of the mammalian blastocysts. Interestingly, while these subpopulations are equivalently and clonally interconvertible under self-renewing conditions, when induced to differentiate both in vivo and in vitro they exhibit different behaviours. Most strikingly

  6. Distribution of LGR5+ cells and associated implications during the early stage of gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Bo Gun Jang

    Full Text Available Lgr5 was identified as a promising gastrointestinal tract stem cell marker in mice. Lineage tracing indicates that Lgr5(+ cells may not only be the cells responsible for the origin of tumors; they may also be the so-called cancer stem cells. In the present study, we investigated the presence of Lgr5(+ cells and their biological significance in normal human gastric mucosa and gastric tumors. RNAscope, a newly developed RNA in situ hybridization technique, specifically labeled Lgr5(+ cells at the basal glands of the gastric antrum. Notably, the number of Lgr5(+ cells was remarkably increased in intestinal metaplasia. In total, 76% of gastric adenomas and 43% of early gastric carcinomas were positive for LGR5. Lgr5(+ cells were found more frequently in low-grade tumors with active Wnt signaling and an intestinal gland type, suggesting that LGR5 is likely involved in the very early stages of Wnt-driven tumorigenesis in the stomach. Interestingly, similar to stem cells in normal tissues, Lgr5(+ cells were often restricted to the base of the tumor glands, and such Lgr5(+ restriction was associated with high levels of intestinal stem cell markers such as EPHB2, OLFM4, and ASCL2. Thus, our findings show that Lgr5(+ cells are present at the base of the antral glands in the human stomach and that this cell population significantly expands in intestinal metaplasias. Furthermore, Lgr5(+ cells are seen in a large number of gastric tumors ; their frequent basal arrangements and coexpression of ISC markers support the idea that Lgr5(+ cells act as stem cells during the early stage of intestinal-type gastric tumorigenesis.

  7. High resolution AFM and single cell resonance Raman spectroscopy of Geobacter sulfurreducens biofilms early in growth.

    Directory of Open Access Journals (Sweden)

    Nikolai eLebedev

    2014-08-01

    Full Text Available AFM and confocal resonance Raman microscopy (CRRM of single-cells were used to study the transition of anode-grown Geobacter sulfurreducens biofilms from lag phase (initial period of low current to exponential phase (subsequent period of rapidly increasing current. Results reveal that lag phase biofilms consist of lone cells and tightly packed single-cell thick clusters crisscrossed with extracellular linear structures that appear to be comprised of nodules approximately 20 nm in diameter aligned end to end. By early exponential phase cell clusters expand laterally and a second layer of closely packed cells begins to form on top of the first. Abundance of c-type cytochromes (c-Cyt is > 3-fold greater in 2-cell thick regions than in 1-cell thick regions. The results indicate that early biofilm growth involves two transformations. The first is from lone cells to 2-dimensionally associated cells during lag phase when current remains low. This is accompanied by formation of extracellular linear structures. The second is from 2- to 3-dimensionally associated cells during early exponential phase when current begins to increases rapidly. This is accompanied by a dramatic increase in c-Cyt abundance.

  8. Sickle Cell Trait Not Linked to Early Death in Study

    Science.gov (United States)

    ... 3, 2016 WEDNESDAY, Aug. 3, 2016 (HealthDay News) -- New research challenges the long-held belief that people with sickle cell trait, who are born with ... span and causes sudden episodes of severe pain. People with the disease carry ... on active duty in the U.S. Army over a four-year period. All had undergone ...

  9. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  10. Signaling Proteins and Transcription Factors in Normal and Malignant Early B Cell Development

    Directory of Open Access Journals (Sweden)

    Patricia Pérez-Vera

    2011-01-01

    Full Text Available B cell development starts in bone marrow with the commitment of hematopoietic progenitors to the B cell lineage. In murine models, the IL-7 and preBCR receptors, and the signaling pathways and transcription factors that they regulate, control commitment and maintenance along the B cell pathway. E2A, EBF1, PAX5, and Ikaros are among the most important transcription factors controlling early development and thereby conditioning mice homeostatic B cell lymphopoiesis. Importantly, their gain or loss of function often results in malignant development in humans, supporting conserved roles for these transcription factors. B cell acute lymphoblastic leukemia is the most common cause of pediatric cancer, and it is characterized by unpaired early B cell development resulting from genetic lesions in these critical signaling pathways and transcription factors. Fine mapping of these genetic abnormalities is allowing more specific treatments, more accurately predicting risk profiles for this disease, and improving survival rates.

  11. The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    M.D. Laurenti

    1999-03-01

    Full Text Available In order to study the role of natural killer (NK cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania amazonensis (HSJD-1 strain. 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 106 spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 106 spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection.

  12. Three Dimensional Simulation Method in Early Process of Division and Growth for Tumour Cells

    Institute of Scientific and Technical Information of China (English)

    XIA Zhi-qiu; ZHAO Ting-ting

    2014-01-01

    The process of division, growth and death for tumour cell mass in the early is simulated. An integrated GUI is provided for users to set the value of each parameters, which are cell growth rates, cell mass division rates, cell mass death rates, simulate type, maximum running time, polarity and cell colour. It can display the growth process of each cell on result GUI. Also, it can display the values of each parameters for observing and analysing in current life cycle on result GUI, which are cell mass division times, cell mass death rate, cell mass division rate and cell mass growth rate. In the process of simulation, The cell growth rate is described by the approach to combine the exponential model with the linear model. In addition, a linked list data structure to store the tumour cells is used by the cellular automata for a reference to determine the position of each cell. It sets up two linked list to store the cells, one of them save the new small division cells and the other one save the big cell. That can make the painting process of cells on result GUI clearer and more organized. At last, the polarity of tumour growth is described for determining the growth direction of cells.

  13. Perforating Disseminated Necrobiosis Lipoidica Diabeticorum

    Directory of Open Access Journals (Sweden)

    Paula Lozanova

    2013-01-01

    Full Text Available Perforating necrobiosis lipoidica is a very rare clinical variant which consists of degeneration and transepidermal elimination of the collagen with few cases reported in the literature. In two-thirds of the patients it associates with diabetes, with no relation with the glucose control. We present a 42-year-old female patient with a 7-year history of diabetes on insulin therapy, referred to our clinic with a 3-year history of multiple asymptomatic firm plaques disseminated on the upper and lower extremities. The clinical and histological findings proved the diagnosis of perforating necrobiosis lipoidica.

  14. Data Dissemination in the Wild

    DEFF Research Database (Denmark)

    Vingelmann, Peter; Pedersen, Morten Videbæk; Heide, Janus;

    2012-01-01

    This paper investigates the problem of efficient data dissemination in Mobile Ad hoc NETworks (MANETs) with high mobility. A testbed is presented; which provides a high degree of mobility in experiments. The testbed consists of 10 autonomous robots with mobile phones mounted on them. The mobile...... phones form an IEEE 802.11g ad hoc network to communicate with each other. A dynamic network topology is assumed, where the mobile devices form a cooperative cluster in order to exchange data packets among each other. In our multimedia exchange scenario, the initial state is that one device carries all...

  15. Disseminated Tuberculosis Mimicking Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Valérie Huyge

    2011-01-01

    Full Text Available Ankylosing spondylitis is a chronic inflammatory disorder affecting mainly the axial skeleton. Here we report a case of a man with a clinical suspicion of ankylosing spondylitis but with a persistence of increased inflammatory markers. In this case, 18F-FDG-PET/CT revealed multiple hypermetabolic lesions in axial skeleton, lymph nodes, and the lung, suggestive of either disseminated tuberculosis or lymphoma. Histological analysis of the pulmonary lesion revealed mycobacterium tuberculosis. This case highlights, firstly, the importance of excluding other diagnoses in the presence of clinical picture of ankylosing spondylitis and high inflammatory markers and, secondly, the determining role of PET/CT.

  16. Whole genome sequence analysis suggests intratumoral heterogeneity in dissemination of breast cancer to lymph nodes.

    Directory of Open Access Journals (Sweden)

    Kevin Blighe

    Full Text Available BACKGROUND: Intratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood. METHODS: Whole genome NGS was performed on 12 µg (range 11.1-13.3 µg of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis. RESULTS: Whole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome. CONCLUSION: This case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples.

  17. Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Houtmeyers François

    2011-01-01

    Full Text Available Abstract Background Epithelial cell adhesion molecule (EpCAM has been used as surrogate marker for the quantification of circulating tumour cells (CTC. Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC. Methods From 48 patients with PDAC (40 resectable, 8 unresectable and 10 patients with chronic pancreatitis undergoing pancreatectomy 10 ml of venous blood was drawn preoperatively (PB and postoperatively (POB, day 1 (D1B, day 7 (D7B and after 6 weeks (6WB. Of all patients undergoing pancreatectomy, 40 ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700 was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7 - 41.3. Results PB was EpCAM-positive (+ in 25% of patients versus 65% of patients in POB (p At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity. Conclusions Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC. Trial registration Clinicaltrials.gov NCT00495924

  18. Ventricular metastasis resulting in disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Davis Ian D

    2005-05-01

    Full Text Available Abstract Background Disseminated Intravascular Coagulation (DIC complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC has rarely been associated with DIC. Case presentation A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient. Conclusion Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.

  19. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease.

    Science.gov (United States)

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-02-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease.

  20. NK cells, displaying early activation, cytotoxicity and adhesion molecules, are associated with mild dengue disease

    Science.gov (United States)

    Azeredo, E L; De Oliveira-Pinto, L M; Zagne, S M; Cerqueira, D I S; Nogueira, R M R; Kubelka, C F

    2006-01-01

    During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3−) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3−, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease. PMID:16412060

  1. Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors.

    Science.gov (United States)

    Kobayashi, Michihiro; Nabinger, Sarah C; Bai, Yunpeng; Yoshimoto, Momoko; Gao, Rui; Chen, Sisi; Yao, Chonghua; Dong, Yuanshu; Zhang, Lujuan; Rodriguez, Sonia; Yashiro-Ohtani, Yumi; Pear, Warren S; Carlesso, Nadia; Yoder, Mervin C; Kapur, Reuben; Kaplan, Mark H; Daniel Lacorazza, Hugo; Zhang, Zhong-Yin; Liu, Yan

    2017-04-01

    The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors. Stem Cells 2017;35:1053-1064.

  2. [Analysis of dissemination pathways for poliovirus].

    Science.gov (United States)

    Ohka, Seii

    2009-06-01

    Poliomyelitis is an acute disease of the central nervous system (CNS) caused by poliovirus (PV). In humans, an infection is initiated by oral ingestion of the virus, followed by multiplication in the alimentary mucosa, from which the virus spreads through the bloodstream. Paralytic poliomyelitis initiates from the invasion of the central nervous system by circulating poliovirus, probably via the blood-brain barrier. After the virus enters the central nervous system, it replicates in neurons, especially in motor neurons, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, a neuron-specific pathway has been reported in humans, monkeys, and PV-sensitive transgenic (Tg) mice carrying the PV receptor (hPVR/CD155) gene. It is important for the efficient virus dissemination to overcome the barriers as follows; i) to access the target tissue, ii) to enter the cells, iii) to reach the place for the replication, iv) to replicate efficiently. PV is easily transferred to humans orally; however, no rodent model for oral infections has been developed. We analyzed the each barrier above, and showed that PV is inactivated by the low pH of the gastric contents in mice. We also demonstrated that type 1 interferon signaling plays an important role in determining permissivity in the alimentary tract. As for the neural pathway, we demonstrated that direct efficient interaction between the cytoplasmic domain and cytoplasmic dynein is essential for the efficient retrograde transport of PV-containing vesicles along microtubules for the hPVR-dependent PV transport. On the other hand, we found that hPVR-independent axonal transport of PV was also observed in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist.

  3. Socioeconomic position and surgery for early-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Starr, Laila Kærgaard; Osler, Merete; Steding-Jessen, Marianne;

    2012-01-01

    AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer....

  4. A comparison of the tube forming potentials of early and late endothelial progenitor cells.

    Science.gov (United States)

    Mukai, Nana; Akahori, Taichi; Komaki, Motohiro; Li, Qin; Kanayasu-Toyoda, Toshie; Ishii-Watabe, Akiko; Kobayashi, Akiko; Yamaguchi, Teruhide; Abe, Mayumi; Amagasa, Teruo; Morita, Ikuo

    2008-02-01

    The identification of circulating endothelial progenitor cells (EPCs) has revolutionized approaches to cell-based therapy for injured and ischemic tissues. However, the mechanisms by which EPCs promote the formation of new vessels remain unclear. In this study, we obtained early EPCs from human peripheral blood and late EPCs from umbilical cord blood. Human umbilical vascular endothelial cells (HUVECs) were also used. Cells were evaluated for their tube-forming potential using our novel in vitro assay system. Cells were seeded linearly along a 60 mum wide path generated by photolithographic methods. After cells had established a linear pattern on the substrate, they were transferred onto Matrigel. Late EPCs formed tubular structures similar to those of HUVECs, whereas early EPCs randomly migrated and failed to form tubular structures. Moreover, late EPCs participate in tubule formation with HUVECs. Interestingly, late EPCs in Matrigel migrated toward pre-existing tubular structures constructed by HUVECs, after which they were incorporated into the tubules. In contrast, early EPCs promote sprouting of HUVECs from tubular structures. The phenomena were also observed in the in vivo model. These observations suggest that early EPCs cause the disorganization of pre-existing vessels, whereas late EPCs constitute and orchestrate vascular tube formation.

  5. Cytodiagnosis of disseminated histoplasmosis in an immunocompetent individual with molluscum contagiosum-like skin lesions and lymphadenopathy

    Science.gov (United States)

    Gupta, Prajwala; Bhardwaj, Minakshi

    2016-01-01

    Disseminated histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). The early clinical manifestations are nonspecific, often lead to diagnostic difficulty, and is misdiagnosed as tuberculosis and seen usually in immunosuppressed states. Fine needle aspiration cytology (FNAC) is a simple, safe, and quick technique to establish the initial diagnosis of H. capsulatum, thereby prompting early treatment. The skin involvement is rare in disseminated disease and we describe a case of disseminated histoplasmosis in an immunocompetent patient with unusual molluscum contagiosum like umbilicated skin lesions and FNAC of the cervical lymph node was the only tool for rapid and early confirmatory diagnosis.

  6. Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Christian Castelli

    2001-01-01

    Full Text Available Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187 for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD values indicating that their plasma membranes were less rough (lower FD than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process.

  7. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  8. Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life.

    Directory of Open Access Journals (Sweden)

    Elodie Belnoue

    Full Text Available Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8⁺ T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC, which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8 is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.

  9. Variations of X chromosome inactivation occur in early passages of female human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Tamar Dvash

    Full Text Available X chromosome inactivation (XCI is a dosage compensation mechanism essential for embryonic development and cell physiology. Human embryonic stem cells (hESCs derived from inner cell mass (ICM of blastocyst stage embryos have been used as a model system to understand XCI initiation and maintenance. Previous studies of undifferentiated female hESCs at intermediate passages have shown three possible states of XCI; 1 cells in a pre-XCI state, 2 cells that already exhibit XCI, or 3 cells that never undergo XCI even upon differentiation. In this study, XCI status was assayed in ten female hESC lines between passage 5 and 15 to determine whether XCI variations occur in early passages of hESCs. Our results show that three different states of XCI already exist in the early passages of hESC. In addition, we observe one cell line with skewed XCI and preferential expression of X-linked genes from the paternal allele, while another cell line exhibits random XCI. Skewed XCI in undifferentiated hESCs may be due to clonal selection in culture instead of non-random XCI in ICM cells. We also found that XIST promoter methylation is correlated with silencing of XIST transcripts in early passages of hESCs, even in the pre-XCI state. In conclusion, XCI variations already take place in early passages of hESCs, which may be a consequence of in vitro culture selection during the derivation process. Nevertheless, we cannot rule out the possibility that XCI variations in hESCs may reflect heterogeneous XCI states in ICM cells that stochastically give rise to hESCs.

  10. The Influence of Interspecies Somatic Cell Nuclear Transfer on Epigenetic Enzymes Transcription in Early Embryos

    DEFF Research Database (Denmark)

    Morovic, Martin; Murin, Matej; Strejcek, Frantisek;

    2016-01-01

    One of the main reason for the incorrect development of embryos derived from somatic cell nuclear transfer is caused by insufficient demethylation of injected somatic chromatin to a state comparable with an early embryonic nucleus. It is already known that the epigenetic enzymes transcription....... In spite of the detection of ooplasmic DNA methyltransferases, the somatic genes for DNMT1 and DNMT3a enzymes were not expressed and the development of intergeneric embryos stopped at the 4-cell stage. Our results indicate that the epigenetic reprogramming during early mammalian development is strongly...

  11. Immunohistochemical markers for corneal stem cells in the early developing human eye

    DEFF Research Database (Denmark)

    Lyngholm, Mikkel; Høyer, Poul E; Vorum, Henrik;

    2008-01-01

    markers and potential markers for LSCs and early transient amplifying cells in human adults. In this study, we describe the development of the ectodermally derived LSCs and the mesodermally derived niche cells from the time at which the cornea is defined (week 6) until the formation of the early limbal...... niche (week 14) in human embryos and fetuses. The expression of SOD2 and CK15 was investigated together with other recently identified limbal proteins. Previously suggested LSC and differentiation markers (PAX6, aquaporin-1 and nestin) were also investigated. Both SOD2 and CK15 were present...

  12. Enhancement of early cardiac differentiation of dedifferentiated fat cells by dimethyloxalylglycine via notch signaling pathway.

    Science.gov (United States)

    Li, Fuhai; Li, Zongzhuang; Jiang, Zhi; Tian, Ye; Wang, Zhi; Yi, Wei; Zhang, Chenyun

    2016-01-01

    Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism. Methods: DFAT cells were prepared from 4 to 6 week-age mice and cultured under hypoxic conditions by adding Prolyl hydroxylase inhibitor and dimethyloxalylglycine (DMOG) into the culture media. To inhibit or block Notch signaling, γ-secretase inhibitor-II (GSI-II) and Notch1 siRNA (si-Notch1) were used. DFAT cell viability was detected using MTT assay. qRT-PCR, immunofluorescence microscopy and western blotting were used to evaluate the cardiac differentiation of DFAT cells and co-immunoprecipitation was used to study the interaction between HIF-1α and Notch signaling. Results: 0.6-mM DMOG failed to affect the viability of DFAT cells, but stimulated the cells to express early cardiac transcription factors including Islet1, Nkx2.5 and Gata4 in a time-dependent manner and increase the number of cTnT(+) cardiomyocytes (detected at the 28(th) day after stimulation). It was also demonstrated that DMOG was involved in HIF-1α and Notch signaling as well as HIF-1α-NICD complex formation. Conclusion: Hypoxia enhanced early cardiac differentiation of DFAT cells through HIF-1α and Notch signaling pathway.

  13. Selective depletion of non-specific T cells as an early event in T cell response to bacterial and viral infections

    Institute of Scientific and Technical Information of China (English)

    JIANG Jiu

    2005-01-01

    @@ Early T cell depletion occurs prior to the development of an effective immune response to infections.Both antigen-specific and non-specific T cells are induced to express early activation markers soon after microbial infections.This is followed by massive depletion of non-specific T cells and extensive proliferation of antigen-specific T cells.Proliferating antigen-specific cells exhibit a broad spectrum of late activation markers while non-specific cells exhibit no sign of further activation before succumbing to apoptosis.These results have crucial implications for the understanding of early events in the development of a robust T cell response.

  14. Enhanced apoptosis during early neuronal differentiation in mouse ES cells with autosomal imbalance

    Institute of Scientific and Technical Information of China (English)

    Yoshiteru Kai; Teruhiko Wakayama; Mitsuo Oshimura; Chi Chiu Wang; Satoshi Kishigami; Yasuhiro Kazuki; Satoshi Abe; Masato Takiguchi; Yasuaki Shirayoshi; Toshiaki Inoue; Hisao Ito

    2009-01-01

    Although particular chromosomal syndromes are phenotypically and clinically distinct, the majority of individuals with autosomai imbalance, such as aneuploidy, manifest mental retardation. A common abnormal phenotype of Down syndrome (DS), the most prevalent autosomal aneuploidy, shows a reduction in both the number and the density of neurons in the brain. As a DS model, we have recently created chimeric mice from ES cells containing a single human chromosome 21. The mice mimicked the characteristic phenotypic features of DS, and ES cells showed a higher incidence of apoptosis during early neuronal differentiation in vitro. In this study, we examined the induction of anomalous early neural development by aneuploidy in mouse ES cells by transferring various human chromosomes or additional mouse chromosomes. Results showed an elevated incidence of apoptosis in all autosome-aneuploid clones examined during early neuronal differentiation in vitro. Further, cDNA microarray analysis revealed a common cluster of down-regulated genes, of which eight known genes are related to cell proliferation, neurite outgrowth and differentiation. Importantly, targeting of these genes by siRNA knockdown in normal mouse ES cells led to enhanced apoptosis during early neuronal differentiation. These findings strongly suggest that autosomal imbalance is associated with general neuronal loss through a common molecular mechanism for apoptosis.

  15. Early cell lineage specification in a marsupial: a case for diverse mechanisms among mammals.

    Science.gov (United States)

    Frankenberg, Stephen; Shaw, Geoff; Freyer, Claudia; Pask, Andrew J; Renfree, Marilyn B

    2013-03-01

    Early cell lineage specification in eutherian mammals results in the formation of a pluripotent inner cell mass (ICM) and trophoblast. By contrast, marsupials have no ICM. Here, we present the first molecular analysis of mechanisms of early cell lineage specification in a marsupial, the tammar wallaby. There was no overt differential localisation of key lineage-specific transcription factors in cleavage and early unilaminar blastocyst stages. Pluriblast cells (equivalent to the ICM) became distinguishable from trophoblast cells by differential expression of POU5F1 and, to a greater extent, POU2, a paralogue of POU5F1. Unlike in the mouse, pluriblast-trophoblast differentiation coincided with a global nuclear-to-cytoplasmic transition of CDX2 localisation. Also unlike in the mouse, Hippo pathway factors YAP and WWTR1 showed mutually distinct localisation patterns that suggest non-redundant roles. NANOG and GATA6 were conserved as markers of epiblast and hypoblast, respectively, but some differences to the mouse were found in their mode of differentiation. Our results suggest that there is considerable evolutionary plasticity in the mechanisms regulating early lineage specification in mammals.

  16. Treatment of Disseminated Intravascular Coagulation.

    Science.gov (United States)

    Makruasi, Nisa

    2015-11-01

    Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic activation of blood coagulation, generation of thrombin, and leading to disturbance of the microvasculature. In this article, definition and diagnostic criteria of DIC depend on the International Society of Thrombosis and Haemostasis (ISTH). There is no gold standard for diagnosis of DIC, only low quality evidence is used in general practice. Many diagnostic tests and repeated measurement are required. For the treatment of DIC, there is no good quality evidence. The most important treatment for DIC is the specific treatment of the conditions associated DIC. Platelets and/or plasma transfusion may be also necessary if indicated. Nevertheless, there is no gold standard for diagnosis and treatment of DIC, we use only low quality evidence in general practice.

  17. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  18. Boolean genetic network model for the control of C. elegans early embryonic cell cycles

    Science.gov (United States)

    2013-01-01

    Background In Caenorhabditis elegans early embryo, cell cycles only have two phases: DNA synthesis and mitosis, which are different from the typical 4-phase cell cycle. Modeling this cell-cycle process into network can fill up the gap in C. elegans cell-cycle study and provide a thorough understanding on the cell-cycle regulations and progressions at the network level. Methods In this paper, C. elegans early embryonic cell-cycle network has been constructed based on the knowledge of key regulators and their interactions from literature studies. A discrete dynamical Boolean model has been applied in computer simulations to study dynamical properties of this network. The cell-cycle network is compared with random networks and tested under several perturbations to analyze its robustness. To investigate whether our proposed network could explain biological experiment results, we have also compared the network simulation results with gene knock down experiment data. Results With the Boolean model, this study showed that the cell-cycle network was stable with a set of attractors (fixed points). A biological pathway was observed in the simulation, which corresponded to a whole cell-cycle progression. The C. elegans network was significantly robust when compared with random networks of the same size because there were less attractors and larger basins than random networks. Moreover, the network was also robust under perturbations with no significant change of the basin size. In addition, the smaller number of attractors and the shorter biological pathway from gene knock down network simulation interpreted the shorter cell-cycle lengths in mutant from the RNAi gene knock down experiment data. Hence, we demonstrated that the results in network simulation could be verified by the RNAi gene knock down experiment data. Conclusions A C. elegans early embryonic cell cycles network was constructed and its properties were analyzed and compared with those of random networks

  19. Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells.

    Science.gov (United States)

    Hirata, Tetsuya; Amano, Tomokazu; Nakatake, Yuhki; Amano, Misa; Piao, Yulan; Hoang, Hien G; Ko, Minoru S H

    2012-01-01

    The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required onlyfor the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

  20. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  1. Generation of multipotent early lymphoid progenitors from human embryonic stem cells.

    Science.gov (United States)

    Larbi, Aniya; Mitjavila-Garcia, Maria Teresa; Flamant, Stéphane; Valogne, Yannick; Clay, Denis; Usunier, Benoît; l'Homme, Bruno; Féraud, Olivier; Casal, Ibrahim; Gobbo, Emilie; Divers, Dominique; Chapel, Alain; Turhan, Ali G; Bennaceur-Griscelli, Annelise; Haddad, Rima

    2014-12-15

    During human embryonic stem cell (ESC) hematopoietic differentiation, the description of the initial steps of lymphopoiesis remains elusive. Using a two-step culture procedure, we identified two original populations of ESC-derived hematopoietic progenitor cells (HPCs) with CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) phenotypes. Bulk cultures and limiting dilution assays, culture with MS5 cells in the presence of Notch ligand Delta-like-1 (DL-1), and ex vivo colonization tests using fetal thymic organ cultures showed that although CD34(+)CD45RA(+)CD7(-) HPCs could generate cells of the three lymphoid lineages, their potential was skewed toward the B cell lineages. In contrast, CD34(+)CD45RA(+)CD7(+) HPCs predominantly exhibited a T/natural killer (NK) cell differentiation potential. Furthermore these cells could differentiate equivalently into cells of the granulo-macrophagic lineage and dendritic cells and lacked erythroid potential. Expression profiling of 18 markers by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs express genes of the lymphoid specification and that CD34(+)CD45RA(+)CD7(-) cells express B-cell-associated genes, while CD34(+)CD45RA(+)CD7(+) HPCs display a T-cell molecular profile. Altogether, these findings indicate that CD34(+)CD45RA(+)CD7(-) and CD34(+)CD45RA(+)CD7(+) HPCs correspond to candidate multipotent early lymphoid progenitors polarized toward either the B or T/NK lineage, respectively. This work should improve our understanding of the early steps of lymphopoiesis from pluripotent stem cells and pave the way for the production of lymphocytes for cell-based immunotherapy and lymphoid development studies.

