WorldWideScience

Sample records for stage cell type

  1. Nuclear and cellular expression data from the whole 16-cell stage Arabidopsis thaliana embryo and a cell type-specific expression atlas of the early Arabidopsis embryo

    NARCIS (Netherlands)

    Palovaara, J.P.J.

    2017-01-01

    SuperSeries contain expression data from the nuclei of cell types involved in patterning events, with focus on root apical stem cell formation, at 16-cell stage, early globular stage and late globular stage in the early Arabidopsis embryo (atlas). Expression data comparing nuclear and cellular RNA

  2. Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells

    Directory of Open Access Journals (Sweden)

    Shuo Liu

    2013-01-01

    Full Text Available By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.

  3. An Atlas for Schistosoma mansoni Organs and Life-Cycle Stages Using Cell Type-Specific Markers and Confocal Microscopy

    Science.gov (United States)

    Cogswell, Alexis; Williams, David L.; Newmark, Phillip A.

    2011-01-01

    Schistosomiasis (bilharzia) is a tropical disease caused by trematode parasites (Schistosoma) that affects hundreds of millions of people in the developing world. Currently only a single drug (praziquantel) is available to treat this disease, highlighting the importance of developing new techniques to study Schistosoma. While molecular advances, including RNA interference and the availability of complete genome sequences for two Schistosoma species, will help to revolutionize studies of these animals, an array of tools for visualizing the consequences of experimental perturbations on tissue integrity and development needs to be made widely available. To this end, we screened a battery of commercially available stains, antibodies and fluorescently labeled lectins, many of which have not been described previously for analyzing schistosomes, for their ability to label various cell and tissue types in the cercarial stage of S. mansoni. This analysis uncovered more than 20 new markers that label most cercarial tissues, including the tegument, the musculature, the protonephridia, the secretory system and the nervous system. Using these markers we present a high-resolution visual depiction of cercarial anatomy. Examining the effectiveness of a subset of these markers in S. mansoni adults and miracidia, we demonstrate the value of these tools for labeling tissues in a variety of life-cycle stages. The methodologies described here will facilitate functional analyses aimed at understanding fundamental biological processes in these parasites. PMID:21408085

  4. Radiotherapy Alone With Curative Intent in Patients With Stage I Extranodal Nasal-Type NK/T-Cell Lymphoma

    International Nuclear Information System (INIS)

    Li Yexiong; Wang Hua; Jin Jing; Wang Weihu; Liu Qingfeng; Song Yongwen; Wang Zhaoyang; Qi Shunan; Wang Shulian; Liu Yueping; Liu Xinfan; Yu Zihao

    2012-01-01

    Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.

  5. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  6. Accelerated split-course (Type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in Stage III inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Iaffaioli, R.V.; Tortoriello, A.; Facchini, G.; Maccauro, M.; Dimitri, P.; Ravo, V.; Muto, P.; Crovella, F.

    1996-01-01

    43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC. (author)

  7. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Science.gov (United States)

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

  8. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Directory of Open Access Journals (Sweden)

    Chenggang Lu

    2015-12-01

    Full Text Available Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s. In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC, a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs, spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.

  9. First Evidence for the Disease-Stage, Cell-Type, and Virus Specificity of microRNAs during Human Immunodeficiency Virus Type-1 Infection

    Directory of Open Access Journals (Sweden)

    Lauren Fowler

    2016-05-01

    Full Text Available The potential involvement of host microRNAs (miRNAs in HIV infection is well documented, and evidence suggests that HIV modulates and also dysregulates host miRNAs involved in maintaining the host innate immune system. Moreover, the dysregulation of host miRNAs by HIV also effectively interferes directly with the host gene expression. In this study, we have simultaneously evaluated the expression of host miRNAs in both CD4+ and CD8+ T-cells derived from HIV-positive (HIV+ individuals (viremic and aviremic individuals while receiving highly active antiretroviral therapy (HAART, therapy-naïve long-term non-progressors (LTNP, and HIV-negative (HIV– healthy controls. miRNAs were run on Affymetrix V2 chips, and the differential expression between HIV+ and HIV− samples, along with intergroup comparisons, was derived using PARTEK software, using an FDR of 5% and an adjusted p-value < 0.05. The miR-199a-5p was found to be HIV-specific and expressed in all HIV+ groups as opposed to HIV– controls. Moreover, these are the first studies to reveal clearly the highly discriminatory miRNAs at the level of the disease state, cell type, and HIV-specific miRNAs.

  10. Early stage fuel cell funding

    International Nuclear Information System (INIS)

    Bergeron, C.

    2004-01-01

    'Full text:' Early stage venture funding requires an in depth understanding of both current and future markets as well as the key technical hurdles that need to be overcome for new technology to commercialize into successful products for mass markets. As the leading fuel cell and hydrogen investor, Chrysalix continuously reviews global trends and new technologies, evaluates them with industry leaders worldwide and tries to match them up with the best possible management teams when selecting its early stage investments. Chrysalix Energy Limited Partnership is an early-stage venture capital firm focusing on fuel cell and related fueling technology companies and is a private equity joint venture between Ballard Power Systems, BASF Venture Capital, The BOC Group, The Boeing Company, Duke Energy, Mitsubishi Corporation and Shell Hydrogen. Operating independently, Chrysalix offers a unique value proposition to its clients throughout the business planning, start-up and operations phases of development. Chrysalix provides early-stage funding to new companies as well as management assistance, technological knowledge, organized networking with industry players and experience in the management of intellectual property. (author)

  11. Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.

    Science.gov (United States)

    Huang, Yu; Yang, Jianliang; Liu, Peng; Zhou, Shengyu; Gui, Lin; He, Xiaohui; Qin, Yan; Zhang, Changgong; Yang, Sheng; Xing, Puyuan; Sun, Yan; Shi, Yuankai

    2017-09-01

    Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

  12. Effector/memory T cells of the weanling mouse exhibit Type 2 cytokine polarization in vitro and in vivo in the advanced stages of acute energy deficit.

    Science.gov (United States)

    Steevels, Tessa A M; Hillyer, Lyn M; Monk, Jennifer M; Fisher, Megan E; Woodward, Bill D

    2010-06-01

    Our objective was to determine whether the polarizing cytokine profile of the effector/memory T-cell compartment reflects the profound decline of cell-mediated inflammatory competence that characterizes acute prepubescent malnutrition. Weanling C57BL/6J mice were permitted free access to a complete purified diet, free access to an isocaloric low-protein diet or restricted intake of the complete diet for 14 days. First, interleukin (IL)-4 and interferon (IFN)-gamma concentrations generated in vitro by splenic and nodal effector/memory T cells were assessed following exposure to plate-bound anti-CD3. Second, net systemic production of IFN-gamma and IL-4 by the effector/memory T-cell compartment was assessed by the in vivo cytokine capture assay following anti-CD3 stimulation. In vitro stimulation generated less IFN-gamma (P=.002) but more IL-4 (P=.05) by T cells from the restricted-intake group relative to the age-matched control group. Similarly, in vivo stimulation generated low serum levels of antibody-captured IFN-gamma in the restricted-intake group vis-à-vis the age-matched control group (P=.01), while the IL-4 response was sustained (P=.39). By contrast, the 14-day low-protein model exhibited no change in T-cell cytokine signature either in vitro or in vivo. However, following extended consumption of the low-protein diet (26 days), carcass energy losses exceeded those of the 14-day protocol and serum levels of in vivo antibody-captured IFN-gamma were low after anti-CD3 challenge relative to the age-matched control group (P=.02), while levels of captured IL-4 remained unaffected (P=.07). Acute weanling malnutrition elicits a Type 2 polarizing cytokine character on the part of the effector/memory T-cell compartment, but only in the most advanced stages of energy decrement. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  13. Two stage-type railgun accelerator

    International Nuclear Information System (INIS)

    Ogino, Mutsuo; Azuma, Kingo.

    1995-01-01

    The present invention provides a two stage-type railgun accelerator capable of spiking a flying body (ice pellet) formed by solidifying a gaseous hydrogen isotope as a fuel to a thermonuclear reactor at a higher speed into a central portion of plasmas. Namely, the two stage-type railgun accelerator accelerates the flying body spiked from a initial stage accelerator to a portion between rails by Lorentz force generated when electric current is supplied to the two rails by way of a plasma armature. In this case, two sets of solenoids are disposed for compressing the plasma armature in the longitudinal direction of the rails. The first and the second sets of solenoid coils are previously supplied with electric current. After passing of the flying body, the armature formed into plasmas by a gas laser disposed at the back of the flying body is compressed in the longitudinal direction of the rails by a magnetic force of the first and the second sets of solenoid coils to increase the plasma density. A current density is also increased simultaneously. Then, the first solenoid coil current is turned OFF to accelerate the flying body in two stages by the compressed plasma armature. (I.S.)

  14. Early-stage mantle cell lymphoma

    DEFF Research Database (Denmark)

    Dabaja, B S; Zelenetz, A D; Ng, A K

    2017-01-01

    Background: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. Patients and methods: In this 13-institution study, we examined...

  15. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

  16. Stages of Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  17. Enteroendocrine cell types revisited

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Egerod, Kristoffer Lihme; Lund, Mari L

    2013-01-01

    The GI-tract is profoundly involved in the control of metabolism through peptide hormones secreted from enteroendocrine cells scattered throughout the gut mucosa. A large number of recently generated transgenic reporter mice have allowed for direct characterization of biochemical and cell...... biological properties of these previously highly elusive enteroendocrine cells. In particular the surprisingly broad co-expression of six functionally related hormones in the intestinal enteroendocrine cells indicates that it should be possible to control not only the hormone secretion but also the type...... and number of enteroendocrine cells. However, this will require a more deep understanding of the factors controlling differentiation, gene expression and specification of the enteroendocrine cells during their weekly renewal from progenitor cells in the crypts of the mucosa....

  18. Augment-type two stage accelerator

    International Nuclear Information System (INIS)

    Ogino, Mutsuo; Azuma, Kingo.

    1995-01-01

    When a flying body accelerated by a gas gun at a first stage enters into an augment rail passing through an introduction tube, an ignition capacitor for initial plasmas is turned ON to apply a voltage between the augment rails. Subsequently, the accelerating gas present behind the flying body is formed into plasmas by a laser, to flow electric current from one of the inner augment rails → plasma armature → the other of the inner augment rails, and additionally accelerate the flying body by Lorentz force formed in this case. Since the plasmas are maintained in a state of higher density than the plasmas obtained by using all of the augment rails, the ignition capacitor for initial plasmas in switched to a power source. As a result, it is possible to flow the maximum current before the plasmas expand, and a large accelerating force and a high magnetic flux density are attained, to improve acceleration performance of the flying body. (N.H.)

  19. Modal intersection types, two-level languages, and staged synthesis

    DEFF Research Database (Denmark)

    Henglein, Fritz; Rehof, Jakob

    2016-01-01

    -linguistic framework for staged program synthesis, where metaprograms are automatically synthesized which, when executed, generate code in a target language. We survey the basic theory of staged synthesis and illustrate by example how a two-level language theory specialized from λ∩ ⎕ can be used to understand......A typed λ-calculus, λ∩ ⎕, is introduced, combining intersection types and modal types. We develop the metatheory of λ∩ ⎕, with particular emphasis on the theory of subtyping and distributivity of the modal and intersection type operators. We describe how a stratification of λ∩ ⎕ leads to a multi...... the process of staged synthesis....

  20. Treatment Options by Stage (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  1. Early stage differentiation of thallus cells of Porphyra haitanensis (Rhodophyta)

    Science.gov (United States)

    Wang, Sujuan; Sun, Yunlong; Lu, Anming; Wang, Guangyuan

    1987-09-01

    The early stage differentiation of thallus cells of Porphyra haitanensis T. J. Chang et B. F. Zheng was studied. Protoplasts or single cells were isolated from the blades using enzyme mixture comprising 2% sea snail gut enzyme and 1% cellulase. The isolated protoplasts or single cells were incubated in the MES medium. The cell differentiations were examined under the microscope at intervals after incubation. Four types of cell differentiation, namely, normal, abnormal, carposporangial and spermatorangial, and rhizoidal types, were observed. Since normal cell differentiations occur mostly in small thalli 50 mm in length and middle portions of big thalli 200 mm in length, it is essential to select tissues from these two kinds of thalli essential for commercial production.

  2. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

    2002-01-01

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

  3. Four stages of a scientific discipline; four types of scientist.

    Science.gov (United States)

    Shneider, Alexander M

    2009-05-01

    In this article I propose the classification of the evolutionary stages that a scientific discipline evolves through and the type of scientists that are the most productive at each stage. I believe that each scientific discipline evolves sequentially through four stages. Scientists at stage one introduce new objects and phenomena as subject matter for a new scientific discipline. To do this they have to introduce a new language adequately describing the subject matter. At stage two, scientists develop a toolbox of methods and techniques for the new discipline. Owing to this advancement in methodology, the spectrum of objects and phenomena that fall into the realm of the new science are further understood at this stage. Most of the specific knowledge is generated at the third stage, at which the highest number of original research publications is generated. The majority of third-stage investigation is based on the initial application of new research methods to objects and/or phenomena. The purpose of the fourth stage is to maintain and pass on scientific knowledge generated during the first three stages. Groundbreaking new discoveries are not made at this stage. However, new ways to present scientific information are generated, and crucial revisions are often made of the role of the discipline within the constantly evolving scientific environment. The very nature of each stage determines the optimal psychological type and modus operandi of the scientist operating within it. Thus, it is not only the talent and devotion of scientists that determines whether they are capable of contributing substantially but, rather, whether they have the 'right type' of talent for the chosen scientific discipline at that time. Understanding the four different evolutionary stages of a scientific discipline might be instrumental for many scientists in optimizing their career path, in addition to being useful in assembling scientific teams, precluding conflicts and maximizing

  4. Staging of intestinal- and diffuse-type gastric cancers with the OLGA and OLGIM staging systems.

    Science.gov (United States)

    Cho, S-J; Choi, I J; Kook, M-C; Nam, B-H; Kim, C G; Lee, J Y; Ryu, K W; Kim, Y-W

    2013-11-01

    Operative link on gastritis assessment (OLGA) and Operative link on gastric intestinal metaplasia assessment (OLGIM) staging systems have been proposed for gastric cancer (GC) risk estimation. To validate the OLGA and OLGIM staging systems in a region with high risk of GC. This retrospective study included 474 GC patients and age- and sex-matched health screening control persons in a cancer centre hospital. We classified gastritis patterns according to the OLGA and OLGIM systems using the histological database that a pathologist prospectively evaluated using the updated Sydney system. GC risk according to the OLGA and OLGIM stages was evaluated using logistic regression analysis. More GC patients had OLGA stages III-IV (46.2%) than controls (26.6%, P diffuse-type GCs (30.9%). OLGA stages III and IV were significantly associated with increased risk of GC [odds ratios (ORs), 2.09; P = 0.008 and 2.04; P = 0.014 respectively] in multivariate analysis. The association was more significant for intestinal-type (ORs, 4.76; P = 0.001 and 4.19; P = 0.002 respectively), but not diffuse-type GC. OLGIM stages from I to IV were significantly associated with increased risk of both intestinal-type (ORs, 3.64, 5.15, 7.89 and 13.20 respectively) and diffuse-type GC (ORs, 1.84, 2.59, 5.08 and 6.32 respectively) with a significantly increasing trend. As high OLGA and OLGIM stages are independent risk factors for gastric cancer, the staging systems may be useful for risk assessment in high-risk regions, especially for intestinal-type gastric cancer. © 2013 John Wiley & Sons Ltd.

  5. Comparative diagnostic study of staging in renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Masaharu; Mori, Masaki; Ito, Sachiko and others

    1986-04-01

    A comparative diagnostic study was carried out on 56 patients with pathologically proven renal cell carcinoma which had been staged by CT, US, angiography (AG) and lymphography (LG) between June, 1980, and May, 1985. The confirmation of the tumor extent was established by surgery and microscopic examination in all patients except three, in whom the extent of the tumor was determined at autopsy. CT and AG were performed in all cases. It was also studied how far various factors such as histologic architecture, cell type, grade, growth mode, tumor necrosis and bleeding were related with prognosis, and how to evaluate them in imaging modality. Concerning the T factor, there was no difference in diagnostic ability between images, and since prognosis of T4 was inferior to those of T2 and T3, diagnosis of T4 was seen to require particular attention. Drawing ability of N and V factors was poor in US. In LG, evaluation of regional lymph nodes was difficult, so this seems to be an unnecessary examination because CT can provide sufficient evaluation. By imaging modality, diagnosis of architecture and cell type was difficult. By AG, avascular to hypovascular tumors were of solid type, and there were many spindle or pleomorphic cell types and combination of tubular-granular types, while the papillary type was few. By macroscopic growth mode, the infiltrating type was poor in prognosis, and the presence or absence of halo was evaluated by CT and AG. Prognosis was favorable in cases having no necrosis in the tumor or accompanied by hemorrhage. For the purpose of diagnosis, CT was found to be sufficient, and it was concluded that AG may be used only for the purpose of renal arterial embolization as a preoperative treatment of low-stage cases subjected to nephrectomy. US is sufficient only if satisfying the role of screening. (J.P.N.).

  6. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the treatment of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type: 13-year follow-up in 135 patients.

    Science.gov (United States)

    Wang, Liang; Xia, Zhong-jun; Huang, Hui-qiang; Lu, Yue; Zhang, Yu-jing

    2012-11-01

    We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.

  7. Embryonic Stem Cell Culture Conditions Support Distinct States Associated with Different Developmental Stages and Potency

    DEFF Research Database (Denmark)

    Martin Gonzalez, Javier; Morgani, Sophie M; Bone, Robert A

    2016-01-01

    . Conversely, the transcriptome of serum-cultured ESCs correlated with later stages of development (E4.5), at which point embryonic cells are more restricted in their developmental potential. Thus, ESC culture systems are not equivalent, but support cell types that resemble distinct developmental stages. Cells...... derived in one condition can be reprogrammed to another developmental state merely by adaptation to another culture condition....

  8. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  9. Prognostic Value of Bismuth Typing and Modified T-stage in Hilar Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Shengen Yi

    2015-01-01

    Conclusion: The majority of our patients with HCC were characterized as Subtype IV in Bismuth typing and Stage T3 in modified T-stage. Both Bismuth typing and modified T-stage showed prognostic value in HCC. Compared with Bismuth typing, modified T-stage is a better indicator of the resectability of HCC.

  10. Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma

    DEFF Research Database (Denmark)

    Norling, Rikke; Buron, Birgitte Marie Due; Therkildsen, Marianne Hamilton

    2014-01-01

    INTRODUCTION: Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US...

  11. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    Energy Technology Data Exchange (ETDEWEB)

    Hoshiba, Takashi [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tanaka, Masaru, E-mail: tanaka@yz.yamagata-u.ac.jp [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan)

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  12. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    International Nuclear Information System (INIS)

    Hoshiba, Takashi; Tanaka, Masaru

    2013-01-01

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression

  13. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... tumors: Yolk sac tumors make a hormone called alpha-fetoprotein (AFP). They can form in the ovary, testicle, ... are used to detect extracranial germ cell tumors: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). For ...

  14. PET/CT staging of T1-stage non-small cell lung cancer

    International Nuclear Information System (INIS)

    Salman, K. A.; Steinmann, C. H.; Von Schulthess, G. K.; Steinert, H. C.; Sukumar, V. P.

    2009-01-01

    Full text:Purpose: To evaluate the value of PET/CT in detecting occult metastases in patients with T 1 -stage non-small cell lung cancer (NSCLC). Method: Patients with proven NSCLC and T 1 -stage ( c m) were retrospectively analyzed. In all patients a whole-body 18 F-FDG PET/CT scan for initial staging was performed. The PET/CT findings were compared with all available clinical information, intra-operative findings and the histopathological results. Results: 95 patients (39 men, 56 women; age range, 19-85 years) were analyzed in our study. PET/CT in 68-95 patients correctly excluded mediastinal and distant metastases. In 17/95 patients (18%) mediastinal lymph-node metastases were proven (N 2 n=15; N 3 n=2). PET/CT correctly detected in 10/17 patients (58.8%) mediastinal nodal disease. The smallest mediastinal lymph-node metastasis detected by PET/CT had a size of 0.7 c m. In 7 patients PET/CT missed N 2 -stage. In three of these patients the SUVmax of the primary was c m. Only in one missed N 2 -stage metastasis was sized > 1.0 c m. The tumor histology (adenocarcinoma, squamous cell carcinoma) and location of the primary (central, periphery) did not influence the missed N 2 -stage by PET/CT. PET/CT diagnosed correctly N 3 -stage in 2 patients. 10/95 patients (10.5%) had distant metastases. PET/CT detected unknown M 1 -stage in 4/10 patients. In one patient a metastasis of the parietal pleura was missed by PET/CT. Conclusion: In our study, 28% patients with T 1 -stage NSCLC showed mediastinal or distant metastases. PET/CT was efficient in the detection of occult metastases. However, the sensitivity of PET/CT in mediastinal staging was only 64%.

  15. A model for cell type localization in the migrating slug of ...

    Indian Academy of Sciences (India)

    PRAKASH

    . Localization of the three major cell types within the migrating slug stage is a dynamic process (Sternfeld 1992;. A model for cell type localization in the migrating slug of Dictyostelium discoideum based on differential chemotactic sensitivity to ...

  16. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2018-01-12

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  17. Location and cellular stages of NK cell development

    Science.gov (United States)

    Yu, Jianhua; Freud, Aharon G.; Caligiuri, Michael A

    2013-01-01

    The identification of distinct tissue-specific natural killer (NK) cell populations that apparently mature from local precursor populations has brought new insight into the diversity and developmental regulation of this important lymphoid subset. NK cells provide a necessary link between the early (innate) and late (adaptive) immune responses to infection. Gaining a better understanding of the processes that govern NK cell development should allow us to better harness NK cell functions in multiple clinical settings as well as to gain further insight into how these cells undergo malignant transformation. In this review, we summarize recent advances in understanding sites and cellular stages of NK cell development in humans and mice. PMID:24055329

  18. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  19. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  20. Current Treatments for Surgically Resectable, Limited-Stage, and Extensive-Stage Small Cell Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2017-12-01

    The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor-1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra-thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited-stage disease, concurrent platinum-etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60-70 Gy. For extensive-stage disease, platinum-etoposide remains the standard first-line therapy, and the standard second-line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10-30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta-like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first-line, maintenance, and second-line settings. This review will provide an update on the standard therapies for surgically resected limited-stage small cell lung cancer and extensive-stage small cell lung cancer that have been investigated in recent clinical trials. © Alpha

  1. A Novel Inflammation-Based Stage (I Stage in Patients with Resectable Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Peng-Cheng Chen

    2016-01-01

    Full Text Available Background. Inflammation plays a key role in cancer. In the current study, we proposed a novel inflammation-based stage, named I stage, for patients with resectable esophageal squamous cell carcinoma (ESCC. Methods. Three hundred and twenty-three patients with resectable ESCC were enrolled in the current study. The I stage was calculated as follows: patients with high levels of C-reactive protein (CRP (>10 mg/L, neutrophil-to-lymphocyte ratio (NLR (>3.5, and platelet-count-to-lymphocyte ratio (PLR (>150 were defined as I3. Patients with two, one, or no abnormal value were defined as I2, I1, or I0, respectively. The prognostic factors were evaluated by univariate and multivariate analyses. Results. There were 112 patients for I0, 97 patients for I1, 66 patients for I2, and 48 patients for I3, respectively. The 5-year cancer-specific survival (CSS in patients with I0, I1, I2, and I3 was 50.0%, 30.9%, 18.2%, and 8.3%, respectively (I0 versus I1, P=0.002; I1 versus I2, P=0.012; I2 versus I3, P=0.020. Multivariate analyses revealed that I stage was an independent prognostic factor in patients with resectable ESCC (P<0.001. Conclusion. The inflammation-based stage (I stage is a novel and useful predictive factor for CSS in patients with resectable ESCC.