  2. Simple mechanisms of early life - simulation model on the origin of semi-cells.

    Science.gov (United States)

    Klein, Adrian; Bock, Martin; Alt, Wolfgang

    2017-01-01

    The development of first cellular structures played an important role in the early evolution of life. Early evolution of life probably took place on a molecular level in a reactive environment. The iron-sulfur theory postulates the formation of cell-like structures on catalytic surfaces. Experiments show that H2S together with FeS and other metallic centers drive auto-catalytic surface reactions, in which organic molecules such as pyruvic and amino acids occur. It is questionable which mechanisms are needed to form cell-like structures under these conditions. To address this question, we implemented a model system featuring the fundamentals of molecular dynamics: heat, attraction, repulsion and formation of covalent bonds. Our basic model exhibits a series of essential processes: self-organization of lipid micelles and bilayers, formation of fluid filled cavities, flux of molecules along membranes, transport of energized groups towards sinks and whole colonies of cell-like structures on a larger scale. The results demonstrate that only a few features are sufficient for discovering hitherto non described phenomena of self-assembly and dynamics of cell-like structures as candidates for early evolving proto-cells. Significance statement The quest for a possible origin of life continues to be one of the most fascinating problems in biology. In one theoretical scenario, early life originated from a solution of reactive chemicals in the ancient deep sea, similar to conditions as to be found in thermal vents. Experiments have shown that a variety of organic molecules, the building blocks of life, form under these conditions. Based on such experiments, the iron-sulfur theory postulates the growth of cell-like structures at certain catalytic surfaces. For an explanation and proof of such a process we have developed a computer model simulating molecular assembly of lipid bilayers and formation of semi-cell cavities. The results demonstrate the possibility of cell-like self

  3. Autophagic flux is highly active in early mitosis and differentially regulated throughout the cell cycle

    OpenAIRE

    Li, Zhiyuan; Ji, Xinmiao; Wang, Dongmei; Liu, Juanjuan; Zhang, Xin

    2016-01-01

    Mitosis is a fast process that involves dramatic cellular remodeling and has a high energy demand. Whether autophagy is active or inactive during the early stages of mitosis in a naturally dividing cell is still debated. Here we aimed to use multiple assays to resolve this apparent discrepancy. Although the LC3 puncta number was reduced in mitosis, the four different cell lines we tested all have active autophagic flux in both interphase and mitosis. In addition, the autophagic flux was highl...

  4. Early cytoskeletal rearrangement during dendritic cell maturation enhances synapse formation and Ca(2+) signaling in CD8(+) T cells.

    Science.gov (United States)

    Averbeck, Marco; Braun, Thorsten; Pfeifer, Gunther; Sleeman, Jonathan; Dudda, Jan; Martin, Stefan F; Kremer, Bernhard; Aktories, Klaus; Simon, Jan C; Termeer, Christian

    2004-10-01

    The interplay between dendritic cells (DC) and T cells is a dynamic process critically depending on DC maturation. Ca(2+) influx is one of the initial events occurring during DC/T cell contacts. To determine how DC maturation influences DC/T cell contacts, time-lapse video microscopy was established using TCR-transgenic CD8(+) T cells from P14 mice. DC maturation shifted DC/T cell contacts from short-lived interactions with transient Ca(2+) influx in T cells to long-lasting interactions and sustained Ca(2+) influx of 30 min and more. Follow-up of DC/T cell interactions after 2 h using confocal microscopy revealed that long-lasting Ca(2+) responses in T cells were preferentially associated with the formation of an immunological synapse involving CD54 and H2-K(b) at the DC/T cell interface. Such synapse formation preceded MHC or B7 up-regulation, since DC developed into potent Ca(2+) stimulators 7 h after initiation of maturation. Instead, the enhanced capacity of 7 h-matured DC to induce sustained Ca(2+) responses in CD8(+) T cells is critically dependent on the polarization and rearrangement of the cytoskeleton, as shown by Clostridium difficile toxin B inhibitor experiments. These data indicate that already very early after receiving a maturation stimulus, DC display enhanced cytoskeletal activity resulting in the rapid formation of immunological synapses and effective CD8(+) T cell stimulation.

  5. Early Growth Response-1 Plays a Non-redundant Role in the Differentiation of B Cells into Plasma Cells.

    Science.gov (United States)

    Oh, Yeon-Kyung; Jang, Eunkyeong; Paik, Doo-Jin; Youn, Jeehee

    2015-06-01

    Early growth response (Egr)-1 is a Cys2-His2-type zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from Egr1 (-/-) mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between Egr1 (-/-) and WT mice. However, Egr1 (-/-) B cells gave rise to fewer plasma cells than WT B cells. Consistently, Egr1 (-/-) mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells.

  6. [Disseminated mucormycosis in immunocompetent patients: A disease that also exists].

    Science.gov (United States)

    Pozo Laderas, Juan Carlos; Pontes Moreno, Antonio; Pozo Salido, Carmen; Robles Arista, Juan Carlos; Linares Sicilia, María José

    2015-01-01

    Mucormycosis is usually an acute angioinvasive infections, which leads to non-suppurative necrosis and significant tissue damage. It represents 1.6% of all the invasive fungal infections and predominates in immunosuppressed patients with risk factors. Incidence has been significantly increased even in immunocompetent patients. Due to finding a case of disseminated mucormycosis caused by Rhizomucor pusillus in a young immunocompetent patient, a systematic review was carried out of reported cases in PubMed of mucormycosis in immunocompetent adults according to the main anatomic locations, and especially in disseminated cases. A review of the main risk factors and pathogenicity, clinical manifestations, techniques of early diagnosis, current treatment options, and prognosis is presented. Taxonomy and classification of the genus Mucor has also been reviewed.

  7. Early adhesive behavior of bone-marrow-derived mesenchymal stem cells on collagen electrospun fibers

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Casey K; Liao, Susan; Lareu, Ricky R; Raghunath, Michael [Division of Bioengineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574 (Singapore); Li, Bojun; Ramakrishna, S [Nanoscience and Nanotechnology Initiative, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Larrick, James W, E-mail: doschanc@nus.edu.s [Panorama Research Institute, 2462 Wyandotte Street, Mountain View, CA 94043 (United States)

    2009-06-15

    A bioabsorbable nanofibrous scaffold was developed for early adhesion of mesenchymal stem cells (MSCs). Collagen nanofibers with diameters of 430 +- 170 nm were fabricated by electrospinning. Over 45% of the MSC population adhered to this collagen nanofiber after 30 min at room temperature. Remarkably, collagen-coated P(LLA-CL) electrospun nanofibers were almost as efficient as collagen nanofibers whereas collagen cast film did not enhance early capture when it was applied on cover slips. The adhesive efficiency could be further increased to over 20% at 20 min and over 55% at 30 min when collagen nanofibers were grafted with monoclonal antibodies recognizing CD29 or CD49a. These data demonstrate that the early adhesive behavior is highly dependent on both the surface texture and the surface chemistry of the substrate. These findings have potential applications for early capture of MSCs in an ex vivo setting under time constraints such as in a surgical setting.

  8. Circulating tumor cells in early bladder cancer: insight into micrometastatic disease.

    Science.gov (United States)

    Raimondi, Cristina; Gradilone, Angela; Gazzaniga, Paola

    2014-05-01

    Although several studies have demonstrated the prognostic and predictive potential of circulating tumor cells (CTCs), to date their evaluation still has not impacted the treatment strategy. There is wide consensus that CTC assessment would be more beneficial in early stage cancer, especially in those tumor types characterized by early progression and a lack of prognostic markers. Non-muscle-invasive bladder cancer represents an optimal model to this purpose. In fact, the rate of metastatic spread ranges between 20 and 40%, which is unacceptable for a 'superficial' tumor and unexpected in an early stage cancer. This may be due to the presence of non-clinically detectable micrometastases. CTCs may be used as a noninvasive, real-time tool for the stratification of early stage bladder cancer patients according to individual risk of progression.

  9. MITOGENIC SIGNALS CONTROL TRANSLATION OF THE EARLY GROWTH-RESPONSE GENE-1 IN MYOGENIC CELLS

    NARCIS (Netherlands)

    MAASS, A; GROHE, C; OBERDORF, S; SUKHATME, VP; VETTER, H; NEYSES, L

    1994-01-01

    Muscle is a major site of expression of the early growth reponse gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle So18 cells. Three groups of responses could be distinguished: 1. AII,

  10. Central Cell-Derived Peptides Regulate Early Embryo Patterning in Flowering Plants

    NARCIS (Netherlands)

    Costa, L.M.; Marshall, E.; Tesfaye, M.; Silverstein, K.A.T.; Mori, M.; Umetsu, Y.; Otterbach, S.L.; Papareddy, R.; Dickinson, H.G.; Boutilier, K.A.; VandenBosch, K.A.; Ohki, S.; Gutierrez-Marcos, J.F.

    2014-01-01

    Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning i

  11. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or heat-inact

  12. Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio; Panigrahy, Ashok; Sreedher, Gayathri; Bailey, Ariel [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Laney, Ernest John [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Rush University Medical Center, Department of Diagnostic Radiology, Chicago, IL (United States); La Colla, Luca [University of Parma, Department of Anesthesiology, Parma (Italy); UPMC Shadyside Hospital, Department of Emergency Medicine, Pittsburgh, PA (United States); Alper, Gulay [Children' s Hospital of Pittsburgh of UPMC, Department of Pediatric Neurology, Neuroimmunology Clinic, Pittsburgh, PA (United States)

    2014-08-15

    MR imaging criteria for diagnosing acute disseminated encephalomyelitis (ADEM) have not been clearly established. Due to the wide spectrum of differential considerations, new imaging features allowing early and accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would be characterized by vasogenic edema due to the potential reversibility of the disease. Sixteen patients who met the diagnostic criteria for ADEM proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) and had complete MR imaging studies performed at our institution during the acute phase of the disease were identified retrospectively and evaluated by experienced pediatric neuroradiologists. Vasogenic edema was demonstrated on diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two patients while the other two patients displayed no changes on DWI/ADC. ADC values for lesions and normal-appearing brain tissue were 1.39 ± 0.45 x 10{sup -3} and 0.81 ± 0.09 x 10{sup -3} mm/s{sup 2}, respectively (p = 0.002). When considering a cutoff of 5 days between acute and subacute disease, no difference between ADC values in acute vs. subacute phase was depicted. However, we found a significant correlation and an inverse and significant relationship between time and ADC value. We propose that vasogenic edema is a reliable diagnostic sign of acute neuroinflammation in ADEM. (orig.)

  13. Federal Mechanisms to Support Intervention Dissemination

    Science.gov (United States)

    Diana, Augusto; Bennett, Nicole

    2015-01-01

    This paper examines federal mechanisms that support program developers and researchers in disseminating effective interventions for public benefit. The purpose of this paper is not to discuss the dissemination of intervention research (i.e., how to inform stakeholders about research findings), nor is it intended to discuss the research of…

  14. The Tenth National Dissemination Conference. A Report.

    Science.gov (United States)

    Herlig, Richard K.

    This report on the Tenth National Dissemination Conference of 1977 outlines the purposes of the conference and summarizes the present state of educational information dissemination. National programs are described, including the National Institute of Education State Capacity Building Program, the National Diffusion Network, the Dissemination…

  15. Curriculum Dissemination as Planned Cultural Diffusion.

    Science.gov (United States)

    Rudduck, Jean

    The author traces the change from the use of the term "diffusion" to the term "dissemination" with reference to curriculum projects in Britain and discusses implications of the change. Although at one time the two terms were used interchangeably, the term "dissemination" now emphasizes techniques of effective management rather than the educational…

  16. D5.1 Dissemination Plan

    DEFF Research Database (Denmark)

    Buus, Lillian; Ryberg, Thomas; Eleftheriou, Paraskevi

    2009-01-01

    at defining the dissemination goals as well as the project’s target audience and channels through which the EATrain2 solution is going to be promoted. It also includes partners competences in the dissemination area and detailed schedule of events thematically related to the project’s scope. The deliverable...

  17. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

    Science.gov (United States)

    Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott C; Chasseing, Norma Alejandra

    2016-10-01

    Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

  18. Conditional Cripto overexpression in satellite cells promotes myogenic commitment and enhances early regeneration.

    Science.gov (United States)

    Prezioso, Carolina; Iaconis, Salvatore; Andolfi, Gennaro; Zentilin, Lorena; Iavarone, Francescopaolo; Guardiola, Ombretta; Minchiotti, Gabriella

    2015-01-01

    Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. Despite extensive studies, knowledge of the molecular mechanisms underlying the early events associated with satellite cell activation and myogenic commitment in muscle regeneration remains still incomplete. Cripto is a novel regulator of postnatal skeletal muscle regeneration and a promising target for future therapy. Indeed, Cripto is expressed both in myogenic and inflammatory cells in skeletal muscle after acute injury and it is required in the satellite cell compartment to achieve effective muscle regeneration. A critical requirement to further explore the in vivo cellular contribution of Cripto in regulating skeletal muscle regeneration is the possibility to overexpress Cripto in its endogenous configuration and in a cell and time-specific manner. Here we report the generation and the functional characterization of a novel mouse model for conditional expression of Cripto, i.e., the Tg:DsRed (loxP/loxP) Cripto-eGFP mice. Moreover, by using a satellite cell specific Cre-driver line we investigated the biological effect of Cripto overexpression in vivo, and provided evidence that overexpression of Cripto in the adult satellite cell compartment promotes myogenic commitment and differentiation, and enhances early regeneration in a mouse model of acute injury.

  19. Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation.

    Science.gov (United States)

    Sunami, Rei; Komuro, Mayuko; Yuminamochi, Tsutomu; Hoshi, Kazuhiko; Hirata, Shuji

    2010-03-01

    Fetus-derived cells are present in the blood and tissues of the maternal body over a long period of time, even after delivery, resulting in fetal cell microchimerism. The exact process by which fetal cells cross the placental barrier to enter the maternal circulation is unclear. The objective of this paper was to determine the time during pregnancy that fetal cells with multilineage potential migrate to the maternal organs. Wild type female mice were crossbred with male transgenic mice, expressing enhanced green fluorescent protein (EGFP). Total hysterectomies were performed at different time points of pregnancy. On day 60 after surgery, mice were injected with either streptozotocin (STZ) to induce insulin-dependent diabetes mellitus, or vehicle. Detection and quantification of fetal cells were then undertaken in a variety of maternal organs via fluorescent microscopy and quantitative PCR amplification of the gfp transgene. In vehicle control mice, fetal cells were detected only in the maternal bone marrow. However on day 30 after STZ injection, fetal cells were detected not only in bone marrow but also in the maternal pancreas, liver and kidney. Histological analysis showed differentiated fetal cells within the pancreatic acinar cells, hepatocytes and tubular epithelial cells. Their morphological appearance was indistinguishable from their maternal counterparts, and their frequency in these organs was constant, regardless of the timing of hysterectomy. These results indicate that most fetal cells with multilineage potential in maternal tissues migrate to the maternal body early after implantation, and thereafter sustain their population over the long term after delivery.

  20. Dissemination of solar photovoltaics: a study on the government programme to promote solar lantern in India

    Energy Technology Data Exchange (ETDEWEB)

    Velayudhan, S.K. [Administrative Staff College of India, Hyderabad (India)

    2003-11-01

    The study examines the reasons for the limited dissemination of solar lanterns in India. It uses ''diffusion of innovation'' framework to examine the dissemination process. The impact of the characteristics of solar lantern on dissemination and also the communication within the community about the product are examined. To understand the influence of the characteristics of solar lantern on dissemination and the information source used by adopters, a survey of 188 users across 15 locations is carried out. The study shows that the benefits promoted by the government programme for disseminating solar lantern are not the reasons for purchase in most cases. The results suggest that the emphasis on subsidy by the support programme shifts the focus to the cost of the solar lantern than its benefits. Contrary to expectation there is no significant difference in the profile of early and late adopters. The subsidy for solar lanterns and the targets set for government officials are the possible influence on the observed profile for adopter categories. The early majority who can afford the solar lantern and take up the innovation on its merits are expected to disseminate the innovation. The programme on the contrary not only fails to identify and promote to the early adopters, but focus on the disadvantaged groups. There are therefore no champions for the innovation and an absence of word-of-mouth communication. The information source is restricted to government agencies, while the potential user looks for evaluative information on the product from existing users. The application of ''diffusion of innovation'' framework to understand the dissemination process of solar lantern suggests reworking the support programmes designed to promote solar lanterns. The lessons can be extended to programmes designed for dissemination of other solar photovoltaic products. (author)

  1. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

    Science.gov (United States)

    Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

    2013-05-01

    The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS.

  2. Everolimus Treatment for an Early Infantile Subependymal Giant Cell Astrocytoma With Tuberous Sclerosis Complex.

    Science.gov (United States)

    Fukumura, Shinobu; Watanabe, Toshihide; Takayama, Rumiko; Minagawa, Kimio; Tsutsumi, Hiroyuki

    2015-08-01

    Subependymal giant cell astrocytomas are benign tumors often observed with tuberous sclerosis complex. These tumors are rarely diagnosed during fetal life or early infancy. Until recently, the only available treatment has been surgical resection. Current clinical research has demonstrated that everolimus can induce these tumors' regression. We report a 19-month-old boy with tuberous sclerosis complex. At 2 months of age, he presented with congenital subependymal giant cell astrocytoma that was complicated by refractory epilepsy and severe mental retardation. Treatment with everolimus was started when he was 10 months old. Three months after initiating everolimus, the tumor was significantly reduced in size, and the reduction was subsequently maintained. His seizures decreased and he showed cognitive and developmental improvement. No severe adverse events have been observed to date. Everolimus has promise as an effective alternative to surgery for subependymal giant cell astrocytomas during early infancy.

  3. Early- and late-born parvalbumin basket cell subpopulations exhibiting distinct regulation and roles in learning.

    Science.gov (United States)

    Donato, Flavio; Chowdhury, Ananya; Lahr, Maria; Caroni, Pico

    2015-02-18

    Brain networks can support learning by promoting acquisition of task-relevant information or by adhering to validated rules, but the mechanisms involved are poorly understood. Upon learning, local inhibitory parvalbumin (PV)-expressing Basket cell networks can switch to opposite configurations that either favor or interfere with further learning, but how this opposite plasticity is induced and relates to distinct learning requirements has remained unclear. Here, we show that PV Basket cells consist of hitherto unrecognized subpopulations, with distinct schedules of neurogenesis, input connectivities, output target neurons, and roles in learning. Plasticity of hippocampal early-born PV neurons was recruited in rule consolidation, whereas plasticity of late-born PV neurons was recruited in new information acquisition. This involved regulation of early-born neuron plasticity specifically through excitation, and of late-born neuron plasticity specifically through inhibition. Therefore, opposite learning requirements are implemented by distinct local networks involving PV Basket cell subpopulations specifically regulated through inhibition or excitation.

  4. Pluripotent Stem Cell Studies Elucidate the Underlying Mechanisms of Early Embryonic Development

    Directory of Open Access Journals (Sweden)

    Lingyu Li

    2011-03-01

    Full Text Available Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

  5. Disseminated lymphoma presenting as acute thigh pain and renal failure.

    LENUS (Irish Health Repository)

    Brown, Catherine

    2009-01-01

    A 66-year-old diabetic man presented with severe right thigh swelling and pain together with acute renal failure. At autopsy, this was found to be due to disseminated high grade B cell lymphoma invading the psoas muscle and multiple organs, including the kidneys. The unique presentation of this case emphasizes the need for increased awareness of the variety of ways in which lymphoma can manifest itself.

  6. Elevated Ratio of Th17 Cell-Derived Th1 Cells (CD161(+)Th1 Cells) to CD161(+)Th17 Cells in Peripheral Blood of Early-Onset Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.

  7. A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

    Science.gov (United States)

    Ono, Noriaki; Ono, Wanida; Nagasawa, Takashi; Kronenberg, Henry M

    2014-12-01

    The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals.

  8. Transcriptional analysis of early lineage commitment in human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Wormald Sam

    2007-03-01

    Full Text Available Abstract Background The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells. Results We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation. Conclusion These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo.

  9. Transcriptional analysis of early lineage commitment in human embryonic stem cells

    Science.gov (United States)

    Laslett, Andrew L; Grimmond, Sean; Gardiner, Brooke; Stamp, Lincon; Lin, Adelia; Hawes, Susan M; Wormald, Sam; Nikolic-Paterson, David; Haylock, David; Pera, Martin F

    2007-01-01

    Background The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells. Results We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling) to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation. Conclusion These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo. PMID:17335568

  10. MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

    Science.gov (United States)

    Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

    2011-02-15

    At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

  11. The influence of interspecies somatic cell nuclear transfer on epigenetic enzymes transcription in early embryos

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    Martin Morovic

    2016-10-01

    Full Text Available One of the main reason for the incorrect development of embryos derived from somatic cell nuclear transfer is caused by insufficient demethylation of injected somatic chromatin to a state comparable with an early embryonic nucleus. It is already known that the epigenetic enzymes transcription in oocytes and early embryos of several species including bovine and porcine zygotes is species-dependent process and the incomplete DNA methylation correlates with the nuclear transfer failure rate in mammals. In this study the transcription of DNA methyltransferase 1 and 3a (DNMT1, DNMT3a genes in early embryonic stages of interspecies (bovine, porcine nuclear transfer embryos (iSCNT by RT-PCR were analyzed. Coming out from the diverse timing of embryonic genome activation (EGA in porcine and bovine preimplantation embryos, the intense effect of ooplasm on transferred somatic cell nucleus was expected. In spite of the detection of ooplasmic DNA methyltransferases, the somatic genes for DNMT1 and DNMT3a enzymes were not expressed and the development of intergeneric embryos stopped at the 4-cell stage. Our results indicate that the epigenetic reprogramming during early mammalian development is strongly infl uenced by the ooplasmic environment.

  12. Early Results of Autologous Cultivated Limbal Stem Cell Transplantation in Total Limbal Stem Cell Deficiency

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    Mohammad Ali Javadi

    2008-12-01

    Full Text Available

    PURPOSE: To report the early results of transplantation of autologous limbal stem cells cultivated on amniotic membrane (AM in patients with total unilateral limbal stem cell deficiency (LSCD. METHODS: Four eyes of 4 patients with total unilateral LSCD confirmed with impression cytology underwent transplantation of autologous limbal stem cell cultivated on AM. At each follow up visit, a complete eye examination with special attention to recurrence or regression of vascularization, corneal opacification, and epithelial defect healing was performed. Digital imaging was performed at each follow up visit. Impression cytology was repeated in all cases after surgery. RESULTS: The patients were followed for 5-13 months. Visual acuity improved in all cases. Decrease in corneal opacification and vascularization was obvious in 3 cases with coverage of the cornea with corneal epithelium. Sectoral conjunctivalization was evident in these 3 cases, however the corneas were ready for transplantation. The procedure failed in one case with total corneal conjunctivalization. CONCLUSION: Transplantation of autologous stem cells cultivated on AM seems to be an effective way for total LSCD. More definite judgment needs longer follow up together with long-term results of corneal transplantation in these patients.

  1. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells.

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    Martin Pook

    Full Text Available Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA. We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain-145 kDa-accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation.

  2. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells.

    Science.gov (United States)

    Pook, Martin; Teino, Indrek; Kallas, Ade; Maimets, Toivo; Ingerpuu, Sulev; Jaks, Viljar

    2015-01-01

    Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain-145 kDa-accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation.

  3. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    Science.gov (United States)

    Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta

    2015-01-01

    In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  4. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    Directory of Open Access Journals (Sweden)

    Ioannis Kokkinopoulos

    Full Text Available In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  5. Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

    Science.gov (United States)

    Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

    2016-09-01

    Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21-2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

  6. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    Science.gov (United States)

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

  7. Power law relationship between cell cycle duration and cell volume in the early embryonic development of Caenorhabditis elegans.

    Science.gov (United States)

    Arata, Yukinobu; Takagi, Hiroaki; Sako, Yasushi; Sawa, Hitoshi

    2014-01-01

    Cell size is a critical factor for cell cycle regulation. In Xenopus embryos after midblastula transition (MBT), the cell cycle duration elongates in a power law relationship with the cell radius squared. This correlation has been explained by the model that cell surface area is a candidate to determine cell cycle duration. However, it remains unknown whether this second power law is conserved in other animal embryos. Here, we found that the relationship between cell cycle duration and cell size in Caenorhabditis elegans embryos exhibited a power law distribution. Interestingly, the powers of the time-size relationship could be grouped into at least three classes: highly size-correlated, moderately size-correlated, and potentially a size-non-correlated class according to C. elegans founder cell lineages (1.2, 0.81, and power law relationship is conserved in Xenopus and C. elegans, while the absolute powers in C. elegans were different from that in Xenopus. Furthermore, we found that the volume ratio between the nucleus and cell exhibited a power law relationship in the size-correlated classes. The power of the volume relationship was closest to that of the time-size relationship in the highly size-correlated class. This correlation raised the possibility that the time-size relationship, at least in the highly size-correlated class, is explained by the volume ratio of nuclear size and cell size. Thus, our quantitative measurements shed a light on the possibility that early embryonic C. elegans cell cycle duration is coordinated with cell size as a result of geometric constraints between intracellular structures.

  8. Cell polarity and patterning by PIN trafficking through early endosomal compartments in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Hirokazu Tanaka

    2013-05-01

    Full Text Available PIN-FORMED (PIN proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture.

  9. Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

    Science.gov (United States)

    Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

    2016-03-03

    Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

  10. Early transcriptional and epigenetic regulation of CD8(+) T cell differentiation revealed by single-cell RNA sequencing.

    Science.gov (United States)

    Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E; He, Zhaoren; Aigner, Stefan; Metz, Patrick J; Yu, Bingfei; Wehrens, Ellen J; Lopez, Justine; Kim, Stephanie H; Zuniga, Elina I; Goldrath, Ananda W; Chang, John T; Yeo, Gene W

    2017-04-01

    During microbial infection, responding CD8(+) T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8(+) T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8(+) T lymphocytes. Our findings suggest a model for the differentiation of terminal effector cells initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, which highlights the power and necessity of single-cell approaches.