  2. Sorting of cells of the same size, shape, and cell cycle stage for a single cell level assay without staining

    Directory of Open Access Journals (Sweden)

    Yomo Tetsuya

    2006-06-01

    Full Text Available Abstract Background Single-cell level studies are being used increasingly to measure cell properties not directly observable in a cell population. High-performance data acquisition systems for such studies have, by necessity, developed in synchrony. However, improvements in sample purification techniques are also required to reveal new phenomena. Here we assessed a cell sorter as a sample-pretreatment tool for a single-cell level assay. A cell sorter is routinely used for selecting one type of cells from a heterogeneous mixture of cells using specific fluorescence labels. In this case, we wanted to select cells of exactly the same size, shape, and cell-cycle stage from a population, without using a specific fluorescence label. Results We used four light scatter parameters: the peak height and area of the forward scatter (FSheight and FSarea and side scatter (SSheight and SSarea. The rat pheochromocytoma PC12 cell line, a neuronal cell line, was used for all experiments. The living cells concentrated in the high FSarea and middle SSheight/SSarea fractions. Single cells without cell clumps were concentrated in the low SS and middle FS fractions, and in the higher FSheight/FSarea and SSheight/SSarea fractions. The cell populations from these viable, single-cell-rich fractions were divided into twelve subfractions based on their FSarea-SSarea profiles, for more detailed analysis. We found that SSarea was proportional to the cell volume and the FSarea correlated with cell roundness and elongation, as well as with the level of DNA in the cell. To test the method and to characterize the basic properties of the isolated single cells, sorted cells were cultured in separate wells. The cells in all subfractions survived, proliferated and differentiated normally, suggesting that there was no serious damage. The smallest, roundest, and smoothest cells had the highest viability. There was no correlation between proliferation and differentiation. NGF increases

  3. Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG).

    Science.gov (United States)

    Deng, Xiu-Wen; Wu, Jun-Xin; Wu, Tao; Zhu, Su-Yu; Shi, Mei; Su, Hang; Wang, Ying; He, Xia; Xu, Li-Ming; Yuan, Zhi-Yong; Zhang, Li-Ling; Wu, Gang; Qu, Bao-Lin; Qian, Li-Ting; Hou, Xiao-Rong; Zhang, Fu-Quan; Zhang, Yu-Jing; Zhu, Yuan; Cao, Jian-Zhong; Lan, Sheng-Min; Dong, Mei; Qi, Shu-Nan; Yang, Yong; Li, Ye-Xiong

    2018-05-05

    This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028). For patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

    International Nuclear Information System (INIS)

    Bradley, A.J.; MacDonald, L.; Whiteside, S.; Johnson, R.J.; Ramani, V.A.C.

    2015-01-01

    Aims: To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Materials and methods: Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7 th edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Results: Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2–5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. Conclusion: The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88

  5. Magnetic resonance imaging in the staging of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

    1987-07-01

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma.

  6. Magnetic resonance imaging in the staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

    1987-01-01

    Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

  7. Surgery in limited stage small cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U; Hansen, H H

    1999-01-01

    The role of surgery in small cell lung cancer (SCLC) is controversial. Surgery has several potential advantages because it may reduce the frequency of local relapses, it does not impede the intensity of chemotherapy, it does not affect the bone marrow, and surgical staging may be of prognostic...

  8. Novel dendritic cell-based vaccination in late stage melanoma.

    Science.gov (United States)

    Schneble, Erika J; Yu, Xianzhong; Wagner, T E; Peoples, George E

    2014-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play an important role in stimulating an immune response of both CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs). As such, DCs have been studied extensively in cancer immunotherapy for their capability to induce a specific anti-tumor response when loaded with tumor antigens. However, when the most relevant antigens of a tumor remain to be identified, alternative approaches are required. Formation of a dentritoma, a fused DC and tumor cells hybrid, is one strategy. Although initial studies of these hybrid cells are promising, several limitations interfere with its clinical and commercial application. Here we present early experience in clinical trials and an alternative approach to manufacturing this DC/tumor cell hybrid for use in the treatment of late stage and metastatic melanoma.

  9. Focus on Merkel cell carcinoma: diagnosis and staging

    International Nuclear Information System (INIS)

    Grandhaye, Marion; Teixeira, Pedro Gondim; Blum, Alain; Henrot, Philippe; Morel, Olivier; Sirveaux, Francois; Verhaeghe, Jean-Luc

    2015-01-01

    Merkel cell carcinoma is a rare lymphophilic skin tumor of neuroendocrine origin with the potential for rapid progression. Small, localized lesions are diagnosed and treated clinically, but advanced tumors often undergo imaging evaluation. Due to its rarity, radiologists are unaware of evocative imaging features and usually do not consider Merkel cell carcinoma in the differential diagnosis of soft tissue tumors. Appropriate staging is important to determine appropriate treatment and has an impact on patient prognosis. Multimodality imaging is usually needed, and there is no consensus on the optimal imaging strategy. The purpose of this article is to review various aspects of Merkel cell carcinoma imaging and look in detail at how optimal multimodality staging should be carried out. (orig.)

  10. Focus on Merkel cell carcinoma: diagnosis and staging

    Energy Technology Data Exchange (ETDEWEB)

    Grandhaye, Marion; Teixeira, Pedro Gondim; Blum, Alain [Imagerie Guilloz CHU de Nancy Hopital Central, Nancy (France); Henrot, Philippe [Service de Radiologie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France); Morel, Olivier [Medecine Nucleaire CHU Nancy Hopital Brabois, Vancoeuvre les Nancy (France); Sirveaux, Francois [Service de Chirurgie Centre chirurgical Emile Galle, Nancy (France); Verhaeghe, Jean-Luc [Service de Chirurgie Institut de Cancerologie de Lorraine, Vandoeuvre les Nancy (France)

    2015-06-01

    Merkel cell carcinoma is a rare lymphophilic skin tumor of neuroendocrine origin with the potential for rapid progression. Small, localized lesions are diagnosed and treated clinically, but advanced tumors often undergo imaging evaluation. Due to its rarity, radiologists are unaware of evocative imaging features and usually do not consider Merkel cell carcinoma in the differential diagnosis of soft tissue tumors. Appropriate staging is important to determine appropriate treatment and has an impact on patient prognosis. Multimodality imaging is usually needed, and there is no consensus on the optimal imaging strategy. The purpose of this article is to review various aspects of Merkel cell carcinoma imaging and look in detail at how optimal multimodality staging should be carried out. (orig.)

  11. Renal cell carcinoma: incidental detection and pathological staging.

    Science.gov (United States)

    Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

    2000-10-01

    In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

  12. Radiofrequency Ablation for Early-Stage Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Takao Hiraki

    2014-01-01

    Full Text Available This review examines studies of radiofrequency ablation (RFA of nonsmall cell lung cancer (NSCLC and discusses the role of RFA in treatment of early-stage NSCLC. RFA is usually performed under local anesthesia with computed tomography guidance. RFA-associated mortality, while being rare, can result from pulmonary events. RFA causes pneumothorax in up to 63% of cases, although pneumothorax requiring chest drainage occurs in less than 15% of procedures. Other severe complications are rare. After RFA of stage I NSCLC, 31–42% of patients show local progression. The 1-, 2-, 3-, and 5-year overall survival rates after RFA of stage I NSCLC were 78% to 100%, 53% to 86%, 36% to 88%, and 25% to 61%, respectively. The median survival time ranged from 29 to 67 months. The 1-, 2-, and 3-year cancer-specific survival rates after RFA of stage I NSCLC were 89% to 100%, 92% to 93%, and 59% to 88%, respectively. RFA has a higher local failure rate than sublobar resection and stereotactic body radiation therapy (SBRT. Therefore, RFA may currently be reserved for early-stage NSCLC patients who are unfit for sublobar resection or SBRT. Various technologies are being developed to improve clinical outcomes of RFA for early-stage NSCLC.

  13. Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

    Science.gov (United States)

    Kurzer, Jason H; Weinberg, Olga K

    2018-05-25

    Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. A Phase II Study of Methotrexate, Etoposide, Dexamethasone and Pegaspargase Sandwiched with Radiotherapy in the Treatment of Newly Diagnosed, Stage IE to IIE Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type

    Directory of Open Access Journals (Sweden)

    Peng-Peng Xu

    2017-11-01

    Interpretation: MESA sandwiched with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM score may be a promising prognostic index of serum metabolites in addition to clinical prognostic index in ENKTL.

  15. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    Directory of Open Access Journals (Sweden)

    STANCA CLAUDIA

    2007-01-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  16. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    Directory of Open Access Journals (Sweden)

    CLAUDIA STANCA

    2007-05-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  17. Fuse Selection for the Two-Stage Explosive Type Switches

    Science.gov (United States)

    Muravlev, I. O.; Surkov, M. A.; Tarasov, E. V.; Uvarov, N. F.

    2017-04-01

    In the two-level explosive switch destruction of a delay happens in the form of electric explosion. Criteria of similarity of electric explosion in transformer oil are defined. The challenge of protecting the power electrical equipment from short circuit currents is still urgent, especially with the growth of unit capacity. Is required to reduce the tripping time as much as possible, and limit the amplitude of the fault current, that is very important for saving of working capacity of life-support systems. This is particularly important when operating in remote stand-alone power supply systems with a high share of renewable energy, working through the inverter transducers, as well as inverter-type diesel generators. The explosive breakers copes well with these requirements. High-speed flow of transformer oil and high pressure provides formation rate of a contact gap of 20 - 100 m/s. In these conditions there is as a rapid increase in voltage on the discontinuity, and recovery of electric strength (Ures) after current interruption.

  18. Regional nodal relapse in surgically staged Merkel cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kiecker, Felix [Charite Universitaetsmedizin Berlin, Department of Dermatology, Berlin (Germany); Schicke, Bernd [Tumor Center Berlin, Berlin (Germany); Haase, Oliver [Charite Universitaetsmedizin Berlin, Department of Surgery, Berlin (Germany)

    2014-10-08

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [German] Untersucht wurde das regionaere Rezidivmuster des Merkelzell-Karzinoms (MCC) nach chirurgischem Staging und stadienadaptierter Therapie. Eingeschlossen wurden 51 Patienten mit lokalisiertem MCC: 33 % hatten UICC-Stadium-I-, 14 % -II-, 53 % -III-Tumoren (davon 4 Lymphknotenmetastasen eines unbekannten Primaertumors). Alle Patienten erhielten ein chirurgisches Staging: 23 Waechterlymphknotenbiopsien (SNB

  19. Dual-Stage Crosslinking of a Gel-Phase Bioink Improves Cell Viability and Homogeneity for 3D Bioprinting.

    Science.gov (United States)

    Dubbin, Karen; Hori, Yuki; Lewis, Kazuomori K; Heilshorn, Sarah C

    2016-10-01

    Current bioinks for cell-based 3D bioprinting are not suitable for technology scale-up due to the challenges of cell sedimentation, cell membrane damage, and cell dehydration. A novel bioink hydrogel is presented with dual-stage crosslinking specifically designed to overcome these three major hurdles. This bioink enables the direct patterning of highly viable, multicell type constructs with long-term spatial fidelity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Treatment of Stage IV Non-small Cell Lung Cancer

    Science.gov (United States)

    Evans, Tracey; Gettinger, Scott; Hensing, Thomas A.; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E.

    2013-01-01

    Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the

  1. REC46 gene of Saccharomyces cerevisiae controls mitotic chromosomal stability, recombination and sporulation: cell-type and life cycle stage specific expression of the rec46-1 mutation

    International Nuclear Information System (INIS)

    Maleas, D.T.; Bjornstad, K.A.; Holbrook, L.L.; Esposito, M.S.

    1986-01-01

    Studies of chromosomal recombination during mitosis and meiosis of Saccharomyces cerevisiae have demonstrated that recombination at these two distinct stages of the yeast life cycle proceeds by mechanisms that appear similar but involve discrete mitosis-specific and meiosis-specific properties. UV radiation induced REC mutants are being employed as a genetic tool to identify the partial reactions comprising recombination and the involvement of individual REC gene products in mitotic and meiotic recombination. The sequence of molecular events that results in genetic recombination in eukaryotes is presently ill-defined. Genetic characterization of REC gene mutants and biochemical analyses of them for discrete defects in DNA metabolic proteins and enzymes (in collaboration with the laboratory of Junko Hosoda) are beginning to remedy this gap in the authors knowledge. This report summarizes the genetic properties of the rec46-1 mutation

  2. The development and plasticity of alveolar type 1 cells

    Science.gov (United States)

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  3. Industrial n-type solar cells with >20% cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Romijn, I.G.; Anker, J.; Burgers, A.R.; Gutjahr, A.; Koppes, M.; Kossen, E.J.; Lamers, M.W.P.E.; Heurtault, Benoit; Saynova-Oosterling, D.S.; Tool, C.J.J. [ECN Solar Energy, Petten (Netherlands)

    2013-03-15

    To realize high efficiencies at low costs, ECN has developed the n-Pasha solar cell concept. The n-Pasha cell concept is a bifacial solar cell concept on n-Cz base material, with which average efficiencies of above 20% have been demonstrated. In this paper recent developments at ECN to improve the cost of ownership (lower Euro/Wp) of the n-Pasha cell concept are discussed. Two main drivers for the manufacturing costs of n-type solar cells are addressed: the n-type Cz silicon material and the silver consumption. We show that a large resistivity range between 2 and 8 cm can be tolerated for high cell efficiency, and that the costs due to the silver metallization can be significantly reduced while increasing the solar cell efficiency. Combining the improved efficiency and cost reduction makes the n-Pasha cell concept a very cost effective solution to manufacture high efficient solar cells and modules.

  4. [Methuosis: a novel type of cell death].

    Science.gov (United States)

    Cai, Hongbing; Liu, Jinkun; Fan, Qin; Li, Xin

    2013-12-01

    Cell death is a major physiological or pathological phenomenon in life activities. The classic forms of cell death include apoptosis, necrosis, and autophagy. Recently, a novel type of cell death has been observed and termed as methuosis, in which excessive stimuli can induce cytoplasmic uptake and accumulation of small bubbles that gradually merge into giant vacuoles, eventually leading to decreased cellular metabolic activity, cell membrane rupture and cell death. In this article, we describe the nomenclature, morphological characteristics and underlying mechanisms of methuosis, compare methuosis with autophagy, oncosis and paraptosis, and review the related researches.

  5. The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management.

    Science.gov (United States)

    Ruiz, Emily Stamell; Karia, Pritesh S; Morgan, Frederick C; Schmults, Chrysalyne D

    2017-02-01

    There is limited evidence on the utility of radiologic imaging for prognostic staging of cutaneous squamous cell carcinoma (CSCC). Review utilization of radiologic imaging of high-stage CSCCs to evaluate whether imaging impacted management and outcomes. Tumors classified as Brigham and Women's Hospital (BWH) tumor (T) stage T2B or T3 over a 13-year period were reviewed to identify whether imaging was performed and whether results affected treatment. Disease-related outcomes (DRO: local recurrence, nodal metastasis, death from disease) were compared between patients by type of imaging used. 108 high-stage CSCCs in 98 patients were included. Imaging (mostly computed tomography, 79%) was utilized in 45 (46%) patients and management was altered in 16 (33%) patients who underwent imaging. Patients that received no imaging were at higher risk of developing nodal metastases (nonimaging, 30%; imaging, 13%; P = .041) and any DRO (nonimaging, 42%; imaging, 20%; P = .028) compared to the imaging group. Imaging was associated with a lower risk for DRO (subhazard ratio, 0.5; 95% CI 0.2-0.9; P = .046) adjusted for BWH T stage, sex, and location. Single institution retrospective design and changes in technology overtime. Radiologic imaging of high-stage CSCC may influence management and appears to positively impact outcomes. Further prospective studies are needed to establish which patients benefit from imaging. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Effects of forage maize type and maturity stage on in vitro rumen fermentation characteristics.

    NARCIS (Netherlands)

    Cone, J.W.; Gelder, van A.H.; Schooten, van H.A.

    2008-01-01

    An experiment with forage maize plants representing early and late-ripening types of Dry Down and Stay Green cultivar types was conducted to study the effects of cultivar and maturity stage on in vitro rumen fermentation characteristics and to investigate the validity of the generally supposed

  7. Activation Of Wild-Type Hras Suppresses The Earliest Stages Of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jamie Weyandt

    2015-08-01

    Conclusions: Loss of wild-type Hras promotes the earliest stages of pancreatic tumorigenesis, and moreover results in more rapid progression of the disease. As such, mechanisms leading to activation of wild-type Ras proteins, including but not limited to redox-dependent reactions, may influence the development of pancreatic cancer.

  8. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum

    OpenAIRE

    Barkla, Bronwyn J.; Vera-Estrella, Rosario

    2015-01-01

    One of the remarkable adaptive features of the halophyte and facultative CAM plant Mesembryathemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC) which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and tr...

  9. [Professor WANG Linpeng's experience of acupuncture for migraine based on different stages and types].

    Science.gov (United States)

    Wang, Shaosong

    2016-07-12

    By using the methods of experience summary and case report, professor WANG Linpeng 's clinical experience of acupuncture for migraine was summarized.Professor WANG proposed the different acupuncture plans should be established according to the active stage and remission stage of migraine; in the active stage acupuncture should be applied at gallbladder meridian with penetration needling technique to reinforce the stimulation intensity; in the remission stage the aim was to regulate zang-fu and back- shu points should be emphasized.In addition, attention should be paid on acupuncture technique and preventive treatment.For menstruation-type and psychological disorder-type migraine, different acupuncture plans should be adopted and regulating meridian and spirit was essential in the treatment.

  10. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Science.gov (United States)

    Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong; Kim, Hee Chan

    2017-01-01

    The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

  11. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks

    Science.gov (United States)

    Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong

    2017-01-01

    The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

  12. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Directory of Open Access Journals (Sweden)

    Jin Woo Choi

    Full Text Available The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN. A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of

  13. Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer

    International Nuclear Information System (INIS)

    Cheruvu, Praveena; Metcalfe, Su K; Metcalfe, Justin; Chen, Yuhchyau; Okunieff, Paul; Milano, Michael T

    2011-01-01

    Standard therapy for metastatic non small cell lung cancer (NSCLC) includes palliative systemic chemotherapy and/or radiotherapy. Recent studies of patients with limited metastases treated with curative-intent stereotactic body radiation therapy (SBRT) have shown encouraging survival. We hypothesized that patients treated with SBRT for limited metastases have comparable outcomes with those treated with curative-intent radiation for Stage III NSCLC. We retrospectively reviewed the records of NSCLC patients treated with curative-intent radiotherapy at the University of Rochester from 2000-2008. We identified 3 groups of patients with NSCLC: stage III, stage IV, and recurrent stage IV (initial stage I-II). All stage IV NSCLC patients treated with SBRT had ≤ 8 lesions. Of 146 patients, 88% had KPS ≥ 80%, 30% had > 5% weight loss, and 95% were smokers. The 5-year OS from date of NSCLC diagnosis for stage III, initial stage IV and recurrent stage IV was 7%, 14%, and 27% respectively. The 5-year OS from date of metastatic diagnosis was significantly (p < 0.00001) superior among those with limited metastases (≤ 8 lesions) versus stage III patients who developed extensive metastases not amenable to SBRT (14% vs. 0%). Stage IV NSCLC is a heterogeneous patient population, with a selected cohort apparently faring better than Stage III patients. Though patients with limited metastases are favorably selected by virtue of more indolent disease and/or less bulky disease burden, perhaps staging these patients differently is appropriate for prognostic and treatment characterization. Aggressive local therapy may be indicated in these patients, though prospective clinical studies are needed

  14. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  15. The Transcription Factor AHR Prevents the Differentiation of a Stage 3 Innate Lymphoid Cell Subset to Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Tiffany Hughes

    2014-07-01

    Full Text Available Accumulating evidence indicates that human natural killer (NK cells develop in secondary lymphoid tissue (SLT through a so-called “stage 3” developmental intermediate minimally characterized by a CD34−CD117+CD94− immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC types that include interleukin-1 receptor (IL-1R1-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ interferon (IFN-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES and T-Box Protein 21 (TBX21 or TBET. Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1hi ILC3s from differentiating into NK cells.

  16. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Science.gov (United States)

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Prognosis of patients with stage IIIb-IVa squamous cell carcinoma of the cervix following intra-arterial neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fujiwaki, R.; Maede, Y.; Ohnishi, Y.; Watanabe, Y.; Hata, K.; Miyazaki, K.

    1999-01-01

    The aim was to determine the long-term prognosis in patients with stage IIIb-IVa squamous cell carcinoma of the cervix who were treated with intra-arterial neoadjuvant chemotherapy (NAC), and to analyze factors related to prognostic value. The authors assessed the disease-free survival of 21 patients with FIGO stage IIIb-IVa squamous cell carcinoma of the cervix treated with intra-arterial NAC followed by irradiation therapy. Before chemotherapy, five factors (age, clinical stage, histologic type, parametrial involvement and serum level of SCC) were evaluated for their correlation with disease-free survival. Univariate Cox's proportional hazard model also demonstrated that age was a significant prognostic factor as a continuous variable. Intra-arterial NAC thus appeared to be effective in treating older patients with stage IIIb-IVa squamous cell carcinoma of the cervix

  18. A loss of profilin-1 in late-stage oral squamous cell carcinoma.

    Science.gov (United States)

    Adami, Guy R; O'Callaghan, Thomas N; Kolokythas, Antonia; Cabay, Robert J; Zhou, Yalu; Schwartz, Joel L

    2017-08-01

    The genes for PFN1 and TMSB4 are both highly expressed in oral tissue and both encode actin monomer binding proteins thought to play a role in cell motility and possibly other crucial parts of tumor progression. Oral brush cytology of epithelium from oral squamous cell carcinoma (OSCC) was used to measure PFN1 and TMSB4 mRNA in OSCC, while immunohistochemical analysis of tissue was used to check protein levels. High but variable expression of mRNAs encoding these two proteins was observed suggesting they may contribute to tumor characteristics in a subset of OSCCs. Both proteins were highly expressed in normal appearing basal epithelium, in the cytoplasm, and perinuclear area, while expression was minimal in upper epithelial layers. In OSCCs, expression of these proteins varied. In tumors classified as later stage, based on size and/or lymph node involvement, PFN1 levels were lower in tumor epithelium. A control gene, KRT13, showed expression in normal differentiated basal and suprabasal oral mucosa epithelial cells and as reported was lost in OSCC cells. Loss of PFN1 in tumor cells has been associated with lymph node invasion and metastasis in other tumor types, strengthening the argument that the protein has the potential to be a tumor suppressor in late-stage OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Analysis of chlorophyll fluorescence reveals stage specific patterns of chloroplast-containing cells during Arabidopsis embryogenesis

    Directory of Open Access Journals (Sweden)

    RICARDO I TEJOS

    2010-01-01

    Full Text Available The basic body plan of a plant is established early in embryogenesis when cells differentiate, giving rise to the apical and basal regions of the embryo. Using chlorophyll fluorescence as a marker for chloroplasts, we have detected specific patterns of chloroplast-containing cells at specific stages of embryogenesis. Non-randomly distributed chloroplast-containing cells are seen as early as the globular stage of embryogenesis in Arabidopsis. In the heart stage of embryogenesis, chloroplast containing cells are detected in epidermal cells as well as a central region of the heart stage embryo, forming a triangular septum of chloroplast-containing cells that divides the embryo into three equal sectors. Torpedo stage embryos have chloroplast-containing epidermal cells and a central band of chloroplast-containing cells in the cortex layer, just below the shoot apical meristem. In the walking-stick stage of embryogenesis, chloroplasts are present in the epidermal, cortex and endodermal cells. The chloroplasts appear reduced or absent from the provascular and columella cells of walking-stick stage embryos. These results suggest that there is a tight regulation of plastid differentiation during embryogenesis that generates specific patterns of chloroplast-containing cells in specific cell layers at specific stages of embryogenesis.