  11. 急性早幼粒细胞白血病合并DIC行造血干细胞移植的护理%Nursing of acute promyelocytic leukemia complicated with disseminated intravascular coagulation after hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    徐晓东; 张蓓蓓; 颜霞; 侯悦; 刘国艳; 张京

    2013-01-01

    目的 1例急性早幼粒细胞白血病合并弥漫性血管内凝血行造血干细胞移植的护理体会,探索造血干细胞移植弥漫性血管内凝血的护理方法.方法 针对此病例的疾病特点,改革造血干细胞移植患者锁骨下双腔静脉插管的静脉输注途径,使用留置针穿刺外周静脉.通过对出凝血指标的监测与评估,采取行之有效的护理方法.结果 通过对患者出凝血指标异常的严密监测,出血部位得到控制.同时,给予全环境保护隔离,患者成功走出层流室.结论 弥漫性血管内凝血,不是一个独立的疾病.该例患者原发病合并DIC,随时有生命危险,因此护理是一个系统工程,只有制订有针对性的护理计划,给予准确的实施,才能保证患者移植成功.%Objective To analyze the procedure of nursing care in one patient with acute promyelocytic leukemia (APL)who developed disseminated intravascular coagulation (DIC)after hematopoietic stem cell transplantation (HSCT).Methods Peripheral venous indwelling needle was used as a pathway of intravenous infusion instead of subclavian central venous catheterization.And coagulation test was monitored and evaluated during HSCT.Results Through the monitoring of coagulation test and environment protective isolation,bleeding was controlled and the patient left laminar flow room successfully.Conclusions DIC is a complicated coagulation disorder.This patient developed life-threatening DIC during HSCT,therefore,for this patient,nursing care is a systematic work.So,only the specified targeted nursing care plans and accurate implementation could ensure the success of HSCT.

  12. Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

    Science.gov (United States)

    Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

    2014-03-01

    Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

  13. Predictors of recurrence in early stage oral tongue squamous cell carcinoma

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    Chandrashekar Mani

    2015-01-01

    Full Text Available Introduction: Many histopathological parameters in oral tongue squamous cell carcinoma (OTSCC have been identified as predictive factors. Certain tumor-related factors increase the risk of nodal metastasis, and many pathological factors affect survival. Objective: The objective of this study is to identify that tumor-related histopathological prognostic factors that can predict recurrence and potentially influence the decision for adjuvant radiotherapy in early stage OTSCC. Materials and Methods: A total of 51 patients who underwent surgery for early stage OTSCC (stage I, II from 2007 to 2013 were selected. Demographic and clinical details were retrieved. Histopathological reports were reviewed for the following parameters-Margin status (close <5 mm, positive - Invasive squamous cell carcinoma [SCC], carcinoma in situ, marked dysplasia, microscopic depth of invasion, skeletal muscle infiltration (SMI, tumor differentiation, perineural invasion, lymphovascular invasion. Overall survival and recurrence-free survival (RFS were calculated using the Kaplan-Meier method. Predictors of recurrence were identified using Univariate analysis. Results: Median follow-up was 22 months (range, 5-89 months, the overall survival and RFS were 88% and 81% respectively. The recurrence rate was 19.5% during this time period. The only significant predictor of recurrence in pathologically early stage OTSCC was SMI (P = 0.003 on univariate analysis. Eighty-seven percentage of the recurrences in our study occurred within the 1 st year, with a disease specific mortality rate of 12.5%. Conclusion: In early stage OTSCC, Failure occurred predominantly in patients who had SMI.

  14. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

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    Sabyasachi Halder

    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.

  15. Optical imaging of disseminated leukemia models in mice with near-infrared probe conjugated to a monoclonal antibody.

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    Sabrina Pesnel

    Full Text Available BACKGROUND: The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI to determine when to start treatments with novel antitumor agents. METHODS: Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. RESULTS: The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. CONCLUSIONS: A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented.

  16. Dissemination of information to General Practitioners: a questionnaire survey

    Directory of Open Access Journals (Sweden)

    Fortnum Heather

    2004-11-01

    Full Text Available Abstract Background Early identification of permanent hearing impairment in children enables appropriate intervention which reduces adverse developmental outcomes. The UK Government has introduced a universal hearing screening programme for neonates. All involved health professionals, including those in Primary Care, need to be aware of the service to enable them to offer appropriate support to their patients. A programme of information dissemination within Primary Care was therefore undertaken. The aim of the current study was to determine the extent to which the information had reached General Practitioners (GPs, the GPs' preferred mode of dissemination and the sources from which GPs accessed information Methods Postal questionnaire survey of a randomised sample of 1000 GPs in the Phase I pilot sites of the Neonatal Hearing Screening Programme (NHSP. Results Responses were received from 54.2% of the sample. Just under 50% of those responding had received information, 62.2% of respondents said they would like to receive more information and the preferred methods of dissemination were the written word and web-sites to allow access when needed. Few GPs perceive themselves to have a core role in the delivery of the NHSP and thence a need for knowledge in the subject. Many are keen to delegate detail to a third party, usually the health visitor, who has traditionally had responsibility for hearing screening. Conclusions Dissemination efforts for service developments of relevance to GPs should concentrate on advertising a website address via brief but memorable posted literature and/or articles in relevant journals and magazines. The website should be GP-friendly, and have a dedicated area for GPs including information of specific relevance and downloadable information sheets.

  17. Endothelial JAM-A promotes reovirus viremia and bloodstream dissemination.

    Science.gov (United States)

    Lai, Caroline M; Boehme, Karl W; Pruijssers, Andrea J; Parekh, Vrajesh V; Van Kaer, Luc; Parkos, Charles A; Dermody, Terence S

    2015-02-01

    Viruses that cause systemic disease often spread through the bloodstream to infect target tissues. Although viremia is an important step in the pathogenesis of many viruses, how viremia is established is not well understood. Reovirus has been used to dissect mechanisms of viral pathogenesis and is being evaluated in clinical trials as an oncolytic agent. After peroral entry into mice, reovirus replicates within the gastrointestinal tract and disseminates systemically via hematogenous or neural routes. Junctional adhesion molecule-A (JAM-A) is a tight junction protein that serves as a receptor for reovirus. JAM-A is required for establishment of viremia and viral spread to sites of secondary replication. JAM-A also is expressed on the surface of circulating hematopoietic cells. To determine contributions of endothelial and hematopoietic JAM-A to reovirus dissemination and pathogenesis, we generated strains of mice with altered JAM-A expression in these cell types and assessed bloodstream spread of reovirus strain type 1 Lang (T1L), which disseminates solely by hematogenous routes. We found that endothelial JAM-A but not hematopoietic JAM-A facilitates reovirus T1L bloodstream entry and egress. Understanding how viruses establish viremia may aid in development of inhibitors of this critical step in viral pathogenesis and foster engineering of improved oncolytic viral vectors.

  18. Disseminated intravascular coagulation in cancer patients

    NARCIS (Netherlands)

    M. Levi

    2009-01-01

    Disseminated intravascular coagulation (DIC) is a syndrome that may complicate a variety of diseases, including malignant disease. DIC is characterized by widespread, intravascular activation of coagulation (leading to intravascular fibrin deposition) and simultaneous consumption of coagulation fact

  19. Smart-tag Based Data Dissemination

    DEFF Research Database (Denmark)

    Bonnet, Philippe; Beaufour, Allan; Leopold, Martin

    2002-01-01

    Monitoring wide, hostile areas requires disseminating data between fixed, disconnected clusters of sensor nodes. It is not always possible to install long-range radios in order to cover the whole area. We propose to leverage the movement of mobile individuals, equipped with smart......-tags, to disseminate data across disconnected static nodes spread across a wide area. Static nodes and mobile smart-tags exchange data when they are in the vicinity of each other; smart-tags disseminate data as they move around. In this paper, we propose an algorithm for update propagation and a model for smart......-tag based data dissemination. We use simulation to study the characteristics of the model we propose. Finally, we present an implementation based on Bluetooth smart-tags....

  20. A Model of Isotope Separation in Cells at the Early Stages of Evolution.

    Science.gov (United States)

    Melkikh, A V; Bokunyaeva, A O

    2016-03-01

    The separation of the isotopes of certain ions can serve as an important criterion for the presence of life in the early stages of its evolution. A model of the separation of isotopes during their transport through the cell membrane is constructed. The dependence of the selection coefficient on various parameters is found. In particular, it is shown that the maximum efficiency of the transport of ions corresponds to the minimum enrichment coefficient. At the maximum enrichment, the efficiency of the transport system approaches ½. Calculated enrichment coefficients are compared with experimentally obtained values for different types of cells, and the comparison shows a qualitative agreement between these quantities.

  1. A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation

    Science.gov (United States)

    Delile, Julien; Herrmann, Matthieu; Peyriéras, Nadine; Doursat, René

    2017-01-01

    The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal `cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework.

  2. Disseminated intravascular coagulation in burn injury.

    Science.gov (United States)

    Lippi, Giuseppe; Ippolito, Luigi; Cervellin, Gianfranco

    2010-06-01

    Disseminated intravascular coagulation (DIC) is a complex and multifaceted disorder characterized by the activation of coagulation and fibrinolytic pathways, consumption of coagulation factors, and depletion of coagulation regulatory proteins. The introduction into the circulation of cellular debris characterized by strong thromboplastic activity due to tissue factor exposition or release (in or from burned tissues), which can thereby activate extrinsic pathway of coagulation system and trigger massive thrombin generation when present in sufficient concentration, represents the most plausible biological explanation to support the development of intravascular coagulation in patients with burn injury. Severe burns left untreated might also lead to an immunological and inflammatory response (activation of the complement cascade), which can amplify fibrinolysis and blood clotting. Overall, the real prevalence of DIC in patients with burns is as yet unclear. Postmortem, retrospective, and even longitudinal investigations are in fact biased by several factors, such as the objective difficulty to establish whether DIC might have occurred as a primary complication of burns or rather as a consequence of other superimposed pathologies (e.g., sepsis, multiple organ failure), the different diagnostic criteria for assessing DIC, and the heterogeneity of the patient samples studied. Nevertheless, the current scientific evidence is consistent with the hypothesis that biochemical changes suggestive for DIC (hypercoagulability, hypo- and hyperfibrinolysis) are commonplace in patients with burn trauma, and their severity increases exponentially with the severity of injury. Overt DIC seems to occur especially in critically ill burn patients or in those with severe burns (up to third degree) and large involvement of body surface area, in whom an appropriate therapy might be effective to prevent the otherwise fulminant course. Although early prophylaxis with antithrombin concentrates

  3. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    Science.gov (United States)

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.

  4. Chordoid glioma with intraventricular dissemination: A case report with perfusion MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ki, So Yeon; Kim, Seul Kee; Heo, Tae Wook; Baek, Byung Hyun; Kim, Hyung Seok; Yoon, Woong [Chonnam National University Medical School, Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2016-02-15

    Chordoid glioma is a rare low grade tumor typically located in the third ventricle. Although a chordoid glioma can arise from ventricle with tumor cells having features of ependymal differentiation, intraventricular dissemination has not been reported. Here we report a case of a patient with third ventricular chordoid glioma and intraventricular dissemination in the lateral and fourth ventricles. We described the perfusion MR imaging features of our case different from a previous report.

  5. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.

    Science.gov (United States)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja; Jensen, Pia Rosgaard; Alnaimi, Ragad Walid; Rolighed, Lars; Engelholm, Lars H; Marcussen, Niels; Andersen, Thomas Levin

    2016-06-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.

  6. Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.

    Science.gov (United States)

    Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

    2009-08-01

    Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.

  7. Second heart field cardiac progenitor cells in the early mouse embryo.

    Science.gov (United States)

    Francou, Alexandre; Saint-Michel, Edouard; Mesbah, Karim; Théveniau-Ruissy, Magali; Rana, M Sameer; Christoffels, Vincent M; Kelly, Robert G

    2013-04-01

    At the end of the first week of mouse gestation, cardiomyocyte differentiation initiates in the cardiac crescent to give rise to the linear heart tube. The heart tube subsequently elongates by addition of cardiac progenitor cells from adjacent pharyngeal mesoderm to the growing arterial and venous poles. These progenitor cells, termed the second heart field, originate in splanchnic mesoderm medial to cells of the cardiac crescent and are patterned into anterior and posterior domains adjacent to the arterial and venous poles of the heart, respectively. Perturbation of second heart field cell deployment results in a spectrum of congenital heart anomalies including conotruncal and atrial septal defects seen in human patients. Here, we briefly review current knowledge of how the properties of second heart field cells are controlled by a network of transcriptional regulators and intercellular signaling pathways. Focus will be on 1) the regulation of cardiac progenitor cell proliferation in pharyngeal mesoderm, 2) the control of progressive progenitor cell differentiation and 3) the patterning of cardiac progenitor cells in the dorsal pericardial wall. Coordination of these three processes in the early embryo drives progressive heart tube elongation during cardiac morphogenesis. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

  8. Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5+ Intestinal Stem Cells

    Directory of Open Access Journals (Sweden)

    Tae-Hee Kim

    2016-08-01

    Full Text Available Lgr5+ intestinal stem cells (ISCs drive epithelial self-renewal, and their immediate progeny—intestinal bipotential progenitors—produce absorptive and secretory lineages via lateral inhibition. To define features of early transit from the ISC compartment, we used a microfluidics approach to measure selected stem- and lineage-specific transcripts in single Lgr5+ cells. We identified two distinct cell populations, one that expresses known ISC markers and a second, abundant population that simultaneously expresses markers of stem and mature absorptive and secretory cells. Single-molecule mRNA in situ hybridization and immunofluorescence verified expression of lineage-restricted genes in a subset of Lgr5+ cells in vivo. Transcriptional network analysis revealed that one group of Lgr5+ cells arises from the other and displays characteristics expected of bipotential progenitors, including activation of Notch ligand and cell-cycle-inhibitor genes. These findings define the earliest steps in ISC differentiation and reveal multilineage gene priming as a fundamental property of the process.

  9. In trans complementation of lethal factor reveal roles in colonization and dissemination in a murine mouse model.

    Directory of Open Access Journals (Sweden)

    David E Lowe

    Full Text Available Lethal factor (LF is a component of the B. anthracis exotoxin and critical for pathogenesis. The roles of LF in early anthrax pathogenesis, such as colonization and dissemination from the initial site of infection, are poorly understood. In mice models of infection, LF-deficient strains either have altered dissemination patterns or do not colonize, precluding analysis of the role of LF in colonization and dissemination from the portal of entry. Previous reports indicate rabbit and guinea pig models infected with LF-deficient strains have decreased virulence, yet the inability to use bioluminescent imaging techniques to track B. anthracis growth and dissemination in these hosts makes analysis of early pathogenesis challenging. In this study, the roles of LF early in infection were analyzed using bioluminescent signature tagged libraries of B. anthracis with varying ratios of LF-producing and LF-deficient clones. Populations where all clones produced LF and populations where only 40% of clones produce LF were equally virulent. The 40% LF-producing clones trans complimented the LF mutants and permitted them to colonize and disseminate. Decreases of the LF producing strains to 10% or 0.3% of the population led to increased host survival and decreased trans complementation of the LF mutants. A library with 10% LF producing clones could replicate and disseminate, but fewer clones disseminated and the mutant clones were less competitive than wild type. The inoculum with 0.3% LF producing clones could not colonize the host. This strongly suggests that between 10% and 0.3% of the population must produce LF in order to colonize. In total, these findings suggest that a threshold of LF must be produced in order for colonization and dissemination to occur in vivo. These observations suggest that LF has a major role in the early stages of colonization and dissemination.

  10. Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer.

    Science.gov (United States)

    Zhang, J-L; Yao, Q; Chen Y Wang, J-H; Wang, H; Fan, Q; Ling, R; Yi, J; Wang, L

    2015-03-20

    The objective of this study was to determine the changes in peripheral blood circulating tumor cells in HER2-positive early breast cancer before and after Herceptin therapy, and to explore the effects of the HER2 gene and Herceptin on circulating tumor cells. CK19 mRNA expression in peripheral blood was evaluated by qRT-PCR as an index of circulating tumor cells in 15 cases of HER-2-positive breast cancer and 18 cases of HER2-negative breast cancer before, and after chemotherapy as well. Ten cases of HER2-positive breast cancer continued on Herceptin therapy for 3 months after chemotherapy, and their peripheral blood was again drawn and assayed for CK-19 mRNA expression. Preoperatively, all cases of HER2-positive cancer were positive for CK19 mRNA in peripheral blood, but 6 cases of HER2-negative breast cancer were positive (33.3%), where there was a substantial difference between the two groups. After 6 cycles of adjuvant chemotherapy, CK19 positive rates in cases of HER2-positive and -negative breast cancer reduced by 93.3 and 11.1%, respectively, with a significant difference still existing. After 3 months of Herceptin therapy, expression of CK19 mRNA declined considerably in 10 cases of HER2 positive breast cancer (113.66 ± 88.65 vs 63.35 ± 49.27, P = 0.025). HER-2 gene expression closely correlated with circulating tumor cells in peripheral blood of early breast cancer patients. Moreover, Herceptin, a monoclonal antibody for HER2, can reduce the number of circulating tumor cells, which can be an early predictive factor for Herceptin therapy effectiveness against breast cancer.

  11. Early introduction and delayed dissemination of pandemic influenza, Gabon.

    Science.gov (United States)

    Lekana-Douki, Sonia Etenna; Mouinga-Ondémé, Augustin; Nkoghe, Dieudonné; Drosten, Christian; Drexler, Jan Felix; Kazanji, Mirdad; Leroy, Eric M

    2013-04-01

    Active surveillance in health care centers in Gabon during 2009-2011 detected 72 clinical cases of pandemic (H1N1) 2009 (pH1N1). We found that pH1N1 virus was introduced in mid-2009 but spread throughout the country in 2010. Thus, Gabon was also affected by pH1N1.

  12. Lanthanum Prevents Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells by Controlling Early Induction Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In a previous study, a salt stress-induced programmed cell death (PCD) model was established in rice root tip cells. Here,by using Wuyunjing 8th rice seedlings, the effects of lanthanum on salt stress-induced PCD early events were studied. The peroxidase (APX). Imidazole (20 mmol/L), the inhibitor of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), could alleviate the occurrence of PCD obviously, and such alleviation could be enhanced by the addition of La3+,indicating the involvement of NADPH oxidase in the salt stress-induced PCD process. Taken together, lanthanum could prevent salt stress-induced PCD occurrence in the rice root tip cells by blocking the calcium influx under stress, which was followed by inhibiting calcium-dependent NADPH oxidase activity to prevent O2·-production and, enhancing the cytosolic antioxidative enzyme activities to scavenge the reactive oxygen species.

  13. Biochemical DSB-repair model for mammalian cells in G1 and early S phases of the cell cycle.

    Science.gov (United States)

    Taleei, Reza; Nikjoo, Hooshang

    2013-08-30

    The paper presents a model of double strand breaks (DSB) repair in G1 and early S phases of the cell cycle. The model is based on a plethora of published information on biochemical modification of DSB induced by ionizing radiation. So far, three main DSB repair pathways have been identified, including nonhomologous end-joining (NHEJ), homologous recombination (HR), and microhomology-mediated end-joining (MMEJ). During G1 and early S phases of the cell cycle, NHEJ and MMEJ repair pathways are activated dependent on the type of double strand breaks. Simple DSB are a substrate for NHEJ, while complex DSB and DSB in heterochromatin require further end processing. Repair of all DSB start with NHEJ presynaptic processes, and depending on the type of DSB pursue simple ligation, further end processing prior to ligation, or resection. Using law of mass action the model is translated into a mathematical formalism. The solution of the formalism provides the step by step and overall repair kinetics. The overall repair kinetics are compared with the published experimental measurements. Our calculations are in agreement with the experimental results and show that the complex types of DSBs are repaired with slow repair kinetics. The G1 and early S phase model could be employed to predict the kinetics of DSB repair for damage induced by high LET radiation.

  14. Transitional B cells in early human B cell development - time to revisit the paradigm?

    Directory of Open Access Journals (Sweden)

    Victoria G Martin

    2016-12-01

    Full Text Available The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig genes, and consequently an equally large number of potential specificities for antigen. As the process is essentially random, then cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B>>immature>>transitional>>naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire, and can be seen both in gene usage and in CDR-H3 characteristics. Age-related changes are small and only the size of the CDR-H3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B>>immature>>transitional>>naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages.

  15. Improvement of early cell adhesion on Thai silk fibroin surface by low energy plasma.

    Science.gov (United States)

    Amornsudthiwat, Phakdee; Mongkolnavin, Rattachat; Kanokpanont, Sorada; Panpranot, Joongjai; Wong, Chiow San; Damrongsakkul, Siriporn

    2013-11-01

    Low energy plasma has been introduced to treat the surface of Thai silk fibroin which should be enhanced for cell adhesion due to its native hydrophobic surface. Plasma surface treatment could introduce desirable hydrophilic functionalities on the surface without using any chemicals. In this work, nitrogen glow discharge plasma was generated by a low energy AC50Hz power supply system. The plasma operating conditions were optimized to reach the highest nitrogen active species by using optical emission spectroscopy. X-ray photoelectron spectroscopy (XPS) revealed that amine, hydroxyl, ether, and carboxyl groups were induced on Thai silk fibroin surface after plasma treatment. The results on Fourier transform infrared attenuated total reflection (FTIR-ATR) spectroscopy confirmed that the plasma treated effects were only on the outermost layer since there was no change in the bulk chemistry. The surface topography was insignificantly changed from the detection with atomic force microscopy (AFM). The plasma-treated effects were the improved surface wettability and cell adhesion. After a 90-s treatment, the water contact angle was at 20°, while the untreated surface was at 70°. The early cell adhesion of L929 mouse fibroblast was accelerated. L929 cells only took 3h to reach 100% cell adhesion on 90 s N2 plasma-treated surface, while there was less than 50% cell adhesion on the untreated Thai silk fibroin surface after 6h of culture. The cell adhesion results were in agreement with the cytoskeleton development. L929 F-actin was more evident on 90 s N2 plasma-treated surface than others. It could be concluded that a lower energy AC50Hz plasma system enhanced early L929 mouse fibroblast adhesion on Thai silk fibroin surface without any significant change in surface topography and bulk chemistry.

  16. Involvement of insulin in early development of mouse one-cell stage embryos

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-sults suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

  17. Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Mohammad S Alzahri

    2015-01-01

    Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

  18. Involvement of insulin in early development of mouse one-cell stase embryos

    Institute of Scientific and Technical Information of China (English)

    YU BingZhi; YU DaHai; ZHANG Zhe; DENG Xin; XU XiaoYan; FENG Chen; LI YanXiao; CUI Cheng; SU WenHui; ZHAO HongMei

    2008-01-01

    Recent studies have suggested that growth factors and hormones play important roles in cell prolif-eration and differentiation during early embryonic development. In the present study, we examined the expression and localization of insulin in the mouse oocytes and one-cell stage embryos by quantitative ELISA, RT-PCR, Western blot and immunofluorescence. In the mouse oocytes and one-cell stage em-bryos, expression of insulin was uniformly distributed in the cytoplasm. We also examined the expres-sion, activity and localization of mTOR (mammalian target of rapamycin) and p70S6K. The expression of mTOR and p70S6K was not significantly different at the cell cycle of mouse one-cell stage embryos. mTOR and S6K were distributed evenly in the cytoplasm at G1, G2 and M phase phase, but at S phase, the distribution of mTOR and S6K was around the pronucleus. At different phases, the activity of mTOR fluctuated. We also used the PI3K specific inhibitor-Wortmannin to investigate the cleavage rate of eggs. The result showed that the rate obviously decreased. When the mTOR specific inhibitor Rapa-mycin was used, the first mitotic division of the mouse one-cell stage embryo was delayed. These re-suits suggested that insulin was expressed both in mouse oocytes and one-cell stage embryos, and may play functional roles in regulation of mouse early embryogenesis by activating the signal pathway of PI3K/PKB/mTOR/S6K.

  19. Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.

    Science.gov (United States)

    Butler, John T; Hall, Lisa L; Smith, Kelly P; Lawrence, Jeanne B

    2009-07-01

    The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different "nuclear landscape" in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display approximately 1-3 large PML structures of two morphological types: long linear "rods" or elaborate "rosettes", which lack substantial SUMO-1, Daxx, and Sp100. These occur primarily between Day 0-2 of differentiation and become rare thereafter. PML rods may be "taut" between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a "gap" in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures.

  20. Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction.

    Science.gov (United States)

    Kuo, Taiyi; Kim-Muller, Ja Young; McGraw, Timothy E; Accili, Domenico

    2016-04-29

    Insulin resistance and β cell dysfunction contribute to the pathogenesis of type 2 diabetes. Unlike insulin resistance, β cell dysfunction remains difficult to predict and monitor, because of the inaccessibility of the endocrine pancreas, the integrated relationship with insulin sensitivity, and the paracrine effects of incretins. The goal of our study was to survey the plasma response to a metabolic challenge in order to identify factors predictive of β cell dysfunction. To this end, we combined (i) the power of unbiased iTRAQ (isobaric tag for relative and absolute quantification) mass spectrometry with (ii) direct sampling of the portal vein following an intravenous glucose/arginine challenge (IVGATT) in (iii) mice with a genetic β cell defect. By so doing, we excluded the effects of peripheral insulin sensitivity as well as those of incretins on β cells, and focused on the first phase of insulin secretion to capture the early pathophysiology of β cell dysfunction. We compared plasma protein profiles with ex vivo islet secretome and transcriptome analyses. We detected changes to 418 plasma proteins in vivo, and detected changes to 262 proteins ex vivo The impairment of insulin secretion was associated with greater overall changes in the plasma response to IVGATT, possibly reflecting metabolic instability. Reduced levels of proteins regulating redox state and neuronal stress markers, as well as increased levels of coagulation factors, antedated the loss of insulin secretion in diabetic mice. These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future β cell failure.

  1. Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection

    Science.gov (United States)

    Feruglio, S L; Tonby, K; Kvale, D; Dyrhol-Riise, A M

    2015-01-01

    Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4+ T regulatory cells (Tregs) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2+ cells increased over time for both CD4+ and CD8+ T cells. The Treg subsets CD25highCD127low, CD25highCD147++ and CD25highCD127lowCD161+ expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25highCD127lowCD39+ Tregs remained unchanged. The fraction of CD25highCD127low Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4+ and CD8+ T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further. PMID:25313008

  2. Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Feruglio, S L; Tonby, K; Kvale, D; Dyrhol-Riise, A M

    2015-03-01

    Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (Tregs ) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+) cells increased over time for both CD4(+) and CD8(+) T cells. The Treg subsets CD25(high) CD127(low) , CD25(high) CD147(++) and CD25(high) CD127(low) CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high) CD127(low) CD39(+) Tregs remained unchanged. The fraction of CD25(high) CD127(low) Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.

  3. Development of a bovine luteal cell in vitro culture system suitable for co-culture with early embryos.

    Science.gov (United States)

    Batista, M; Torres, A; Diniz, P; Mateus, L; Lopes-da-Costa, L

    2012-10-01

    The cross talk between the corpus luteum (CL) and the early embryo, potentially relevant to pregnancy establishment, is difficult to evaluate in the in vivo bovine model. In vitro co-culture of bovine luteal cells and early embryos (days 2-8 post in vitro fertilization) may allow the deciphering of this poorly understood cross talk. However, early embryos and somatic cells require different in vitro culture conditions. The objective of this study was to develop a bovine luteal cell in vitro culture system suitable for co-culture with early embryos in order to evaluate their putative steroidogenic and prostanoid interactions. The corpora lutea of the different stages of the estrous cycle (early, mid, and late) were recovered postmortem and enriched luteal cell populations were obtained. In experiments 1 and 2, the effects of CL stage, culture medium (TCM, DMEM-F12, or SOF), serum concentration (5 or 10%), atmosphere oxygen tension (5 or 20%), and refreshment of the medium on the ability of luteal cells to produce progesterone (P(4)) were evaluated. The production of P(4) was significantly increased in early CL cultures, and luteal cells adapted well to simple media (SOF), low serum concentrations (5%), and oxygen tensions (5%). In experiment 3, previous luteal cell cryopreservation did not affect the production of P(4), PGF(2α), and PGE(2) compared to fresh cell cultures. This enables the use of pools of frozen-thawed cells to decrease the variation in cell function associated with primary cell cultures. In experiment 4, mineral oil overlaying culture wells resulted in a 50-fold decrease of the P(4) quantified in the medium, but had no effect on PGF(2α) and PGE(2) quantification. In conclusion, a luteal cell in vitro culture system suitable for the 5-d-long co-culture with early embryos was developed.

  4. A hazard-independent approach for the standardised multi-channel dissemination of warning messages

    Science.gov (United States)

    Esbri Palomares, M. A.; Hammitzsch, M.; Lendholt, M.

    2012-04-01

    The tsunami disaster affecting the Indian Ocean region on Christmas 2004 demonstrated very clearly the shortcomings in tsunami detection, public warning processes as well as intergovernmental warning message exchange in the Indian Ocean region. In that regard, early warning systems require that the dissemination of early warning messages has to be executed in way that ensures that the message delivery is timely; the message content is understandable, usable and accurate. To that end, diverse and multiple dissemination channels must be used to increase the chance of the messages reaching all affected persons in a hazard scenario. In addition to this, usage of internationally accepted standards for the warning dissemination such as the Common Alerting Protocol (CAP) and Emergency Data Exchange Language (EDXL) Distribution Element specified by the Organization for the Advancement of Structured Information Standards (OASIS) increase the interoperability among different warning systems enabling thus the concept of system-of-systems proposed by GEOSS. The project Distant Early Warning System (DEWS), co-funded by the European Commission under the 6th Framework Programme, aims at strengthening the early warning capacities by building an innovative generation of interoperable tsunami early warning systems based on the above mentioned concepts following a Service-oriented Architecture (SOA) approach. The project focuses on the downstream part of the hazard information processing where customized, user-tailored warning messages and alerts flow from the warning centre to the responsible authorities and/or the public with their different needs and responsibilities. The information logistics services within DEWS generate tailored EDXL-DE/CAP warning messages for each user that must receive the message according to their preferences, e.g., settings for language, interested areas, dissemination channels, etc.. However, the significant difference in the implementation and

  5. The relationship between interfragmentary movement and cell differentiation in early fracture healing under locking plate fixation.

    Science.gov (United States)

    Miramini, Saeed; Zhang, Lihai; Richardson, Martin; Mendis, Priyan; Oloyede, Adekunle; Ebeling, Peter

    2016-03-01

    Interfragmentary movement (IFM) at the fracture site plays an important role in fracture healing, particularly during its early stage, via influencing the mechanical microenvironment of mesenchymal stem cells within the fracture callus. However, the effect of changes in IFM resulting from the changes in the configuration of locking plate fixation on cell differentiation has not yet been fully understood. In this study, mechanical experiments on surrogate tibia specimens, manufactured from specially formulated polyurethane, were conducted to investigate changes in IFM of fractures under various locking plate fixation configurations and loading magnitudes. The effect of the observed IFM on callus cell differentiation was then further studied using computational simulation. We found that during the early stage, cell differentiation in the fracture callus is highly influenced by fracture gap size and IFM, which in turn, is highly sensitive to locking plate fixation configuration. The computational model predicted that a small gap size (e.g. 1 mm) under a relatively flexible configuration of locking plate fixation (larger bone-plate distances and working lengths) could experience excessive strain and fluid flow within the fracture site, resulting in excessive fibrous tissue differentiation and delayed healing. By contrast, a relatively flexible configuration of locking plate fixation was predicted to improve cartilaginous callus formation and bone healing for a relatively larger gap size (e.g. 3 mm). If further confirmed by animal and human studies, the research outcome of this paper may have implications for orthopaedic surgeons in optimising the application of locking plate fixations for fractures in clinical practice.

  6. Clinical profile of disseminated cryptococcal infection-a case series

    Institute of Scientific and Technical Information of China (English)

    Vishwanath Sathyanarayanan; Ragini Bekur; Abdul Razak; Joydeep Chakraborty

    2010-01-01

    Objective:To study disseminated cryptococcal infection in a tertiary care hospital in Southern India.Methods:The clinical profile of 12 disseminated cryptococcosis patients with the age group of28-52years was retrospectively analyzed.Results:7(58.3%) presented with fever 30 days whereas2(16.7%)did not have fever. All the12(100%) had headache, 2(16.7%)had altered sensorium, one(8%)seizure.5(41.7%) had diarrhea and vomiting.6(50%) had oral candidiasis, and anemia.9(75%)had elevated erythrocyte sedimentation rate (ESR). 6(50%) had neck stiffness. Cerebrospinal fluid (CSF) pressure was elevated in all12(100%) patients. Blood culture positive for Cryptococcus neoformans(C. neoformans) in11(91.7%) andCSF culture positive in all12 (100%), one(8%)had urine culture positive. India ink preparation was positive in 10(83.3%). CD4 count was less than50/microl in 4 (33.3%), between 50-100 in6(50%)and2(16.7%) in the range of100-200. 6(50%) were treated with parenteral amphotericin B (0.7 mg/kg/d) during intensive phase followed by oral fluconazole400 mg/d for8 weeks then maintenance oral fluconazole 200 mg/d.5(41.6%) were treated with fluconazole alone.8(66.7%) improved and4(33.3%) patients died. Among those who succumbed to the illness,2(16.7%) received amphotericin and fluconazole,2(16.7%) patients received fluconazole alone.Conclusions: Disseminated cryptococcosis can cause considerable mortality inHIV patients and immunocompromised non-HIV individuals. At times, its presentation closely mimics that of Tuberculosis. Early diagnosis and appropriate treatment should be started as early as possible.

  7. Cell death and cell proliferation in mouse submandibular gland during early post-irradiation phase.

    Directory of Open Access Journals (Sweden)

    Bralic,Marina

    2005-08-01

    Full Text Available

    The effects of irradiation on different cell compartments in the submandibular gland were analyzed in adult C57BL/6 mice exposed to X-ray irradiation and followed up for 10 days. Apoptosis was quantified using the terminal deoxynucleotidyl transferase (TdT-mediated dUTP-digoxigenin nick end labeling method (TUNEL. Cell proliferation was detected using immunohistochemistry for proliferating cell nuclear antigen (PCNA. Radiation-induced apoptosis occurred rapidly, reaching a maximum 3 days post-irradiation. The percentage of apoptotic cells increased with the irradiation dose. At day 1 post-irradiation, cell proliferation was significantly reduced in comparison to sham-irradiated controls. After post-irradiation arrest of the cell cycle, proliferation increased in all gland compartments, reaching a maximum at day 6 post-irradiation. The proliferation response corresponded to the dose of irradiation. We suggest that the reason for gland dysfunction could be the coexistence of high apoptotic and proliferative activity in the irradiated gland.

  8. Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development.

    Science.gov (United States)

    Zhou, H; Aziza, J; Sol, J C; Courtade-Saïdi, M; Chatelin, S; Evra, C; Parant, O; Lazorthes, Y; Jozan, S

    2006-04-01

    Adult adrenal chromaffin cells are being utilized for therapeutic transplantation. With the prospect of using fetal chromaffin cells in pain therapy, we studied their phenotype, proliferative power, function, and growth in vitro and in situ in order to determine the optimal time for implantation. Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of chromaffin cells with a noradrenergic phenotype akin to that observed, in situ. Among the adherent chromaffin cells first observed in vitro, only a few samples expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which appeared later, expressed it. However, neither of the two types of populations expressed an adrenergic phenotype in line with that observed in situ. At the upper limits of the voluntary abortion period authorized in France, this phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ. For the first time in man, we demonstrate the secretion of noradrenaline in vitro by the two populations of cells. Consistent with this result, we also noted dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within this period. These observations on the expression of these biological factors indicate that 9-10 GW would be the best stage for sampling these cells for preclinical transplantation experiments.

  9. Early Development of Squamous Cell Carsinoma in Two Sister Cases with pidermodysplasia Verruciformis

    Directory of Open Access Journals (Sweden)

    Ömer Çalka

    2010-06-01

    Full Text Available Epidermodysplasia verruciformis (Lewandowsky-Lutz syndrome is an uncommon disease characterized by multiple plane warts, pityriasis versicolor-like lesions, defects of cell-mediated immunity, and tendency to develop skin malignancies, primarily on sun-exposed areas. Most commonly it is inherited as an autosomal recessive trait. Squamous cell carcinoma is the most common type of skin cancer found in patient with epidermodysplasia verruciformis. Human papilloma virus 5, 8, and 47 are found in more than 90% of epidermodysplasia verruciformis skin cancers. Treatment for epidermodysplasia verruciformis consists largely of preventive measures. Photoprotection remains essential for management. In this report, two sister case of epidermodisplasia verruciformis with plane warts, pityriasis versicolor-like lesions, and squamous cell carcinomas on sun-exposed areas of skin was presented for it is a rarely encountered disease and associated with early development of malignancy.

  10. Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin.

    Science.gov (United States)

    Shi, C; Fan, L Y; Cai, Z; Liu, Y Y; Yang, C L

    2012-01-01

    The flavonol aglycone isorhamnetin shows anti-proliferative activity in a variety of cancer cells. Previous work, from our laboratory showed that isorhamnetin inhibits the proliferation of human esophageal squamous carcinoma Eca-109 cells in vitro, but only after 72 h of exposure. This led us to propose that isorhamnetin exposure induces a cellular stress response that inhibits the antiproliferative and apoptotic effects of the compound during early exposure. To test this hypothesis, the present study examined the effects of isorhamnetin on Eca-109 cells during the first 72 h of exposure. Cell growth was assessed using the trypan blue exclusion assay, and expression of IκBα, NF-κB/p65, NF-κB/p50, phospho-Akt, Bcl-2, COX-2, Mcl-1, Bax, p53 and Id-1 were analyzed by Western blot. During the first 72 h of exposure, NF-κB/p65 and NF-κB/p50 accumulated in nuclei and expression of COX-2, Bcl-2 and Mcl-1 increased. In contrast, expression of IκBα and Bax fell initially but later increased. Expression of phospho-Akt and p53 showed no detectable change during the first 48 h. Pretreatment with the NF-κB inhibitor MG132 before exposure to isorhamnetin blocked the nuclear accumulation of p50 and p65, thereby inhibiting cell proliferation. These results show that during early exposure of Eca-109 cells to isorhamnetin, the NF-κB signaling pathway is activated and COX-2 expression increases, and this increase in expression partially inhibits isorhamnetin-induced apoptosis. Beyond 72 h of exposure, however, the apoptotic effect of isorhamnetin dominates, leading to inhibition of the NF-κB pathway and of cellular proliferation. These results will need to be taken into account when exploring the use of isorhamnetin against cancer in vivo.

  11. Transitional B Cells in Early Human B Cell Development – Time to Revisit the Paradigm?

    Science.gov (United States)

    Martin, Victoria G.; Wu, Yu-Chang Bryan; Townsend, Catherine L.; Lu, Grace H. C.; O’Hare, Joselli Silva; Mozeika, Alexander; Coolen, Anthonius C. C.; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

    2016-01-01

    The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig) genes and consequently an equally large number of potential specificities for antigen. As the process is essentially random, the cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B ≫ immature ≫ transitional ≫ naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood, and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire and can be seen both in gene usage and in CDRH3 characteristics. Age-related changes are small, and only the size of the CDRH3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B ≫ immature ≫ transitional ≫ naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages. PMID:27994589

  12. The calpain/calpastatin system has opposing roles in growth and metastatic dissemination of melanoma.

    Directory of Open Access Journals (Sweden)

    Quentin Raimbourg

    Full Text Available Conventional calpains are ubiquitous cysteine proteases whose activity is promoted by calcium signaling and specifically limited by calpastatin. Calpain expression has been shown to be increased in human malignant cells, but the contribution of the calpain/calpastatin system in tumorigenesis remains unclear. It may play an important role in tumor cells themselves (cell growth, migration, and a contrario cell death and/or in tumor niche (tissue infiltration by immune cells, neo-angiogenesis. In this study, we have used a mouse model of melanoma as a tool to gain further understanding of the role of calpains in tumor progression. To determine the respective importance of each target, we overexpressed calpastatin in tumor and/or host in isolation. Our data demonstrate that calpain inhibition in both tumor and host blunts tumor growth, while paradoxically increasing metastatic dissemination to regional lymph nodes. Specifically, calpain inhibition in melanoma cells limits tumor growth in vitro and in vivo but increases dissemination by amplifying cell resistance to apoptosis and accelerating migration process. Meanwhile, calpain inhibition restricted to host cells blunts tumor infiltration by immune cells and angiogenesis required for antitumor immunity, allowing tumor cells to escape tumor niche and disseminate. The development of highly specific calpain inhibitors with potential medical applications in cancer should take into account the opposing roles of the calpain/calpastatin system in initial tumor growth and subsequent metastatic dissemination.

  13. Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine.

    Science.gov (United States)

    Li, Hui Joyce; Kapoor, Archana; Giel-Moloney, Maryann; Rindi, Guido; Leiter, Andrew B

    2012-11-15

    Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells, respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+) cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+) cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.

  14. DISSEMINATED HISTOPLASMOSIS IN IMMUNOCOMPETENT INDIVIDUALS- NOT A SO RARE ENTITY

    Directory of Open Access Journals (Sweden)

    Dibyendu De

    2015-04-01

    Full Text Available Introduction: Histoplasmosis is a rare fungal disease caused by dimorphic fungi Histoplasma capsulatum. The causative fungus is present in soil, infects through inhalation and manifests in three main types-acute primary, chronic cavitary and progressive disseminated Histoplasmosis. Disseminated Histoplasmosis (DH is defined as a clinical condition where fungus is present in more than one location. Among the forms of histoplasmosis, DH is the rarest and generally found in immune-compromised individual. Here we are presenting our experiences of the series of cases of Disseminated Histoplasmosis in immune-competent individuals who have been diagnosed in our institute in last 5 years. Materials and methods: This is a single centre retrospective observational study, from May 2009 to April 2014. Only cases with Disseminated Histoplasmosis in otherwise healthy immune-competent individuals were included in the study. The Histoplasmosis is confirmed by either presence of Histoplasma in biopsy specimen from extra-pulmonary organ or by positive growth in fungal culture Result: Total seven patients met the inclusion criteria. Five out of 7 patients were male. The mean age was 35 years. Five of the 7 patients presented with fever for long duration. Six patients complained of significant weight loss before diagnosis. On examination, one patient had skin nodules, five patients had hepato-splenomegaly, and two patients had lymphadenopathy. The laboratory investigation revealed anaemia in six out of 7 patients, and pancytopenia in 3 patients. Two patients had features of hemophagocytic syndrome in the bone marrow. All of the patient had undergone treatment with conventional amphotericine B  deoxy-cholate and azole antifungal. One patient with adrenal involvement died in hospital. The patient with skin nodule had recurrent relapses. The other patients had resolution of symptoms and clinically cured. Conclusion: Disseminated Histoplasmosis is not an uncommon

  15. Molecular biology of the stress response in the early embryo and its stem cells.

    Science.gov (United States)

    Puscheck, Elizabeth E; Awonuga, Awoniyi O; Yang, Yu; Jiang, Zhongliang; Rappolee, Daniel A

    2015-01-01

    Stress is normal during early embryogenesis and transient, elevated stress is commonplace. Stress in the milieu of the peri-implantation embryo is a summation of maternal hormones, and other elements of the maternal milieu, that signal preparedness for development and implantation. Examples discussed here are leptin, adrenaline, cortisol, and progesterone. These hormones signal maternal nutritional status and provide energy, but also signal stress that diverts maternal and embryonic energy from an optimal embryonic developmental trajectory. These hormones communicate endocrine maternal effects and local embryonic effects although signaling mechanisms are not well understood. Other in vivo stresses affect the embryo such as local infection and inflammation, hypoxia, environmental toxins such as benzopyrene, dioxin, or metals, heat shock, and hyperosmotic stress due to dehydration or diabetes. In vitro, stresses include shear during handling, improper culture media and oxygen levels, cryopreservation, and manipulations of the embryo to introduce sperm or mitochondria. We define stress as any stimulus that slows stem cell accumulation or diminishes the ability of cells to produce normal and sufficient parenchymal products upon differentiation. Thus stress deflects downwards the normal trajectories of development, growth and differentiation. Typically stress is inversely proportional to embryonic developmental and proliferative rates, but can be proportional to induction of differentiation of stem cells in the peri-implantation embryo. When modeling stress it is most interesting to produce a 'runting model' where stress exposures slow accumulation but do not create excessive apoptosis or morbidity. Windows of stress sensitivity may occur when major new embryonic developmental programs require large amounts of energy and are exacerbated if nutritional flow decreases and removes energy from the normal developmental programs and stress responses. These windows correspond

  16. The microprocessor component, DGCR8, is essential for early B-cell development in mice.

    Science.gov (United States)

    Brandl, Andreas; Daum, Patrick; Brenner, Sven; Schulz, Sebastian R; Yap, Desmond Yat-Hin; Bösl, Michael R; Wittmann, Jürgen; Schuh, Wolfgang; Jäck, Hans-Martin

    2016-12-01

    microRNAs (miRNAs) are important posttranscriptional regulators during hematopoietic lineage commitment and lymphocyte development. Mature miRNAs are processed from primary miRNA transcripts in two steps by the microprocessor complex, consisting of Drosha and its partner DiGeorge Critical Region 8 (DGCR8), and the RNAse III enzyme, Dicer. Conditional ablations of Drosha and Dicer have established the importance of both RNAses in B- and T-cell development. Here, we show that a cre-mediated B-cell specific deletion of DGCR8 in mice results in a nearly complete maturation block at the transition from the pro-B to the pre-B cell stage, and a failure to upregulate Ig μ heavy chain expression in pro-B cells. Furthermore, we found that the death of freshly isolated DGCR8-deficient pro-B cells could be partially prevented by enforced Bcl2 expression. We conclude from these findings that the microprocessor component DGCR8 is essential for survival and differentiation of early B-cell progenitors.

  17. Symbiosis in cell evolution: Life and its environment on the early earth

    Science.gov (United States)

    Margulis, L.

    1981-01-01

    The book treats cell evolution from the viewpoint of the serial endosymbiosis theory of the origin of organelles. Following a brief outline of the symbiotic theory, which holds that eukaryotes evolved by the association of free-living bacteria with a host prokaryote, the diversity of life is considered, and five kingdoms of organisms are distinguished: the prokaryotic Monera and the eukaryotic Protoctista, Animalia, Fungi and Plantae. Symbiotic and traditional direct filiation theories of cell evolution are compared. Recent observations of cell structure and biochemistry are reviewed in relation to early cell evolution, with attention given to the geological context for the origin of eukaryotic cells, the origin of major bacterial anaerobic pathways, the relationship between aerobic metabolism and atmospheric oxygen, criteria for distinguishing symbiotic organelles from those that originated by differentiation, and the major classes of eukaryotic organelles: mitochondria, cilia, microtubules, the mitotic and meiotic apparatuses, and pastids. Cell evolution during the Phanerozoic is also discussed with emphasis on the effects of life on the biosphere

  18. Characterization of early transient accumulation of PrP(Sc) in immune cells.

    Science.gov (United States)

    Elhelaly, Abdelazim Elsayed; Inoshima, Yasuo; Ishiguro, Naotaka

    2013-09-27

    PrP(Sc) is known to elicit no specific immune response and the immune cells are suspected to support its accumulation. In the present study, we investigated the response of some immune cell types to PrP(Sc) to characterize an observed early transient accumulation of PrP(Sc). After cells were treated with PrP(Sc)-brain homogenate, PrP(Sc) was transiently accumulated for the first 8-12h post-exposure then completely cleared by the 5th day of the experiment. The accumulated PrP(Sc) was not a de novo product of the cell PrP(C). Further investigation of this phenomenon revealed some potential factors influencing it. These factors included cholesterol homeostasis, temperature, the degradation power of the cell and the availability of sufficient PrP(C). Our in vitro results suggest that immune cells, especially macrophages are potential risk factors for the accumulation and intercellular spread of PrP(Sc) if the complete clearance of PrP(Sc) were not fulfilled.

  19. The tale of early hematopoietic cell seeding in the bone marrow niche.

    Science.gov (United States)

    Yaniv, Isaac; Stein, Jerry; Farkas, Daniel L; Askenasy, Nadir

    2006-02-01

    Since introduction of the notion of a "niche" that hosts engraftment and activity of hematopoietic cells, there is a massive effort to discover its structure and decipher its function. Our understanding of the niche is continuously changing with reinterpretation of traditional concepts and apprehension of new insights into the biology of hematopoietic cell homing, seeding, and engraftment. Here we discuss some of the early events in hematopoietic stem cell seeding and engraftment and propose a perspective based on visualization of labeled bone marrow cells in real time in vivo. Primary seeding of hematopoietic cells in the bone marrow niches evolves as a complex and dynamic process; however, it follows discrete topological and chronological patterns. Initial seeding occurs on the endosteal surface of the marrow, which includes heterogeneous niches for primary seeding. Several days after transplantation the endosteal niches become more restrictive, hosting primarily mitotically quiescent cells, and gradual centripetal migration is accompanied by engagement in proliferation and differentiation. The hematopoietic niches evolve as heterogeneous three-dimensional microenvironments that are continuously changing over time.

  20. MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation

    Science.gov (United States)

    Schaefer, Inga-Marie; Wang, Yuexiang; Liang, Cher-wei; Bahri, Nacef; Quattrone, Anna; Doyle, Leona; Mariño-Enríquez, Adrian; Lauria, Alexandra; Zhu, Meijun; Debiec-Rychter, Maria; Grunewald, Susanne; Hechtman, Jaclyn F.; Dufresne, Armelle; Antonescu, Cristina R.; Beadling, Carol; Sicinska, Ewa T.; van de Rijn, Matt; Demetri, George D.; Ladanyi, Marc; Corless, Christopher L.; Heinrich, Michael C.; Raut, Chandrajit P.; Bauer, Sebastian; Fletcher, Jonathan A.

    2017-01-01

    KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs. MAX genomic inactivation is associated with p16 silencing in the absence of p16 coding sequence deletion and MAX induction restores p16 expression and inhibits GIST proliferation. Hence, MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs. PMID:28270683

  1. Early cytoplasmic vacuolization of African green monkey kidney cells by SV40.

    Science.gov (United States)

    Miyamura, T; Kitahara, T

    1975-01-01

    As early as 3--4 hours after infection with SV40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10--20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by preincubating the virus with specific antiserum, or by heating the virus with MgCl2. The ECV could be induced by UV-irradiated SV40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV40 virion and the vacuolization is not associated with the replication of SV40.

  2. Early cytoplasmic vacuolization of African green monkey kidney cells by SV40. [uv radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miyamura, T.; Kitahara, T.

    1975-01-01

    As early as 3 to 4 hours after infection with SV 40 at a high input multiplicity, African green monkey (Cercopithecus aethiops) kidney (AGMK) cells developed cytoplasmic vacuolization. At 10 to 20 hours after infection, the vacuolization reached its maximal level, then disappeared and SV 40 specific cytopathic change followed. This vacuolization developed before the synthesis of the specific T and V antigens. This early cytoplasmic vacuolization (ECV) was prevented by pre-incubating the virus with specific antiserum, or by heating the virus with MgCl/sub 2/. The ECV could be induced by uv-irradiated SV 40. Addition of metabolic inhibitors had no effect on the induction of the ECV. These results suggest that the capacity to induce the ECV resides in a structural component(s) of SV 40 virion and the vacuolization is not associated with the replication of SV 40.

  3. Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: Report of two cases

    Directory of Open Access Journals (Sweden)

    Reddy I

    2005-01-01

    Full Text Available Disseminated strongyloidiasis is a rare manifestation in patients on immunosuppressive drugs. We report two cases of fatal disseminated Strongyloides stercoralis infestation. The first was in a patient of pemphigus vulgaris who developed an exacerbation of symptoms, one year after diagnosis and was given intravenous dexamethasone and azathioprine and in the third week of hospitalization developed features of septicemia, respiratory failure and petechial hemorrhages which were proven to be due to disseminated strongyloidiasis. The second patient was diagnosed to have stage IV diffuse large cell type of non-Hodgkin lymphoma and after the second cycle of chemotherapy, developed generalized symptoms of septicemia, respiratory failure, purpuric macules and patches. This was also proven to be disseminated strongyloidiasis.

  4. Streaming the Archives: Repurposing Systems to Advance a Small Media Digitization and Dissemination Program

    Science.gov (United States)

    Anderson, Talea

    2015-01-01

    In 2013-2014, Brooks Library at Central Washington University (CWU) launched library content in three systems: a digital asset-management system, an institutional repository (IR), and a web-based discovery layer. In early 2014, the archives at the library began to use these systems to disseminate media recently digitized from legacy formats. As…

  5. Final Report: Appalachian Consortium. Evaluation of a Dissemination and Diffusion Design.

    Science.gov (United States)

    Elsbery Systems Analysis, Ltd., Flushing, NY.

    The Appalachian Consortium was evaluated as an organization for the dissemination of educational information regarding programs for the early identification of preschool handicapped children. Chapter I provides a historical overview and discusses the Consortium's independence from the Appalachian Educational Laboratory. The chapter also indicates…

  6. Dissemination of CERN's Technology Transfer: Added Value from Regional Transfer Agents

    Science.gov (United States)

    Hofer, Franz

    2005-01-01

    Technologies developed at CERN, the European Organization for Nuclear Research, are disseminated via a network of external technology transfer officers. Each of CERN's 20 member states has appointed at least one technology transfer officer to help establish links with CERN. This network has been in place since 2001 and early experiences indicate…

  7. Agricultural information dissemination using ICTs: A review and analysis of information dissemination models in China

    Directory of Open Access Journals (Sweden)

    Yun Zhang

    2016-03-01

    Full Text Available Over the last three decades, China’s agriculture sector has been transformed from the traditional to modern practice through the effective deployment of Information and Communication Technologies (ICTs. Information processing and dissemination have played a critical role in this transformation process. Many studies in relation to agriculture information services have been conducted in China, but few of them have attempted to provide a comprehensive review and analysis of different information dissemination models and their applications. This paper aims to review and identify the ICT based information dissemination models in China and to share the knowledge and experience in applying emerging ICTs in disseminating agriculture information to farmers and farm communities to improve productivity and economic, social and environmental sustainability. The paper reviews and analyzes the development stages of China’s agricultural information dissemination systems and different mechanisms for agricultural information service development and operations. Seven ICT-based information dissemination models are identified and discussed. Success cases are presented. The findings provide a useful direction for researchers and practitioners in developing future ICT based information dissemination systems. It is hoped that this paper will also help other developing countries to learn from China’s experience and best practice in their endeavor of applying emerging ICTs in agriculture information dissemination and knowledge transfer.