  20. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    Science.gov (United States)

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  1. Stem Cell Treatment for Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-03-01

    Full Text Available Type 1 diabetes mellitus (T1DM is a common chronic disease in children, characterized by a loss of  cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal  cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs such as bone marrow-, adipose tissue- and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.

  2. Endothelial Cells Control Pancreatic Cell Fate at Defined Stages through EGFL7 Signaling

    Directory of Open Access Journals (Sweden)

    Der-I Kao

    2015-02-01

    Full Text Available Although endothelial cells have been shown to affect mouse pancreatic development, their precise function in human development remains unclear. Using a coculture system containing human embryonic stem cell (hESC-derived progenitors and endothelial cells, we found that endothelial cells play a stage-dependent role in pancreatic development, in which they maintain pancreatic progenitor (PP self-renewal and impair further differentiation into hormone-expressing cells. The mechanistic studies suggest that the endothelial cells act through the secretion of EGFL7. Consistently, endothelial overexpression of EGFL7 in vivo using a transgenic mouse model resulted in an increase of PP proliferation rate and a decrease of differentiation toward endocrine cells. These studies not only identified the role of EGFL7 as the molecular handle involved in the crosstalk between endothelium and pancreatic epithelium, but also provide a paradigm for using hESC stepwise differentiation to dissect the stage-dependent roles of signals controlling organogenesis.

  3. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

    2018-04-19

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

  4. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Mercado, Luis; Coll, Julio

    2018-01-01

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright–Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells. PMID:29671811

  5. Stem cell therapy for end-stage heart failure : indispensable role for the cell?

    NARCIS (Netherlands)

    Vrijsen, K. R.; Chamuleau, S. A. J.; Noort, W. A.; Doevendans, P. A.; Sluijter, J. P. G.

    2009-01-01

    Purpose of review For heart failure patients, the urgent need for heart transplantation exceeds the availability of donor hearts. Therefore, cell transplantation has emerged as an interesting and potential solution. This review will focus on the capability of different types of stem cells to

  6. TOX sets the stage for innate lymphoid cells

    NARCIS (Netherlands)

    Spits, Hergen

    2015-01-01

    Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process

  7. A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

    Science.gov (United States)

    Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

    2017-06-01

    A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

  8. Roles of IFN-γ and γδ T cells in protective immunity against blood-stage malaria

    Directory of Open Access Journals (Sweden)

    Shin-Ichi eInoue

    2013-08-01

    Full Text Available Malaria is caused by infection with Plasmodium parasites. Various studies with knockout mice have indicated that IFN-γ plays essential roles in protective immunity against blood-stage Plasmodium infection. However, after Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity, but also in immunopathology. Recent reports have shown that IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages, but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. However, the effects of IFN-γ on hematopoietic stem cells and progenitor cells are unclear. Therefore, the regulation of hematopoiesis by IFN-γ during Plasmodium infection remains to be clarified. Although there are conflicting reports concerning the significance of γδ T cells in protective immunity against Plasmodium infection, γδ T cells may respond to infection and produce IFN-γ as innate immune cells in the early phase of blood-stage malaria. Our recent studies have shown that γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as part of the immune response to eliminate Plasmodium parasites. These data suggest that the function of γδ T cells is similar to that of NK cells. Although several reports suggest that γδ T cells have the potential to act as memory cells for various infections, it remains to be determined whether memory γδ T cells are generated by Plasmodium infection and whether memory γδ T cells can contribute to the host defense against re-infection with Plasmodium. Here, we summarize and discuss the effects of IFN-γ and the various functions of γδ T cells in blood-stage Plasmodium infection.

  9. Sleep-stage transitions during polysomnographic recordings as diagnostic features of type 1 narcolepsy

    DEFF Research Database (Denmark)

    Christensen, Julie Anja Engelhard; Carrillo, Oscar; Leary, Eileen B.

    2015-01-01

    Objective: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep......-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. Methods: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were...... of 19 cases and 708 sleep-clinic patients was used for the validation. Results: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly...

  10. Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population

    Science.gov (United States)

    Dantas, Thinali Sousa; de Barros Silva, Paulo Goberlânio; Sousa, Eric Fernandes; da Cunha, Maria do PSS; de Aguiar, Andréa Silvia Walter; Costa, Fábio Wildson Gurgel; Mota, Mário Rogério Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu

    2016-01-01

    Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia. PMID:26817864

  11. Treatment Options By Stage (Ovarian Germ Cell Tumors)

    Science.gov (United States)

    ... Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview Go to Health Professional Version Key Points ... and restore) the body’s blood cells. New treatment options Combination chemotherapy (the use of more than one ...

  12. Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

    NARCIS (Netherlands)

    El Sharouni, S.Y.

    2009-01-01

    This thesis concerns the treatment of stage III non-small cell lung cancer (NSCLC) and limited disease small-cell lung cancer (SCLC). We described a systematic review on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCLC stage III with the aim to define the

  13. Specific features of the flow structure in a reactive type turbine stage

    Science.gov (United States)

    Chernikov, V. A.; Semakina, E. Yu.

    2017-04-01

    The results of experimental studies of the gas dynamics for a reactive type turbine stage are presented. The objective of the studies is the measurement of the 3D flow fields in reference cross sections, experimental determination of the stage characteristics, and analysis of the flow structure for detecting the sources of kinetic energy losses. The integral characteristics of the studied stage are obtained by averaging the results of traversing the 3D flow over the area of the reference cross sections before and behind the stage. The averaging is performed using the conservation equations for mass, total energy flux, angular momentum with respect to the axis z of the turbine, entropy flow, and the radial projection of the momentum flux equation. The flow parameter distributions along the channel height behind the stage are obtained in the same way. More thorough analysis of the flow structure is performed after interpolation of the experimentally measured point parameter values and 3D flow velocities behind the stage. The obtained continuous velocity distributions in the absolute and relative coordinate systems are presented in the form of vector fields. The coordinates of the centers and the vectors of secondary vortices are determined using the results of point measurements of velocity vectors in the cross section behind the turbine stage and their subsequent interpolation. The approach to analysis of experimental data on aerodynamics of the turbine stage applied in this study allows one to find the detailed space structure of the working medium flow, including secondary coherent vortices at the root and peripheral regions of the air-gas part of the stage. The measured 3D flow parameter fields and their interpolation, on the one hand, point to possible sources of increased power losses, and, on the other hand, may serve as the basis for detailed testing of CFD models of the flow using both integral and local characteristics. The comparison of the numerical and

  14. Study of homogeneous fuel cells type 10 x 10

    International Nuclear Information System (INIS)

    Montes, J.L.; Perusquia, R.; Ortiz, J.J.; Francois, J.L.; Marquez, C.M.

    2005-01-01

    At the moment in the National Institute of Nuclear Research (ININ) are carried out studies with the purpose of to establish a methodology that allows to carry out the neutron design of fuel cells of type 10 x 10. During the initial stage of the process of cells design, starting from the data that have to do with the planned energy demand it requires to be estimated the average value of the enrichment in U 235 w/o of the one assemble. The experience has shown that the accuracy that is achieved in this estimate it depends, among other factors, of the information (e.g. concentrations of U 235 and Gd 2 O 3 ) of the cells that its are disposed in that moment. For what we consider convenient to enlarge the available information by means of a series of calculations of cell physics; and to the one same time some aspects can be studied on the parameters that define the characteristics of a fuel cell. In this work the effect of the presence of different distributions of the concentrations of the fissile material is analyzed and of burnup poisons on the reactivity parameters of the cell as well as in the peak factor of local power (LPPF-Local Power Peaking Factor). (Author)

  15. Two stage bioethanol refining with multi litre stacked microbial fuel cell and microbial electrolysis cell.

    Science.gov (United States)

    Sugnaux, Marc; Happe, Manuel; Cachelin, Christian Pierre; Gloriod, Olivier; Huguenin, Gérald; Blatter, Maxime; Fischer, Fabian

    2016-12-01

    Ethanol, electricity, hydrogen and methane were produced in a two stage bioethanol refinery setup based on a 10L microbial fuel cell (MFC) and a 33L microbial electrolysis cell (MEC). The MFC was a triple stack for ethanol and electricity co-generation. The stack configuration produced more ethanol with faster glucose consumption the higher the stack potential. Under electrolytic conditions ethanol productivity outperformed standard conditions and reached 96.3% of the theoretically best case. At lower external loads currents and working potentials oscillated in a self-synchronized manner over all three MFC units in the stack. In the second refining stage, fermentation waste was converted into methane, using the scale up MEC stack. The bioelectric methanisation reached 91% efficiency at room temperature with an applied voltage of 1.5V using nickel cathodes. The two stage bioethanol refining process employing bioelectrochemical reactors produces more energy vectors than is possible with today's ethanol distilleries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

    2000-06-01

    Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

  17. Two-staged management for all types of congenital pouch colon

    Directory of Open Access Journals (Sweden)

    Rajendra K Ghritlaharey

    2013-01-01

    Full Text Available Background: The aim of this study was to review our experience with two-staged management for all types of congenital pouch colon (CPC. Patients and Methods: This retrospective study included CPC cases that were managed with two-staged procedures in the Department of Paediatric Surgery, over a period of 12 years from 1 January 2000 to 31 December 2011. Results: CPC comprised of 13.71% (97 of 707 of all anorectal malformations (ARM and 28.19% (97 of 344 of high ARM. Eleven CPC cases (all males were managed with two-staged procedures. Distribution of cases (Narsimha Rao et al.′s classification into types I, II, III, and IV were 1, 2, 6, and 2, respectively. Initial operative procedures performed were window colostomy (n = 6, colostomy proximal to pouch (n = 4, and ligation of colovesical fistula and end colostomy (n = 1. As definitive procedures, pouch excision with abdomino-perineal pull through (APPT of colon in eight, and pouch excision with APPT of ileum in three were performed. The mean age at the time of definitive procedures was 15.6 months (ranges from 3 to 53 months and the mean weight was 7.5 kg (ranges from 4 to 11 kg. Good fecal continence was observed in six and fair in two cases in follow-up periods, while three of our cases lost to follow up. There was no mortality following definitive procedures amongst above 11 cases. Conclusions: Two-staged procedures for all types of CPC can also be performed safely with good results. The most important fact that the definitive procedure is being done without protective stoma and therefore, it avoids stoma closure, stoma-related complications, related cost of stoma closure and hospital stay.

  18. The study on a gas-coupled two-stage stirling-type pulse tube cryocooler

    Science.gov (United States)

    Wu, X. L.; Chen, L. B.; Zhu, X. S.; Pan, C. Z.; Guo, J.; Wang, J. J.; Zhou, Y.

    2017-12-01

    A two-stage gas-coupled Stirling-type pulse tube cryocooler (SPTC) driven by a linear dual-opposed compressor has been designed, manufactured and tested. Both of the stages adopted coaxial structure for compactness. The effect of a cold double-inlet at the second stage on the cooling performance was investigated. The test results show that the cold double-inlet will help to achieve a lower cooling temperature, but it is not conducive to achieving a higher cooling capacity. At present, without the cold double-inlet, the second stage has achieved a no-load temperature of 11.28 K and a cooling capacity of 620 mW/20 K with an input electric power of 450 W. With the cold double-inlet, the no-load temperature is lowered to 9.4 K, but the cooling capacity is reduced to 400 mW/20 K. The structure of the developed cryocooler and the influences of charge pressure, operating frequency and hot end temperature will also be introduced in this paper.

  19. Types and distribution of mucous cells of the abalone Haliotis ...

    African Journals Online (AJOL)

    user

    2012-05-08

    May 8, 2012 ... Key words: Haliotis diversicolor; mucous cells, types, distribution. .... Figure 2. The shape of the mucous cells. O (oval or circle-like); c (cup- like); s ... (J) mucous cells at base of gill filaments, small cells, type II and type III; (K) a ...

  20. Unexpected HIMU-type late-stage volcanism on the Walvis Ridge

    Science.gov (United States)

    Homrighausen, S.; Hoernle, K.; Geldmacher, J.; Wartho, J.-A.; Hauff, F.; Portnyagin, M.; Werner, R.; van den Bogaard, P.; Garbe-Schönberg, D.

    2018-06-01

    Volcanic activity at many oceanic volcanoes, ridges and plateaus often reawakens after hiatuses of up to several million years. Compared to the earlier magmatic phases, this late-stage (rejuvenated/post-erosional) volcanism is commonly characterized by a distinct geochemical composition. Late-stage volcanism raises two hitherto unanswered questions: Why does volcanism restart after an extended hiatus and what is the origin of this volcanism? Here we present the first 40Ar/39Ar age and comprehensive trace element and Sr-Nd-Pb-Hf isotopic data from seamounts located on and adjacent to the Walvis Ridge in the South Atlantic ocean basin. The Walvis Ridge is the oldest submarine part of the Tristan-Gough hotspot track and is famous as the original type locality for the enriched mantle one (EM I) end member. Consistent with the bathymetric data, the age data indicates that most of these seamounts are 20-40 Myr younger than the underlying or nearby Walvis Ridge basement. The trace element and isotope data reveal a distinct compositional range from the EM I-type basement. The composition of the seamounts extend from the St. Helena HIMU (high time-integrated 238U/204Pb mantle with radiogenic Pb isotope ratios) end member to an enriched (E) Mid-Ocean-Ridge Basalt (MORB) type composition, reflecting a two-component mixing trend on all isotope diagrams. The EMORB end member could have been generated through mixing of Walvis Ridge EM I with normal (N) MORB source mantle, reflecting interaction of Tristan-Gough (EM I-type) plume melts with the upper mantle. The long volcanic quiescence and the HIMU-like geochemical signature of the seamounts are unusual for classical hotspot related late-stage volcanism, indicating that these seamounts are not related to the Tristan-Gough hotspot volcanism. Two volcanic arrays in southwestern Africa (Gibeon-Dicker Willem and Western Cape province) display similar ages to the late-stage Walvis seamounts and also have HIMU-like compositions

  1. A Germanium Back Contact Type Thermophotovoltaic Cell

    International Nuclear Information System (INIS)

    Nagashima, Tomonori; Okumura, Kenichi; Yamaguchi, Masafumi

    2007-01-01

    A Ge back contact type photovoltaic cell has been proposed to reduce resistance loss for high current densities in thermophotovoltaic systems. The back contact structure requires less surface recombination velocities than conventional structures with front grid contacts. A SiO2/SiNx double anti-reflection coating including a high refractive index SiNx layer was studied. The SiNx layer has an enough passivation effect to obtain high efficiency. The quantum efficiency of the Ge cell was around 0.8 in the 800-1600 nm wavelength range. The conversion efficiency for infrared lights was estimated at 18% for a blackbody surface and 25% for a selective emitter by using the quantum efficiency and a simulation analysis

  2. Errors analysis of problem solving using the Newman stage after applying cooperative learning of TTW type

    Science.gov (United States)

    Rr Chusnul, C.; Mardiyana, S., Dewi Retno

    2017-12-01

    Problem solving is the basis of mathematics learning. Problem solving teaches us to clarify an issue coherently in order to avoid misunderstanding information. Sometimes there may be mistakes in problem solving due to misunderstanding the issue, choosing a wrong concept or misapplied concept. The problem-solving test was carried out after students were given treatment on learning by using cooperative learning of TTW type. The purpose of this study was to elucidate student problem regarding to problem solving errors after learning by using cooperative learning of TTW type. Newman stages were used to identify problem solving errors in this study. The new research used a descriptive method to find out problem solving errors in students. The subject in this study were students of Vocational Senior High School (SMK) in 10th grade. Test and interview was conducted for data collection. Thus, the results of this study suggested problem solving errors in students after learning by using cooperative learning of TTW type for Newman stages.

  3. Types and distribution of mucous cells of the abalone Haliotis ...

    African Journals Online (AJOL)

    The types and distribution of mucous cells of Haliotis diversicolorwere observed and analyzed using the alcian blue and periodic acid schiffs (AB-PAS) reaction and histological procedures. According to the color of the mucous cells, they were divided into four types: Type I, pure red; type II, pure blue; type III, purple reddish; ...

  4. Preoperative chemoradiotherapy for stage 2 or 3 esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kawai, Takaharu; Kochi, Mitsugu; Fujii, Masashi

    2016-01-01

    The goal of this retrospective study was to investigate the efficacy and safety of preoperative chemoradiotherapy (NACR) in patients with Stage 2 or Stage 3 esophageal squamous cell carcinoma (SCC). Between 2004 and 2014, a total of 86 patients underwent surgical resection in conjunction with NACR for esophageal SCC at our institute. Thirty-one patients (36.0%) had Stage 2 disease and 55 patients (64.0%) had Stage 3 disease. The median age was 64 (43-81) years. A total of 78 patients received the full NACR regimen. The most common major Grade 3 hematologic toxic effects of NACR were leukopenia and neutropenia (48 cases), while the most common major Grade 3 non-hematologic toxic effect was anorexia (12 cases). One patient died in the hospital and no patients died within 30 days after surgery. A pathological complete response was achieved in 23 cases. Pathological staging (number of cases) was Stage 0 (23), Stage 1 (8), Stage 2 (28), Stage 3 (25), and Stage 4 (2). The 5-year overall survival rate (OS) was 51.0%, and was 83.2% in Stage 2 patients and 29.9% in Stage 3 patients. Preoperative NACR is safe and may improve OS and down-staging rates in patients with esophageal SCC. (author)

  5. Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

    Directory of Open Access Journals (Sweden)

    Giulia Fregni

    Full Text Available Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR and Natural Killer Group 2D (NKG2D receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46 by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

  6. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    International Nuclear Information System (INIS)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil

    1999-01-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m 2 ) on day 1 and oral Etoposide (50 mg/m 2 /day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor

  7. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  8. Comorbidity and KPS are independent prognostic factors in stage I non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Firat, Selim; Bousamra, Michael; Gore, Elizabeth; Byhardt, Roger W.

    2002-01-01

    Purpose: To determine the prognostic role of comorbidity in Stage I non-small-cell lung cancer (NSCLC) treated with surgery or radiotherapy (RT). Methods and Materials: One hundred sixty-three patients with clinical Stage I NSCLC were analyzed for overall survival (OS) and comorbidity. One hundred thirteen patients underwent surgery (surgical group) and 50 patients received definitive radiotherapy (RT group). Ninety-six percent of the surgical group had lobectomy or pneumonectomy, and negative margins were achieved in 96% of the patients. The median dose to the tumor for the RT group was 61.2 Gy (range 30.8-77.4). The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and the Charlson scale were used to rate comorbidity. Karnofsky performance scores (KPS) were available in 42 patients; the rest of the scores were determined retrospectively by two physicians independently, with 97% agreement. Results: The OS was 44% for the surgical group and 5% for the RT group at 5 years. Noncancer-related mortality was observed in 31% and 62% of the surgical and RT patients, respectively. On univariate analysis, performed on all patients (n=163), squamous cell histologic type (p 4 cm (p=0.065), >40 pack-year tobacco use (p 2 (p 2 (p=0.004), KPS 40 pack-year tobacco use, KPS <70, and presence of CIRS-G(4) were independently associated with an inferior OS. Treatment modality, T stage, and age did not have any statistically significant effect on OS. Statistically significant differences were found between the surgical and RT groups in Charlson score (p=0.001), CIRS-G total score (p=0.004), severity index (p=0.006), CIRS-G4(+) (p<0.001), KPS (p<0.001), amount of tobacco use (p=0.002), clinical tumor size (p<0.001), clinical T stage (p=0.01), forced expiratory volume in 1 s (p=0.001), and age (p=0.008), in favor of the surgical group. Conclusion: The presence of significant comorbidity and KPS of <70 are both important prognostic factors, but were found to be independent of each

  9. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  10. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  11. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2017-10-16

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  12. Wedge resection and segmentectomy in patients with stage I non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Konstantinos Reveliotis

    2014-09-01

    Full Text Available The use of sublobar resections as definitive management in stage I non-small cell lung carcinoma is a controversial topic in the medical community. We intend to report the latest developments and trends in relative indications for each of the above-mentioned surgical approaches for the treatment of stage I non-small cell lung carcinoma as well as the results of studies regarding local recurrence, disease-free survival and five-year survival rates. We reviewed 45 prospective and retrospective studies conducted over the last 25 years listed in the Pubmed and Scopus electronic databases. Trials were identified through bibliographies and a manual search in journals. Authors, citations, objectives and results were extracted. No meta-analysis was performed. Validation of results was discussed. Segmentectomies are superior to wedge resections in terms of local recurrences and cancer-related mortality rates. Sublobar resections are superior to lobectomy in preserving the pulmonary parenchyma. High-risk patients should undergo segmentectomy, whereas lobectomies are superior to segmentectomies only for tumors >2 cm (T2bN0M0 in terms of disease-free and overall 5-year survival. In most studies no significant differences were found in tumors <2 cm. Disease-free surgical margins are crucial to prevent local recurrences. Systematic lymphadenectomy is mandatory regardless of the type of resection used. In sublobar resections with less thorough nodal dissections, adjuvant radiotherapy can be used. This approach is preferable in case of prior resection. In pure bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are associated with a shorter hospital stay. The selection of the type of resection in T1aN0M0 tumors should depend on characteristic of the patient and the tumor. Patient age, cardiopulmonary reserve and tumor size are the most important factors to be considered. However further prospective randomized trials are needed to

  13. T cell maturation stage prior to and during GMP processing informs on CAR T cell expansion in patients

    NARCIS (Netherlands)

    Y. Klaver (Yarne); S.C.L. van Steenbergen; S. Sleijfer (Stefan); J.E.M.A. Debets (Reno); C.H.J. Lamers (Cor)

    2016-01-01

    textabstractAutologous T cells were genetically modified to express a chimeric antigen receptor (CAR) directed toward carboxy-anhydrase-IX (CAIX) and used to treat patients with CAIX-positive metastatic renal cell carcinoma. In this study, we questioned whether the T cell maturation stage in the

  14. Outcome of combination chemotherapy in extensive stage small-cell lung cancer

    DEFF Research Database (Denmark)

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

    1998-01-01

    During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

  15. The postnatal progeny development of males whose sexual cells were irradiated during different stages of spermatogenesis

    International Nuclear Information System (INIS)

    Lepekhin, N.P.; Palyga, G.F.