  8. Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse.

    Directory of Open Access Journals (Sweden)

    Marc Bajénoff

    Full Text Available Memory CD8(+ T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m. Memory CD8(+ T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+ T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+ T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+ T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+ T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+ T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+ T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+ T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+ T cells provide a local response by secreting effector molecules around infected cells.

  9. Postoperative systemic dissemination of injected elemental mercury.

    Science.gov (United States)

    Kang, Suk-Hyung; Park, Seung Won; Moon, Kyung-Yoon

    2011-04-01

    There were only a few reports of mercury on pulmonary artery. However, there is no data on surgery related mercury dissemination. The objective of the present article is to describe one case of postoperative injected mercury dissemination. A 19-year-old man presented severe neck pain including meningeal irritation sign and abdominal pain after injection of mercury for the purpose of suicide. Radiologic study showed injected mercury in the neck involving high cervical epidural space and subcutaneous layer of abdomen. Partial hemilaminectomy and open mercury evacuation of spinal canal was performed. For the removal of abdominal subcutaneous mercury, C-arm guided needle aspiration was done. After surgery, radiologic study showed disseminated mercury in the lung, heart, skull base and low spinal canal. Neck pain and abdominal pain were improved after surgery. During 1 month after surgery, there was no symptom of mercury intoxication except increased mercury concentration of urine, blood and hair. We assumed the bone work during surgery might have caused mercury dissemination. Therefore, we recommend minimal invasive surgical technique for removal of injected mercury. If open exposures are needed, cautious surgical technique to prohibit mercury dissemination is necessary and normal barrier should be protected to prevent the migration of mercury.

  10. Comprehensive analysis of information dissemination in disasters

    Science.gov (United States)

    Zhang, N.; Huang, H.; Su, Boni

    2016-11-01

    China is a country that experiences a large number of disasters. The number of deaths caused by large-scale disasters and accidents in past 10 years is around 900,000. More than 92.8 percent of these deaths could be avoided if there were an effective pre-warning system deployed. Knowledge of the information dissemination characteristics of different information media taking into consideration governmental assistance (information published by a government) in disasters in urban areas, plays a critical role in increasing response time and reducing the number of deaths and economic losses. In this paper we have developed a comprehensive information dissemination model to optimize efficiency of pre-warning mechanics. This model also can be used for disseminating information for evacuees making real-time evacuation plans. We analyzed every single information dissemination models for pre-warning in disasters by considering 14 media: short message service (SMS), phone, television, radio, news portals, Wechat, microblogs, email, newspapers, loudspeaker vehicles, loudspeakers, oral communication, and passive information acquisition via visual and auditory senses. Since governmental assistance is very useful in a disaster, we calculated the sensitivity of governmental assistance ratio. The results provide useful references for information dissemination during disasters in urban areas.

  11. Smart-tag Based Data Dissemination

    DEFF Research Database (Denmark)

    Bonnet, Philippe; Beaufour, Allan; Leopold, Martin

    2002-01-01

    Monitoring wide, hostile areas requires disseminating data between fixed, disconnected clusters of sensor nodes. It is not always possible to install long-range radios in order to cover the whole area. We propose to leverage the movement of mobile individuals, equipped with smart-tags, to dissemi......-tag based data dissemination. We use simulation to study the characteristics of the model we propose. Finally, we present an implementation based on Bluetooth smart-tags.......Monitoring wide, hostile areas requires disseminating data between fixed, disconnected clusters of sensor nodes. It is not always possible to install long-range radios in order to cover the whole area. We propose to leverage the movement of mobile individuals, equipped with smart......-tags, to disseminate data across disconnected static nodes spread across a wide area. Static nodes and mobile smart-tags exchange data when they are in the vicinity of each other; smart-tags disseminate data as they move around. In this paper, we propose an algorithm for update propagation and a model for smart...

  12. Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis.

    Science.gov (United States)

    Elzinga-Tinke, Jenny E; Dohle, Gert R; Looijenga, Leendert Hj

    2015-01-01

    Malignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in situ(CIS) as their common precursor, originating from an embryonic germ cell blocked in its maturation process. The overall cure rate of TGCT is more than 90%, however, men surviving TGCT can present long-term side effects of systemic cancer treatment. In contrast, men diagnosed and treated for CIS only continue to live without these long-term side effects. Therefore, early detection of CIS has great health benefits, which will require an informative screening method. This review described the etiology and early pathogenesis of TGCT, as well as the possibilities of early detection and future potential of screening men at risk for TGCT. For screening, a well-defined risk profile based on both genetic and environmental risk factors is needed. Since 2009, several genome wide association studies (GWAS) have been published, reporting on single-nucleotide polymorphisms (SNPs) with significant associations in or near the genes KITLG, SPRY4, BAK1, DMRT1, TERT, ATF7IP, HPGDS, MAD1L1, RFWD3, TEX14, and PPM1E, likely to be related to TGCT development. Prenatal, perinatal, and postnatal environmental factors also influence the onset of CIS. A noninvasive early detection method for CIS would be highly beneficial in a clinical setting, for which specific miRNA detection in semen seems to be very promising. Further research is needed to develop a well-defined TGCT risk profile, based on gene-environment interactions, combined with noninvasive detection method for CIS.

  13. Fatal disseminated toxoplasmosis in an immunocompetent cat

    Directory of Open Access Journals (Sweden)

    Susanna S. Nagel

    2013-02-01

    Full Text Available A 10-year-old domestic short hair cat was referred for investigation of anorexia and polydipsia of 3 days’ duration. Clinically the cat was obese, pyrexic (39.8 °C, had acute abdominal pain and severe bilirubinuria. Haematology and serum biochemistry revealed severe panleukopenia, thrombocytopenia, markedly elevated alanine aminotransferase (ALT and five-fold increased pre-prandial bile acids. Ultrasonographic evaluation of the abdomen did not identify any abnormalities. Serum tests for feline immunodeficiency virus (FIV and feline leukaemia virus (FeLV were negative. Broad-spectrum antibiotic treatment for infectious hepatitis was to no avail; the cat deteriorated and died 72 h after admission. Necropsy revealed mild icterus and anaemia, severe multifocal hepatic necrosis, serofibrinous hydrothorax, pulmonary oedema and interstitial pneumonia. Histopathology confirmed the macroscopic findings and revealed multifocal microgranulomata in the brain and myocardium, as well as areas of necrosis in lymph nodes and multifocally in splenic red pulp. Long bone shaft marrow was hyperplastic with a predominance of leukocyte precursors and megakaryocytes and splenic red pulp showed mild extramedullary haemopoiesis. Immunohistochemical staining for Toxoplasma gondii was strongly positive, with scattered cysts and tachyzoites in the liver, lymph nodes, spleen, lungs, brain, salivary glands and intracellularly in round cells in occasional blood vessels. Immunohistochemical staining for corona virus on the same tissues was negative, ruling out feline infectious peritonitis (FIP. Polymerase chain reaction (PCR on formalin-fixed paraffin-wax embedded tissues was positive for Toxoplasma sp., but attempts at sequencing were unsuccessful. This was the first case report of fulminant disseminated toxoplasmosis in South Africa, in which detailed histopathology in an apparently immunocompetent cat was described.

  14. Porcine pluripotency cell signaling develops from the inner cell mass to the epiblast during early development

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane; Christensen, Josef; Gao, Yu;

    2009-01-01

    (LIF, LIFR, GP130), FGF pathway (bFGF, FGFR1, FGFR2), BMP pathway (BMP4), and downstream-activated genes (STAT3, c-Myc, c-Fos, and SMAD4). We discovered two different expression profiles exist in the developing porcine embryo. The D6 porcine blastocyst (inner cell mass stage) is devoid...

  15. Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos.

    Directory of Open Access Journals (Sweden)

    Tony Y-C Tsai

    2014-02-01

    Full Text Available During the early development of Xenopus laevis embryos, the first mitotic cell cycle is long (∼85 min and the subsequent 11 cycles are short (∼30 min and clock-like. Here we address the question of how the Cdk1 cell cycle oscillator changes between these two modes of operation. We found that the change can be attributed to an alteration in the balance between Wee1/Myt1 and Cdc25. The change in balance converts a circuit that acts like a positive-plus-negative feedback oscillator, with spikes of Cdk1 activation, to one that acts like a negative-feedback-only oscillator, with a shorter period and smoothly varying Cdk1 activity. Shortening the first cycle, by treating embryos with the Wee1A/Myt1 inhibitor PD0166285, resulted in a dramatic reduction in embryo viability, and restoring the length of the first cycle in inhibitor-treated embryos with low doses of cycloheximide partially rescued viability. Computations with an experimentally parameterized mathematical model show that modest changes in the Wee1/Cdc25 ratio can account for the observed qualitative changes in the cell cycle. The high ratio in the first cycle allows the period to be long and tunable, and decreasing the ratio in the subsequent cycles allows the oscillator to run at a maximal speed. Thus, the embryo rewires its feedback regulation to meet two different developmental requirements during early development.

  16. Solanum lycopersicum AUXIN RESPONSE FACTOR 9 regulates cell division activity during early tomato fruit development

    Science.gov (United States)

    de Jong, Maaike; Wolters-Arts, Mieke; Schimmel, Bernardus C. J.; Stultiens, Catharina L. M.; de Groot, Peter F. M.; Powers, Stephen J.; Tikunov, Yury M.; Bovy, Arnoud G.; Mariani, Celestina; Vriezen, Wim H.; Rieu, Ivo

    2015-01-01

    The transformation of the ovary into a fruit after successful completion of pollination and fertilization has been associated with many changes at transcriptomic level. These changes are part of a dynamic and complex regulatory network that is controlled by phytohormones, with a major role for auxin. One of the auxin-related genes differentially expressed upon fruit set and early fruit development in tomato is Solanum lycopersicum AUXIN RESPONSE FACTOR 9 (SlARF9). Here, the functional analysis of this ARF is described. SlARF9 expression was found to be auxin-responsive and SlARF9 mRNA levels were high in the ovules, placenta, and pericarp of pollinated ovaries, but also in other plant tissues with high cell division activity, such as the axillary meristems and root meristems. Transgenic plants with increased SlARF9 mRNA levels formed fruits that were smaller than wild-type fruits because of reduced cell division activity, whereas transgenic lines in which SlARF9 mRNA levels were reduced showed the opposite phenotype. The expression analysis, together with the phenotype of the transgenic lines, suggests that, in tomato, ARF9 negatively controls cell division during early fruit development. PMID:25883382

  17. Early Transcriptional Responses of HepG2-A 16 Liver Cells to Infection by Plasmodium falciparum Sporozoites

    Science.gov (United States)

    2011-07-29

    286, ’JC 30, pp Early Transcriptional Responses of HepG2-A 16 Liver Cells to Infection by Plasmodium falciparum Sporozoites*[i] Received for...7500 and󈧏Sun BioMedical Technologies Inc., Ridgecrest, California 93555 Invasion of hepatocytes by Plasmodium sporozoites depos- ited by Anopheles...expression profiling of human HepG2-A16liver cells infected with Plasmodium falciparum sporozoites to understand the host early cellular events and

  18. Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway Regulated-Circulating microRNA

    Science.gov (United States)

    2016-05-01

    Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway -Regulated Circulating microRNA PRINCIPAL...TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway - Regulated Circulating microRNA Sb. GRANT NUMBER...panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized that serum

  19. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Gangaraju Rajashekhar

    Full Text Available Diabetic retinopathy (DR is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC could therapeutically rescue early stage DR features. Streptozotocin (STZ induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved "b" wave amplitude (as measured by electroretinogram within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration.

  20. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.

    Science.gov (United States)

    Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V

    2015-04-15

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.

  1. Expression of Apoptosis and Inducible Nitric Oxide Synthase in Trophoblastic Cells in Early Spontaneous Abortion

    Institute of Scientific and Technical Information of China (English)

    夏革清; 孙永玉

    2001-01-01

    Objective To investigate the effect of apoptosis and inducible nitric oxide (Inos) on the early spontaneous abortion Methods TUNEL method was used to detect the apoptosis in trophoblast cells in early pregnancy with and without spontaneous abortion (the experiment group and the control group), while Inos was detected by both in situ hybridization and immunohis tochemistry. By computer color magic image analysis system (CMIAS), positive cell indexes were represented by D (density) and N/S (number/square) in both apoptosis and in situ hybridization, in immunohistochemistry were N/S and PU (positive unit).Results Positive cell indexes of apoptosis D and N/S were significntly higher in the experiment group (0. 48± 0. 004, 0. 045±0. 002) than that in the control group( 0. 35 +0. 06, 0. 031±0. 003. P<0. 001). D and N/S of inducible nitric oxide synthase in situ hybridization were 0. 33± 0. 028, 0. 074± 0. 001 respectively in the experiment group and 0. 13± 0. 015, 0. 019± 0. 004 respectively in the control group. N/S and PU were significantly higher in the experiment group( 0. 058± 0. 007, 11. 94± 2. 01)than that in the control group (0. 007± 0. 001, 1. 18± 0. 35, P<0. 01). There existed a positive correlation between Inos and apoptosis too.Conclution Apoptosis and Inos in trophoblasts might play an important role in early spontaneous abortion and there was a positive correlation between apoptosis and Inos.

  2. The influence of early embryo traits on human embryonic stem cell derivation efficiency.

    Science.gov (United States)

    O'Leary, Thomas; Heindryckx, Björn; Lierman, Sylvie; Van der Jeught, Margot; Menten, Björn; Deforce, Dieter; Cornelissen, Ria; de Sousa Lopes, Susana Chuva; De Sutter, Petra

    2011-05-01

    Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.

  3. Tracking Users for a Targeted Dissemination

    Directory of Open Access Journals (Sweden)

    Philippe Bautier

    2015-12-01

    Full Text Available How to build a dissemination and communication strategy in a world where users have easy access to a deluge of data and information from various origins and where IT tools and design standards change so quickly that users behaviour and their expectations are continuously modified? The first challenge of Eurostat is clearly to know what users want: we know our different types of users but we have to identify how they get our data, what they do with our data, how they react to our outputs and which sort of new service they would like us to propose. Translating these needs into a visual dissemination is a new challenge undertaken by Eurostat through a new portal, new mobile apps and new info graphs and basic application as well as increasing the visibility on Google. The objective of this paper is to share Eurostat's experience in identifying user Leeds and to show how concretely this information has been visually disseminated.

  4. A rare case of disseminated cysticercosis

    Directory of Open Access Journals (Sweden)

    Debananda Gonjhu

    2015-01-01

    Full Text Available Cysticercosis is a common tropical disease and a common cause of seizures and neurological morbidity. Neurocysticercosis (NCC is the most common manifestation of the disease involving the central nervous system (CNS. One of the uncommon manifestations of cysticercosis is its disseminated form. The most commonly affected organs are the subcutaneous tissues, skeletal muscles, lungs, brain, eyes, liver, and occasionally the heart, thyroid, and pancreas but in widespread dissemination it can involve any organ in the body. We report here a case of a 35-year-old-female with disseminated cysticercosis (DCC. She attended our hospital with headache, fever, and symptoms of multiple palpable nodules. After the investigations, she was diagnosed with DCC involving the brain and subcutaneous tissues all over the body. Then she was successfully treated with albendazole and steroids.

  5. Pineocytoma with diffuse dissemination to the leptomeninges

    Directory of Open Access Journals (Sweden)

    Michael Selch

    2011-10-01

    Full Text Available Pineal parenchymal tumors are rare. Of the three types of pineal parenchymal tumors, pineocytomas are the least aggressive and are not known to diffusely disseminate. In this paper, we report the successful treatment of a case of pineocytoma with diffuse leptomeningeal relapse following initial stereotactic radiotherapy. A 39-year-old female presented with headaches, balance impairment, urinary incontinence, and blunted affect. A pineal mass was discovered on magnetic resonance imaging (MRI. A diagnosis of pineocytoma was established with an endoscopic pineal gland biopsy, and the patient received stereotactic radiotherapy. Ten years later, she developed diffuse leptomeningeal dissemination. The patient was then successfully treated with craniospinal radiation therapy. Leptomeningeal spread may develop as late as 10 years after initial presentation of pineocytoma. Our case demonstrates the importance of long-term follow-up of patients with pineal parenchymal tumors following radiation therapy, and the efficacy of craniospinal radiation in the treatment of leptomeningeal dissemination.

  6. Primary disseminated extrapulmonary multidrug resistant tuberculosis

    Directory of Open Access Journals (Sweden)

    S K Das

    2012-01-01

    Full Text Available Disseminated tuberculosis is a common mode of presentation of tuberculosis in patients both with and without HIV/AIDS in India. However, primary multidrug resistance in disseminated tuberculosis involving only the extrapulmonary sites in an immunocompetent adult is rare. Here, we report a case of a 19-year-old man who had disseminated tuberculosis involving left pleura, pericardium, peritoneum and intraabdominal lymph nodes. He was initially taking WHO category I antituberculous drugs, but was not responding in spite of 5 months of chemotherapy. Culture of the pleural biopsy specimen grew Mycobacterium tuberculosis which was resistant to isoniazid and rifampicin. He was put on therapy for multidrug resistant tuberculosis,following 24 months of chemotherapyhe had an uneventful recovery.

  7. Early interactions of Edwardsiella ictaluri, with Pangasianodon catfish and its invasive ability in cell lines.

    Science.gov (United States)

    Dung, T T; Chiers, K; Tuan, N A; Sorgeloos, P; Haesebrouck, F; Decostere, A

    2012-06-01

    Commercial Pangasianodon catfish production is heavily impacted by Bacillary Necrosis of Pangasius (BNP) caused by Edwardsiella ictaluri. This study aimed to investigate the early bacterium-host interactions following immersion challenge and to compare the retrieved data with the invasion ability of the used isolates in fish cell lines. Firstly, Pangasianodon hypophthalmus fingerlings were challenged via immersion using E. ictaluri isolate HO2 or 223. At different times post inoculation, fish were sacrificed and gill and internal organ samples were taken for bacteriological, histological and immunohistochemical evaluation. The bacterial load was higher for fish inoculated with isolate HO2 compared with 223. Histological and immunohistochemical analysis revealed multifocal necrotic areas in kidney, spleen and liver of HO2 inoculated fish at 72 h post inoculation with short rod-shaped immunoperoxidase positive bacteria clustered inside cells respectively. Bacteria especially were present in the gills and intestinal tract of HO2 inoculated fish, suggesting the gastrointestinal tract and gills act as portals of entry. Following, the ability of HO2, 223 and four additional isolates to invade a Chinook salmon embryo cell line, a fat head minnow cell line and a rainbow trout liver cell line was tested. All E. ictaluri isolates were invasive in all cell lines albeit at different degrees. Isolate HO2 was highly invasive in all cell lines with a significantly higher invasion capacity than isolate 223 in the Chinook salmon embryo cell line. A correlation between in vivo virulence and in vitro invasiveness hence is suggested although further studies are needed to confirm this hypothesis.

  8. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies...... was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  9. Finds decorated with garnets from Early Avar contexts in the light of their cell techniques

    OpenAIRE

    Heinrich-Tamáska, Orsolya

    2016-01-01

    The present contribution concerns the Early Avar (late 6th and first half of the 7th century AD) metal objects ornamented with garnets from the perspective of the inlay techniques employed. Such inlays occur exclusively on objects made of precious metals, indicating the high value placed on these stones. Besides standard cloisonné, it has been possible to identify techniques such as soldered band settings of single and multiple cells and open-work cellwork (pseudo cloisonné, champlevé à jour)...

  10. RAF kinase activity regulates neuroepithelial cell proliferation and neuronal progenitor cell differentiation during early inner ear development.

    Directory of Open Access Journals (Sweden)

    Marta Magariños

    Full Text Available BACKGROUND: Early inner ear development requires the strict regulation of cell proliferation, survival, migration and differentiation, coordinated by the concerted action of extrinsic and intrinsic factors. Deregulation of these processes is associated with embryonic malformations and deafness. We have shown that insulin-like growth factor I (IGF-I plays a key role in embryonic and postnatal otic development by triggering the activation of intracellular lipid and protein kinases. RAF kinases are serine/threonine kinases that regulate the highly conserved RAS-RAF-MEK-ERK signaling cascade involved in transducing the signals from extracellular growth factors to the nucleus. However, the regulation of RAF kinase activity by growth factors during development is complex and still not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of qRT-PCR, Western blotting, immunohistochemistry and in situ hybridization, we show that C-RAF and B-RAF are expressed during the early development of the chicken inner ear in specific spatiotemporal patterns. Moreover, later in development B-RAF expression is associated to hair cells in the sensory patches. Experiments in ex vivo cultures of otic vesicle explants demonstrate that the influence of IGF-I on proliferation but not survival depends on RAF kinase activating the MEK-ERK phosphorylation cascade. With the specific RAF inhibitor Sorafenib, we show that blocking RAF activity in organotypic cultures increases apoptosis and diminishes the rate of cell proliferation in the otic epithelia, as well as severely impairing neurogenesis of the acoustic-vestibular ganglion (AVG and neuron maturation. CONCLUSIONS/SIGNIFICANCE: We conclude that RAF kinase activity is essential to establish the balance between cell proliferation and death in neuroepithelial otic precursors, and for otic neuron differentiation and axonal growth at the AVG.

  11. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice.

    Directory of Open Access Journals (Sweden)

    Meredith H Shaffer

    Full Text Available BACKGROUND: Ezrin/radixin/moesin (ERM proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/- mice likely arise as a consequence of nutritional stress. CONCLUSIONS/SIGNIFICANCE: We conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin.

  12. Molecular and functional heterogeneity of early postnatal porcine satellite cell populations is associated with bioenergetic profile

    Science.gov (United States)

    Miersch, Claudia; Stange, Katja; Hering, Silvio; Kolisek, Martin; Viergutz, Torsten; Röntgen, Monika

    2017-01-01

    During postnatal development, hyperplastic and hypertrophic processes of skeletal muscle growth depend on the activation, proliferation, differentiation, and fusion of satellite cells (SC). Therefore, molecular and functional SC heterogeneity is an important component of muscle plasticity and will greatly affect long-term growth performance and muscle health. However, its regulation by cell intrinsic and extrinsic factors is far from clear. In particular, there is only minor information on the early postnatal period which is critical for muscle maturation and the establishment of adult SC pools. Here, we separated two SC subpopulations (P40/50, P50/70) from muscle of 4-day-old piglets. Our results characterize P40/50 as homogeneous population of committed (high expression of Myf5), fast-proliferating muscle progenitors. P50/70 constituted a slow-proliferating phenotype and contains high numbers of differentiated SC progeny. During culture, P50/70 is transformed to a population with lower differentiation potential that contains 40% Pax7-positive cells. A reversible state of low mitochondrial activity that results from active down-regulation of ATP-synthase is associated with the transition of some of the P50/70 cells to this more primitive fate typical for a reserve cell population. We assume that P40/50 and P50/70 subpopulations contribute unequally in the processes of myofiber growth and maintenance of the SC pool. PMID:28344332

  13. Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection

    OpenAIRE

    Shinji Maeba; Shunji Hasegawa; Maiko Shimomura; Takuya Ichimura; Kazumasa Takahashi; Masashi Motoyama; Shinnosuke Fukunaga; Yoshinori Ito; Takashi Ichiyama; Shouichi Ohga

    2015-01-01

    Background - Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report - We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose cor...

  14. "The Only 13-Year-Old on Planet Earth without a Cell Phone": Meanings of Cell Phones in Early Adolescents' Everyday Lives

    Science.gov (United States)

    Blair, Bethany L.; Fletcher, Anne C.

    2011-01-01

    Cellular telephones have become an increasingly prevalent feature of contemporary American life, with usage often beginning during early adolescence. With this in mind, twenty 7th graders and their mothers participated in separate qualitative interviews regarding early adolescents' use of cell phones as well as perceived risks and benefits of such…

  15. Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

    Science.gov (United States)

    Mateos, Melina V; Kamerbeek, Constanza B; Giusto, Norma M; Salvador, Gabriela A

    2016-06-01

    This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells.

  16. T helper cell 2 immune skewing in pregnancy/early life

    DEFF Research Database (Denmark)

    McFadden, J P; Thyssen, J P; Basketter, D A

    2015-01-01

    During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells...... that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider...... the immunophysiology of Th2 immune skewing during pregnancy. In particular, we explore the possibility that altered and increased patterns of exposure to certain chemicals have served to accentuate this normal Th2 skewing and therefore further promote the persistence of a Th2 bias in neonates. Furthermore, we propose...

  17. Prostate Biopsy Sampling Causes Hematogenous Dissemination of Epithelial Cellular Material

    Directory of Open Access Journals (Sweden)

    Sam Ladjevardi

    2014-01-01

    Full Text Available The extent of epithelial cellular material (ECM occurring in venous blood samples after diagnostic core needle biopsy (CNB was studied in 23 patients with CNB diagnosed prostate cancer without provable metastases and 15 patients without cancer. The data show a significant increase of ECM in the peripheral blood sampled 20 seconds or 30 minutes after the last of 10 CNB procedures compared to the number of ECM detectable in the blood samples taken before the performance of CNB. The data indicate that diagnostic CNB of prostate cancer causes an extensive tissue trauma with a potential risk of cancer cell dissemination.

  18. Global Effects Of Early Life Stress On Neurons And Glial Cells.

    Science.gov (United States)

    Zulma, Dueñas; Carlos, Caicedo-Mera Juan; Luz, Torner

    2017-02-24

    Early life stress is considered a risk factor for the development of many diseases in both adolescence and adulthood. It has been reported that chronic stress (for instance, due to maternal separation during breast feeding), causes damage to the central nervous system at the level of neurons and glial cells, which are reflected in behavioral disturbances and susceptibility to the development of primarily emotional psychopathology. The aim of this review is to identify the overall state of the scientific literature that relates the information about the consequences of early life stress, contextualizing the mechanisms that may be altered, the behavioral consequences that have been studied and the possible dimorphic effects and its causes. At the end a short overview of pharmacological treatments that have been proposed to reduce the behavioral and neuroendocrine consequences caused by early life stress is presented. This review pretends to integrate general but relevant information based primarily on studies in animal models, which allow the experimental approach and the study of the mechanisms involved. A series of questions remains for reflection and surely will be answered in the near future.

  19. Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells.

    Science.gov (United States)

    Kim, Sang Chon; Kim, Yoo Hoon; Son, Sung Wook; Moon, Eun-Yi; Pyo, Suhkneung; Um, Sung Hee

    2015-11-27

    Fisetin (3,7,3',4'-tetrahydroxyflavone) is a naturally found flavonol in many fruits and vegetables and is known to have anti-aging, anti-cancer and anti-viral effects. However, the effects of fisetin on early adipocyte differentiation and the epigenetic regulator controlling adipogenic transcription factors remain unclear. Here, we show that fisetin inhibits lipid accumulation and suppresses the expression of PPARγ in 3T3-L1 cells. Fisetin suppressed early stages of preadipocyte differentiation, and induced expression of Sirt1. Depletion of Sirt1 abolished the inhibitory effects of fisetin on intracellular lipid accumulation and on PPARγ expression. Mechanistically, fisetin facilitated Sirt1-mediated deacetylation of PPARγ and FoxO1, and enhanced the association of Sirt1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity, thereby repressing adipogenesis. Lowering Sirt1 levels reversed the effects of fisetin on deacetylation of PPARγ and increased PPARγ transactivation. Collectively, our results suggest the effects of fisetin in increasing Sirt1 expression and in epigenetic control of early adipogenesis.

  20. Early Squamous Cell Carcinoma of the Anal Canal Resected by Endoscopic Submucosal Dissection

    Directory of Open Access Journals (Sweden)

    Yuzuru Tamaru

    2015-04-01

    Full Text Available The standard treatment approach for squamous cell carcinoma (SCC of the anal canal includes abdominoperineal resection and chemoradiotherapy. However, there are currently very few reports of early SCC of the anal canal resected by endoscopic submucosal dissection (ESD. We report 2 rare cases of SCC of the anal canal resected by ESD. In case 1, a 66-year-old woman underwent a colonoscopy due to blood in her stool, and an elevated lesion, 15 mm in size, was identified from the rectum to the dentate line of the anal canal on internal hemorrhoids. The lesion was diagnosed as an early SCC of the anal canal, and ESD was successfully performed. The histopathological diagnosis was SCC in situ. In case 2, a 71-year-old woman underwent a colonoscopy due to constipation, and an elevated lesion, 25 mm in size, was identified from the dentate line to the anal canal. The lesion was diagnosed as early-stage SCC of the anal canal, and ESD was successfully performed. The histopathological diagnosis was SCC in situ. No complications or recurrence after ESD occurred in either case.

  1. Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET.

    Science.gov (United States)

    Alexeeva, Svetlana; Gadella, Theodorus W J; Verheul, Jolanda; Verhoeven, Gertjan S; den Blaauwen, Tanneke

    2010-07-01

    The bacterial cell division machinery is organized in the so-called divisome composed of highly dynamic but low abundant interacting (membrane-bound) proteins. In order to elucidate the molecular interactions between these proteins, we developed a robust background-insensitive quantitative spectral unmixing method for estimating FRET efficiencies at near endogenous protein levels using fluorescent protein fusions. The assembly of the division machinery of Escherichia coli occurs in two steps that are discrete in time: first the FtsZ-ring and the so-called early localizing proteins that together seem to prepare the division assembly at midcell. Subsequently, the late localizing protein complexes that contain the peptidoglycan-synthesizing proteins PBP1B and FtsI (PBP3) are recruited to the division site, which initiates septation. Physical interactions were observed between members within each group but also between the early and late localizing proteins strongly suggesting that these proteins despite their differential localization in time are linked at the molecular and functional level. Interestingly, we find FtsN, one of the latest proteins in the divisome assembly, interacting with late assembling proteins FtsI and FtsW, but also with early (proto-ring) protein ZapA. This is in line with the recently described role of FtsN in divisome stabilization including the proto-ring elements.

  2. Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation

    Directory of Open Access Journals (Sweden)

    Alessi Marie-Christine

    2008-02-01

    Full Text Available Abstract Background It is well established that adipose tissue plays a key role in energy storage and release but is also a secretory organ and a source of stem cells. Among different lineages, stem cells are able to differentiate into adipocytes and osteoblasts. As secreted proteins could regulate the balance between both lineages, we aimed at characterizing the secretome of human multipotent adipose-derived stem cell (hMADS at an early step of commitment to adipocytes and osteoblasts. Results A proteomic approach, using mono-dimensional electrophoresis and tandem mass spectrometry, allowed us to identify a total of 73 proteins at day 0 and day 3 of adipocyte and osteoblast differentiation. Analysis of identified proteins showed that 52 % corresponded to classical secreted proteins characterized by a signal peptide, that 37 % previously described in the extracellular compartment were devoid of signal peptide and that 11 % neither exhibited a signal peptide nor had been previously described extracellularly. These proteins were classified into 8 clusters according to their function. Quantitative analysis has been performed for 8 candidates: PAI-1, PEDF, BIGH3, PTX3, SPARC, ENO1, GRP78 and MMP2. Among them, PAI-1 was detected at day 0 and day 3 of osteoblast differentiation but never in adipocyte secretome. Furthermore we showed that PAI-1 mRNA was down-regulated in the bone of ovariectomized mice. Conclusion Given its regulation during the early events of hMADS cell differentiation and its status in ovariectomized mice, PAI-1 could play a role in the adipocyte/osteoblast balance and thus in bone diseases such as osteoporosis.

  3. Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation

    Science.gov (United States)

    Chiellini, Chiara; Cochet, Olivia; Negroni, Luc; Samson, Michel; Poggi, Marjorie; Ailhaud, Gérard; Alessi, Marie-Christine; Dani, Christian; Amri, Ez-Zoubir

    2008-01-01

    Background It is well established that adipose tissue plays a key role in energy storage and release but is also a secretory organ and a source of stem cells. Among different lineages, stem cells are able to differentiate into adipocytes and osteoblasts. As secreted proteins could regulate the balance between both lineages, we aimed at characterizing the secretome of human multipotent adipose-derived stem cell (hMADS) at an early step of commitment to adipocytes and osteoblasts. Results A proteomic approach, using mono-dimensional electrophoresis and tandem mass spectrometry, allowed us to identify a total of 73 proteins at day 0 and day 3 of adipocyte and osteoblast differentiation. Analysis of identified proteins showed that 52 % corresponded to classical secreted proteins characterized by a signal peptide, that 37 % previously described in the extracellular compartment were devoid of signal peptide and that 11 % neither exhibited a signal peptide nor had been previously described extracellularly. These proteins were classified into 8 clusters according to their function. Quantitative analysis has been performed for 8 candidates: PAI-1, PEDF, BIGH3, PTX3, SPARC, ENO1, GRP78 and MMP2. Among them, PAI-1 was detected at day 0 and day 3 of osteoblast differentiation but never in adipocyte secretome. Furthermore we showed that PAI-1 mRNA was down-regulated in the bone of ovariectomized mice. Conclusion Given its regulation during the early events of hMADS cell differentiation and its status in ovariectomized mice, PAI-1 could play a role in the adipocyte/osteoblast balance and thus in bone diseases such as osteoporosis. PMID:18302751

  4. Three cases of severely disseminated Staphylococcus aureus infection in patients treated with tocilizumab

    DEFF Research Database (Denmark)

    Nguyen, Mai; Pødenphant, Jan; Ravn, Pernille

    2013-01-01

    We report three cases of severe disseminated Staphylococcus aureus infection in patients with rheumatoid arthritis (RA) treated with tocilizumab. Tocilizumab is a new drug, unknown to most internists, and injections given weeks before admission may not be considered by the patient as part......-intensive diagnostic work-up and early treatment should be performed. Systematic postmarketing studies are needed to clarify if there is a true increased risk of disseminated S aureus infections. We suggest caution when prescribing tocilizumab to patients with prosthetic joints and/or prior invasive S aureus...

  5. Early gestation chorionic villi-derived stromal cells for fetaltissue engineering

    Institute of Scientific and Technical Information of China (English)

    Lee Lankford; Taryn Selby; James Becker; Volodymyr Ryzhuk; Connor Long; Diana Farmer; Aijun Wang

    2015-01-01

    AIM To investigate the potential for early gestationplacenta-derived mesenchymal stromal cells (PMSCs) forfetal tissue engineering.METHODS: PMSCs were isolated from early gestationchorionic villus tissue by explant culture. Chorionic villussampling (CVS)-size tissue samples (mean = 35.93 mg)were used to test the feasibility of obtaining large cellnumbers from CVS within a clinically relevant timeframe.We characterized PMSCs isolated from 6 donor placentasby flow cytometry immunophenotyping, multipotencyassays, and through immunofluorescent staining. Proteinsecretion from PMSCs was examined using two cytokinearray assays capable of probing for over 70 factorsin total. Delivery vehicle compatibility of PMSCs wasdetermined using three common scaffold systems: fibringlue, collagen hydrogel, and biodegradable nanofibrousscaffolds made from a combination of polylactic acid (PLA)and poly(lactic-co-glycolic acid) (PLGA). Viral transductionof PMSCs was performed using a Luciferase-GFPcontaininglentiviral vector and efficiency of transductionwas tested by fluorescent microscopy and flow cytometryanalysis.RESULTS: We determined that an average of 2.09 ×106 (SD ± 8.59 × 105) PMSCs could be obtained fromCVS-size tissue samples within 30 d (mean = 27 d, SD± 2.28), indicating that therapeutic numbers of cells canbe rapidly expanded from very limited masses of tissue.Immunophenotyping by flow cytometry demonstratedthat PMSCs were positive for MSC markers CD105,CD90, CD73, CD44, and CD29, and were negative forhematopoietic and endothelial markers CD45, CD34,and CD31. PMSCs displayed trilineage differentiationcapability, and were found to express developmentaltranscription factors Sox10 and Sox17 as well as neuralrelatedstructural proteins NFM, Nestin, and S100β.Cytokine arrays revealed a robust and extensive profileof PMSC-secreted cytokines and growth factors, anddetected 34 factors with spot density values exceeding103. Detected factors

  6. Effect of Mitochondrial Transplantation from Cumulus Granular Cells to the Early Embryos of Aged Mice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To assess the role of mitochondria in the early embryonic development of ageing mice.Methods Mitochondria isolated from cumulus granular cells of aged mice were microinjected into oocytes or zygotes of aged mice. In the setting of oocyte injection, mitochondria were transferred via intracytoplasmic sperm injection (ICSI+MIT), and ICSI without mitochondrial transfer. In the setting of zygote injection, mitochondria were directly microinjected into fertilized oocytes (MIT), and those injected with buffer alone (mock injection) or not injected (uninjected) served as controls.Results Although the rates of oocyte cleavage between ICSI and ICSI+MIT groups were not statistically different (P>0.05), the rate of blastocyst in the ICSI+MIT group was significantly higher than that in ICSI group (P<0.05). Although both the cleavage and blastocyst rates of mock injection group were significantly lower than those of uninjected group (P<0.05), likely due to mechanical damages of the cells by microinjection, the decrease of these rates was prevented by mitochondrial transfer. After mitochondrial transfer, the rates of both cleavage and blastocyst were significantly improved over the mock-injection group (P<0.05).Conclusion Mitochondrial transplantation can improve the developmental potential of early embryos of aged mice.

  7. Early maternal deprivation in rats induces gender-dependent effects on developing hippocampal and cerebellar cells.

    Science.gov (United States)

    Llorente, Ricardo; Gallardo, Meritxell López; Berzal, Alvaro Llorente; Prada, Carmen; Garcia-Segura, Luis Miguel; Viveros, María-Paz

    2009-05-01

    Adult animals submitted to a single prolonged episode of maternal deprivation [24h, postnatal day 9-10] show behavioral alterations that resemble specific symptoms of schizophrenia. According to the neurodevelopmental theory, these behavioral deficits might be mediated by detrimental neurodevelopmental processes that might be associated, at least partially, with stress-induced corticosterone responses. In order to address this hypothesis, we have focused on the hippocampus and cerebellar cortex, two brain regions that show high density of glucocorticoid receptors, and analyzed possible neuronal and glial alterations by immunohistochemical techniques. To evaluate the presence of degenerated neurons we used Fluoro-Jade-C (FJ-C) staining and for the study of astrocytes we employed glial fibrillary acidic protein (GFAP). Within control animals, females showed significantly more GFAP positive cells than males and a trend towards more FJ-C positive cells. Maternal deprivation induced neuronal degeneration and astroglial changes in the hippocampus and cerebellar cortex of neonatal rats that, in general, were more marked in males. This differential effect may be attributable to a greater vulnerability of males to this kind of early environmental insult and/or to sex-dependent differences in the onset and/or progression of the effects. The present experimental procedure may be instrumental in elucidating sex-dependent mechanisms of neurodevelopmental psychiatric disorders with a basis in early environmental insults.

  8. Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

    Science.gov (United States)

    Bhalla, Sherry; Chaudhary, Kumardeep; Kumar, Ritesh; Sehgal, Manika; Kaur, Harpreet; Sharma, Suresh; Raghava, Gajendra P. S.

    2017-01-01

    In this study, an attempt has been made to identify expression-based gene biomarkers that can discriminate early and late stage of clear cell renal cell carcinoma (ccRCC) patients. We have analyzed the gene expression of 523 samples to identify genes that are differentially expressed in the early and late stage of ccRCC. First, a threshold-based method has been developed, which attained a maximum accuracy of 71.12% with ROC 0.67 using single gene NR3C2. To improve the performance of threshold-based method, we combined two or more genes and achieved maximum accuracy of 70.19% with ROC of 0.74 using eight genes on the validation dataset. These eight genes include four underexpressed (NR3C2, ENAM, DNASE1L3, FRMPD2) and four overexpressed (PLEKHA9, MAP6D1, SMPD4, C11orf73) genes in the late stage of ccRCC. Second, models were developed using state-of-art techniques and achieved maximum accuracy of 72.64% and 0.81 ROC using 64 genes on validation dataset. Similar accuracy was obtained on 38 genes selected from subset of genes, involved in cancer hallmark biological processes. Our analysis further implied a need to develop gender-specific models for stage classification. A web server, CancerCSP, has been developed to predict stage of ccRCC using gene expression data derived from RNAseq experiments. PMID:28349958

  9. Early central nervous system complications after reduced-intensity stem cell transplantation.

    Science.gov (United States)

    Kishi, Yukiko; Miyakoshi, Shigesaburo; Kami, Masahiro; Ikeda, Masayuki; Katayama, Yuta; Murashige, Naoko; Kusumi, Eiji; Yuji, Koichiro; Kobayashi, Kazuhiko; Kato, Daisuke; Hamaki, Tamae; Matsumura, Tomoko; Kim, Sung-Won; Morinaga, Shinichi; Mori, Shinichiro; Kanemaru, Mineo; Hayashi, Tatsuyuki; Takaue, Yoichi; Taniguchi, Shuichi

    2004-08-01

    To investigate clinical characteristics of early central nervous system (CNS) complications after reduced-intensity stem cell transplantation (RIST), we reviewed the medical records of 232 patients who had undergone RIST for hematologic diseases at our institutions between September 1999 and June 2003. All patients had received purine analog-based preparative regimens. Stem cell sources comprised granulocyte colony-stimulating factor-mobilized blood from HLA-identical or 1 locus-mismatched related donors (n = 151), unrelated bone marrow (n = 44), or unrelated cord blood (n = 37). Graft-versus-host disease prophylaxis incorporated cyclosporine with or without methotrexate. Diagnosis of CNS complications was based on clinical, radiologic, and microbiological findings. CNS complications occurred in 18 patients (7.8%), with a median onset of 22 days, and were infectious (n = 1), metabolic (n = 15), or cerebrovascular (n = 2). Symptoms included seizures (n = 7), visual disturbance (n = 2), headache (n = 8), nausea (n = 8), vomiting (n = 6), impaired consciousness (n = 16), and hemiparesis (n = 3). Complications improved promptly in 10 patients, and 8 patients died without improvement within 30 days. Multivariate analysis with logistic regression identified umbilical cord blood transplantation as a significant risk factor for early CNS complications (odds ratio, 14.5; 95% confidence interval, 3.7-56.9; P <.0001). CNS complications are a significant problem after RIST, particularly with umbilical cord blood. Limbic encephalopathy is an unrecognized subtype of neurotoxicity after umbilical cord blood transplantation.

  10. B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.

    Directory of Open Access Journals (Sweden)

    Yuichi Okuda

    2010-05-01

    Full Text Available The B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through in situ hybridization, RT-PCR, and microarray analyses. Importantly, these phenotypic analyses revealed that the B1 SOX proteins regulate the following distinct processes: (1 early dorsoventral patterning by controlling bmp2b/7; (2 gastrulation movements via the regulation of pcdh18a/18b and wnt11, a non-canonical Wnt ligand gene; (3 neural differentiation by regulating the Hes-class bHLH gene her3 and the proneural-class bHLH genes neurog1 (positively and ascl1a (negatively, and regional transcription factor genes, e.g., hesx1, zic1, and rx3; and (4 neural patterning by regulating signaling pathway genes, cyp26a1 in RA signaling, oep in Nodal signaling, shh, and mdkb. Chromatin immunoprecipitation analysis of the her3, hesx1, neurog1, pcdh18a, and cyp26a1 genes further suggests a direct regulation of these genes by B1 SOX. We also found an interesting overlap between the early phenotypes of the B1 sox quadruple knockdown embryos and the maternal-zygotic spg embryos that are devoid of pou5f1 activity. These findings indicate that the B1 SOX proteins control a wide range of developmental regulators in the early embryo through partnering in part with Pou5f1 and possibly with other factors, and suggest that the B1 sox functions are central to coordinating cell fate

  11. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection.

    Directory of Open Access Journals (Sweden)

    Clara Bayarri-Lara

    Full Text Available Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC.56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR expression.51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1% (p = 0.035. The mean number of CTCs was 3.16 per 10 ml (range 0-84 preoperatively and 0.66 (range 0-3 in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018 and a shorter disease free survival (DFS (p = .008. In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010 and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043 were independent prognostic factors for DFS.CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.

  12. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

    Science.gov (United States)

    Cueto Ladrón de Guevara, Antonio; Puche, Jose L.; Ruiz Zafra, Javier; de Miguel-Pérez, Diego; Ramos, Abel Sánchez-Palencia; Giraldo-Ospina, Carlos Fernando; Navajas Gómez, Juan A.; Delgado-Rodriguez, Miguel; Lorente, Jose A.; Serrano, María Jose

    2016-01-01

    Background Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. Patients and Methods 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. Results 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0–84) preoperatively and 0.66 (range 0–3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50–21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091–0.961, p = 0.043) were independent prognostic factors for DFS. Conclusion CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence. PMID:26913536

  13. Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis

    Science.gov (United States)

    Vera-Rodriguez, Maria; Chavez, Shawn L.; Rubio, Carmen; Pera, Renee A. Reijo; Simon, Carlos

    2015-01-01

    Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature. PMID:26151134

  14. A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation

    Science.gov (United States)

    Delile, Julien; Herrmann, Matthieu; Peyriéras, Nadine; Doursat, René

    2017-01-01

    The study of multicellular development is grounded in two complementary domains: cell biomechanics, which examines how physical forces shape the embryo, and genetic regulation and molecular signalling, which concern how cells determine their states and behaviours. Integrating both sides into a unified framework is crucial to fully understand the self-organized dynamics of morphogenesis. Here we introduce MecaGen, an integrative modelling platform enabling the hypothesis-driven simulation of these dual processes via the coupling between mechanical and chemical variables. Our approach relies upon a minimal ‘cell behaviour ontology' comprising mesenchymal and epithelial cells and their associated behaviours. MecaGen enables the specification and control of complex collective movements in 3D space through a biologically relevant gene regulatory network and parameter space exploration. Three case studies investigating pattern formation, epithelial differentiation and tissue tectonics in zebrafish early embryogenesis, the latter with quantitative comparison to live imaging data, demonstrate the validity and usefulness of our framework. PMID:28112150

  15. CHRONIC DISSEMINATED HISTOPLASMOSIS WITH PROLONGED LATENCY

    Science.gov (United States)

    A case of chronic disseminated histoplasmosis in an ex-serviceman is described. Evidence is presented to support a latency period of over sixty years between acquisition of infection and clinical manifestation. This is the longest latency period for histoplasmosis described in the medical literature...

  16. Data Dissemination in Mobile Phone Sensor Networks

    NARCIS (Netherlands)

    Le, Viet-Duc; Le, Viet-Duc

    2012-01-01

    Deploying sensors over large areas is costly in terms of configuration, hardware, and maintenance. Using onboard sensors of today mobile phones can significantly reduce the expenses in monitoring areas and disseminating events or data. Via the available short-range Bluetooth and/or WiFi interfaces,

  17. Disseminated Gastrointestinal Mucormycosis in Immunocompromised Disease

    Directory of Open Access Journals (Sweden)

    Tae Sun Ha

    2015-11-01

    Full Text Available Mucormycosis is an uncommon opportunistic fungal infection mostly affecting immunocompromised patients and gastrointestinal mucormycosis is a rare and life-threatening. We describe a 31-year-old man with a history of idiopathic cyclic neutropenia who developed perforations of the stomach and intestine and intra-abdominal bleeding due to disseminated gastrointestinal mucormycosis after the initial operation.

  18. Disseminated Enteroviral Infection Associated with Obinutuzumab.

    Science.gov (United States)

    Dendle, Claire; Gilbertson, Michael; Korman, Tony M; Golder, Vera; Morand, Eric; Opat, Stephen

    2015-09-01

    Two cases of disseminated enteroviral infection occurred in patients who received the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis, edema, and a dermatomyositis-like syndrome. These manifestations may be unfamiliar to clinicians and are possibly responsive to intravenous immunoglobulin. Clinicians should remain vigilant for enteroviral infections in patients receiving obinutuzumab.

  19. Disseminated Enteroviral Infection Associated with Obinutuzumab

    OpenAIRE

    Dendle, Claire; Gilbertson, Michael; Korman, Tony M; Golder, Vera; Morand, Eric; Opat, Stephen

    2015-01-01

    Two cases of disseminated enteroviral infection occurred in patients who received the CD20 monoclonal antibody obinutuzumab. Clinical features included hepatitis, edema, and a dermatomyositis-like syndrome. These manifestations may be unfamiliar to clinicians and are possibly responsive to intravenous immunoglobulin. Clinicians should remain vigilant for enteroviral infections in patients receiving obinutuzumab.

  20. Strategies for Production and Dissemination of CAI.

    Science.gov (United States)

    Olivier, W. P.; Scott, G. F.

    The Individualization Project at the Ontario Institute for Studies in Education (OISE) was organized on a cooperative basis with a federal agency and several community colleges. The main design goals were to produce needed courseware, move smoothly from research and development to a production mode of operation, and to emphasize dissemination of…

  1. Disseminating Traffic Information in Vehicular Networks

    Directory of Open Access Journals (Sweden)

    Muhammad Alyas Shahid

    2015-11-01

    Full Text Available In this paper Wifi based system is described for disseminating traffic information in vehicular networks. Basic aim of this approach is to distribute information regarding the traffic conditions such as traffic congestions or safety warnings to vehicles in an effective way.

  2. The FAIR-INNOVATION dissemination project.

    Science.gov (United States)

    Gormley, R

    2001-08-01

    The goal of the FAIR-INNOVATION dissemination project (FLAIR-FLOW 3) (1997-2000) was to disseminate R&D results from the EU FAIR programme to small and medium-sized food enterprises (SMEs), health professionals (HPs) and consumer groups (CGs) in 19 European countries. The dissemination routes were: (i) one-page technical documents on research results; (ii) their reproduction on the internet; (iii) their reproduction in journals Europe-wide; (iv) workshops on results from EU-supported food research programmes; and (v) lectures and poster presentations by FLAIR-FLOW network personnel. Of the 135 one-pagers produced, 62% were targeted at SMEs, 18% at HPs and 5% at CGs. The remaining 15% were on food safety and were common to the three target groups. There were 1047 publications arising from one-pages in trade journals, and over 8000 requests (paper route) were received for follow-up information. These were in addition to 240 k downloads from the FLAIR-FLOW 3 web site (www.flair-flow.com). Initiatives for HPs included specially collated versions of the one-pagers for major conferences, 20 focused workshops, and interaction with the European Federation of Associations of Dieticians. Currently, dissemination is continuing through FLAIR-FLOW 4 (2001-2003) in 24 countries. FLAIR-FLOW 4 is co-ordinated by M. Jean François Quillien from INRA-CRIAA (FR) at criaa@rennes.inra.fr.

  3. Evolution of diffusion and dissemination theory.

    Science.gov (United States)

    Dearing, James W

    2008-01-01

    The article provides a review and considers how the diffusion of innovations Research paradigm has changed, and offers suggestions for the further development of this theory of social change. Main emphases of diffusion Research studies are compared over time, with special attention to applications of diffusion theory-based concepts as types of dissemination science. A considerable degree of paradigmatic evolution is observed. The classical diffusion model focused on adopter innovativeness, individuals as the locus of decision, communication channels, and adoption as the primary outcome measures in post hoc observational study designs. The diffusion systems in question were centralized, with fidelity of implementation often assumed. Current dissemination Research and practice is better characterized by tests of interventions that operationalize one or more diffusion theory-based concepts and concepts from other change approaches, involve complex organizations as the units of adoption, and focus on implementation issues. Foment characterizes dissemination and implementation Research, Reflecting both its interdisciplinary Roots and the imperative of spreading evidence-based innovations as a basis for a new paradigm of translational studies of dissemination science.

  4. ESEA III Evaluation and Dissemination: An Assessment.

    Science.gov (United States)

    Balyeat, Ralph R.; Norman, C. Douglas

    This study surveyed evaluation and dissemination/diffusion practices of ESEA III projects funded in the 1969 fiscal year, which projects are nearing the end of their operations as federally supported programs. The study attempted to discover if (1) the projects were evaluated in accordance with generally accepted procedures, (2) the project…

  5. The Hawaii Educational Dissemination Diffusion System Plan.

    Science.gov (United States)

    Min, Kellet; And Others

    Hawaii's endeavor to use information technology to improve educational practices within the state is described in four major sections: (1) the framework of the plan, including a brief history of dissemination, the goals of the plan, and philosophic statements on resources, linkages, and leadership; (2) the resource component, including an…

  6. Building State Capacity in Dissemination: Literature Review.

    Science.gov (United States)

    Strang, Ernest W.

    This review was developed by and principally for the National Testing Service (NTS) Dissemination Project Staff. It is one of eight activities being used by NTS to develop a design for an evaluation of the State Capacity Building Program. The review is in two parts. The first part provides background information, evaluation methodologies and…

  7. A Proposed Framework for Educational Innovation Dissemination

    Science.gov (United States)

    Hazen, Benjamin T.; Wu, Yun; Sankar, Chetan S.; Jones-Farmer, L. Allison

    2012-01-01

    Although the need for new educational technologies is increasing, the process for disseminating these innovations remains a challenge. A literature review shows that few studies have thoroughly investigated this area. Furthermore, there is no comprehensive framework or coordinated research agenda that may be used to guide such investigation. This…

  8. Differential diagnosis of disseminated periventricular calcifications

    Energy Technology Data Exchange (ETDEWEB)

    Rieger, P.; Piepgras, U.

    1986-08-01

    Juvenile disseminated periventricular calcifications may occur in tuberous sclerosis, toxoplasmosis, cytomegaly, and in tuberculous meningitis. Cysticercosis, by contrast, does not result in corresponding intracerebral foci until an older age. Differential diagnosis is no problem if clinical findings are typical (tuberous sclerosis) or if serological verification is positive. However, any unclear clinical diagnosis can often be secured by CT.