    1995-01-01

    Distinct genetic radiosensitivity if germinal cells of males irradiated during different stages of spermatogenesis with doses of 0.25-5.0 Gy leads to reduction in vital newborn rats number in the first generation progeny and to elevated postnatal mortality rate. These postnatal ontogeny disorders depend on the irradiation dose and spermatogenesis stage for a moment irradiation. 11 refs.; 4 tabs

  16. Stage of change and motivation to healthy diet and habitual physical activity in type 2 diabetes.

    Science.gov (United States)

    Centis, E; Trento, M; Dei Cas, A; Pontiroli, A E; De Feo, P; Bruno, A; Sasdelli, A S; Arturi, F; Strollo, F; Vigili De' Kreutzenberg, S; Invitti, C; Di Bonito, P; Di Mauro, M; Pugliese, G; Molteni, A; Marchesini, G

    2014-08-01

    Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with diabetes, it may be difficult to start changing. We investigated the stage of change toward healthier lifestyles according to Prochaska's model, and the associated psychological factors in T2DM patients, as a prerequisite to improve strategies to implement behavior changes in the population. A total of 1,353 consecutive outpatients with T2DM attending 14 tertiary centers for diabetes treatment completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments to define the stage of change for HD and HPA, respectively. Logistic regression was used to determine the factors associated with stages that may hinder behavioral changes. A stage of change favoring progress to healthier behaviors was more common in the area of HD than in HPA, with higher scores in action and maintenance. Differences were observed in relation to gender, age and duration of disease. After adjustment for confounders, resistance to change toward HD was associated with higher body mass index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08). Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10) and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing lifestyle, particularly in the area of HPA, is not perceived as an essential part of treatment by many subjects with T2DM. This evidence must be considered when planning behavioral programs, and specific interventions are needed to promote adherence to HPA.

  17. Combined effect of angioinfarction with immunotherapy in patients with stage IV renal cell carcinoma

    International Nuclear Information System (INIS)

    Oh, Joo Hyeong; Yoon, Yup; Jeong, Yu Mee; Ko, Young Tae; Chang, Sung Goo

    1994-01-01

    To assess the combined effectiveness of angioinfarction and immunotherapy for improving survival in patients with stage IV renal cell carcinoma. During the past 3 years, 13 patients of stage IV renal cell carcinoma were treated with angioinfarction and immunotherapy. Angioinfarction was performed on these 13 patients using absolute ethanol and occlusive balloon catheter. After angioinfarction, Interferon alpha was used for immunotherapy. For our analysis, 12 control patients of stage IV renal cell carcinoma without treatment were included in the study. Survival has been calculated according to the Kaplan and Meier method. The 1 year survival rate and median survival time in patients treated with angioinfarction and immunotherapy, were 46% and 13 months and in patients without treatment, 16% and 4 months, respectively. The combined treatment of angioinfarction and immunotherapy is of considerable value for improving survival in patients with stage IV renal cell carcinoma

  18. Development of a Combination Cell and Gene Therapy Approach for Early-Stage Breast Cancer

    National Research Council Canada - National Science Library

    Lewis, Michael T

    2005-01-01

    The unique biology of the breast presents the opportunity to these cell and gene therapy techniques in a way that circumvents many of these technical limitations for the treatment of early stage breast cancer...

  19. Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage.

    Science.gov (United States)

    Dashtsoodol, Nyambayar; Shigeura, Tomokuni; Aihara, Minako; Ozawa, Ritsuko; Kojo, Satoshi; Harada, Michishige; Endo, Takaho A; Watanabe, Takashi; Ohara, Osamu; Taniguchi, Masaru

    2017-03-01

    Although invariant V α 14 + natural killer T cells (NKT cells) are thought to be generated from CD4 + CD8 + double-positive (DP) thymocytes, the developmental origin of CD4 - CD8 - double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (T H 1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.

  20. Impact of cancer, type, site, stage and treatment on the nutritional status of patients

    International Nuclear Information System (INIS)

    Bozzeti, F.

    1982-01-01

    This study analyzed the nutritional status of cancer patients in relation to type and site of origin of the tumor, stage of disease, and previous chemical or radiation therapy. The analysis was performed on 321 patients (280 with cancer and 41 controls). The nutritional parameters included per cent of weight loss, anthropometric indices (arm circumference, triceps skinfold, arm muscle circumference), creatinine-height index, serum protein, albumin, total iron binding capacity and cholinesterase, C 3 and C 4 components of complement, total peripheral lymphocytes, and skin tests. The statistical comparison between patients with different tumors and controls, between patients treated with or without previous chemical or radiation therapy led to the following conclusions: (1) malnutrition is mainly related to the type and site of origin of the tumor and, in the early stages of disease, is more pronounced in patients with cancer of the esophagus and stomach; (2) except in patients with breast and cervix cancer, malnutrition gets more severe as the disease becomes advanced; (3) chemical or radiation therapy has a variable impact on the nutritional status, but in selected patients it causes a drop in body weight, arm circumference, arm muscle circumference, and peripheral lymphocytes; (4) body weight, cutaneous delayed hypersensitivity and serum albumin are the most commonly altered parameters

  1. 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.

  2. Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

    Directory of Open Access Journals (Sweden)

    Cristina Sobacchi

    2017-05-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

  3. Preoperative radiation therapy in regionally localized stage III non-small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Reddy, S.; Faber, L.P.; Baumann, L.M.; Lee, M.S.; Jensik, R.J.; Kittle, C.F.; Bonomi, P.; Taylor, S.; Hendrickson, F.R.

    1988-01-01

    Seventy-four patients seen from January 1975 through December 1982 with clinical stage III M0 non-small-cell carcinoma of the lung were treated with a course of preoperative radiation therapy to be followed by surgical resection. Surgical resection was attempted 4 weeks later. All the patients except two were followed up for a minimum of 5 years or until death. Sixty-four patients (86%) had T3 tumors, while mediastinal nodal involvement was found in 41 (55%). The actuarial 5-year survival and disease-free survival rates for the entire group were 20% and 26%, respectively. Patients with a pathologically complete response had an actuarial disease-free survival rate of 50% at 5 years, compared with only 17% for those with gross residual disease at surgery. One-half of the patients with clinically uninvolved nodes were living disease free at 5 years, compared with only 20% of the patients with N2 disease. The patterns of failure are presented according to the histologic type and stage of the disease

  4. The preventive role of type 2 NKT cells in the development of type 1 diabetes.

    Science.gov (United States)

    Sørensen, Jakob Ørskov; Buschard, Karsten; Brogren, Carl-Henrik

    2014-03-01

    In the last two decades, natural killer T (NKT) cells have emerged as an important factor in preventing type 1 diabetes (T1D) when investigated in the experimental non-obese diabetic (NOD) mouse model. So far, investigations have largely focused on type 1 NKT cells with invariant T-cell receptors, whereas the role of type 2 NKT cells with diverse T-cell receptors is less well understood. However, there have been several findings which indicate that in fact type 2 NKT cells may regulate the progression of type 1 diabetes in NOD mice, including a fraction of these cells which recognize β-cell-enriched sulfatide. Therefore, the focus for this review is to present the current evidence of the effect of type 2 NKT cells on the development of T1D. In general, there is still uncertainty surrounding the mechanism of activation and function of NKT cells. Here, we present two models of the effector mechanisms, respectively, Th1/Th2 polarization and the induction of tolerogenic dendritic cells (DC). In conclusion, this review points to the importance of immunoregulation by type 2 NKT cells in preventing the development of T1D and highlights the induction of tolerogenic DC as a likely mechanism. The possible therapeutic role of type 1 and type 2 NKT cells are evaluated and future experiments concerning type 2 NKT cells and T1D are proposed. © 2013 APMIS. Published by John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall......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...

  6. Novel approaches of chemoradiotherapy in unresectable stage IIIA and stage IIIB non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Bogart, Jeffrey A

    2012-01-01

    Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.

  7. Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease

    DEFF Research Database (Denmark)

    Idorn, Thomas; Knop, Filip K; Jørgensen, Morten B

    2016-01-01

    OBJECTIVE: To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: Twenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes...

  8. Screening and staging for non-small cell lung cancer by serum laser Raman spectroscopy.

    Science.gov (United States)

    Wang, Hong; Zhang, Shaohong; Wan, Limei; Sun, Hong; Tan, Jie; Su, Qiucheng

    2018-08-05

    Lung cancer is the leading cause of cancer-related death worldwide. Current clinical screening methods to detect lung cancer are expensive and associated with many complications. Raman spectroscopy is a spectroscopic technique that offers a convenient method to gain molecular information about biological samples. In this study, we measured the serum Raman spectral intensity of healthy volunteers and patients with different stages of non-small cell lung cancer. The purpose of this study was to evaluate the application of serum laser Raman spectroscopy as a low cost alternative method in the screening and staging of non-small cell lung cancer (NSCLC). The Raman spectra of the sera of peripheral venous blood were measured with a LabRAM HR 800 confocal Micro Raman spectrometer for individuals from five groups including 14 healthy volunteers (control group), 23 patients with stage I NSCLC (stage I group), 24 patients with stage II NSCLC (stage II group), 19 patients with stage III NSCLC (stage III group), 11 patients with stage IV NSCLC (stage IV group). Each serum sample was measured 3 times at different spots and the average spectra represented the signal of Raman spectra in each case. The Raman spectrum signal data of the five groups were statistically analyzed by analysis of variance (ANOVA), principal component analysis (PCA), linear discriminant analysis (LDA), and cross-validation. Raman spectral intensity was sequentially reduced in serum samples from control group, stage I group, stage II group and stage III/IV group. The strongest peak intensity was observed in the control group, and the weakest one was found in the stage III/IV group at bands of 848 cm -1 , 999 cm -1 , 1152 cm -1 , 1446 cm -1 and 1658 cm -1 (P Raman spectroscopy can effectively identify patients with stage I, stage II or stage III/IV Non-Small Cell Lung cancer using patient serum samples. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Effect of cell cycle stage, dose rate and repair of sublethal damage of radiation-induced apoptosis in F9 teratocarcinoma cells

    International Nuclear Information System (INIS)

    Langley, R.E.; Quartuccio, S.G.; Kennealey, P.T.

    1995-01-01

    There are at least two different models of cell death after treatment with ionizing radiation. The first is a failure to undergo sustained cell division despite metabolic survival, and we refer to this end point as open-quotes classical reproductive cell death.close quotes The second is a process that results in loss of cell integrity. This second category includes cellular necrosis as well as apoptosis. Earlier studies in our laboratory showed that the predominant mechanism of cell death for irradiated F9 cell is apoptosis, and there is no indication that these cells die by necrosis. We have therefore used cells of this cell line to reassess basic radiobiological principles with respect to apoptosis. Classical reproductive cell death was determined by staining colonies derived from irradiated cells and scoring colonies of less than 50 cells as reproductively dead and colonies of more than 50 cells as survivors. Cells that failed to produce either type of colony (detached from the plate or disintegrated) were scored as having undergone apoptosis. Using these criteria we found that the fraction of the radiation-killed F9 cells that died by apoptosis did not vary when cells were irradiated at different stages of the cell cycle despite large variations in overall survival. This suggests that the factors that influence radiation sensitivity throughout the cell cycle have an equal impact on apoptosis and classical reproductive cell death. There was no difference in cell survival between split doses and single doses of X rays, suggesting that sublethal damage repair is not a factor in radiation-induced apoptosis of F9 cells. Apoptosis was not affected by changes in dose rate in the range of 0.038-4.96 Gy/min. 48 refs., 6 figs., 1 tab

  10. FDG-PET in the initial staging of squamous cell oesophageal carcinoma

    International Nuclear Information System (INIS)

    Buchmann, I.; Schreckenberger, M.; Bartenstein, P.; Hansen, T.; Brochhausen, C.; Kneist, W.; Junginger, T.; Oberholzer, K.

    2006-01-01

    Squamous cell oesophageal carcinoma is the most common carcinoma of the oesophagus worldwide. The tumour stage as most important prognostic factor determines the clinical management. Aim of this study was to evaluate the value of FDG-PET 1. in imaging the primary tumour and 2. in N- and M-staging of squamous cell oesophogeal carcinoma. Patients, methods: in 20 patients with histological proven squamous cell carcinoma of the upper and middle oesophagus, FDG-PET was performed in standard technique prior to therapy. FDG uptake in the primary was determined by calculation of the SUVmax. NM-staging due to PET findings was performed as designated by the AJCC/UICC group classification and was compared with pathological and clinically based staging. Sensitivities, specificities and accuracies were calculated. Results: in 19 of 20 patients, primary squamous cell oesopohageal carcinoma was detected by FDG-PET findings with a maximum SUV of 12.5 (mean) ± 5.1 (median 11.5; range 4.8-23.8). One carcinoma in situ was missed. The sensitivity of FDG-PET in imaging the primary tumour was 96%. The sensitivities, specificities and accuracies were 20%, 100%, 58% for N-staging, and 60%, 86% and 93% for M-staging. PET findings caused changes of therapy in 5% (1 patient). Conclusions: FDG-PET was excellent in imaging the primary of squamous cell oesophageal carcinoma in stage T1-T4 and was efficient in M-staging. The low sensitivity in N-staging is of inferior clinical importance. The efficacy of FDG-PET seems to be not significantly be influenced by the histological subtype of oesophageal carcinoma. (orig.)

  11. Insights to the effects of free cells on community structure of attached cells and chalcopyrite bioleaching during different stages.

    Science.gov (United States)

    Feng, Shoushuai; Yang, Hailin; Wang, Wu

    2016-01-01

    The effects of free cells on community structure of attached cells and chalcopyrite bioleaching by Acidithiobacillus sp. during different stages were investigated. The attached cells of Acidithiobacillus thiooxidans owned the community advantage from 14thd to the end of bioprocess in the normal system. The community structure of attached cells was greatly influenced in the free cells-deficient systems. Compared to A. thiooxidans, the attached cells community of Acidithiobacillus ferrooxidans had a higher dependence on its free cells. Meanwhile, the analysis of key biochemical parameters revealed that the effects of free cells on chalcopyrite bioleaching in different stages were diverse, ranging from 32.8% to 64.3%. The bioleaching contribution of free cells of A. ferrooxidans in the stationary stage (8-14thd) was higher than those of A. thiooxidans, while the situation was gradually reversed in the jarosite passivation inhibited stage (26-40thd). These results may be useful in guiding chalcopyrite bioleaching. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Non small cell lung cancer – Comparison between clinical and pathological staging

    Directory of Open Access Journals (Sweden)

    G. Fernandes

    2006-07-01

    Full Text Available Lung cancer (LC staging remains a clinical challenge as it determines the disease's prognosis and treatment. Surgery is the best option for controlling non-small cell lung cancer (NSCLC and the only potential cure. In this setting, lung cancer staging helps select patients who will benefit from surgery, excluding inoperable patients and including patients with resectable lesions. The aim of this study is to compare clinical staging (TNMc with pathological staging (TNMp and to evaluate diagnosis, complementary treatment and survival of these patients.This is a retrospective study that included patients with non-small cell lung cancer or with highly sus- picious lesions who had undergone surgery and were followed up in the Hospital de São João lung cancer unit between January 1999 and December 2003. It is based on clinical files and pathology reports.73.3% of this group of 60 patients were male, with median age 59.2 years. The most frequent TNMc stages were 41.7% T1N0M0 and 36.7% T2N0M0. Thoracotomy for therapeutic purpose was performed in 80% and thoracotomy for diagnostic purpose also in the remaining 20%. In 6.7% the resection was incomplete. The most frequent TNMp stages were T2N0p in 33.3%, T2N1p in 15.0% and T2N2p in 13.3%. There was a significant difference between the two staging types, with upstaging in 65.0%, down staging in 67% and only 28.3% keeping the same stage. The most frequent differences were from T1N0c to T2N0p and from T2N0c to T2N1p. The global agreement between both staging methods was 21.7%. Median global survival was 43 months.In conclusion, while clinical staging was less accurate, it did not determine important changes in therapeutic strategy and survival. For the future, we should consider using other diagnostic tools and other biological factors to complement the anatomical information that we currently use. Resumo: O estadiamento do cancro do pulmão (CP permanece um desafio clínico, sendo fundamental para

  13. High efficiency 40 K single-stage Stirling-type pulse tube cryocooler

    Science.gov (United States)

    Wu, X. L.; Chen, L. B.; Pan, C. Z.; Cui, C.; Wang, J. J.; Zhou, Y.

    2017-12-01

    A high efficiency single-stage Stirling-type coaxial pulse tube cryocooler (SPTC) operating at around 40 K has been designed, built and tested. The double-inlet and the inertance tubes together with the gas reservoir were adopted as the phase shifters. Under the conditions of 2.5 MPa charging pressure and 30 Hz operating frequency, the prototype has achieved a no-load temperature of 23.8 K with 330 W of electric input power at a rejection temperature of 279 K. When the input power increases to 400 W, it can achieve a cooling capacity of 4.7 W/40 K while rejecting heat at 279 K yielding an efficiency of 7.02% relative to Carnot. It achieves a cooling capacity of 5 W/40 K with an input power of 450 W. It takes 10 minutes for the SPTC to cool to its no-load temperature of 40 K from 295 K.

  14. Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, Niels; Platz, P

    1987-01-01

    The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 pati...

  15. Study of the brain glucose metabolism in different stage of mixed-type multiple system atrophy

    International Nuclear Information System (INIS)

    Wang Ying; Zhang Benshu; Cai Li; Zhang Meiyun; Gao Shuo

    2014-01-01

    Objective: To investigate the brain glucose metabolism in different stage of mixed-type multiple system atrophy (MSA). Methods: Forty-six MSA patients with cerebellar or Parkinsonian symptoms and 18 healthy controls with similar age as patients were included. According to the disease duration,the patients were divided into three groups: group 1 (≤ 12 months, n=14), group 2 (13-24 months, n=13), group 3 (≥ 25 months, n=19). All patients and controls underwent 18 F-FDG PET/CT brain imaging. To compare metabolic distributions between different groups, SPM 8 software and two-sample t test were used for image data analysis. When P<0.005, the result was considered statistically significant. Results: At the level of P<0.005, the hypometabolism in group 1 (all t>3.49) was identified in the frontal lobe, lateral temporal lobe, insula lobe, anterior cingulate cortex, caudate nucleus and anterior cerebellar hemisphere. The regions of hypometabolism extended to posterolateral putamen and part of posterior cerebellar hemisphere in group 2 (all t>3.21). In group 3, the whole parts of putamen and cerebellar hemisphere were involved as hypometabolism (all t>4.08). In addition to the hypometabolism regions, there were also stabled hypermetabolism regions mainly in the parietal lobe, medial temporal lobe and the thalamus in all patient groups (all t>3.27 in group 1, all t>3.02 in group 2,all t>3.30 in group 3). Conclusions: Disease duration is closely related to the FDG metabolism in the MSA patients. Frontal lobe, lateral temporal lobe, anterior cingulate cortex and caudate nucleus can be involved at early stage of the disease. Putaminal hypometabolism begins in its posterolateral part. Cerebellar hypometabolism occurs early at its anterior part. Besides, thalamus shows hypermetabolism in the whole duration. 18 F-FDG metabolic changes of brain can reflect the development of mixed-type MSA. (authors)

  16. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy

    Directory of Open Access Journals (Sweden)

    V Viswanathan

    2015-01-01

    Full Text Available This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM. A total of 65 (M: F; 42:23 T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10 nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22, microalbuminuric (n = 22 and macroalbuminuric (n = 21. Estimated glomerular filtration rate (eGFR was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval for normoalbuminuria was 0.65 (0.47-0.97, microalbuminuria was 0.99 (0.55-1.97 and macroalbuminuria was 5.16 (1.8-14.5, (P = 0.005. In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects.

  17. Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary.

    Science.gov (United States)

    Färkkilä, Anniina; Haltia, Ulla-Maija; Tapper, Johanna; McConechy, Melissa K; Huntsman, David G; Heikinheimo, Markku

    2017-08-01

    Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis. However, every third of the patients relapse, typically in 4-7 years from diagnosis, leading to death in 50% of these patients. Anti-Müllerian Hormone and inhibin B are currently the most accurate circulating biomarkers. Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2. The FOXL2 402C->G mutation leads to increased proliferation and survival of granulosa cells, and promotes hormonal changes. Histological diagnosis of adult-type granulosa cell tumor is challenging, therefore testing for the FOXL2 mutation is crucial for differential diagnosis. Large international collaborations utilizing molecularly defined cohorts are essential to improve and validate new treatment strategies for patients with high-risk or relapsed adult-type granulosa cell tumor. Key Messages: Adult-type granulosa cell tumor is a unique ovarian cancer with an indolent, albeit unpredictable disease course. Adult-type granulosa cell tumors harbor a pathognomonic somatic missense mutation in transcription factor FOXL2. The key challenges in the treatment of patients with adult-type granulosa cell tumor lie in the identification and management of patients with high-risk or relapsed disease.

  18. A Web-Server of Cell Type Discrimination System

    Directory of Open Access Journals (Sweden)

    Anyou Wang

    2014-01-01

    Full Text Available Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and somatic cells (SCs. Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells.

  19. The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis.

    Science.gov (United States)

    Kato, Mihoko; Sternberg, Paul W

    2009-12-01

    Cell migration is a common event during organogenesis, yet little is known about how migration is temporally coordinated with organ development. We are investigating stage-specific programs of cell migration using the linker cell (LC), a migratory cell crucial for male gonadogenesis of C. elegans. During the L3 and L4 larval stages of wild-type males, the LC undergoes changes in its position along the migratory route, in transcriptional regulation of the unc-5 netrin receptor and zmp-1 zinc matrix metalloprotease, and in cell morphology. We have identified the tailless homolog nhr-67 as a cell-autonomous, stage-specific regulator of timing in LC migration programs. In nhr-67-deficient animals, each of the L3 and L4 stage changes is either severely delayed or never occurs, yet LC development before the early L3 stage or after the mid-L4 stage occurs with normal timing. We propose that there is a basal migration program utilized throughout LC migration that is modified by stage-specific regulators such as nhr-67.

  20. Utilization of radiographic and ultrasonic testing for an evaluation of plate type fuel elements during manufacturing stages

    International Nuclear Information System (INIS)

    Brito, Mucio Jose Drummond de; Silva Junior, Silverio Ferreira da; Messias, Jose Marcos; Braga, Daniel Martins; Paula, Joao Bosco de

    2005-01-01

    Structural discontinuities can be introduced in the plate type fuel elements during the manufacturing stages due to mechanical processing conditions. The use of nondestructive testing methods to monitoring the fuel elements during the manufacturing stages presents a significant importance, contributing for manufacturing process improvement and cost reducing. This paper describes a procedure to be used detection and evaluation of structural discontinuities in plate type fuel elements during the manufacturing stages using the ultrasonic testing method and the radiographic testing method. The main results obtained are presented and discussed. (author)

  1. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

    Directory of Open Access Journals (Sweden)

    Richard J. Davis

    2017-07-01

    Full Text Available Age-related macular degeneration (AMD is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC-derived RPE cells (RPESC-RPE preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

  2. Repopulation of denuded tracheal grafts with alveolar type II cells

    International Nuclear Information System (INIS)

    Johnson, N.F.

    1988-01-01

    Repopulation of denuded heterotopic tracheal grafts with populations of specific epithelial cell types is one approach to study the differentiation potential of various cell types. This technique has been adopted to delineate the differentiation pathways of alveolar type II cells isolated from rat lungs. Under the conditions of this experiment, the reestablished epithelial lining was alveolar-like, however, ultrastructural analysis of the cells showed them to be like Clara cells. These preliminary results suggest that the secretary cells of the lung parenchyma and terminal airways may share a common ancestry. (author)

  3. FDG-PET imaging for the staging and follow-up of small cell lung cancer

    International Nuclear Information System (INIS)

    Schumacher, T.; Brink, I.; Mix, M.; Reinhardt, M.; Moser, E.; Nitzsche, E.; Herget, G.; Digel, W.; Henke, M.

    2001-01-01

    The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6 x limited disease, 12 x extensive disease, 5 x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic

  4. Erythropoietin Receptor Positive Circulating Progenitor Cells and Endothelial Progenitor Cells in Patients with Different Stages of Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Liu-mei Hu; Guo-xu Xu; Guo-tong XU; Wei-ye Li; Xia Lei; Bo Ma; Yu Zhang; Yan Yan; Ya-lan Wu; Ge-zhi Xu; Wen Ye; Ling Wang

    2011-01-01

    Objective To investigate the possible involvement of erythropoietin (EPO)/erythropoietin receptor(EPOR) system in neovascularization and vascular regeneration in diabetic retinopathy (DR).Methods EPOR positive circulating progenitor cells (CPCs: CD34+) and endothelial progenitor cells (EPCs: CD34+KDR+) were assessed by flow cytometry in type 2 diabetic patients with different stages of DR. The cohort consisted of age- and sex-matched control patients without diabetes (n=7), non-prolif-erative DR (NPDR, n=7), proliferative DR (PDR, n=8), and PDR complicated with diabetic nephropathy (PDR-DN, n=7). Results The numbers of EPOR+ CPCs and EPOR+ EPCs were reduced remarkably in NPDR compared with the control group (both P<0.01), whereas rebounded in PDR and PDR-DN groups in varying degrees. Similar changes were observed in respect of the proportion of EPOR+ CPCs in CPCs (NPDR vs.control, P< 0.01) and that of EPOR+ EPCs in EPCs (NPDR vs. control, P< 0.05). Conclusion Exogenous EPO, mediated via the EPO/EPOR system of EPCs, may alleviate the im-paired vascular regeneration in NPDR, whereas it might aggravate retinal neovascularization in PDR due to a rebound of EPOR+ EPCs associated with ischemia.

  5. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2018-05-18

    CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  6. Role of type I interferon receptor signaling on NK cell development and functions.

    Directory of Open Access Journals (Sweden)

    Jean Guan

    Full Text Available Type I interferons (IFN are unique cytokines transcribed from intronless genes. They have been extensively studied because of their anti-viral functions. The anti-viral effects of type I IFN are mediated in part by natural killer (NK cells. However, the exact contribution of type I IFN on NK cell development, maturation and activation has been somewhat difficult to assess. In this study, we used a variety of approaches to define the consequences of the lack of type I interferon receptor (IFNAR signaling on NK cells. Using IFNAR deficient mice, we found that type I IFN affect NK cell development at the pre-pro NK stage. We also found that systemic absence of IFNAR signaling impacts NK cell maturation with a significant increase in the CD27+CD11b+ double positive (DP compartment in all organs. However, there is tissue specificity, and only in liver and bone marrow is the maturation defect strictly dependent on cell intrinsic IFNAR signaling. Finally, using adoptive transfer and mixed bone marrow approaches, we also show that cell intrinsic IFNAR signaling is not required for NK cell IFN-γ production in the context of MCMV infection. Taken together, our studies provide novel insights on how type I IFN receptor signaling regulates NK cell development and functions.

  7. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

    Science.gov (United States)

    Bárez-López, Soledad; Bosch-García, Daniel; Gómez-Andrés, David; Pulido-Valdeolivas, Irene; Montero-Pedrazuela, Ana; Obregon, Maria Jesus; Guadaño-Ferraz, Ana

    2014-01-01

    Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms. This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed. The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  8. Numerical simulation of a three-stage stirling-type pulse-tube refrigerator

    Energy Technology Data Exchange (ETDEWEB)

    Etaati, M.A.

    2011-06-22

    The pulse-tube refrigerator (PTR) is a rather new device for cooling down to extremely low temperatures, i.e. below 4 K. The PTR works by the cyclic compression and expansion of helium that flows through a regenerator made of porous material, a cold heat exchanger, a tube, a hot heat exchanger and an orifice, in series. In a Stirling-type PTR compression and expansion are generated by a piston. The compression increases the temperature of the helium in the tube and makes it flow towards the orifice; the expansion decreases the temperature and makes the helium flow backwards to the regenerator. The net effect of warmer helium flowing in one direction and colder helium in the opposite direction is that of cooling power at the cold heat exchanger. Three PTRs are inter-connected aiming to obtain the desired 4 K lowest temperature. The conservation laws of mass, momentum and energy, and an equation of state, are simplified using asymptotic analysis based on low Mach-numbers. The regenerator is modelled one-dimensionally with Darcy's law for flow resistance. The tube is modelled either one-dimensionally without resistance or two-dimensionally with axisymmetric laminar viscous flow. The heat transfer in the porous medium of the regenerator and in the solid tube wall is taken into account. The gas can be either ideal or real. All the material properties, including viscosity and conductivity, are taken temperature and pressure dependent. Three single-stage PTRs are connected with the regenerators in series and the tubes in parallel and six flow possibilities at the junctions are considered. Three by-passes (double-inlets) are used to enhance and tune the performance. The governing equations are numerically solved with a finite-difference method of nominally second-order accuracy in space and time. Pressure correction, flux limiter, 1D-2D connections and domain decomposition are the keywords here. Special attention is paid to suitable initial conditions, high resolution

  9. A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

    Science.gov (United States)

    Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

    2016-12-01

    An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European

  10. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  11. Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

    2011-01-01

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  12. [Value of surgery for stage IIIa non-small cell lung cancer].

    Science.gov (United States)

    Liu, Huihui; Wang, Mengzhao; Hu, Ke; Xu, Yan; Ma, Manjiao; Zhong, Wei; Zhao, Jing; Li, Longyun; Wang, Huazhu

    2013-12-01

    Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which

  13. Single cell analysis facilitates staging of Blimp1-dependent primordial germ cells derived from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    John J Vincent

    Full Text Available The cell intrinsic programming that regulates mammalian primordial germ cell (PGC development in the pre-gonadal stage is challenging to investigate. To overcome this we created a transgene-free method for generating PGCs in vitro (iPGCs from mouse embryonic stem cells (ESCs. Using labeling for SSEA1 and cKit, two cell surface molecules used previously to isolate presumptive iPGCs, we show that not all SSEA1+/cKit+ double positive cells exhibit a PGC identity. Instead, we determined that selecting for cKit(bright cells within the SSEA1+ fraction significantly enriches for the putative iPGC population. Single cell analysis comparing SSEA1+/cKit(bright iPGCs to ESCs and embryonic PGCs demonstrates that 97% of single iPGCs co-express PGC signature genes Blimp1, Stella, Dnd1, Prdm14 and Dazl at similar levels to e9.5-10.5 PGCs, whereas 90% of single mouse ESC do not co-express PGC signature genes. For the 10% of ESCs that co-express PGC signature genes, the levels are significantly lower than iPGCs. Microarray analysis shows that iPGCs are transcriptionally distinct from ESCs and repress gene ontology groups associated with mesoderm and heart development. At the level of chromatin, iPGCs contain 5-methyl cytosine bases in their DNA at imprinted and non-imprinted loci, and are enriched in histone H3 lysine 27 trimethylation, yet do not have detectable levels of Mvh protein, consistent with a Blimp1-positive pre-gonadal PGC identity. In order to determine whether iPGC formation is dependent upon Blimp1, we generated Blimp1 null ESCs and found that loss of Blimp1 significantly depletes SSEA1/cKit(bright iPGCs. Taken together, the generation of Blimp1-positive iPGCs from ESCs constitutes a robust model for examining cell-intrinsic regulation of PGCs during the Blimp1-positive stage of development.

  14. Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos

    DEFF Research Database (Denmark)

    Smith, Steven D.; Soloy, Eva; Kanka, Jiri

    1996-01-01

    Nucleus transfer for the production of multiple embryos derived from a donor embryo relies upon the reprogramming of the donor nucleus so that it behaves similar to a zygotic nucleus. One indication of nucleus reprogramming is the RNA synthetic activity. In normal bovine embryogenesis, the embryo....... NTE were produced using either a MII phase (nonactivated) cytoplasts at 32 hr of maturation or S-phase (activated) cytoplasts activated with calcium ionophore A23187 and cycloheximide treatment approximately 8 hr prior to fusion with a blastomere from an in-vitro-produced morula stage embryo at 32 hr...... of maturation. Control in-vitro-produced embryos were 3H-uridine-labelled and fixed at the 2-, 4-, early 8-, and late 8-cell stages. NTE were similarly prepared at 1, 3, and 20 hr postfusion and at the 2-, 4-, and 8-cell stages. In the control embryos, RNA synthesis was absent in the 2-, 4-, and early 8-cell...

  15. A Two-stage DC-DC Converter for the Fuel Cell-Supercapacitor Hybrid System

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2009-01-01

    A wide input range multi-stage converter is proposed with the fuel cells and supercapacitors as a hybrid system. The front-end two-phase boost converter is used to optimize the output power and to reduce the current ripple of fuel cells. The supercapacitor power module is connected by push...... and designed. A 1kW prototype controlled by TMS320F2808 DSP is built in the lab. Simulation and experimental results confirm the feasibility of the proposed two stage dc-dc converter system.......-pull-forward half bridge (PPFHB) converter with coupled inductors in the second stage to handle the slow transient response of the fuel cells and realize the bidirectional power flow control. Moreover, this cascaded structure simplifies the power management. The control strategy for the whole system is analyzed...

  16. Doppler Ultrasound Detection of Preclinical Changes in Foot Arteries in Early Stage of Type 2 Diabetes

    International Nuclear Information System (INIS)

    Leoniuk, Jolanta; Łukasiewicz, Adam; Szorc, Małgorzata; Sackiewicz, Izabela; Janica, Jacek; Łebkowska, Urszula

    2014-01-01

    There are few reports regarding the changes within the vessels in the initial stage of type 2 diabetes. The aim of this study was to estimate the hemodynamic and morphological parameters in foot arteries in type 2 diabetes subjects and to compare these parameters to those obtained in a control group of healthy volunteers. Ultrasound B-mode, color Doppler and pulse wave Doppler imaging of foot arteries was conducted in 37 diabetic patients and 36 non-diabetic subjects to determine their morphological (total vascular diameter and flow lumen diameter) and functional parameters (spectral analysis). In diabetic patients, the overall vascular diameter and wall thickness were statistically significantly larger when compared to the control group in the right dorsalis pedis artery (P=0.01; P=0.001), left dorsalis pedis artery (P=0.007; P=0.006), right posterior tibial artery (P=0.005; P=0.0005), and left posterior tibial artery (P=0.007; P=0.0002). No significant differences were observed in both groups in flow lumen diameters and blood flow parameters (PSV, EDV, PI, RI). In the diabetic group, the level of HbA1c positively correlated with flow resistance index in the right dorsalis pedis artery (r=0.38; P=0.02), right posterior tibial artery (r=0.38; P=0.02) and left posterior tibial artery (r=0.42; P=0.009). The pulsatility index within the dorsalis pedis artery decreased with increased trophic skin changes (r=–0.431, P=0.009). In the diabetic group, overall artery diameters larger than and flow lumina comparable to the control group suggest vessel wall thickening occurring in the early stage of diabetes. Doppler flow parameters are comparable in both groups. In the diabetic group, the level of HbA1c positively correlated with flow resistance index and negative correlation was observed between the intensity of trophic skin changes and the pulsatility index

  17. The percentage of iNKT cells among other immune cells at various clinical stages of laryngeal cancer

    Directory of Open Access Journals (Sweden)

    Janusz Klatka

    2016-04-01

    Full Text Available Introduction: Invariant natural killer T (iNKT cells constitute a small population of immune cells that share functional and phenotypic characteristics of T lymphocytes and NK cells. Due to their involvement in specific and non-specific immune responses, iNKT cells may represent an important component of antitumor and anti-infectious immunity. Material and methods: Using flow cytometry, we analyzed the percentages of iNKT cells as well as T and B lymphocytes in peripheral blood of 50 laryngeal cancer patients at various clinical stages in comparison to healthy controls (n=15. Moreover, we determined the expression of CD25, CD69 and CD95 antigens on T lymphocytes.Results: The percentage of CD4+/CD3+ T lymphocytes in the controls was higher than in laryngeal cancer patients, both with early and late stages of the disease. The percentage of CD8+/CD3+ T lymphocytes in healthy controls was lower than in patients with early and late clinical stages of laryngeal cancer. Patients with advanced laryngeal cancer showed a lower percentage of iNKT cells and higher frequencies of T regulatory cells (Tregs than the controls. Advanced clinical stages of laryngeal cancer are associated with impaired activation of lymphocytes.Conclusions: Our study confirmed that laryngeal cancer cells exert a strong suppressor effect on the immune system of the host. This is reflected by a decrease in the percentage of iNKT cells that are capable of cancer cell elimination, and a concomitant increase in the percentage of Tregs. However, further studies are needed in order to explain the underlying mechanisms of immunosuppression and understand interactions between immune and cancer cells.

  18. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  19. VMAT2 identified as a regulator of late-stage β-cell differentiation.

    Science.gov (United States)

    Sakano, Daisuke; Shiraki, Nobuaki; Kikawa, Kazuhide; Yamazoe, Taiji; Kataoka, Masateru; Umeda, Kahoko; Araki, Kimi; Mao, Di; Matsumoto, Shirou; Nakagata, Naomi; Andersson, Olov; Stainier, Didier; Endo, Fumio; Kume, Kazuhiko; Uesugi, Motonari; Kume, Shoen

    2014-02-01

    Cell replacement therapy for diabetes mellitus requires cost-effective generation of high-quality, insulin-producing, pancreatic β cells from pluripotent stem cells. Development of this technique has been hampered by a lack of knowledge of the molecular mechanisms underlying β-cell differentiation. The present study identified reserpine and tetrabenazine (TBZ), both vesicular monoamine transporter 2 (VMAT2) inhibitors, as promoters of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Neurog3 (referred to henceforth as Ngn3)-positive endocrine precursors. VMAT2-controlled monoamines, such as dopamine, histamine and serotonin, negatively regulated β-cell differentiation. Reserpine or TBZ acted additively with dibutyryl adenosine 3',5'-cyclic AMP, a cell-permeable cAMP analog, to potentiate differentiation of embryonic stem (ES) cells into β cells that exhibited glucose-stimulated insulin secretion. When ES cell-derived β cells were transplanted into AKITA diabetic mice, the cells reversed hyperglycemia. Our protocol provides a basis for the understanding of β-cell differentiation and its application to a cost-effective production of functional β cells for cell therapy.

  20. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; von der Maase, Hans; Sørensen, Flemming Brandt

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors.METHODS: The tissue material consisted of bladder tumors from three groups of patients......; group 1, 23 patients with recurrent stage Ta (non-invasive) tumors; group 2, 22 patients presenting at their first admission with T2-4 (muscle invasive) tumors; group 3, 24 patients who experienced disease progression from Ta or T1 (invasive in connective tissue) to a higher stage...

  1. External beam abdominal radiotherapy in patients with seminoma stage I: field type, testicular dose, and spermatogenesis

    International Nuclear Information System (INIS)

    Jacobsen, Kari Dolven; Olsen, Dag Rune; Fossaa, Kristian; Fossaa, Sophie Dorothea

    1997-01-01

    Purpose: To establish a predictive model for the estimation of the gonadal dose during adjuvant para-aortic (PA) or dog leg (DL: PA plus ipsilateral iliac) field radiotherapy in patients with testicular seminoma. Methods and Materials: The surface gonadal dose was measured in patients with seminoma Stage I receiving PA or DL radiotherapy. Sperm cell analysis was performed before and 1 year after irradiation. PA and DL radiotherapy were simulated in the Alderson phantom while we measured the dose to the surface and middle of an artificial testicle, varying its position within realistic anatomical constraints. The symphysis-to-testicle distance (STD), field length, and thickness of the patient were experimental variables. The developed mathematical model was validated in subsequent patients. Results: The mean gonadal dose in patients was 0.09 and 0.32 Gy after PA and DL irradiation, respectively (p < 0.001). DL radiotherapy, but not PA irradiation led to significant reduction of the sperm count 1 year after irradiation. The gonadal dose-reducing effect of PA irradiation was confirmed in the Alderson phantom. A significant correlation was found between the STD and the gonadal dose during DL irradiation. A mathematical model was established for calculation of the gonadal dose and confirmed by measurements in patients. Conclusions: During radiotherapy of seminoma, the gonadal dose decreases with increasing STD. It is possible to predict the individual gonadal dose based on delivered midplane dose and STD

  2. Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.

    Science.gov (United States)

    Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung

    2014-01-01

    The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.

  3. CT and MRI appearances and radiologic staging of pediatric renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Downey, Ryan T. [University of Michigan Health System, Department of Radiology, Ann Arbor, MI (United States); Dillman, Jonathan R.; Ladino-Torres, Maria F.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); McHugh, Jonathan B. [University of Michigan Health System, Department of Pathology, Ann Arbor, MI (United States); Ehrlich, Peter F. [University of Michigan Health System, Department of Surgery, Section of Pediatric Surgery, Ann Arbor, MI (United States)

    2012-04-15

    Renal cell carcinoma (RCC) is an uncommon but noteworthy primary pediatric renal malignancy. There is a paucity of published data regarding the CT/MRI appearances and accuracy of pretreatment radiologic staging of this form of cancer in children. To review the various CT/MRI appearances of pediatric RCC and assess the accuracy of pretreatment radiologic staging using these imaging modalities. Institutional Departments of Pathology and Radiology records were searched from 1995 through 2010 for children (younger than 18 years of age) with RCC. Available pretreatment contrast-enhanced abdominopelvic CT and MRI examinations were reviewed by two radiologists. Pertinent imaging findings were documented by consensus, and correlation was made between radiologic and surgicopathological TNM staging. Pretreatment imaging studies from 10 RCCs in nine children (four girls and five boys; mean age 12.9 years) were reviewed. The mean size of the primary tumor was 6.2 cm (range, 1.5-12.6 cm). Ninety percent of RCCs demonstrated heterogeneous postcontrast enhancement. Fifty percent of masses had associated hemorrhage, while 40% contained internal calcification. Regarding TNM staging, N staging was correct for 10 of 10 tumors, while M staging was correct for 10 of 10 tumors. Imaging correctly staged only 4 of 10 tumors with respect to T stage. Radiologic and surgicopathological overall staging were concordant for 8 of 10 tumors. Pediatric RCCs typically present as large, heterogeneous masses, and they commonly hemorrhage and contain internal calcification. Radiologic and surgicopathological overall TNM staging are frequently concordant, although radiologic T staging is often incorrect. (orig.)

  4. Improved fuel-cell-type hydrogen sensor

    Science.gov (United States)

    Rudek, F. P.; Rutkowski, M. D.

    1968-01-01

    Modified hydrogen sensor replaces oxygen cathode with a cathode consisting of a sealed paste of gold hydroxide and a pure gold current collector. The net reaction which occurs during cell operation is the reduction of the gold hydroxide to gold and water, with a half-cell potential of 1.4 volts.

  5. Impact of lymph node micrometastasis for the UICC stage in non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Ouyang Weiwei; Lu Bing; He Chang; Long Yiguo; Wang Ping

    2007-01-01

    Objective: To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods: From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) antibody AE1/AE3 was applied to detect cytokeratin with Envision TM method in routine pathological negative region lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results: The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67%(4/6)in stage p- I, p-II and p-III, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the micrometastasis group in two groups, the survival rate difference was statistically significant. Comparing the armnal survival rate and median sur- vival time in pCK-III A stage with p- I -II stage, pCK-III A stage annual survival rate and median survival time was significantly different(P=0.020). Similarly, comparing the survival rate in pCK-II B stage with p- I B stage, pCK- II B stage survival rate was significantly different( P = 0. 059). Comparing the survival time of pCK-IIIA stage with p-III stage, pCK-II B stage, with p-II B stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions: The rate of positive cytokeratin increase is accompanied by the disease progress in NSCLC. Positive cytokeratin has disadvantageous prognosis. It is showed that pCK-N1 may

  6. System-level Reliability Assessment of Power Stage in Fuel Cell Application

    DEFF Research Database (Denmark)

    Zhou, Dao; Wang, Huai; Blaabjerg, Frede

    2016-01-01

    reliability. In a case study of a 5 kW fuel cell power stage, the parameter variations of the lifetime model prove that the exponential factor of the junction temperature fluctuation is the most sensitive parameter. Besides, if a 5-out-of-6 redundancy is used, it is concluded both the B10 and the B1 system......High efficient and less pollutant fuel cell stacks are emerging and strong candidates of the power solution used for mobile base stations. In the application of the backup power, the availability and reliability hold the highest priority. This paper considers the reliability metrics from...... the component-level to the system-level for the power stage used in a fuel cell application. It starts with an estimation of the annual accumulated damage for the key power electronic components according to the real mission profile of the fuel cell system. Then, considering the parameter variations in both...

  7. Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

    Directory of Open Access Journals (Sweden)

    Soledad Bárez-López

    Full Text Available BACKGROUND: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4 but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2. To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO did not find gross neurological alterations, possibly due to compensatory mechanisms. AIM: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. RESULTS: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice. No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction and skeletal muscle (33% reduction, but not in the cerebellum where other deiodinase (type 1 is expressed. CONCLUSIONS: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

  8. Immature murine NKT cells pass through a stage of developmentally programmed innate IL-4 secretion

    Science.gov (United States)

    Dickgreber, Nina; Farrand, Kathryn J.; van Panhuys, Nicholas; Knight, Deborah A.; McKee, Sara J.; Chong, Mei L.; Miranda-Hernandez, Socorro; Baxter, Alan G.; Locksley, Richard M.; Le Gros, Graham; Hermans, Ian F.

    2012-01-01

    We assessed the production of the canonical Th2 cytokine IL-4 by NKT cells directly in vivo using IL-4-substituting strains of reporter mice that provide faithful and sensitive readouts of cytokine production without the confounding effects of in vitro stimulation. Analysis in naïve animals revealed an “innate” phase of IL-4 secretion that did not need to be triggered by administration of a known NKT cell ligand. This secretion was by immature NKT cells spanning Stage 1 of the maturation process in the thymus (CD4+ CD44lo NK1.1− cells) and Stage 2 (CD4+ CD44hi NK1.1− cells) in the spleen. Like ligand-induced IL-4 production by mature cells, this innate activity was independent of an initial source of IL-4 protein and did not require STAT6 signaling. A more sustained level of innate IL-4 production was observed in animals on a BALB/c background compared with a C57BL/6 background, suggesting a level of genetic regulation that may contribute to the “Th2-prone” phenotype in BALB/c animals. These observations indicate a regulated pattern of IL-4 expression by maturing NKT cells, which may endow these cells with a capacity to influence the development of surrounding cells in the thymus. PMID:22941735

  9. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  10. Multi-stage high cell continuous fermentation for high productivity and titer.