  9. Computer software management, evaluation, and dissemination

    Science.gov (United States)

    1983-01-01

    The activities of the Computer Software Management and Information Center involving the collection, processing, and distribution of software developed under the auspices of NASA and certain other federal agencies are reported. Program checkout and evaluation, inventory control, customer services and marketing, dissemination, program maintenance, and special development tasks are discussed.

  10. Knowledge Management and Global Information Dissemination

    Science.gov (United States)

    Umunadi, Ejiwoke Kennedy

    2014-01-01

    The paper looked at knowledge management and global information dissemination. Knowledge is a very powerful tool for survival, growth and development. It can be seen as the information, understanding and skills that you gain through education or experience. The paper was addressed under the following sub-headings: Knowledge management knowledge…

  11. A Primer on Disseminating Applied Quantitative Research

    Science.gov (United States)

    Bell, Bethany A.; DiStefano, Christine; Morgan, Grant B.

    2010-01-01

    Transparency and replication are essential features of scientific inquiry, yet scientific communications of applied quantitative research are often lacking in much-needed procedural information. In an effort to promote researchers dissemination of their quantitative studies in a cohesive, detailed, and informative manner, the authors delineate…

  12. Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy

    Science.gov (United States)

    Lauer, Georg M.; Lucas, Michaela; Timm, Joerg; Ouchi, Kei; Kim, Arthur Y.; Day, Cheryl L.; zur Wiesch, Julian Schulze; Paranhos-Baccala, Glaucia; Sheridan, Isabelle; Casson, Deborah R.; Reiser, Markus; Gandhi, Rajesh T.; Li, Bin; Allen, Todd M.; Chung, Raymond T.; Klenerman, Paul; Walker, Bruce D.

    2005-01-01

    Multispecific CD8+ T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8+ T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8+ T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8+ T-cell responses, as well as CD4+ T-cell responses. Rapid recrudescence also occurred despite broad CD8+ T-cell responses. Importantly, in vivo suppression of CD3+ T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8+ T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses. PMID:16189000

  13. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

    DEFF Research Database (Denmark)

    Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J

    2008-01-01

    of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

  14. Sufficient numbers of early germ cells are essential for female sex development in zebrafish.

    Directory of Open Access Journals (Sweden)

    Xiangyan Dai

    Full Text Available The sex determination for zebrafish is controlled by a combination of genetic and environmental factors. The determination of sex in zebrafish has been suggested to rely on a mechanism that is affected by germ cell-derived signals. To begin our current study, a simplified and efficient germ cell-specific promoter of the dead end (dnd gene was identified. Utilizing the metrodinazole (MTZ/ bacterial nitroreductase (NTR system for inducible germ cell ablation, several stable Tg (dnd:NTR-EGFP(-3'UTR and Tg (dnd:NTR-EGFP(+3'UTR zebrafish lines were then generated with the identified promoter. A thorough comparison of the expression patterns and tissue distributions of endogenous dnd and ntr-egfp transcripts in vivo revealed that the identified 2032-bp zebrafish dnd promoter can recapitulate dnd expression faithfully in stable transgenic zebrafish. The correlation between the levels of the germ cell-derived signals and requirement for maintaining the female fate has been also explored with different durations of the MTZ treatments. Our results revealed the decreasing ratios of female presented in the treated transgenic group are fairly associated with the reducing levels of the early germ cell-derived signals. After the juvenile transgenic fish treated with 5 mM MTZ for 20 days, all MTZ-treated transgenic fish exclusively developed into males with subfertilities. Taken together, our results identified here a simplified and efficient dnd promoter, and provide clear evidence indicating that it was not the presence but the sufficiency of signals derived from germ cells that is essential for female sex development in zebrafish. Our model also provides a unique system for sex control in zebrafish studies.

  15. Early outgrowth cells release soluble endocrine antifibrotic factors that reduce progressive organ fibrosis.

    Science.gov (United States)

    Yuen, Darren A; Connelly, Kim A; Zhang, Yanling; Advani, Suzanne L; Thai, Kerri; Kabir, Golam; Kepecs, David; Spring, Christopher; Smith, Christopher; Batruch, Ihor; Kosanam, Hari; Advani, Andrew; Diamandis, Eleftherios; Marsden, Philip A; Gilbert, Richard E

    2013-11-01

    Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-β- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 10(6) EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy.

  16. Broad early immune response of porcine epithelial jejunal IPI-2I cells to Entamoeba histolytica.

    Science.gov (United States)

    Meurens, François; Girard-Misguich, Fabienne; Melo, Sandrine; Grave, Aurore; Salmon, Henri; Guillén, Nancy

    2009-02-01

    Amoebiasis caused by Entamoebahistolytica triggers an acute inflammatory response at early stages of intestinal infection. The patho-physiological study of intestinal amoebiasis requires the development of powerful animal models. Swine provide robust model for human diseases and they could be used to study intestinal amoebiasis. Here, we introduce an in vitro model of swine intestinal epithelial cell (IPI-2I) co-cultured with E. histolytica. Intestinal epithelial cells (IECs) have crucial roles in sensing pathogens and initiating innate immune response, which qualitatively influence adaptive immune response against them. The contact between the two cells induces marked macroscopic lesions of IEC monolayer and striking alteration of the IPI-2I cell phenotype including blebbing, such as loss of attachment before to be phagocyte by the trophozoite. Increase in Lactate Dehydrogenase (LDH) levels in the culture supernatant of IECs was observed when ameba is present and could reflect the cellular cytotoxicity exerted by the parasite. Using quantitative real-time PCR, we identified the up-regulation of cytokines/chemokines implicated in neutrophil chemoattraction and inflammation, such as CCL2, CCL20, CXCL2, CXCL3, GM-CSF, IL1 alpha, IL6 and IL8, in response to the parasite that can further regulate the immunoregulatory functions of the immune cells of the host. The study points a cardinal role of these pro-inflammatory compounds as central mediators in the interaction IECs/ameba and suggests mechanisms by which they coordinate intestinal immune response. This will focus future efforts on delineating the molecular and cellular mechanisms of other cell partners by the way of in vivo infection of swine.

  17. Morphological changes among hippocampal dentate granule cells exposed to early kindling-epileptogenesis.

    Science.gov (United States)

    Singh, Shatrunjai P; He, Xiaoping; McNamara, James O; Danzer, Steve C

    2013-12-01

    Temporal lobe epilepsy is associated with changes in the morphology of hippocampal dentate granule cells. These changes are evident in numerous models that are associated with substantial neuron loss and spontaneous recurrent seizures. By contrast, previous studies have shown that in the kindling model, it is possible to administer a limited number of stimulations sufficient to produce a lifelong enhanced sensitivity to stimulus evoked seizures without associated spontaneous seizures and minimal neuronal loss. Here we examined whether stimulation of the amygdala sufficient to evoke five convulsive seizures (class IV or greater on Racine's scale) produce morphological changes similar to those observed in models of epilepsy associated with substantial cell loss. The morphology of GFP-expressing granule cells from Thy-1 GFP mice was examined either 1 day or 1 month after the last evoked seizure. Interestingly, significant reductions in dendritic spine density were evident 1 day after the last seizure, the magnitude of which had diminished by 1 month. Further, there was an increase in the thickness of the granule cell layer 1 day after the last evoked seizure, which was absent a month later. We also observed an increase in the area of the proximal axon, which again returned to control levels a month later. No differences in the number of basal dendrites were detected at either time point. These findings demonstrate that the early stages of kindling epileptogenesis produce transient changes in the granule cell body layer thickness, molecular layer spine density, and axon proximal area, but do not produce striking rearrangements of granule cell structure.

  18. Disseminated tuberculosis following reduced-intensity cord blood transplantation for adult patients with hematological diseases.

    Science.gov (United States)

    Maeda, T; Kusumi, E; Kami, M; Kawabata, M; Le Pavoux, A; Hara, S; Chizuka, A; Murashige, N; Tanimoto, T E; Matsumura, T; Yuji, K; Yuji, Ko; Wake, A; Miyakoshi, S; Morinaga, S; Taniguchi, S

    2005-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are prone to infections. The incidences of mycobacterial infections after allo-SCT in several case series vary from less than 0.1-5.5%. However, no study has been published on tuberculosis following unrelated cord blood transplantation (UCBT). We retrospectively reviewed medical records of 113 adult patients with a median age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were diagnosed in three patients (2.7%), of these two patients developed primary infection and one patient developed reactivation of latent tuberculosis. The interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61 days. All the patients had disseminated disease at diagnosis. Histological examination showed the lack of granuloma in caseous necrosis. Combination antituberculous treatments showed limited efficacy, and two patients died immediately after diagnosis. M. tuberculosis caused life-threatening illness, rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous necrosis suggests the impaired T-cell function in early post transplant phase of RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of fever of unknown source after RI-UCBT.

  19. Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

    Science.gov (United States)

    Zhang, Jian; Wei, Wei; Jin, Hui-Cheng; Ying, Rong-Chao; Zhu, A-Kao; Zhang, Fang-Jie

    2015-01-01

    Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

  20. Live cell imaging of the nascent inactive X chromosome during the early differentiation process of naive ES cells towards epiblast stem cells.

    Directory of Open Access Journals (Sweden)

    Aurélia Guyochin

    Full Text Available Random X-chromosome inactivation ensures dosage compensation in mammals through the transcriptional silencing of one of the two X chromosomes present in each female cell. Silencing is initiated in the differentiating epiblast of the mouse female embryos through coating of the nascent inactive X chromosome by the non-coding RNA Xist, which subsequently recruits the Polycomb Complex PRC2 leading to histone H3-K27 methylation. Here we examined in mouse ES cells the early steps of the transition from naive ES cells towards epiblast stem cells as a model for inducing X chromosome inactivation in vitro. We show that these conditions efficiently induce random XCI. Importantly, in a transient phase of this differentiation pathway, both X chromosomes are coated with Xist RNA in up to 15% of the XX cells. In an attempt to determine the dynamics of this process, we designed a strategy aimed at visualizing the nascent inactive X-chromosome in live cells. We generated transgenic female XX ES cells expressing the PRC2 component Ezh2 fused to the fluorescent protein Venus. The fluorescent fusion protein was expressed at sub-physiological levels and located in nuclei of ES cells. Upon differentiation of ES cell towards epiblast stem cell fate, Venus-fluorescent territories appearing in interphase nuclei were identified as nascent inactive X chromosomes by their association with Xist RNA. Imaging of Ezh2-Venus for up to 24 hours during the differentiation process showed survival of some cells with two fluorescent domains and a surprising dynamics of the fluorescent territories across cell division and in the course of the differentiation process. Our data reveal a strategy for visualizing the nascent inactive X chromosome and suggests the possibility for a large plasticity of the nascent inactive X chromosome.

  1. Thyroid Storm Complicated by Bicytopenia and Disseminated Intravascular Coagulation

    Science.gov (United States)

    Tokushima, Yoshinori; Sakanishi, Yuta; Nagae, Kou; Tokushima, Midori; Tago, Masaki; Tomonaga, Motosuke; Yoshioka, Tsuneaki; Hyakutake, Masaki; Sugioka, Takashi; Yamashita, Shu-ichi

    2014-01-01

    Patient: Male, 23 Final Diagnosis: Thyroid storm Symptoms: Delirium • diarrhea • fever • hypertension • hyperventilation • tachycardia • weight loss Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: The clinical presentation of thyroid storm includes fever, tachycardia, hypertension, and neurological abnormalities. It is a serious condition with a high mortality rate. Furthermore, some other complications affect the clinical course of thyroid storm. Although it is reported that prognosis is poor when thyroid storm is complicated by disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of such cases are rare. Case Report: A 23-year-old man presented with delirium, high pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis of his symptom-complex and laboratory data that confirmed the presence of hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and disseminated intravascular coagulation, all of which are very rare complications of thyroid storm. We successfully treated him with combined therapy including anti-thyroid medication, despite leukopenia. Conclusions: Early diagnosis and treatment are essential in ensuring a good outcome for patients with this rare combination of medical problems. PMID:25072662

  2. Disseminated pleomorphic myofibrosarcoma in a grizzly bear (Ursus arctos horribilis).

    Science.gov (United States)

    Mete, A; Woods, L; Famini, D; Anderson, M

    2012-01-01

    The pathological and diagnostic features of a widely disseminated pleomorphic high-grade myofibroblastic sarcoma are described in a 23-year-old male brown bear (Ursus arctos horribilis). Firm, solid, white to tan neoplastic nodules, often with cavitated or soft grey-red necrotic centres, were observed throughout most internal organs, subcutaneous tissues and skeletal muscles on gross examination. Microscopically, the tumour consisted of pleomorphic spindle cells forming interlacing fascicles with a focal storiform pattern with large numbers of bizarre polygonal multinucleate cells, frequently within a collagenous stroma. Immunohistochemistry, Masson's trichrome stain and transmission electron microscopy designated the myofibroblast as the cell of origin. This is the first case of a high-grade myofibrosarcoma in a grizzly bear.

  3. Fetal Nerve Cell Transplantation in Early Post-Resuscitation Period in Rats

    Directory of Open Access Journals (Sweden)

    Damira Tazhibayeva

    2015-02-01

    was less than in the control group. Moreover, cell therapy improved the reflexes in the experimental animals. Conclusions. The study revealed the positive neuroprotective effect of the fetal nerve cells on the recovery in the early post-resuscitation period. This was confirmed by the normalization of enzymatic reactions, improvement reflective activity, and increase in the survival rate of the resuscitated animals in the group treated with fetal nerve cell transplantation. These findings warrant future research on the mechanisms associated with reflex improvement. 

  4. Role of mechanical stretching and lipopolysaccharide in early apoptosis and IL-8 of alveolar epithelial typeⅡ cells A549

    Institute of Scientific and Technical Information of China (English)

    Qiao-Ming Ning; Xiao-Ning Sun; Xin-Kai Zhao

    2012-01-01

    Objective:To investigate the effects of mechanical stretching and lipopolysaccharide (LPS) on the early apoptosis and IL-8 production of alveolar epithelial typeⅡ cellsA549.Methods:The experimental matrix consisted of three integrated studies.In the first study,A549 cells were subjected to different stretching strain frequency and duration time to see the effects on the early apoptosis.In the second study,A549 cells were subjected to mechanical stretch(15%4 h, 0.5Hz) andLPS(1 or100 ng/mL) to see whether mechanical strain andLPS also have an addictive effect on the early apoptosis.In the third study to investigate whether this addictive effect could be induced byLPS and mechanical stretch onIL-8 production,A549 cells were subjected to LPS(100 ng/mL) and mechanical strain(15%,0.5Hz,4 h).Real timePCR and enzyme linked immunosorbent assay were used to measure mRNA and protein level ofIL-8.The early apoptosis was detected by flow cytometry.Results:Mechanical stretch induced the early apoptosis in a force and frequency and time-dependent manner.In the presence ofLPS, mechanical stretch enhancedLPS-induced early apoptosis, especially in100 ng/mLLPS group compared with1 ng/mLLPS and the control group.Mechanical stretch increasedIL-8 production and enhancedLPS-inducedIL-8 screation both in mRNA and protein levels.Conclusions:Mechanical stretch can induce the early apoptosis andIL-8 secretion.Mechanical stretch andLPS have an addictive effect on the early apoptosis andIL-8 production in alveolar type2 cells, which is one of the mechanisms of ventilator-induced lung injury.

  5. Deletion of the NSm virulence gene of Rift Valley fever virus inhibits virus replication in and dissemination from the midgut of Aedes aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Rebekah C Kading

    2014-02-01

    Full Text Available BACKGROUND: Previously, we investigated the role of the Rift Valley fever virus (RVFV virulence genes NSs and NSm in mosquitoes and demonstrated that deletion of NSm significantly reduced the infection, dissemination, and transmission rates of RVFV in Aedes aegypti mosquitoes. The specific aim of this study was to further characterize midgut infection and escape barriers of RVFV in Ae. aegypti infected with reverse genetics-generated wild type RVFV (rRVF-wt or RVFV lacking the NSm virulence gene (rRVF-ΔNSm by examining sagittal sections of infected mosquitoes for viral antigen at various time points post-infection. METHODOLOGY AND PRINCIPAL FINDINGS: Ae. aegypti mosquitoes were fed an infectious blood meal containing either rRVF-wt or rRVF-ΔNSm. On days 0, 1, 2, 3, 4, 6, 8, 10, 12, and 14 post-infection, mosquitoes from each experimental group were fixed in 4% paraformaldehyde, paraffin-embedded, sectioned, and examined for RVFV antigen by immunofluorescence assay. Remaining mosquitoes at day 14 were assayed for infection, dissemination, and transmission. Disseminated infections were observed in mosquitoes as early as three days post infection for both virus strains. However, infection rates for rRVF-ΔNSm were statistically significantly less than for rRVF-wt. Posterior midgut infections in mosquitoes infected with rRVF-wt were extensive, whereas midgut infections of mosquitoes infected with rRVF-ΔNSm were confined to one or a few small foci. CONCLUSIONS/SIGNIFICANCE: Deletion of NSm resulted in the reduced ability of RVFV to enter, replicate, and disseminate from the midgut epithelial cells. NSm appears to have a functional role in the vector competence of mosquitoes for RVFV at the level of the midgut barrier.

  6. Dissemination Matters: Influences of Dissemination Activities on User Types in an Online Educational Community

    Directory of Open Access Journals (Sweden)

    Min Yuan

    2014-09-01

    Full Text Available Emerging online educational communities provide spaces for teachers to find resources, create instructional activities, and share these activities with others. Within these online communities, individual users’ activities may vary widely, and thus different user types can be identified. In addition, users’ patterns of activities in online communities are dynamic, and further can be affected by dissemination activities. Through analyzing usage analytics in an online teacher community called the Instructional Architect, this study explores the influences of dissemination activities on the usage patterns of different user types. Results show that dissemination activities can play an important role in encouraging users’ active participation, while the absence of dissemination activities can further increase participation inequality.

  7. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas.

    Science.gov (United States)

    Won, Minho; Ro, Hyunju; Dawid, Igor B

    2015-10-06

    The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use.

  8. T-cell chimerism is valuable in predicting early mortality in steroid-resistant acute graft-versus-host disease after myeloablative allogeneic cell transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Madsen, Hans O.; Sengeløv, Henrik

    2014-01-01

    The main aim of this study was to evaluate the impact of early T-cell chimerism status on the incidence and clinical course of acute graft-versus-host disease (aGVHD) in allogeneic transplant recipients after myeloablative conditioning. Of 62 patients, 38 (61%) had complete T-cell donor chimerism...

  9. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori; Tanabe, Kazunari [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan)

    2016-06-15

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. (orig.)

  10. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  11. The early history of odontogenic ghost cell lesions: from Thoma to Gorlin.

    Science.gov (United States)

    Ide, Fumio; Kikuchi, Kentaro; Miyazaki, Yuji; Kusama, Kaoru; Saito, Ichiro; Muramatsu, Takashi

    2015-03-01

    To reappraise the early history of odontogenic ghost cell lesions (OGCL), the extensive world literature published from 1838 to 1962 was reviewed. In light of the long history of OGCL, the term "calcifying epithelioma of Malherbe" first appeared in a 1931 French report, and the term "ghost cells" had its origin in two American seminal articles by Thoma and Goldman in 1946. Although Gorlin et al. coined the term "calcifying odontogenic cyst" (COC) in 1962, this type of cyst was initially reported three decades earlier by Rywkind in Russia, and almost concurrently by Blood good in the United States and Sato in Japan. In 1948, Willis provided the initial histological evidence of a peripheral COC in his British pathology textbook. Credit for the earliest clinical presentation of odontoma associated calcifying cystic odontogenic tumor belongs to the American radiology textbook by Thoma in 1917. A Scandinavian journal report published in 1953 by Husted and Pindborg was the first to address a dentinogenic ghost cell tumor, and its peripheral counterpart was originally reported in the Swiss literature 7 years later. The current concept of COC was undoubtedly established by Gorlin et al. but the history of OGCL really started with Thoma's pioneering work about a century ago.

  12. High-sensitivity Mass Spectrometry for Probing Gene Translation in Single Embryonic Cells in the Early Frog (Xenopus Embryo

    Directory of Open Access Journals (Sweden)

    Camille Lombard-Banek

    2016-10-01

    Full Text Available Direct measurement of protein expression with single-cell resolution promises to deepen the understanding of basic molecular processes during normal and impaired development. High-resolution mass spectrometry provides detailed coverage of the proteomic composition of large numbers of cells. Here we discuss recent mass spectrometry developments based on single-cell capillary electrophoresis that extend discovery proteomics to sufficient sensitivity to enable the measurement of proteins in single cells. The single-cell mass spectrometry system is used to detect a large number of proteins in single embryonic cells in blastomeres in the 16-cell embryo of the South African clawed frog (Xenopus laevis that give rise to distinct tissue types. Single-cell measurements of protein expression provide complementary information on gene transcription during early development of the vertebrate embryo, raising a potential to understand how differential gene expression coordinates normal cell heterogeneity during development.

  13. DNA vaccination in fish promotes an early chemokine-related recruitment of B cells to the muscle

    DEFF Research Database (Denmark)

    Castro, R.; Martínez-Alonso, S.; Fischer, U.

    2013-01-01

    cells that infiltrate the muscle at the site of DNA delivery in vaccinated fish and the chemokines that may be involved in their infiltration. It was observed that B lymphocytes, both IgM+ and IgT+, represent a major infiltrating cell type in fish vaccinated with a viral hemorrhagic septicemia virus...... (VHSV) DNA vaccine, whereas in control fish injected with an oil adjuvant mainly granulocytes were attracted. While IgM+ cells were the major B cell population at early time points post vaccination, IgT+ cells represented the predominant cell type later on. Among twelve chemokine genes studied...... might explain the recruitment of immune cells to the site of DNA injection. Our results suggest that B cells are involved in the initial phase of the immune response to intramuscular DNA vaccination against VHSV. This appears to be a major difference to what we know from mammalian models where T cells...

  14. Low Counts of Plasmacytoid Dendritic Cells after Engraftment Are Associated with High Early Mortality after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Gonçalves, Matheus Vescovi; Yamamoto, Mihoko; Kimura, Eliza Yurico Sugano; Colturato, Vergílio Antônio Rensi; de Souza, Mair Pedro; Mauad, Marcos; Ikoma, Maura Valerio; Novis, Yana; Rocha, Vanderson; Ginani, Valeria Cortez; Wanderley de Oliveira Felix, Olga Margareth; Seber, Adriana; Kerbauy, Fabio Rodrigues; Hamerschlak, Nelson; Orfao, Alberto; Rodrigues, Celso Arrais

    2015-07-01

    Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.

  15. The early detection of blood coagulation indictors and its changes after intervention in acute leukemia children complicated with disseminated intravascular coagulation%急性白血病并发弥散性血管内凝血患儿期及干预后血凝指标变化

    Institute of Scientific and Technical Information of China (English)

    杨静; 孙秀芳; 孙立荣; 李学荣; 仲任; 赵艳霞

    2012-01-01

    目的:探讨急性白血病(AL)患儿并发弥散性血管内凝血(DIC)早期及干预后血凝指标变化.方法:本实验分3组即健康对照组;AL组;AL并发DIC组,均于清晨抽取空腹血检测D-二聚体(DD)、纤维蛋白原水平(FBG)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及抗凝血酶-Ⅲ(AT-Ⅲ).对AL并发DIC组患儿应用低分子肝素治疗,比较治疗前后各指标变化,采用SPSS 10.0软件将各组进行统计学分析.结果:AL组与健康对照组比较,PT延长,FBG降低,DD明显升高,差异有统计学意义(P<0.05),AL并发DIC组与AL组比较,DD明显升高,AT-Ⅲ降低,差异有统计学意义(P<0.05),且与AL组相比,AL并发DIC组DD、AT-Ⅲ阳性率明显升高,且在DIC发病的不同临床阶段均保持在较高水平(80%以上),DD检测阳性率在血栓形成期高达100%.经肝素抗凝治疗后,AT-Ⅱ及FBG明显升高,DD降低,差异有统计学意义(P<0.05).结论:AL并发DIC患儿存在凝血、纤溶系统的激活,AT-Ⅲ及DD可作为DIC早期诊断的指标,低分子肝素应用有助于改善DIC患儿的预后.%Objective: To explore the early changes of blood coagulation indictors in acute leukemia children complicated with disseminated intravascular coagulation (DIC) and the efficacy ot low molecular weight heparin intervention. Method; The cases in our experiment were divided into three groups: the healthy control group, AL group and AL complicated with DIC group. Plasma level of AT-Ⅲ , D-dimer, fibrinogen, activated partial throm-boplastin time and prothrombin time were detected. The changes of indictors before and after treatment with low molecular weight heparin in AL group complicated with DIC were compared. And the results were compared between the three groups by SPSS 10. 0 software. Result: PT prolonged, fibrinogen reduced and the D-dimer increased significantly in AL group than those in healthy control group (P<0. 05). The plasma level of D-dimer in AL

  16. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

    Directory of Open Access Journals (Sweden)

    Atar Lev

    Full Text Available The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2-deficient severe combined immunodeficiency (SCID patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR and the B cell receptor (BCR repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

  17. High-frequency stimulation induces gradual immediate early gene expression in maturing adult-generated hippocampal granule cells.

    Science.gov (United States)

    Jungenitz, Tassilo; Radic, Tijana; Jedlicka, Peter; Schwarzacher, Stephan W

    2014-07-01

    Increasing evidence shows that adult neurogenesis of hippocampal granule cells is advantageous for learning and memory. We examined at which stage of structural maturation and age new granule cells can be activated by strong synaptic stimulation. High-frequency stimulation of the perforant pathway in urethane-anesthetized rats elicited expression of the immediate early genes c-fos, Arc, zif268 and pCREB133 in almost 100% of mature, calbindin-positive granule cells. In contrast, it failed to induce immediate early gene expression in immature doublecortin-positive granule cells. Furthermore, doublecortin-positive neurons did not react with c-fos or Arc expression to mild theta-burst stimulation or novel environment exposure. Endogenous expression of pCREB133 was increasingly present in young cells with more elaborated dendrites, revealing a close correlation to structural maturation. Labeling with bromodeoxyuridine revealed cell age dependence of stimulation-induced c-fos, Arc and zif268 expression, with only a few cells reacting at 21 days, but with up to 75% of cells activated at 35-77 days of cell age. Our results indicate an increasing synaptic integration of maturing granule cells, starting at 21 days of cell age, but suggest a lack of ability to respond to activation with synaptic potentiation on the transcriptional level as long as immature cells express doublecortin.