    Science.gov (United States)

    Chang, Ho Nam; Kim, Nag-Jong; Kang, Jongwon; Jeong, Chang Moon; Choi, Jin-dal-rae; Fei, Qiang; Kim, Byoung Jin; Kwon, Sunhoon; Lee, Sang Yup; Kim, Jungbae

    2011-05-01

    We carried out the first simulation on multi-stage continuous high cell density culture (MSC-HCDC) to show that the MSC-HCDC can achieve batch/fed-batch product titer with much higher productivity to the fed-batch productivity using published fermentation kinetics of lactic acid, penicillin and ethanol. The system under consideration consists of n-serially connected continuous stirred-tank reactors (CSTRs) with either hollow fiber cell recycling or cell immobilization for high cell-density culture. In each CSTR substrate supply and product removal are possible. Penicillin production is severely limited by glucose metabolite repression that requires multi-CSTR glucose feeding. An 8-stage C-HCDC lactic acid fermentation resulted in 212.9 g/L of titer and 10.6 g/L/h of productivity, corresponding to 101 and 429% of the comparable lactic acid fed-batch, respectively. The penicillin production model predicted 149% (0.085 g/L/h) of productivity in 8-stage C-HCDC with 40 g/L of cell density and 289% of productivity (0.165 g/L/h) in 7-stage C-HCDC with 60 g/L of cell density compared with referring batch cultivations. A 2-stage C-HCDC ethanol experimental run showed 107% titer and 257% productivity of the batch system having 88.8 g/L of titer and 3.7 g/L/h of productivity. MSC-HCDC can give much higher productivity than batch/fed-batch system, and yield a several percentage higher titer as well. The productivity ratio of MSC-HCDC over batch/fed-batch system is given as a multiplication of system dilution rate of MSC-HCDC and cycle time of batch/fed-batch system. We suggest MSC-HCDC as a new production platform for various fermentation products including monoclonal antibody.

  11. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    Science.gov (United States)

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  12. Evaluation of the recombination in somatic cells induced by radiation in different stages of Drosophila larval development

    International Nuclear Information System (INIS)

    Cruces, M.P.; Morales R, P.

    1997-01-01

    The mitotic recombination can happen spontaneously and its frequency is very low, however the recombination rate of a cell can be increased by the exposure to agents which cause damage to DNA. This type of agents are knew commonly as recombinogens. The ionizing radiation and a numerous chemical agents can be mentioned (Vogel, 1992). The objective of this work is to determine if the mutation/recombination rate induced by gamma rays varies with the development stage. In order to realize this investigation it was used the mutation and somatic recombination test of Drosophila wing (Graf and col. 1984). The mwh/ mwh and flr 3 /TM3, Ser stocks were used. (Author)

  13. PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell survival during the peri-implantation stage

    DEFF Research Database (Denmark)

    Li, Shaohua; Bordoy, Randi; Stanchi, Fabio

    2005-01-01

    PINCH1 is composed of 5 LIM domains, binds integrin-linked kinase (ILK) and locates to integrin-mediated adhesion sites. In order to investigate PINCH1 function we generated mice and embryonic stem (ES) cell-derived embryoid bodies (EBs) lacking the PINCH1 gene. Similar to mice lacking beta1...... integrin or Ilk, loss of PINCH1 arrested development at the peri-implantation stage. In contrast to beta1 integrin or Ilk mutants, however, disruption of the PINCH1 gene produced implantation chambers with visible cell clumps even at embryonic day 9.5. In order to define the phenotype leading to the peri...... not observed in beta1 integrin- or ILK-deficient mice or EBs, included abnormal cell-cell adhesion of endoderm and epiblast as well as the presence of apoptotic cells in the endodermal cell layer. Although ILK and PINCH1 were shown to be involved in the phosphorylation of serine-473 of PKB/Akt, immunostaining...

  14. Can duplex Doppler ultrasound replace computerized tomography in staging patients with renal cell carcinoma?

    NARCIS (Netherlands)

    Bos, SD; Mensink, HJA

    The purpose of this study was to evaluate the accuracy and reliability of duplex Doppler ultrasound (US) and computerized tomography (CT) in staging patients with renal cell carcinoma (RCC). Sixty-six patients were evaluated pre-operatively with duplex Doppler ultrasound and CT. The results were

  15. Evaluation on prognosis of esophageal squamous cell carcinoma patients after three-dimensional conformal radiotherapy with different clinical stage system

    International Nuclear Information System (INIS)

    Wang Yuxiang; Zhu Shuchai; Qiu Rong; Liu Zhikun; Shen Wenbin

    2011-01-01

    Objective: To evaluate the prognostic significance of 3 clinical stage system in 3-dimensional conformal radiotherapy (3DCRT) for esophageal squamous cell carcinoma. Methods: From January 2004 to August 2007, 179 cases of esophageal squamous cell carcinoma were treated with 3DCRT. Before radiation, each patient was staged with UICC 2003 TNM stage, stage of Chinese esophageal cancer cooperation group (cooperation group' stage), and Zhu's clinical stage respectively. Concordance of each clinical stage and prognosis was analyzed with SPSS 11.5. Results In 179 cases of esophageal cancer, Concordance was better in T stage (Kappa = 0.271) than in TNM stage (Kappa = 0.167) between cooperation group' stage and Zhu's stage. Among them, 98 cases was staged with UICC stage, concordance of T stage was better between UICC-T and cooperation group' T stage (Kappa =0.261) than between UICCT and Zhu's T stage (Kappa = 0.045) ;concordance of TNM stage was better between UICC-TNM and Zhu's TNM stage (Kappa = 0.597) than between UICC-TNM and cooperation group' TNM stage (Kappa =0.299). With multivariate analysis, T (χ 2 value is 11.58, 26.00 and 51.05, all P 2 value is 15.28, 16.10 and 16.10, all P 2 value is 5.59, 27.78 and 27.78, all P 2 value is 15.77, 34, 35 and 51.10, all P 1 - T 3 was difficult to definite and the prognosis was not significantly different in T 1 - T 3 stage. Conclusions: In this study, 3 kinds of clinical stage could evaluate prognosis of esophageal cancer after radiotherapy; cooperation group' stage and Zhu's stage need further application, with further accuracy needed. (authors)

  16. T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia.

    Science.gov (United States)

    Mirro, J; Kitchingman, G; Behm, F G; Murphy, S B; Goorha, R M

    1987-03-01

    T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the beta-chain portion of the Ti heterodimer. RNA transcripts of Ti beta-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the alpha-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus the absence of surface T3 (and presumably Ti) coincides with the absence of Ti alpha-chain RNA, suggesting that transcription of alpha-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti beta-chain genes but lack Ti alpha-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed.

  17. Association of Exercise Stages of Change with Glycemic Control in Individuals with Type 2 Diabetes.

    Science.gov (United States)

    Natarajan, Sundar; Clyburn, Ernest B.; Brown, Ronald T.

    2002-01-01

    Investigated the distribution of diabetic patients' stages of change to follow an exercise regimen, examining whether later stages of change were associated with better glycemic control. Data on participants from a primary care clinic (who were predominantly black, female, and indigent) indicated that over half of were in pre-contemplation,…

  18. Radiation effects on polyethylene foam of open cell type

    International Nuclear Information System (INIS)

    Tang Beilin; Kanako Kaji; Iwao Yoshizawa; Choji Kohara; Motoyoshi Hatada

    1991-01-01

    The effects of electron beam irradiation on polyethylene foam of open cell type have been studied. Experiments for determining of gel fraction and physical-mechanical properties of irradiated polyethylene foam of open cell type as a function of dose, respectively, were carried out. The dimensional stability of irradiated specimens at elevated temperatures was measured. It was found that tensile strength did not change and gel fraction increased when the specimen was irradiated in nitrogen atmosphere with increasing dose up to 300 kGy. The result shows that dimensional stability of polyethylene foam of open cell type after being kept in an oven at 70 deg C and 110 deg C for 22 h is improved by irradiation in nitrogen atmosphere. The similar results of irradiated EVA foam of open cell type irradiated foam of open cell type were obtained

  19. Birth of rats following nuclear exchange at the 2-cell stage.

    Science.gov (United States)

    Roh, Sangho; Guo, Jitong; Malakooti, Nakisa; Morrison, John R; Trounson, Alan O; Du, Zhong Tao

    2003-11-01

    We report full-term development of nuclear transfer embryos following nuclear exchange at the 2-cell stage. Nuclei from 2-cell rat embryos were transferred into enucleated 2-cell embryos and developed to term after transfer to recipients (NT2). Pronuclear exchange in zygotes was used for comparison (NT1). Zygotes and 2-cell embryos were harvested from 4-week-old female Sprague-Dawley rats. Nuclear transfer was performed by transferring the pronuclei or karyoplasts into the perivitelline space of recipient embryos followed by electrofusion to reconstruct embryos. Fused couplets were cultured for 4 or 24 h before being transferred into day 1 pseudopregnant recipients (Hooded Wistar) at the 1- or 2-cell stage. In vitro culture was also carried out to check the developmental competence of the embryos. In vitro development to the blastocyst stage was not significantly different between the two groups (NT1, 34.3%; NT2, 45.0%). Two of three recipients from NT1 and two of five recipients from NT2 became pregnant. Six pups (3 from NT1, 3 from NT2) were delivered from the four foster mothers. Three female pups survived; 2 from NT1 and 1 from NT2. At 2 months of age these pups appeared healthy, and were mated with Sprague-Dawley males. One rat derived from NT1 delivered 15 pups (5 males, 10 females) as did the rat from NT2 (7 males, 8 females). Our results show that by using karyoplasts from 2-cell stage embryos as nuclear donors and reconstructing them with enucleated 2-cell embryos, healthy rats can be produced.

  20. Association of choroidal thickness with early stages of diabetic retinopathy in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun; Shen; Xiu-Fen; Yang; Jun; Xu; Chong-Yang; She; Wen-Wen; Wei; Wan-Lu; Zhu; Ning-Pu; Liu

    2017-01-01

    AIM:To assess the correlation between choroidal thickness(CT) and the early stages of diabetic retinopathy(DR) in type 2 diabetic patients.METHODS:We divided 83 diabetic patients(51-80 years of age;50 females) into non diabetic retinopathy group(NDR) and mild/moderate nonproliferative diabetic retinopathy(NPDR) group,and compared them with 26 non-diabetic control subjects(51-78 years of age;16 females).Subfoveal choroidal thickness(SFCT) and parafoveal choroidal thickness(PFCT) were measured using enhanced depth imaging spectral-domain optical coherence tomography(EDI-OCT).Ocular health status,disease duration,body mass index,and hemoglobin A1c(Hb A1c) were recorded.RESULTS:The mean ages of the NDR,NPDR,and control groups were 68.0±6.9y,67.8±6.4y,and 65.1±6.3y,respectively(P=0.17).Pearson correlation of the right and left eyes for the control subjects was 0.95 and for the NDR subjects was 0.93.SFCT for the right eyes of the controls was 252.77± 41.10 μm,which was significantly thicker than that of the right eyes in NDR group(221.51±46.56 μm) and the worse eyes of the NPDR group(207.18±61.87 μm;ANOVA,P<0.01).In the diabetic patients pooled together,age was the only variable significantly associated with SFCT(multiple linear regression analysis,P=0.01).CONCLUSION:CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with the control eyes.Age is significantly associated with SFCT in the diabetic patients.Diabetic choroidopathy may be present before clinical retinopathy.

  1. Cell-type-specific predictive network yields novel insights into mouse embryonic stem cell self-renewal and cell fate.

    Directory of Open Access Journals (Sweden)

    Karen G Dowell

    Full Text Available Self-renewal, the ability of a stem cell to divide repeatedly while maintaining an undifferentiated state, is a defining characteristic of all stem cells. Here, we clarify the molecular foundations of mouse embryonic stem cell (mESC self-renewal by applying a proven Bayesian network machine learning approach to integrate high-throughput data for protein function discovery. By focusing on a single stem-cell system, at a specific developmental stage, within the context of well-defined biological processes known to be active in that cell type, we produce a consensus predictive network that reflects biological reality more closely than those made by prior efforts using more generalized, context-independent methods. In addition, we show how machine learning efforts may be misled if the tissue specific role of mammalian proteins is not defined in the training set and circumscribed in the evidential data. For this study, we assembled an extensive compendium of mESC data: ∼2.2 million data points, collected from 60 different studies, under 992 conditions. We then integrated these data into a consensus mESC functional relationship network focused on biological processes associated with embryonic stem cell self-renewal and cell fate determination. Computational evaluations, literature validation, and analyses of predicted functional linkages show that our results are highly accurate and biologically relevant. Our mESC network predicts many novel players involved in self-renewal and serves as the foundation for future pluripotent stem cell studies. This network can be used by stem cell researchers (at http://StemSight.org to explore hypotheses about gene function in the context of self-renewal and to prioritize genes of interest for experimental validation.

  2. Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced by X rays in male mouse germ cells

    International Nuclear Information System (INIS)

    Backer, L.C.; Sontag, M.R.; Allen, J.W.

    1991-01-01

    Synaptonemal complexes (SCs) reveal mutagen-induced effects in germ cell meiotic chromosomes. The study was aimed at characterizing relationships between SC and metaphase I chromosome damage following radiation exposure at various stages of spermatogenesis. Male mice were irradiated with doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as many rearrangements were observed in SCs as in metaphase I chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related increases in SC breakage and rearrangements (including novel forms) and in metaphase chromosomal aberrations. Following prophase exposure, various types and levels of SC and metaphase damage were observed. Irradiation of zygotene cells led to high frequencies of chromosome multivalents in metaphase I without a correspondingly high level of damage in preceding prophase SCs. Thus, irradiation of premeiotic and meiotic cells results in variable relationships between SC and metaphase chromosome damage

  3. Cell Type-Specific Contributions to the TSC Neuropathology

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

  4. Transcriptome atlas of eight liver cell types uncovers effects of ...

    Indian Academy of Sciences (India)

    ... types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression ...

  5. Stage-dependent prognostic impact of molecular signatures in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Weber T

    2014-05-01

    0.75 to 0.78. In patients with "organ-confined" ccRCC, no disease-related deaths occurred in the group with p21-expression below the threshold of 32.5% p21-positive cells (log rank test: P=0.002.Conclusion: The prognostic information of the studied protein biomarkers depended on anatomic tumor stages, which displayed different acquired biological tumor characteristics. Analysis of prognostic factors within different clinical ccRCC groups could help to enhance their prognostic power. The p21-staining was an independent prognostic factor and increased prognostic accuracy in a predictive model in "organ-confined" ccRCC.Keywords: survival, prognostic groups, localized, p21, advanced

  6. Experimental study on an innovative multifunction heat pipe type heat recovery two-stage sorption refrigeration system

    International Nuclear Information System (INIS)

    Li, T.X.; Wang, R.Z.; Wang, L.W.; Lu, Z.S.

    2008-01-01

    An innovative multifunction heat pipe type sorption refrigeration system is designed, in which a two-stage sorption thermodynamic cycle based on two heat recovery processes was employed to reduce the driving heat source temperature, and the composite sorbent of CaCl 2 and activated carbon was used to improve the mass and heat transfer performances. For this test unit, the heating, cooling and heat recovery processes between two reactive beds are performed by multifunction heat pipes. The aim of this paper is to investigate the cycled characteristics of two-stage sorption refrigeration system with heat recovery processes. The two sub-cycles of a two-stage cycle have different sorption platforms though the adsorption and desorption temperatures are equivalent. The experimental results showed that the pressure evolutions of two beds are nearly equivalent during the first stage, and desorption pressure during the second stage is large higher than that in the first stage while the desorption temperatures are same during the two operation stages. In comparison with conventional two-stage cycle, the two-stage cycle with heat recovery processes can reduce the heating load for desorber and cooling load for adsorber, the coefficient of performance (COP) has been improved more than 23% when both cycles have the same regeneration temperature of 103 deg. C and the cooling water temperature of 30 deg. C. The advanced two-stage cycle provides an effective method for application of sorption refrigeration technology under the condition of low-grade temperature heat source or utilization of renewable energy

  7. The stream of precursors that colonizes the thymus proceeds selectively through the early T lineage precursor stage of T cell development

    Science.gov (United States)

    Benz, Claudia; Martins, Vera C.; Radtke, Freddy; Bleul, Conrad C.

    2008-01-01

    T cell development in the thymus depends on continuous colonization by hematopoietic precursors. Several distinct T cell precursors have been identified, but whether one or several independent precursor cell types maintain thymopoiesis is unclear. We have used thymus transplantation and an inducible lineage-tracing system to identify the intrathymic precursor cells among previously described thymus-homing progenitors that give rise to the T cell lineage in the thymus. Extrathymic precursors were not investigated in these studies. Both approaches show that the stream of T cell lineage precursor cells, when entering the thymus, selectively passes through the early T lineage precursor (ETP) stage. Immigrating precursor cells do not exhibit characteristics of double-negative (DN) 1c, DN1d, or DN1e stages, or of populations containing the common lymphoid precursor 2 (CLP-2) or the thymic equivalent of circulating T cell progenitors (CTPs). It remains possible that an unknown hematopoietic precursor cell or previously described extrathymic precursors with a CLP, CLP-2, or CTP phenotype feed into T cell development by circumventing known intrathymic T cell lineage progenitor cells. However, it is clear that of the known intrathymic precursors, only the ETP population contributes significant numbers of T lineage precursors to T cell development. PMID:18458114

  8. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    Science.gov (United States)

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  9. Characterization of xylan in the early stages of secondary cell wall formation in tobacco bright yellow-2 cells.

    Science.gov (United States)

    Ishii, Tadashi; Matsuoka, Keita; Ono, Hiroshi; Ohnishi-Kameyama, Mayumi; Yaoi, Katsuro; Nakano, Yoshimi; Ohtani, Misato; Demura, Taku; Iwai, Hiroaki; Satoh, Shinobu

    2017-11-15

    The major polysaccharides present in the primary and secondary walls surrounding plant cells have been well characterized. However, our knowledge of the early stages of secondary wall formation is limited. To address this, cell walls were isolated from differentiating xylem vessel elements of tobacco bright yellow-2 (BY-2) cells induced by VASCULAR-RELATED NAC-DOMAIN7 (VND7). The walls of induced VND7-VP16-GR BY-2 cells consisted of cellulose, pectic polysaccharides, hemicelluloses, and lignin, and contained more xylan and cellulose compared with non-transformed BY-2 and uninduced VND7-VP16-GR BY-2 cells. A reducing end sequence of xylan containing rhamnose and galaturonic acid- residues is present in the walls of induced, uninduced, and non-transformed BY-2 cells. Glucuronic acid residues in xylan from walls of induced cells are O-methylated, while those of xylan in non-transformed BY-2 and uninduced cells are not. Our results show that xylan changes in chemical structure and amounts during the early stages of xylem differentiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Functional cell types in taste buds have distinct longevities.

    Directory of Open Access Journals (Sweden)

    Isabel Perea-Martinez

    Full Text Available Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  11. Functional cell types in taste buds have distinct longevities.

    Science.gov (United States)

    Perea-Martinez, Isabel; Nagai, Takatoshi; Chaudhari, Nirupa

    2013-01-01

    Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU) to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor) taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic) taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  12. Electrical Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2012-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  13. Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2011-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  14. Different effects of dose rate on radiation-induced mutation frequency in various germ-cell stages of the mouse, and their implications for the analysis of tumorigenesis

    International Nuclear Information System (INIS)

    Russell, W.L.

    1979-01-01

    The following factors affecting mutation induction by radiation in mice are discussed: dose rate, cell stage, and sex. It is suggested that for cancers of presumed mutational origin, the risk from chronic radiation exposure may be only one-third the risk from acute exposure. This is based only on responses of spermatogonia; other cell types behave quite differently. Specific and general applications are discussed

  15. Radiotherapy for stage I-II non-small cell lung cancer

    International Nuclear Information System (INIS)

    Okamoto, Yoshiaki; Murakami, Masao; Mizowaki, Takashi; Nakajima, Toshifumi; Kuroda, Yasumasa

    1999-01-01

    Surgery has been regarded as the standard treatment for patients with non-small cell lung cancer in the early stage, while radiotherapy has become an effective alternative for medically inoperable patients and those who refuse surgery. We reviewed the records of 31 patients with stage I-II non-small cell lung cancer treated by radiotherapy between 1980 and 1997. There were 15 patients in stage I and 16 in stage II. The variables analyzed for influence on cause-specific survival and loco-regional control were: age, performance status, clinical stage, tumor size, tumor site, radiation field, radiation dose, and combination with chemotherapy. The overall and cause-specific 1-, 2-, 3-, and 5-years survival rates were 71% and 77%; 63% and 73%; 34% and 48%; and 17% and 32%, respectively. Five-year survival rate for patients with peripheral tumor in the lung was 72%, with 70% loco-regional control, while the 5-year survival rate of patients whose tumor originated in the central region was 20%, with 25% loco-regional control. These differences had marginal significance on univariate analysis (P=0.07), but only tumor site (central vs peripheral) showed marginal significant influence on cause-specific survival (P=0.08) and loco-regional control (P=0.07) on multivariate analysis. There were no fatal complications, including radiation-induced myelopathy. The present series showed satisfactory results with definitive radiotherapy for patients with medically inoperable stage I-II non-small cell lung cancer, with results similar to those in recent reports of radiotherapy. The only significant variable was that patients with peripheral tumors had a better prognosis than patients with central tumors. (author)

  16. Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress

    Directory of Open Access Journals (Sweden)

    Paul-Christian Burda

    2017-04-01

    Full Text Available A crucial step in the life cycle of Plasmodium parasites is the transition from the liver stage to the blood stage. Hepatocyte-derived merozoites reach the blood vessels of the liver inside host cell-derived vesicles called merosomes. The molecular basis of merosome formation is only partially understood. Here we show that Plasmodium berghei liver stage merozoites, upon rupture of the parasitophorous vacuole membrane, destabilize the host cell membrane (HCM and induce separation of the host cell actin cytoskeleton from the HCM. At the same time, the phospholipid and protein composition of the HCM appears to be substantially altered. This includes the loss of a phosphatidylinositol 4,5-bisphosphate (PIP2 reporter and the PIP2-dependent actin-plasma membrane linker ezrin from the HCM. Furthermore, transmembrane domain-containing proteins and palmitoylated and myristoylated proteins, as well as glycosylphosphatidylinositol-anchored proteins, lose their HCM localization. Collectively, these findings provide an explanation of HCM destabilization during Plasmodium liver stage egress and thereby contribute to our understanding of the molecular mechanisms that lead to merosome formation.

  17. The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

    Science.gov (United States)

    Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

    2016-11-01

    To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Renal cell carcinoma in long-term survivors of advanced stage neuroblastoma in early childhood

    International Nuclear Information System (INIS)

    Fleitz, Julie M.; Wootton-Gorges, Sandra L.; Kurzrock, Eric A.; Wyatt-Ashmead, Josephine; McGavran, Loris; Koyle, Martin; Odom, Lorrie F.; West, Daniel C.; Martin, Kenneth W.

    2003-01-01

    Renal cell carcinoma (RCC) is rare in children and comprises only 1-3% of all pediatric primary renal tumors. Recently, several case reports have described RCC developing in patients previously treated for advanced stage neuroblastoma (NB). Our experience with four patients treated for advanced stage NB during early childhood who developed RCC later in life are added to 14 others in the literature. These patients and our review of the literature suggest an association between RCC and NB that warrants further study. (orig.)

  19. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type...... II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

  20. The Risk of Colorectal Cancer in Patients With Type 2 Diabetes : Associations With Treatment Stage and Obesity

    NARCIS (Netherlands)

    Peeters, Paul J H L; Bazelier, Marloes T; Leufkens, Hubert G M; de Vries, Frank; De Bruin, Marie L

    2014-01-01

    OBJECTIVE: To assess the risk of colorectal cancer associated with type 2 diabetes, as compared with a nondiabetic reference population, and to study additional associations between treatment stage and duration of obesity and colorectal cancer risk. RESEARCH DESIGN AND METHODS: We conducted an

  1. L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation

    NARCIS (Netherlands)

    Zeimet, A.G.; Reimer, D.; Huszar, M.; Winterhoff, B.; Puistola, U.; Azim, S.A.; Muller-Holzner, E.; Ben-Arie, A.; Kempen, L.C.L.T. van; Petru, E.; Jahn, S.; Geels, Y.P.; Massuger, L.F.A.G.; Amant, F.; Polterauer, S.; Lappi-Blanco, E.; Bulten, J.; Meuter, A.; Tanouye, S.; Oppelt, P.; Stroh-Weigert, M.; Reinthaller, A.; Mariani, A.; Hackl, W.; Netzer, M.; Schirmer, U.; Vergote, I.; Altevogt, P.; Marth, C.; Fogel, M.