  18. Targeting regulatory T cells to improve vaccine immunogenicity in early life

    Directory of Open Access Journals (Sweden)

    Jorjoh eNdure

    2014-09-01

    Full Text Available Human newborns and infants are bombarded with multiple pathogens on leaving the sterile intra-uterine environment, and yet have suboptimal innate immunity and limited immunological memory, thus leading to increased susceptibility to infections in early life. They are thus the target age group for a host of vaccines against common bacterial and viral pathogens. They are also the target group for many vaccines in development, including those against tuberculosis (TB, malaria and HIV infection. However, neonatal and infant responses to many vaccines are suboptimal, and in the case of the polysaccharide vaccines, it has been necessary to develop the alternative conjugated formulations in order to induce immunity in early life. Immunoregulatory factors are an intrinsic component of natural immunity necessary to dampen or control immune responses, with the caveat that they may also decrease immunity to infections or lead to chronic infection. This review explores the key immunoregulatory factors at play in early life, with a particular emphasis on regulatory T cells (Tregs. It goes on to explore the role that Tregs play in limting vaccine immunogenicity, and describes animal and human studies in which Tregs have been depleted in order to enhance vaccine responses. A deeper understanding of the role that Tregs play in limiting or controlling vaccine induced immunity would provide strategies to improve vaccine immunogenicity in this critical age group. New adjuvants and drugs are being developed that can transiently suppress Treg function, and their use as part of human vaccination strategies against infections is becoming a real prospect for the future.

  19. Effect of Somatic Cell Types and Culture Medium on in vitro Maturation, Fertilization and Early Development Capability of Buffalo Oocytes

    Directory of Open Access Journals (Sweden)

    H. Jamil*, H. A. Samad, N. Rehman, Z. I. Qureshi and L. A. Lodhi

    2011-04-01

    Full Text Available This study was designed to evaluate the efficacy of different somatic cell types and media in supporting in vitro maturation (IVM, in vitro fertilization (IVF and early embryonic development competence of buffalo follicular oocytes. Cumulus oocyte complexes were collected for maturation from follicles (>6mm of buffalo ovaries collected at the local abattoir. Oocytes were co-cultured in tissue culture medium (TCM-199 with either granulosa cells, cumulus cells, or buffalo oviductal epithelial cells (BOEC @ 3x106 cells/ml or in TCM-199 without helper cells (control at 39°C and 5%CO2 in humidified air. Fresh semen was prepared in modified Ca++ free Tyrode medium. Fertilization was carried out in four types of media: i Tyrode lactate albumin pyruvate (TALP, ii TALP+BOEC, iii modified Ca++ free Tyrode and iv modified Ca++ free Tyrode+BOEC. Fertilized oocytes were cultured for early embryonic development in TCM-199 with and without BOEC. Higher maturation rates were observed in the granulosa (84.24% and cumulus cells (83.44% than BOEC co culture system (73.37%. Highest fertilization rate was obtained in modified Ca++ free Tyrode with BOEC co culture (70.42%, followed by modified Ca++ free Tyrode alone (63.77%, TALP with BOEC (36.92% and TALP alone (10.94%. Development of early embryos (8-cell stage improved in TCM-199 with BOEC co culture than TCM-199 alone. From the results of this study, it can be concluded that addition of somatic cells (granulosa cells, cumulus cells results in higher maturation rates of buffalo follicular oocytes than BOEC co culture system, while fertilization rate improved in modified Ca++ free Tyrode with and without BOEC. Addition of BOEC to TCM-199 improved the developmental capacity of early embryo.

  20. EMPOWER. Deliverable no 7.1 Dissemination Plan

    NARCIS (Netherlands)

    Meeuwissen, M.; Fioreze, T.; Thomas, T.; Pickerden, C.; Hof, T.

    2015-01-01

    This deliverable describes the general plan regarding all dissemination activities of the consortium partners and work packages during the project. This links directly to D7.4 where the realization of different dissemination activities will be reported.

  1. Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

    Science.gov (United States)

    Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

    2008-01-01

    We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

  2. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2014-01-01

    Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

  3. Early hepatic stellate cell activation predicts severe hepatitis C recurrence after liver transplantation.

    Science.gov (United States)

    Gawrieh, Samer; Papouchado, Bettina G; Burgart, Lawrence J; Kobayashi, Shogo; Charlton, Michael R; Gores, Gregory J

    2005-10-01

    Only a subset of hepatitis C virus (HCV)-infected patients develop progressive hepatic fibrosis after liver transplantation (LT). Hepatic stellate cell (HSC) activation is a pivotal step in hepatic fibrosis and precedes clinically apparent fibrosis. We determined whether early HSC activation, measured in 4-month protocol post-LT biopsies, is predictive of subsequent development of more histologically severe recurrence of HCV. Early (4 month) post-LT HSC activation, as measured by alpha-smooth muscle actin (alpha-SMA) staining, was determined in liver biopsies from recipients with severe (fibrosis score > or = 2, n = 13) and with mild (fibrosis score of 0, n = 13) recurrence of HCV at one-year post-LT. Immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) was used to generate HSC activation scores (regional and total). Total HSC activation scores at 4 months were similar in patients with severe and mild HCV recurrence (3.9 +/- 2.0 vs. 2.7 +/- 2.2, P = 0.2). Regional HSC activation, assessed as parenchymal (zones 1, 2, and 3) or mesenchymal (portal tracts and fibrous septa), was different between the study groups, with higher mesenchymal scores predictive of progression. No patients in the mild recurrence group had detectable mesenchymal alpha-SMA staining vs. 46% (6/13) of patients with severe recurrence (P HCV or HSC-targeted therapy.

  4. Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Joseph Landry

    2008-10-01

    Full Text Available We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor, the largest subunit of NURF (Nucleosome Remodeling Factor in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf(-/- embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf(-/- embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo.

  5. Basal cell carcinoma with halo phenomenon in a young female: Significance of dermatoscopy in early diagnosis

    Directory of Open Access Journals (Sweden)

    Pinar Yuksel Basak

    2015-01-01

    Full Text Available Halo phenomenon of nevus may be observed as a circular reaction, although it is unusual around tumors. A 29-year-old woman presented with a pigmented lesion on the cheek since three years. She noted whitening of the skin around the lesion almost after a year following its appearance. Dermatologic examination revealed a pigmented nodular lesion with a hypopigmented halo on the left infraorbital region. The clinical impression was halo nevus, whereas basal cell carcinoma (BCC was considered in dermatoscopic differential diagnosis. The diagnosis was infiltrative-type BCC histopathologically. The persistence of a perilesional halo around an enlarging pigmented lesion should be carefully examined with accompanying dermatoscopic findings even in young patients for early diagnosis of tumoral lesions.

  6. Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.

    Science.gov (United States)

    Mozzoni, Paola; Banda, Iris; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Acampa, Olga; Balestra, Valeria; Ampollini, Luca; Casalini, Angelo; Carbognani, Paolo; Mutti, Antonio

    2013-12-01

    Lung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

  7. β-Pix directs collective migration of anterior visceral endoderm cells in the early mouse embryo.

    Science.gov (United States)

    Omelchenko, Tatiana; Rabadan, M Angeles; Hernández-Martínez, Rocío; Grego-Bessa, Joaquim; Anderson, Kathryn V; Hall, Alan

    2014-12-15

    Collective epithelial migration is important throughout embryonic development. The underlying mechanisms are poorly understood but likely involve spatially localized activation of Rho GTPases. We previously reported that Rac1 is essential for generating the protrusive activity that drives the collective migration of anterior visceral endoderm (AVE) cells in the early mouse embryo. To identify potential regulators of Rac1, we first performed an RNAi screen of Rho family exchange factors (guanine nucleotide exchange factor [GEF]) in an in vitro collective epithelial migration assay and identified β-Pix. Genetic deletion of β-Pix in mice disrupts collective AVE migration, while high-resolution live imaging revealed that this is associated with randomly directed protrusive activity. We conclude that β-Pix controls the spatial localization of Rac1 activity to drive collective AVE migration at a critical stage in mouse development.

  8. Early host cell targets of Yersinia pestis during primary pneumonic plague.

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    Roger D Pechous

    Full Text Available Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal syndrome with mortality rates approaching 100%. Pneumonic plague progression is biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in the absence of host inflammation, followed by a pro-inflammatory phase marked by extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue destruction. Using a FRET-based probe to quantitate injection of effector proteins by the Y. pestis type III secretion system, we show that these bacteria target alveolar macrophages early during infection of mice, followed by a switch in host cell preference to neutrophils. We also demonstrate that neutrophil influx is unable to limit bacterial growth in the lung and is ultimately responsible for the severe inflammation during the lethal pro-inflammatory phase.

  9. Autocrine regulation of interferon gamma in mesenchymal stem cells plays a role in early osteoblastogenesis.

    Science.gov (United States)

    Duque, Gustavo; Huang, Dao Chao; Macoritto, Michael; Rivas, Daniel; Yang, Xian Fang; Ste-Marie, Louis Georges; Kremer, Richard

    2009-03-01

    Interferon (IFN)gamma is a strong inhibitor of osteoclast differentiation and activity. However, its role in osteoblastogenesis has not been carefully examined. Using microarray expression analysis, we found that several IFNgamma-inducible genes were upregulated during early phases of osteoblast differentiation of human mesenchymal stem cells (hMSCs). We therefore hypothesized that IFNgamma may play a role in this process. We first observed a strong and transient increase in IFNgamma production following hMSC induction to differentiate into osteoblasts. We next blocked this endogenous production using a knockdown approach with small interfering RNA and observed a strong inhibition of hMSC differentiation into osteoblasts with a concomitant decrease in Runx2, a factor indispensable for osteoblast development. Additionally, exogenous addition of IFNgamma accelerated hMSC differentiation into osteoblasts in a dose-dependent manner and induced higher levels of Runx2 expression during the early phase of differentiation. We next examined IFNgamma signaling in vivo in IFNgamma receptor 1 knockout (IFNgammaR1(-/-)) mice. Compared with their wild-type littermates, IFNgammaR1(-/-) mice exhibited a reduction in bone mineral density. As in the in vitro experiments, MSCs obtained from IFNgammaR1(-/-) mice showed a lower capacity to differentiate into osteoblasts. In summary, we demonstrate that the presence of IFNgamma plays an important role during the commitment of MSCs into the osteoblastic lineage both in vitro and in vivo, and that this process can be accelerated by exogenous addition of IFNgamma. These data therefore support a new role for IFNgamma as an autocrine regulator of hMSC differentiation and as a potential new target of bone-forming cells in vivo.

  10. SPOC1-Mediated Antiviral Host Cell Response Is Antagonized Early in Human Adenovirus Type 5 Infection

    Science.gov (United States)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin; Mund, Andreas; Wimmer, Peter; Schubert, Tobias; Groitl, Peter; Will, Hans; Dobner, Thomas

    2013-01-01

    Little is known about immediate phases after viral infection and how an incoming viral genome complex counteracts host cell defenses, before the start of viral gene expression. Adenovirus (Ad) serves as an ideal model, since entry and onset of gene expression are rapid and highly efficient, and mechanisms used 24–48 hours post infection to counteract host antiviral and DNA repair factors (e.g. p53, Mre11, Daxx) are well studied. Here, we identify an even earlier host cell target for Ad, the chromatin-associated factor and epigenetic reader, SPOC1, recently found recruited to double strand breaks, and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its functional association with the Ad major core protein pVII that enters with the viral genome, followed by E1B-55K/E4orf6-dependent proteasomal degradation of SPOC1. Mimicking removal of SPOC1 in the cell, knock down of this cellular restriction factor using RNAi techniques resulted in significantly increased Ad replication, including enhanced viral gene expression. However, depletion of SPOC1 also reduced the efficiency of E1B-55K transcriptional repression of cellular promoters, with possible implications for viral transformation. Intriguingly, not exclusive to Ad infection, other human pathogenic viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host cells should provide new perspectives for developing antiviral agents and therapies. Conversely, for Ad vectors used in gene therapy, counteracting mechanisms eradicating incoming

  11. Feasibility of using fluorescence in situ hybridization (FISH) to detect early gene changes in sputum cells from uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Neft, R.E.; Rogers, J.L.; Belinsky, S.A. [and others

    1995-12-01

    Epidemiological studies have shown that combined exposure to radon progeny and tobacco smoke produce a greater than additive or synergistic increase in lung cancer risk. Lung cancer results from multiple genetic changes over a long period of time. An early change that occurs in lung cancer is trisomy 7 which is found in 50% of non-small cell lung cancer and in the far margins of resected lung tumors. The 80% mortality associated with lung cancer is in part related to the high proportion of patients who present with an advanced, unresectable tumor. Therefore, early detection of patients at risk for tumor development is critical to improve treatment of this disease. Currently, it is difficult to detect lung cancer early while it is still amendable by surgery. Saccomanno, G. has shown that premalignant cytologic changes in sputum cells collected from uranium miners can be detected by a skilled, highly trained cytopathologist. A more objective alternative for identifying premalignant cells in sputum may be to determine whether an early genetic change such as trisomy 7 is present in these cells. Fluorescence in situ hybridization (FISH) can be used to identify cells with trisomy 7. The results of this investigation indicate that FISH may prove to be an accurate, efficient method to test at-risk individuals for genetic alterations in bronchial epithelial cells from sputum.

  12. Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney.

    Science.gov (United States)

    Martina, Maria N; Noel, Sanjeev; Saxena, Ankit; Bandapalle, Samatha; Majithia, Richa; Jie, Chunfa; Arend, Lois J; Allaf, Mohamad E; Rabb, Hamid; Hamad, Abdel Rahim A

    2016-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4(+) T cells, natural killer T cells, and CD4(+)CD25(+)FoxP3(+) Tregs in AKI pathogenesis. We recently identified CD4(-)CD8(-) (double-negative; DN) T cells as an important subset of αβ T cell receptor-positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4(+) and CD8(+) T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4(+) T cells. Within the first 3-24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10-dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ(+) T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.

  13. Melatonin promotes development of haploid germ cells from early developing spermatogenic cells of Suffolk sheep under in vitro condition.

    Science.gov (United States)

    Deng, Shou-Long; Chen, Su-Ren; Wang, Zhi-Peng; Zhang, Yan; Tang, Ji-Xin; Li, Jian; Wang, Xiu-Xia; Cheng, Jin-Mei; Jin, Cheng; Li, Xiao-Yu; Zhang, Bao-Lu; Yu, Kun; Lian, Zheng-Xing; Liu, Guo-Shi; Liu, Yi-Xun

    2016-05-01

    Promotion of spermatogonial stem cell (SSC) differentiation into functional sperms under in vitro conditions is a great challenge for reproductive physiologists. In this study, we observed that melatonin (10(-7) M) supplementation significantly enhanced the cultured SSCs differentiation into haploid germ cells. This was confirmed by the expression of sperm special protein, acrosin. The rate of SSCs differentiation into sperm with melatonin supplementation was 11.85 ± 0.93% which was twofold higher than that in the control. The level of testosterone, the transcriptions of luteinizing hormone receptor (LHR), and the steroidogenic acute regulatory protein (StAR) were upregulated with melatonin treatment. At the early stage of SSCs culture, melatonin suppressed the level of cAMP, while at the later stage, it promoted cAMP production. The similar pattern was observed in testosterone content. Expressions for marker genes of meiosis anaphase, Dnmt3a, and Bcl-2 were upregulated by melatonin. In contrast, Bax expression was downregulated. Importantly, the in vitro-generated sperms were functional and they were capable to fertilize oocytes. These fertilized oocytes have successfully developed to the blastula stage.

  14. Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

    Directory of Open Access Journals (Sweden)

    Bertin Jonathan

    2012-03-01

    Full Text Available Abstract Background Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS. Leukotriene B4 (LTB4 and cysteinyl-leukotrienes such as LTC4 are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs in HIV-1 infection of microglial cells. Methods To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2 or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR. Results We report in this study that virus replication is reduced upon treatment of MDMis with LTB4 and LTC4. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5 surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C. Conclusions These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.

  15. Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

    Science.gov (United States)

    Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

    2006-02-01

    Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all

  16. Modeling abnormal early development with induced pluripotent stem cells from aneuploid syndromes.

    Science.gov (United States)

    Li, Wen; Wang, Xianming; Fan, Wenxia; Zhao, Ping; Chan, Yau-Chi; Chen, Shen; Zhang, Shiqiang; Guo, Xiangpeng; Zhang, Ya; Li, Yanhua; Cai, Jinglei; Qin, Dajiang; Li, Xingyan; Yang, Jiayin; Peng, Tianran; Zychlinski, Daniela; Hoffmann, Dirk; Zhang, Ruosi; Deng, Kang; Ng, Kwong-Man; Menten, Bjorn; Zhong, Mei; Wu, Jiayan; Li, Zhiyuan; Chen, Yonglong; Schambach, Axel; Tse, Hung-Fat; Pei, Duanqing; Esteban, Miguel A

    2012-01-01

    Many human diseases share a developmental origin that manifests during childhood or maturity. Aneuploid syndromes are caused by supernumerary or reduced number of chromosomes and represent an extreme example of developmental disease, as they have devastating consequences before and after birth. Investigating how alterations in gene dosage drive these conditions is relevant because it might help treat some clinical aspects. It may also provide explanations as to how quantitative differences in gene expression determine phenotypic diversity and disease susceptibility among natural populations. Here, we aimed to produce induced pluripotent stem cell (iPSC) lines that can be used to improve our understanding of aneuploid syndromes. We have generated iPSCs from monosomy X [Turner syndrome (TS)], trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome) and partial trisomy 11;22 (Emanuel syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells in all tested assays. TS iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells, but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body formation. These data support that abnormal organogenesis and early lethality in TS are not caused by a tissue-specific differentiation blockade, but rather involves other abnormalities including impaired placentation.

  17. Early-Stage Induction of SWI/SNF Mutations during Esophageal Squamous Cell Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Hidetsugu Nakazato

    Full Text Available The SWI/SNF chromatin remodeling complex is frequently inactivated by somatic mutations of its various components in various types of cancers, and also by aberrant DNA methylation. However, its somatic mutations and aberrant methylation in esophageal squamous cell carcinomas (ESCCs have not been fully analyzed. In this study, we aimed to clarify in ESCC, what components of the SWI/SNF complex have somatic mutations and aberrant methylation, and when somatic mutations of the SWI/SNF complex occur. Deep sequencing of components of the SWI/SNF complex using a bench-top next generation sequencer revealed that eight of 92 ESCCs (8.7% had 11 somatic mutations of 7 genes, ARID1A, ARID2, ATRX, PBRM1, SMARCA4, SMARCAL1, and SMARCC1. The SMARCA4 mutations were located in the Forkhead (85Ser>Leu and SNF2 family N-terminal (882Glu>Lys domains. The PBRM1 mutations were located in a bromodomain (80Asn>Ser and an HMG-box domain (1,377Glu>Lys. For most mutations, their mutant allele frequency was 31-77% (mean 61% of the fraction of cancer cells in the same samples, indicating that most of the cancer cells in individual ESCC samples had the SWI/SNF mutations on one allele, when present. In addition, a BeadChip array analysis revealed that a component of the SWI/SNF complex, ACTL6B, had aberrant methylation at its promoter CpG island in 18 of 52 ESCCs (34.6%. These results showed that genetic and epigenetic alterations of the SWI/SNF complex are present in ESCCs, and suggested that genetic alterations are induced at an early stage of esophageal squamous cell carcinogenesis.

  18. Dissemination of CERN Technologies Through External Entrepreneurs

    CERN Document Server

    Lande, Bjørnulf Visdal; Huuse, Henning

    2008-01-01

    This study focuses on dissemination of innovations through external entrepreneurs. The innovations studied are developed at the European Organization for Nuclear Research (CERN) and commercialized by entrepreneurs establishing spin-off companies on the outside of the Organization. The objective of this study is to provide knowledge to facilitate future external entrepreneurs to increase dissemination of CERN technologies. The research questions looks at the timeline from preparations for creating the spin-off company, until having a product for commercialization in the market. A qualitative cross case investigation was conducted to assess the experiences of four spin-off companies. A framework was created to structure the discussion by finding and categorizing impeding- and success factors seen from the entrepreneurs point of view. The findings where structured in three phases respectively, the time before starting the company, the beginning of the company and the final development before selling products. Th...

  19. Dissemination of Educational Tools and Programs

    Science.gov (United States)

    Christian, C.

    1998-05-01

    The IDEAS program is oriented towards innovative approaches to education and therefore result in a wide range of programs including Astro Capella (the creation of a capella astronomy songs written and performed by a group from NASA/GSFC, Smale, Boyd, and Granger), video kiosks in the Air and Space Museum (SAO, Dow), teaching astronomy in the parks (U of Wisconsin, Bjorkman, Wilcots), as well as the more bread and butter programs of teacher training and curriculum development. In addition to describing some of the diverse programs to come out of the IDEAS programs, I will discuss the dissemination of the results of those programs, and especially the role of the broker/facilitator in that dissemination. The audience is invited to participate in this discussion.

  20. Inducing effects of macrophage stimulating protein on the expansion of early hematopoietic progenitor cells in liquid culture

    Institute of Scientific and Technical Information of China (English)

    MA Li-xia; HUANG Yan-hong; CHENG La-mei; LEI Jun; WANG Qi-ru

    2007-01-01

    Background Macrophage stimulating protein (MSP) is produced by human bone marrow endothelial cells. In this study,we sought to observe its effects on inducing the expansion of early hematopoietic progenitor cells which were cultured in a liquid culture system in the presence of the combination of stem cell factor (SCF), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) (Cys) and MSP or of Cys and bone marrow endothelial cell conditioned medium (EC-CM).Methods Human bone marrow CD34+ cells were separated and cultured in a liquid culture system for 6 days.Granulocyte-macrophage colony forming unit (CFU-GM) and colony forming unit-granulocyte, erythrocyte, macrophage,megakaryocyte (CFU-GEMM) were employed to assay the effects of different treatment on the proliferation of hematopoeitic stem/progenitor cells. The nitroblue tetrazolium (NBT) reductive test and hoechest 33258 staining were employed to reflect the differentiation and apoptosis of the cells respectively.Results MSP inhibited the proliferation of CFU-GM and CFU-GEMM in semi-solid culture and the inhibitory effect on CFU-GEMM was stronger than on CFU-GM. MSP inhibited the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators. Bone marrow (BM) CFU-GEMM was 2.3-fold or 1.7-fold increase or significantly decreased in either Cys+EC-CM, Cys+MSP or Cys compared with 0 hour control in liquid culture system after 6 days.Conclusion MSP, a hematopoietic inhibitor, inhibits the differentiation of early hematopoietic progenitor cells induced by hematopoietic stimulators and makes the early hematopoietic progenitor cells expand in a liquid culture system.

  1. Disseminated histoplasmosis with oral and cutaneous manifestations

    Directory of Open Access Journals (Sweden)

    S Vidyanath

    2013-01-01

    Full Text Available Histoplasmosis is a systemic mycotic infection caused by the dimorphic fungus, Histoplasma capsulatum. Systemic histoplasmosis has emerged as an important opportunistic infection in human immunodeficiency virus (HIV patients and those in endemic areas. Reported cases of histoplasmosis have been low in India with less than 50 cases being reported. We are reporting a case of disseminated histoplasmosis with oral and cutaneous involvement in an HIV seronegative patient.

  2. Tension Hydrothorax Related to Disseminated Endometriosis

    Directory of Open Access Journals (Sweden)

    AnnaKate Deal, MD

    2016-01-01

    Full Text Available We present the case of a 34-year-old woman presenting to the emergency department (ED with dyspnea, cough, and fever. She was found to have a tension hydrothorax and was treated with ultrasound-guided thoracentesis in the ED. Subsequent inpatient evaluation showed the patient had disseminated endometriosis. Tension hydrothorax has not been previously described in the literature as a complication of this disease.

  3. [Disseminated intravascular coagulation in solid tumours].

    Science.gov (United States)

    Ferrand, François Régis; Garcia-Hejl, Carine; Moussaid, Yassine; Schernberg, Antoine; Bidard, François-Clément; Pavic, Michel; Khenifer, Safia; Stoclin, Annabelle

    2014-06-01

    Disseminated intravascular coagulation (DIC) is a complex abnormality of hemostasis with dramatic consequences and long described as associated with tumors. Yet the diagnosis and management of paraneoplastic DIC are poorly defined. The purpose of this paper is to review DIC associated with solid tumors, at the pathophysiological and therapeutic levels in particular. We also report data from a recent retrospective series of patients with DIC in the context of a solid tumor, to illustrate the epidemiological, clinical and prognostic.

  4. Disseminated cutaneous histoplasmosis in an immunocompetent adult

    Directory of Open Access Journals (Sweden)

    Manoj Harnalikar

    2012-01-01

    Full Text Available Histoplasmosis, a systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum var capsulatum and Histoplasma capsulatum var duboisii is endemic to many parts of the world. The clinical manifestations range from acute or chronic pulmonary infection to a progressive disseminated disease. After initial exposure to the fungus, the infection is self-limited and restricted to the lungs in 99% of healthy individuals. The remaining 1%, however, progress to either disseminated or chronic disease involving the lungs, liver, spleen, lymph nodes, bone marrow or rarely, the skin and mucous membranes. Mucocutaneous histoplasmosis is frequently reported in patients with acquired immune deficiency syndrome (AIDS, but it is rare in immunocompetent hosts. A 60-year-old male presented with asymptomatic swelling of the hard palate and crusted papules and nodules over the extremities, face and trunk. Clinically, the diagnoses of cutaneous cryptococcosis versus histoplasmosis was considered in this patient. A chest X-ray revealed hilar lymphadenopathy. Enzyme-linked immunosorbent assay (ELISA for human immunodeficiency virus (HIV was nonreactive. Skin biopsy revealed multiple tiny intracellular round yeast forms with a halo in the mid-dermis. Culture of the skin biopsy in Sabouraud′s dextrose agar showed colonies of Histoplasma capsulatum. Despite an investigation including no evidence of underlying immunosuppression was found, he was started on IV amphotericin-B (0.5 mg/kg/day. However, the patient succumbed to his disease 2 days after presentation. We report a rare case of disseminated cutaneous histoplasmosis in an immunocompetent individual.

  5. Use of UDP for efficient imagery dissemination

    Science.gov (United States)

    Prandolini, Robert; Au, T. A.; Lui, Andrew K.; Owen, Michael J.; Grigg, Mark W.

    2000-05-01

    In the defence organization, imagery represents an important information source for users in the tactical, operational and strategic environments. Its wider dissemination may rely on deployed communication networks that are often unstable with high bit error rates and outages. This paper presents efficient techniques for imagery dissemination using the user datagram protocol (UDP). The use of UDP is compared with the popular transmission control protocol and shown to be superior in performance for error prone IP networks. We have employed a wavelet based coder producing an embedded bit-stream. The packetization of the bit-stream is investigated and we show that it is better to tile an image into independent embedded bit-streams when the network performance is poor. Variable-size tiling is compared with, and shown to be superior to, a fixed-size tiling approach. Selective re-transmission of lost packets is implemented for efficient imagery dissemination using UDP. The selective re- transmission scheme is a function of network bandwidth, delay times, error rates and the significance of the packet.

  6. Frequency of Early and Late Chromosome Aberrations in Different Types of Cells After Proton and Fe Ion Irradiation

    Science.gov (United States)

    Lu, Tao; Wu, Honglu; Zhang, Ye; Yeshitla, Samrawit; Kadhim, Munira; Wilson, Bobby; Bowler, Deborah