    2013-01-01

    BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to

  2. Value of Surgery for Stage IIIa Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Huihui LIU

    2013-12-01

    Full Text Available Background and objective Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC. However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Methods Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS and progression-free survival (PFS, and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. Results Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041, but the PFS of them had no

  3. Development of a Flat Type Six-Axis Stage Based on Piezoelectric Actuators

    Directory of Open Access Journals (Sweden)

    Hau-Wei Lee

    2014-01-01

    Full Text Available This study presents and investigates a six-DOF (degrees of freedom piezoelectric based stage for positioning error compensation. The relationship between the displacement of the piezoelectric actuators and the stage can be computed according to the geometric relationships of the actuators installed. In this study, a feedforward compensator based on the hysteresis model has been designed for compensation and a PI controller was used for positioning. The combination of a feedforward compensator and PI controller gives the stage good positioning and tracking performance. Stage position information is feedback from a six-DOF optical measurement system comprised of three modular two-dimensional measurement devices. Each module employs a quadrant photodiode (QPD, a laser diode, and a lens. The measurement signal is acquired and processed using an FPGA based processor for real time control. The linear and angular positioning resolution is 0.02 μm and 0.1 arcsec, respectively. When the stage is controlled in a closed loop, the positioning errors are in the range of ±0.1 μm and ±0.5 arcsec. The stage is controlled to track a sinusoidal wave with an amplitude of 2.5 μm and a frequency of 5 Hz; tracking errors were within ±0.1 μm and ±0.2 arcsec.

  4. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset.

    Science.gov (United States)

    Dasgupta, Suryasarathi; Kumar, Vipin

    2016-08-01

    Type II natural killer T cells (NKT) are a subset of the innate-like CD1d-restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease.

  5. Inducible Costimulator Expressing T Cells Promote Parasitic Growth During Blood Stage Plasmodium berghei ANKA Infection

    Directory of Open Access Journals (Sweden)

    Gajendra M. Jogdand

    2018-05-01

    Full Text Available The lethality of blood stage Plasmodium berghei ANKA (PbA infection is associated with the expression of T-bet and production of cytokine IFN-γ. Expression of inducible costimulator (ICOS and its downstream signaling has been shown to play a critical role in the T-bet expression and IFN-γ production. Although earlier studies have examined the role of ICOS in the control of acute blood-stage infection of Plasmodium chabaudi chabaudi AS (a non-lethal model of malaria infection, its significance in the lethal blood-stage of PbA infection remains unclear. Thus, to address the seminal role of ICOS in lethal blood-stage of PbA infection, we treated PbA-infected mice with anti-ICOS antibody and observed that these mice survived longer than their infected counterparts with significantly lower parasitemia. Anti-ICOS treatment notably depleted ICOS expressing CD4+ and CD8+ T cells with a concurrent reduction in plasma IFN-γ, which strongly indicated that ICOS expressing T cells are major IFN-γ producers. Interestingly, we observed that while ICOS expressing CD4+ and CD8+ T cells produced IFN-γ, ICOS−CD8+ T cells were also found to be producers of IFN-γ. However, we report that ICOS+CD8+ T cells were higher producers of IFN-γ than ICOS−CD8+ T cells. Moreover, correlation of ICOS expression with IFN-γ production in ICOS+IFN-γ+ T cell population (CD4+ and CD8+ T cells suggested that ICOS and IFN-γ could positively regulate each other. Further, master transcription factor T-bet importantly involved in regulating IFN-γ production was also found to be expressed by ICOS expressing CD4+ and CD8+ T cells during PbA infection. As noted above with IFN-γ and ICOS, a positive correlation of expression of ICOS with the transcription factor T-bet suggested that both of them could regulate each other. Taken together, our results depicted the importance of ICOS expressing CD4+ and CD8+ T cells in malaria parasite growth and lethality through IFN

  6. Prognostic value of stem cell quantification in stage II colon cancer.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vaz

    Full Text Available BACKGROUND: Cancer stem cells (CSCs are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. METHODS: One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. RESULTS: The average patient age was 68 years (patients were between 45-92 years of age and median follow up was 5.8 years. There was recurrent disease in 17 (17%; CD133 expression (defined by >10% positivity was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS or overall survival (OS. However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

  7. PKH26 staining defines distinct subsets of normal human colon epithelial cells at different maturation stages.

    Directory of Open Access Journals (Sweden)

    Anna Pastò

    Full Text Available BACKGROUND AND AIM: Colon crypts are characterized by a hierarchy of cells distributed along the crypt axis. Aim of this paper was to develop an in vitro system for separation of epithelial cell subsets in different maturation stages from normal human colon. METHODOLOGY AND MAJOR FINDINGS: Dissociated colonic epithelial cells were stained with PKH26, which allows identification of distinct populations based on their proliferation rate, and cultured in vitro in the absence of serum. The cytofluorimetric expression of CK20, Msi-1 and Lgr5 was studied. The mRNA levels of several stemness-associated genes were also compared in cultured cell populations and in three colon crypt populations isolated by microdissection. A PKH(pos population survived in culture and formed spheroids; this population included subsets with slow (PKH(high and rapid (PKH(low replicative rates. Molecular analysis revealed higher mRNA levels of both Msi-1 and Lgr-5 in PKH(high cells; by cytofluorimetric analysis, Msi-1(+/Lgr5(+ cells were only found within PKH(high cells, whereas Msi-1(+/Lgr5(- cells were also observed in the PKH(low population. As judged by qRT-PCR analysis, the expression of several stemness-associated markers (Bmi-1, EphB2, EpCAM, ALDH1 was highly enriched in Msi-1(+/Lgr5(+ cells. While CK20 expression was mainly found in PKH(low and PKH(neg cells, a small PKH(high subset co-expressed both CK20 and Msi-1, but not Lgr5; cells with these properties also expressed Mucin, and could be identified in vivo in colon crypts. These results mirrored those found in cells isolated from different crypt portions by microdissection, and based on proliferation rates and marker expression they allowed to define several subsets at different maturation stages: PKH(high/Lgr5(+/Msi-1(+/CK20(-, PKH(high/Lgr5(-/Msi-1(+/CK20(+, PKH(low/Lgr5(-/Msi-1(+/Ck20(-, and PKH(low/Lgr5(-/Msi-1(-/CK20(+ cells. CONCLUSIONS: Our data show the possibility of deriving in vitro, without any

  8. Treatment of Early Stage Non-Small Cell Lung Cancer: Surgery or Stereotactic Ablative Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Esengül Koçak Uzel

    2015-03-01

    Full Text Available The management of early-stage Non-small Cell Lung Cancer (NSCLC has improved recently due to advances in surgical and radiation modalities. Minimally-invasive procedures like Video-assisted thoracoscopic surgery (VATS lobectomy decreases the morbidity of surgery, while the numerous methods of staging the mediastinum such as endobronchial and endoscopic ultrasound-guided biopsies are helping to achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy (SABR has become the frontrunner as the standard of care in medically inoperable early stage NSCLC patients, and has also been branded as tolerable and highly effective. Ongoing researches using SABR are continuously validating the optimal dosing and fractionation schemes, while at the same time instituting its role for both inoperable and operable patients.

  9. Freedom of expression: cell-type-specific gene profiling.

    Science.gov (United States)

    Otsuki, Leo; Cheetham, Seth W; Brand, Andrea H

    2014-01-01

    Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling. © 2014 Wiley Periodicals, Inc.

  10. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    Directory of Open Access Journals (Sweden)

    Zhang Xin

    2009-07-01

    Full Text Available Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5% were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%. Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated

  11. The role of radiation therapy for stage IIIB non-small cell lung cancer. Impact of clinical nodal stage on survival

    International Nuclear Information System (INIS)

    Hayakawa, Kazushige; Mitsuhashi, Norio; Furuta, Masaya; Saito, Yoshihiro; Nakayama, Yuko; Katano, Susumu; Ohno, Tatsuya; Niibe, Hideo

    1996-01-01

    From 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital. All patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation. The actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage N0-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months; p<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0-1 and those with status of 2-3 (p=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years. These results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage. (author)

  12. Glutathione synthesis and homeostasis in isolated type II alveolar cells

    International Nuclear Information System (INIS)

    Saito, K.; Warshaw, J.B.; Prough, R.A.

    1986-01-01

    After isolation of Type II cells from neonatal rat lung, the glutathione (GSH) levels in these cells were greatly depressed. The total glutathione content could be increased 5-fold within 12-24 h by incubating the cells in media containing sulfur amino acids. Similarly, the activity of γ-glutamyltranspeptidase was low immediately after isolation, but was increased 2-fold during the first 24 h culture. Addition of either GSH or GSSG to the culture media increased the GSH content of Type II cells 2-2.5-fold. Buthionine sulfoximine and NaF prevented this replenishment of GSH during 24 h culture. When the rates of de novo synthesis of GSH and GSSG from 35 S-cysteine were measured, the amounts of newly formed GSH decreased to 80% in the presence of GSH or GSSG. This suggests that exogenous GSH/GSSG can be taken up by the Type II cells to replenish the intracellular pool of GSH. Methionine was not as effective as cysteine in the synthesis of GSH. These results suggest that GSH levels in the isolated Type II cell can be maintained by de novo synthesis or uptake of exogenous GSH. Most of the GSH synthesized from cysteine, however, was excreted into the media of the cultured cells indicative of a potential role for the type II cell in export of the non-protein thiol

  13. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum.

    Directory of Open Access Journals (Sweden)

    Bronwyn Jane Barkla

    2015-06-01

    Full Text Available One of the remarkable adaptive features of the halophyte and facultative CAM plant Mesembryathemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples was used to identify 352 significantly differing metabolites (268 after correction for FDR. Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na and Cl ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggest large alterations in Mesembryanthemum crystallinum epidermal bladder cells.

  14. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum.

    Science.gov (United States)

    Barkla, Bronwyn J; Vera-Estrella, Rosario

    2015-01-01

    One of the remarkable adaptive features of the halophyte Mesembryanthemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC) which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF) and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples identified 352 significantly differing metabolites (268 after correction for FDR). Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na(+) and Cl(-) ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggests large alterations in M. crystallinum epidermal bladder cells.

  15. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum

    Science.gov (United States)

    Barkla, Bronwyn J.; Vera-Estrella, Rosario

    2015-01-01

    One of the remarkable adaptive features of the halophyte Mesembryanthemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC) which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF) and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples identified 352 significantly differing metabolites (268 after correction for FDR). Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na+ and Cl− ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggests large alterations in M. crystallinum epidermal bladder cells. PMID:26113856

  16. Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Bölke E

    2009-09-01

    Full Text Available Abstract Background Breast cancer (BC represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting. Materials and methods Circulating tumour cells (CTC of 63 BC patients were isolated from peripheral blood (PB through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls. Results Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed. Conclusion Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

  17. Intensified Multifactorial Intervention in Type 2 Diabetes and Microalbuminuria Reduces End Stage Renal Disease and Mortality

    DEFF Research Database (Denmark)

    Oellgaard, Jens; Gæde, Peter; Rossing, Peter

    2016-01-01

    -label trial. Duration of the intervention was 8 years, where after all patients were recommended intensified treatment. Total follow-up of up to 21 years of 24 hour urinary albumin excretion rate and GFR (51Cr-EDTA-clearance) assessed at 6 study visits. Information on end stage renal disease (ESRD......) and mortality was obtained from national registries. Outcome measures were progression to macroalbuminuria (>300 mg/24h), decline-rates of GFR and progression to end stage renal disease (ESRD) or death. Results: Progression to macroalbuminuria was reduced in the original intensive-therapy group with a hazard...

  18. Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.

    Science.gov (United States)

    Weng, Xiufang; He, Ying; Visvabharathy, Lavanya; Liao, Chia-Min; Tan, Xiaosheng; Balakumar, Arjun; Wang, Chyung-Ru

    2017-10-01

    Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation. Transgenic mice with the Lck promoter directing CD1d overexpression on T cells in Jα18 wild-type (Lck-CD1dTgJα18 + ; type I NKT cell sufficient) and Jα18-deficient (Lck-CD1dTgJα18 o , type I NKT cell deficient) mice were analyzed for liver pathology and crosstalk between type II NKT cells and conventional T cells. CD1d expression on T cells in peripheral blood samples and liver sections from autoimmune hepatitis patients and healthy individuals were also examined. Lck-CD1dTgJα18 o and Lck-CD1dTgJα18 + mice developed similar degrees of liver pathology resembling chronic autoimmune hepatitis in humans. Increased CD1d expression on T cells promoted the activation of type II NKT cells and other T cells. This resulted in T h 1-skewing and impaired T h 2 cytokine production in type II NKT cells. Dysfunction of type II NKT cells was accompanied by conventional T cell activation and pro-inflammatory cytokine production, leading to a hepatic T/B lymphocyte infiltration, elevated autoantibodies and hepatic injury in Lck-CD1dTg mice. A similar mechanism could be extended to humans as CD1d expression is upregulated on activated human T cells and increased presence of CD1d-expressing T cells was observed in autoimmune hepatitis patients. Our data reveals enhanced crosstalk between type II NKT cells and conventional T cells, leading to a T h 1-skewed inflammatory milieu, and consequently, to the development of chronic autoimmune liver disease. Lay summary: CD1d overexpression on T cells enhances crosstalk between type II NKT cells and T cells, resulting in their aberrant activation and leading to the

  19. Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

    Science.gov (United States)

    Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

    2016-10-01

    We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

  20. Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

    Science.gov (United States)

    Nagasaka, Misako; Gadgeel, Shirish M

    2018-01-01

    Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

  1. Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hofman, Michael S. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)]|[Southern Health, Nuclear Medicine, Melbourne (Australia); Smeeton, Nigel C. [King' s College London, Division of Health and Social Care Research, London (United Kingdom); Rankin, Sheila C.; Nunan, Tom; O' Doherty, Michael J. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)

    2009-02-15

    Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of {sup 18}F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa ({kappa}) was used to compare ratings from two categories and weighted kappa ({kappa}{sub w}) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement ({kappa} = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver {kappa}{sub w} = 0.79, 0.91; interobserver {kappa}{sub w} = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease ({kappa} = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial ({kappa}{sub w} = 0.71-0.88), but lower for hilar nodes (10; {kappa}{sub w} = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; {kappa}{sub w} = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. (orig.)

  2. Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Hofman, Michael S.; Smeeton, Nigel C.; Rankin, Sheila C.; Nunan, Tom; O'Doherty, Michael J.

    2009-01-01

    Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of 18 F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (κ) was used to compare ratings from two categories and weighted kappa (κ w ) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (κ = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver κ w = 0.79, 0.91; interobserver κ w = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (κ = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (κ w = 0.71-0.88), but lower for hilar nodes (10; κ w = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; κ w = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. (orig.)

  3. Retrofit designs for small bench-type blood cell counters.

    Science.gov (United States)

    Ferris, C D

    1991-01-01

    This paper describes several retrofit designs to correct operational problems associated with small bench-type blood cell counters. Replacement electronic circuits as well as modifications to the vacuum systems are discussed.

  4. Mid-infrared spectroscopy in skin cancer cell type identification

    Science.gov (United States)

    Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

    2017-07-01

    Mid infrared spectroscopy samples were developed for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin cancer diagnostics.

  5. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.

    2016-09-01

    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  6. Extra gonadal germ cell tumors. Clinico pathologic findings, staging and treatment experience in 14 patients

    Energy Technology Data Exchange (ETDEWEB)

    Berkmen, F.; Peker, F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara, Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy (Turkey)

    2000-09-01

    Extra gonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. The modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

  7. Extragonadal germ cell tumors. Clinicaopathologic findings, staging and treatment experience in 14 patients

    Energy Technology Data Exchange (ETDEWEB)

    Berkmen, F.; Peker, A.F.; Ayyildiz, A.; Basay, S.; Arik, A.I.; Ugur, I. [Ankara Oncology Education and Research Hospital, Dept. of Urologic Oncology and Radiotherapy, Ankara (Turkey)

    2000-09-01

    Extragonadal germ cell tumors (EGCT) are a rare group of neoplasms histologically identical to testicular counterparts. Fourteen cases of primary mediastinal and retroperitoneal germ cell tumors were treated with chemotherapy and radiotherapy between 1987 and 1999 in Ankara Oncology Hospital. There were 9 (64%) complete remissions (CR), one (7%) partial remission (PR) and 2 (14%) stable diseases (SD). The remaining 2 patients were lost due to dissemination of disease. The median duration of response was 19 months. Our modified chemotherapeutic results were similar to original doses of PVB and BEP but toxicity was less. The necessity of a uniform staging system and treatment programs are discussed.

  8. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.

    Directory of Open Access Journals (Sweden)

    Lei Shong Lau

    2014-05-01

    Full Text Available To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

  9. β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

    Science.gov (United States)

    Sui, Lina; Danzl, Nichole; Campbell, Sean R; Viola, Ryan; Williams, Damian; Xing, Yuan; Wang, Yong; Phillips, Neil; Poffenberger, Greg; Johannesson, Bjarki; Oberholzer, Jose; Powers, Alvin C; Leibel, Rudolph L; Chen, Xiaojuan; Sykes, Megan; Egli, Dieter

    2018-01-01

    β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These β-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-β-cells maintain normal blood glucose levels after ablation of the mouse endogenous β-cells. Cystic structures, but no teratomas, were observed in NT-ES-β-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in β-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-β-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy. © 2017 by the American Diabetes Association.

  10. Stage-specific effects of FGF2 on the differentiation of dental pulp cells

    Science.gov (United States)

    Sagomonyants, Karen; Mina, Mina

    2015-01-01

    Dentinogenesis is a complex and multistep process, which is regulated by various growth factors, including members of the Fibroblast Growth Factor (FGF) family. Both positive and negative effects of FGFs on dentinogenesis have been reported but the underlying mechanisms of these conflicting results are still unclear. To gain better insight into the role of FGF2 in dentinogenesis, we used dental pulp cells from various transgenic mice, in which fluorescent protein expression identifies cells at different stages of odontoblast differentiation. Our results showed that continuous exposure of pulp cells to FGF2 inhibited mineralization and revealed both stimulatory and inhibitory effects of FGF2 on expression of markers of dentinogenesis and various transgenes. During the proliferation phase of in vitro growth FGF2 increased expression of markers of dentinogenesis and the percentages of DMP1-GFP+ functional odontoblasts and DSPP-Cerulean+ odontoblasts. Additional exposure to FGF2 during the differentiation/mineralization phase of in vitro growth decreased the extent of mineralization, expression of markers of dentinogenesis, and expression of DMP1-GFP and DSPP-Cerulean transgenes. Recovery experiments showed that the inhibitory effects of FGF2 on dentinogenesis were related to the blocking of differentiation of cells into mature odontoblasts. These observations together showed stage-specific effects of FGF2 on dentinogenesis by dental pulp cells and provide critical information for the development of improved treatments for vital pulp therapy and dentin regeneration. PMID:25823776

  11. Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients

    DEFF Research Database (Denmark)

    Obara, Elisabeth Anne; Hannibal, Jens; Heegaard, Steffen

    2016-01-01

    Purpose: Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim...... of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma. Methods: Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital...... difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts...

  12. Sarcopenia is a novel poor prognostic factor in male patients with pathological Stage I non-small cell lung cancer.

    Science.gov (United States)

    Tsukioka, Takuma; Nishiyama, Noritoshi; Izumi, Nobuhiro; Mizuguchi, Shinjiro; Komatsu, Hiroaki; Okada, Satoshi; Toda, Michihito; Hara, Kantaro; Ito, Ryuichi; Shibata, Toshihiko

    2017-04-01

    Sarcopenia is the progressive loss of muscle mass and strength, and has a risk of adverse outcomes such as disability, poor quality of life and death. As prognosis depends not only on disease aggressiveness, but also on a patient's physical condition, sarcopenia can predict survival in patients with various cancer types. However, its effects on postoperative prognosis in patients with localized non-small cell lung cancers (NSCLC) have never been reported. We retrospectively investigated 215 male patients with pathological Stage I NSCLC. L3 muscle index is defined as the cross-section area of muscle at the third lumbar vertebra level, normalized for height, and is a clinical measurement of sarcopenia. We then investigated the effect of preoperative sarcopenia on their postoperative prognosis. Our 215 subjects included 30 patients with sarcopenia. Sarcopenia was significantly associated with body mass index, nutritional condition, serum CYFRA 21-1 level and pathological stage, but not with preoperative respiratory function or performance status. Frequency of postoperative complications, length of postoperative hospital stay, thoracic drainage period or causes of death were not correlated with the presence of sarcopenia. The sarcopenia group had a significantly shorter median overall survival (32 months) than the no-sarcopenia group. Sarcopenia might not affect short-term outcomes in patients with early-stage lung cancer. Sarcopenia was a predictor of poor prognosis in male patients with Stage I NSCLC. As sarcopenic patients with NSCLC patients are at risk for significantly worse outcomes, their treatments require careful planning, even for those with Stage I disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Single Stage Reconstruction of Type IIA Defect of the Ear Lobule ...

    African Journals Online (AJOL)

    its loss causes an obvious aesthetic abnormality.[3,4]. There are key ... The aesthetic results are generally well acceptable and there is a good color match between the neolobule and the surrounding skin. Key words: Ear lobule, Limberg flap, reconstruction, ... burden on the patient from a two‑stage procedure, an unnatural ...

  14. [Functional properties of taste bud cells. Mechanisms of afferent neurotransmission in Type II taste receptor cells].

    Science.gov (United States)

    Romanov, R A

    2013-01-01

    Taste Bud cells are heterogeneous in their morphology and functionality. These cells are responsible for sensing a wide variety of substances and for associating detected compounds with a different taste: bitter, sweet, salty, sour and umami. Today we know that each of the five basic tastes corresponds to distinct cell populations organized into three basic morpho-functional cell types. In addition, some receptor cells of the taste bud demonstrate glia-related functions. In this article we expand on some properties of these three morphological receptor cell types. Main focus is devoted to the Type II cells and unusual mechanism for afferent neurotransmission in these cells. Taste cells of the Type II consist of three populations detecting bitter, sweet and umami tastes, and, thus, evoke a serious scientific interest.

  15. Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

    Science.gov (United States)

    Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

    2017-07-15

    The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. CT staging of renal cell carcinoma using the revised 1997 TNM staging criteria: in comparison with the previous one

    International Nuclear Information System (INIS)

    Sung, Deuk Jae; Kim, Yun Hwan; Chung, Hwan Hoon; Chung, Kyoo Byung; Suh, Won Hyuck

    2001-01-01

    To assess the accuracy of preoperative CT staging of RCC and to compare the relationship between T stage and the incidence of metastasis on the basis of the old (1992) and the new (1997) UICC and AJCC tumor classification system. In 112 cases of surgically resected RCC, the stagings of preoperative CT scans were determined retrospectively by two radiologists and were compared with the results of pathologic examinations. In 70 cases which had been followed up over three years after surgery, the incidence of metastasis at initial diagnosis and during the follow-up period was assessed. All cases were reconsidered, and using the old and the new TNM classification, the incidence of metastasis was compared. According to the old TNM classification, 5 cases (4%) were staged at T1, 73(65%) at T2, 21(19%) at T3a, 9(8%) at T3b, 0 at T3c, and 4(4%) at T4. Using the new TNM classification, we also staged 54 cases (48%) at T1 and 24(21%) at T2. Overall, using this new classification, CT correctly staged 79% of patients (88/112) overstaged 15%(17/112) and understaged 6%(7/112). CT had a sensitivity of 84% and specificity of 91% in new T1 tumors, 71% and 95%, respectively, in new T2 tumors, 69% and 88% in T3a tumors, 78% and 98% in T3b tumors, and 75% and 99% in T4 tumors. CT had a sensitivity of 44% and a specificity of 99% in old T1 tumors, and 82% and 71%, respectively, in old T2 tumors. The incidence of metastasis in CT-staged (cT) tumors was 0% (0/4) in old cT1, 8% (3/39) in new cT1, 29% (4/14) in new cT2, 67% (6/9) in cT3a, and 75% (6/8) in cT3b. In the staging of T1 tumors, CT is more sensitive when the new TNM classification is used. Even though the cut off point between T1 and T2 tumors had been in creased from 2.5 to 7.0 cm, T1 tumors staged according to the new system did not show a significantly higher incidence of metastasis than those staged according to the old

  17. Identification of growth stage molecular markers in Trichoderma sp. 'atroviride type B' and their potential application in monitoring fungal growth and development in soil.

    Science.gov (United States)

    Mendoza-Mendoza, Artemio; Steyaert, Johanna; Nieto-Jacobo, Maria Fernanda; Holyoake, Andrew; Braithwaite, Mark; Stewart, Alison

    2015-11-01

    Several members of the genus Trichoderma are biocontrol agents of soil-borne fungal plant pathogens. The effectiveness of biocontrol agents depends heavily on how they perform in the complex field environment. Therefore, the ability to monitor and track Trichoderma within the environment is essential to understanding biocontrol efficacy. The objectives of this work were to: (a) identify key genes involved in Trichoderma sp. 'atroviride type B' morphogenesis; (b) develop a robust RNA isolation method from soil; and (c) develop molecular marker assays for characterizing morphogenesis whilst in the soil environment. Four cDNA libraries corresponding to conidia, germination, vegetative growth and conidiogenesis were created, and the genes identified by sequencing. Stage specificity of the different genes was confirmed by either Northern blot or quantitative reverse-transcriptase PCR (qRT-PCR) analysis using RNA from the four stages. con10, a conidial-specific gene, was observed in conidia, as well as one gene also involved in subsequent stages of germination (L-lactate/malate dehydrogenase encoding gene). The germination stage revealed high expression rates of genes involved in amino acid and protein biosynthesis, while in the vegetative-growth stage, genes involved in differentiation, including the mitogen-activated protein kinase kinase similar to Kpp7 from Ustilago maydis and the orthologue to stuA from Aspergillus nidulans, were preferentially expressed. Genes involved in cell-wall synthesis were expressed during conidiogenesis. We standardized total RNA isolation from Trichoderma sp. 'atroviride type B' growing in soil and then examined the expression profiles of selected genes using qRT-PCR. The results suggested that the relative expression patterns were cyclic and not accumulative.

  18. The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

    Science.gov (United States)

    Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

    2014-12-01

    To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

  19. Ultraprecision XY stage using a hybrid bolt-clamped Langevin-type ultrasonic linear motor for continuous motion.

    Science.gov (United States)

    Lee, Dong-Jin; Lee, Sun-Kyu

    2015-01-01

    This paper presents a design and control system for an XY stage driven by an ultrasonic linear motor. In this study, a hybrid bolt-clamped Langevin-type ultrasonic linear motor was manufactured and then operated at the resonance frequency of the third longitudinal and the sixth lateral modes. These two modes were matched through the preload adjustment and precisely tuned by the frequency matching method based on the impedance matching method with consideration of the different moving weights. The XY stage was evaluated in terms of position and circular motion. To achieve both fine and stable motion, the controller consisted of a nominal characteristics trajectory following (NCTF) control for continuous motion, dead zone compensation, and a switching controller based on the different NCTFs for the macro- and micro-dynamics regimes. The experimental results showed that the developed stage enables positioning and continuous motion with nanometer-level accuracy.

  20. Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

    Directory of Open Access Journals (Sweden)

    Jan Krivanek

    2017-06-01

    Full Text Available Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

  1. Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    McClusky, L M

    2005-01-01

    To understand the processes involved in the spatial and temporal maturation of testicular cells in Squalus acanthias, we used standard morphometry, proliferating-cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) immunohistochemistry. Except for immature spermatocysts (germinal zone, GZ; early-stage pre-meiotic, E-PrM), the number of cysts in all subsequent stages and the total number of cysts in the spermatogenic progression varied seasonally. The spermatogenic cycle spans about 2 years and is interrupted by germcell clone deletion via apoptosis at the mitosis-meiosis transition in April/May, manifesting as a zone of degeneration (ZD). Rate of displacement of the ZD across the testis diameter indicates that late-stage premeiotic (L-PrM) generations 12-13 require 9-10 months to reach the mature-spermatid stage. Also, the number of cysts completing spermatogenesis is approximately 4-5-fold less than the number that entered spermatogenesis proper 2 years earlier. Pronounced gonocytogenesis in the germinal ridge was coincident with ZD formation in April/May, but it was absent in the fall when mature spermatogonial and meiotic activities had resumed. Whereas strong Sertoli cell PCNA immunoreactivity dominated the GZ cyst cell-cycle activities throughout the year, except during the spring/summer months, the spermatogonial- and Sertoli-cell PCNA indices in E-PrM cysts were inversely related. PCNA immunoreactivity in spermatocytes was seasonal and dependent on the stage of meiosis. TUNEL labelling was limited to spermatogonia and increased stage-dependently in the PrM region (L-PrM = mid-stage PrM >E-PrM >GZ), correlating with ZD formation, in a season-dependent manner. Results imply that effects of normal regulatory factors in Squalus are stage- and process-specific.

  2. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

  3. Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

    Science.gov (United States)

    Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

    2016-05-01

    Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. © 2015 UICC.

  4. Cerebral blood flow imaging in staging of dementia of Alzheimer type. A study using statistical parametric mapping (SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Kawahata, Nobuya; Daitoh, Nobuyuki; Gotoh, Chiharu; Yokoyama, Sakura [Narita Memorial Hospital, Toyohashi, Aichi (Japan)

    2001-10-01

    One hundred twenty-two patients with dementia of Alzheimer type (DAT) were selected from consecutive referrals to the Memory Clinic at Narita Memorial Hospital. All fulfilled the NINCDS-ADRDA diagnostic criteria for probable Alzheimer's disease. Patients with DAT were subdivided on the results of their score on the Japanese version of Alzheimer's Disease Assessment Scale (ADAS-J cog.), into mild (score lower than or equal to 15, n=47), moderate (score 16 to 35, n=63), and severe (score greater than or equal to 36, n=12) groups. Seventy age-matched controls who had no signs or symptoms of dementia were recruited from the Memory Clinic. The reconstructed {sup 123}I-IMP-SPECT data were analyzed using a statistical parametric mapping technique. In mild stage of DAT, SPM analysis demonstrated that bilateral posterior parietal lobes, superior occipital lobes, and posterior cingulated gyri were significantly decreased in CBF as compared with the normal controls. In moderate stage of DAT, extension of the hypoperfusion to the frontal lobes was detected as compared with the mild stage of DAT. In severe stage of DAT, SPM image showed the diffuse hypoperfusion in bilateral hemispheres. The frequency of hypoperfusions in the DAT group was observed with the following: 15.0% in the mild stage, 34.9% in the moderate stage, and 66.7% in the severe stage. Our results indicate that the frequency and progression of the hypoperfusion in the temporoparietal regions and/or the other regions in DAT is related to the severity of the dementia. (author)

  5. Cerebral blood flow imaging in staging of dementia of Alzheimer type. A study using statistical parametric mapping (SPM)

    International Nuclear Information System (INIS)

    Kawahata, Nobuya; Daitoh, Nobuyuki; Gotoh, Chiharu; Yokoyama, Sakura

    2001-01-01

    One hundred twenty-two patients with dementia of Alzheimer type (DAT) were selected from consecutive referrals to the Memory Clinic at Narita Memorial Hospital. All fulfilled the NINCDS-ADRDA diagnostic criteria for probable Alzheimer's disease. Patients with DAT were subdivided on the results of their score on the Japanese version of Alzheimer's Disease Assessment Scale (ADAS-J cog.), into mild (score lower than or equal to 15, n=47), moderate (score 16 to 35, n=63), and severe (score greater than or equal to 36, n=12) groups. Seventy age-matched controls who had no signs or symptoms of dementia were recruited from the Memory Clinic. The reconstructed 123 I-IMP-SPECT data were analyzed using a statistical parametric mapping technique. In mild stage of DAT, SPM analysis demonstrated that bilateral posterior parietal lobes, superior occipital lobes, and posterior cingulated gyri were significantly decreased in CBF as compared with the normal controls. In moderate stage of DAT, extension of the hypoperfusion to the frontal lobes was detected as compared with the mild stage of DAT. In severe stage of DAT, SPM image showed the diffuse hypoperfusion in bilateral hemispheres. The frequency of hypoperfusions in the DAT group was observed with the following: 15.0% in the mild stage, 34.9% in the moderate stage, and 66.7% in the severe stage. Our results indicate that the frequency and progression of the hypoperfusion in the temporoparietal regions and/or the other regions in DAT is related to the severity of the dementia. (author)

  6. Detection of EGFR mutations with mutation-specific antibodies in stage IV non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Viteri Santiago

    2010-12-01

    Full Text Available Abstract Background Immunohistochemistry (IHC with mutation-specific antibodies may be an ancillary method of detecting EGFR mutations in lung cancer patients. Methods EGFR mutation status was analyzed by DNA assays, and compared with IHC results in five non-small-cell lung cancer (NSCLC cell lines and tumor samples from 78 stage IV NSCLC patients. Results IHC correctly identified del 19 in the H1650 and PC9 cell lines, L858R in H1975, and wild-type EGFR in H460 and A549, as well as wild-type EGFR in tumor samples from 22 patients. IHC with the mAb against EGFR with del 19 was highly positive for the protein in all 17 patients with a 15-bp (ELREA deletion in exon 19, whereas in patients with other deletions, IHC was weakly positive in 3 cases and negative in 9 cases. IHC with the mAb against the L858R mutation showed high positivity for the protein in 25/27 (93% patients with exon 21 EGFR mutations (all with L858R but did not identify the L861Q mutation in the remaining two patients. Conclusions IHC with mutation-specific mAbs against EGFR is a promising method for detecting EGFR mutations in NSCLC patients. However these mAbs should be validated with additional studies to clarify their possible role in routine clinical practice for screening EGFR mutations in NSCLC patients.

  7. Comparison between surgery and radiofrequency ablation for stage I non-small cell lung cancer

    International Nuclear Information System (INIS)

    Kim, So Ri; Han, Hyo Jin; Park, Seoung Ju; Min, Kyung Hoon; Lee, Min Hee; Chung, Chi Ryang; Kim, Min Ho; Jin, Gong Yong; Lee, Yong Chul

    2012-01-01

    Surgical resection remains as the treatment of choice for non-small cell lung cancer (NSCLC) and provides the best opportunity for cure and long-term survival. Minimally invasive percutaneous ablative therapies, such as radiofrequency ablation (RFA) for treating lung cancers, are currently being studied as treatment alternatives. But, to date, there is little information on comparison of therapeutic effects between surgery and RFA in patients with early stage lung malignancy. We aimed to investigate the clinical significance of RFA as an alternative curative modality for the early stage lung cancer through analyzing the long-term mortality of both treatment groups; surgery vs. RFA. Twenty-two patients of stage I NSCLC were included for this comparative analysis. To minimize confounding effects, we conducted a matching process. In which patients of RFA group (n = 8) were matched with patients of surgery group (n = 14) on the following variables; gender, age (±3 years), tumor node metastasis stage, and calendar year of surgery or RFA (±2 years). The mean survival duration of RFA group and surgery group were 33.18 ± 7.90 and 45.49 ± 7.21, respectively (months, p = 0.297). Log-rank analysis showed that there was no significant difference in overall survival (p = 0.054) between two groups. These results have shown that RFA can offer the survival comparable to that by surgery to stage I NSCLC patients, especially to the patients impossible for the surgery. This study provides an evidence for the use of RFA as a treatment alternative with low procedural morbidity for inoperable early-stage NSCLC patients.

  8. Chemical and functional properties of cell wall polymers from two cherry varieties at two developmental stages.

    Science.gov (United States)

    Basanta, María F; de Escalada Plá, Marina F; Stortz, Carlos A; Rojas, Ana M

    2013-01-30

    The cell wall polysaccharides of Regina and Sunburst cherry varieties at two developmental stages were extracted sequentially, and their changes in monosaccharide composition and functional properties were studied. The loosely-attached pectins presented a lower d-galacturonic acid/rhamnose ratio than ionically-bound pectins, as well as lower thickening effects of their respective 2% aqueous solution: the lowest Newtonian viscosity and shear rate dependence during the pseudoplastic phase. The main constituents of the cell wall matrix were covalently bound pectins (probably through diferulate cross-linkings), with long arabinan side chains at the RG-I cores. This pectin domain was also anchored into the XG-cellulose elastic network. Ripening occurred with a decrease in the proportion of HGs, water extractable GGM and xylogalacturonan, and with a concomitant increase in neutral sugars. Ripening was also associated with higher viscosities and thickening effects, and to larger distribution of molecular weights. The highest firmness and compactness of Regina cherry may be associated with its higher proportion of calcium-bound HGs localized in the middle lamellae of cell walls, as well as to some higher molar proportion of NS (Rha and Ara) in covalently bound pectins. These pectins showed significantly better hydration properties than hemicellulose and cellulose network. Chemical composition and functional properties of cell wall polymers were dependent on cherry variety and ripening stage, and helped explain the contrasting firmness of Regina and Sunburst varieties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. The Dynamics of an Impulsive Predator-Prey System with Stage Structure and Holling Type III Functional Response

    Directory of Open Access Journals (Sweden)

    Zhixiang Ju

    2015-01-01

    Full Text Available Based on the biological resource management of natural resources, a stage-structured predator-prey model with Holling type III functional response, birth pulse, and impulsive harvesting at different moments is proposed in this paper. By applying comparison theorem and some analysis techniques, the global attractivity of predator-extinction periodic solution and the permanence of this system are studied. At last, examples and numerical simulations are given to verify the validity of the main results.

  10. Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

    Science.gov (United States)

    Ko, Jennifer S; Prieto, Victor G; Elson, Paul J; Vilain, Ricardo E; Pulitzer, Melissa P; Scolyer, Richard A; Reynolds, Jordan P; Piliang, Melissa P; Ernstoff, Marc S; Gastman, Brian R; Billings, Steven D

    2016-02-01

    Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, PMerkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

  11. T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

    Science.gov (United States)

    Beausang, John F; Wheeler, Amanda J; Chan, Natalie H; Hanft, Violet R; Dirbas, Frederick M; Jeffrey, Stefanie S; Quake, Stephen R

    2017-11-28

    Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment. Copyright © 2017 the Author(s). Published by PNAS.

  12. Generation of multiple cell types in Bacillus subtilis.

    Science.gov (United States)

    Lopez, Daniel; Vlamakis, Hera; Kolter, Roberto

    2009-01-01

    Bacillus subtilis is a Gram-positive bacterium that is well known for its ability to differentiate into metabolically inactive spores that are highly resistant to environmental stresses. In fact, populations of genetically identical B. subtilis comprise numerous distinct cell types. In addition to spores, cells can become genetically competent, motile, produce extracellular matrix or degradative enzymes, or secrete toxins that allow them to cannibalize their neighbors. Many of the cell fates listed above appear to be mutually exclusive. In this review, we discuss how individual cells within a population control their gene expression to ensure that proper regulation of differentiation occurs. These different cell fates are regulated by an intricate network that relies primarily on the activity of three major transcriptional regulators: Spo0A, DegU, and ComK. While individual cells must choose distinct cell fates, the population as a whole exhibits a spectrum of phenotypes whose diversity may increase fitness.

  13. Time to Treatment in Patients With Stage III Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Wang Li; Correa, Candace R.; Hayman, James A.; Zhao Lujun; Cease, Kemp; Brenner, Dean; Arenberg, Doug; Curtis, Jeffery; Kalemkerian, Gregory P.; Kong, F.-M.

    2009-01-01

    Purpose: To determine whether time to treatment (TTT) has an effect on overall survival (OS) in patients with unresectable or medically inoperable Stage III non-small cell lung cancer (NSCLC) and whether patient or treatment factors are associated with TTT. Methods and Materials: Included in the study were 237 consecutive patients with Stage III NSCLC treated at University of Michigan Hospital (UM) or the Veterans Affairs Ann Arbor Healthcare System (VA). Patients were treated with either palliative or definitive radiotherapy and radiotherapy alone (n = 106) or either sequential (n = 69) or concurrent chemoradiation (n = 62). The primary endpoint was OS. Results: Median follow-up was 69 months, and median TTT was 57 days. On univariate analysis, the risk of death did not increase significantly with longer TTT (p = 0.093). However, subset analysis showed that there was a higher risk of death with longer TTT in patients who survived ≥ 5 years (p = 0.029). Younger age (p = 0.027), male sex (p = 0.013), lower Karnofsky Performance Score (KPS) (p = 0.002), and treatment at the VA (p = 0.001) were significantly associated with longer TTT. However, on multivariate analysis, only lower KPS remained significantly associated with longer TTT (p = 0.003). Conclusion: Time to treatment is significantly associated with OS in patients with Stage III NSCLC who lived longer than 5 years, although it is not a significant factor in Stage III patients as a whole. Lower KPS is associated with longer TTT.

  14. Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milisavljevic, Slobodan

    1997-01-01

    Purpose: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy. Methods and Materials: Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given. Results: The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity. Conclusion: The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC

  15. [Prognostic factors of advanced stage non-small-cell lung cancer].

    Science.gov (United States)

    Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

    2017-09-01

    Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

    Science.gov (United States)

    Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

    2017-08-01

    We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

  17. Postoperative Radiation Therapy in Resected N2 Stage Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lee, Chang Geol

    1993-01-01

    A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were 26.3%, 27.3% and median survival 23.5 months. The 5 year survival rates by T-stage were T1 66.7%, T2 25.6% and T3 12.5%. Loco-regional failure rate was 14.3% and distant metastasis rate was 42.9% and both 2.9%. Statistically significant factor affecting distant failure rate was number of positive lymph nodes(>= 4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis

  18. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Andrea J O'Hara

    2009-04-01

    Full Text Available MicroRNAs (miRNA have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS and (ii to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

  19. Advanced-Stage Primary Cutaneous T-Cell Lymphoma Treated with Bexarotene and Denileukin Diftitox

    Directory of Open Access Journals (Sweden)

    Iván Cervigón-González

    2011-02-01

    Full Text Available Advanced-stage primary cutaneous T-cell lymphoma has an unfavorable prognosis and low survival rates. Aggressive treatment with chemotherapy is not curative and causes considerable side effects. The combination of bexarotene and denileukin diftitox is associated with an acceptable safety profile and a likely synergistic effect because bexarotene is capable of modulating expression of IL-2 receptor and enhance the susceptibility of T-cell leukemia cells to denileukin diftitox. In the case reported here, the response to this combined treatment was satisfactory and well tolerated. The patient showed a complete regression of pruritus, restlessness, and insomnia. Skin lesions improved partially, and lymphadenopathy was reduced and finally disappeared completely.

  20. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  1. Cell type discovery using single-cell transcriptomics: implications for ontological representation.

    Science.gov (United States)

    Aevermann, Brian D; Novotny, Mark; Bakken, Trygve; Miller, Jeremy A; Diehl, Alexander D; Osumi-Sutherland, David; Lasken, Roger S; Lein, Ed S; Scheuermann, Richard H

    2018-05-01

    Cells are fundamental function units of multicellular organisms, with different cell types playing distinct physiological roles in the body. The recent advent of single-cell transcriptional profiling using RNA sequencing is producing 'big data', enabling the identification of novel human cell types at an unprecedented rate. In this review, we summarize recent work characterizing cell types in the human central nervous and immune systems using single-cell and single-nuclei RNA sequencing, and discuss the implications that these discoveries are having on the representation of cell types in the reference Cell Ontology (CL). We propose a method, based on random forest machine learning, for identifying sets of necessary and sufficient marker genes, which can be used to assemble consistent and reproducible cell type definitions for incorporation into the CL. The representation of defined cell type classes and their relationships in the CL using this strategy will make the cell type classes being identified by high-throughput/high-content technologies findable, accessible, interoperable and reusable (FAIR), allowing the CL to serve as a reference knowledgebase of information about the role that distinct cellular phenotypes play in human health and disease.

  2. Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions.

    Science.gov (United States)

    Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

    2013-12-01

    Determine correlation between complications and stage of the disease and their impact on quality of life in patients with different types of ileal urinary derivation after radical cystectomy, and upon estimation of acquired results, to suggest the most acceptable type of urinary diversion. In five year period a prospective clinical study was performed on 106 patients, to whom a radical cystectomy was performed due to bladder cancer. Patients were divided into two groups, 66 patients with ileal conduit derivation and 40 patients with orthotopic derivation, whereby in each group a comparison between reflux and anti-reflux technique of orthotopic bladder was made. All patients from both groups filled the Sickness Impact Profile score six months after the operation. All patients had CT urography or Intravenous urography performed, as well as standard laboratory, vitamin B12 blood values, in order to evaluate early (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic bladder, urine extravazation) and late complications (VUR, urethral stricture, ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of vitamin B12, increased resorption of bone calcium, urinary infection, kidney damage, relapse of primary disease), so as disease stage and it's impact on quality of life. From gained results we observe that each category of SIP score correlates with different rate of correlation with the type of operation, group, T, N, and R grade, except work category. Average value of SIP score rises depending on the type of operation and T stage. It is notable that there is no difference in T1 stage, no matter the type of operation. So the average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2 stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8. Average value of SIP score in T3 stage for conduit was 38.03, for Abol

  3. Natural history of β-cell adaptation and failure in type 2 diabetes

    Science.gov (United States)

    Alejandro, Emilyn U.; Gregg, Brigid; Blandino-Rosano, Manuel; Cras-Méneur, Corentin; Bernal-Mizrachi, Ernesto

    2014-01-01

    Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure. PMID:25542976

  4. PPARgamma in immunity and inflammation: cell types and diseases.

    Science.gov (United States)

    Széles, Lajos; Töröcsik, Dániel; Nagy, László

    2007-08-01

    The lipid activated transcription factor, PPARgamma appears to have multiple functions in the immune system. There are several cell types expressing the receptor, most prominently antigen presenting cells, such as macrophages and dendritic cells. The receptor's activation leads to primary transcriptional activation of many, mostly lipid metabolism-related genes. However, gene regulation also occurs on immunity and inflammation-related genes. Key questions are: in what way lipid metabolism and immune regulation are connected and how activation and/or repression of gene expression may modulate inflammatory and anti-inflammatory responses and in what way can these be utilized in therapy. Here we provide a cell type and disease centric review on the role of this lipid activated transcription factor in the various cells of the immune system it is expressed in, and in some major inflammatory diseases such as atherosclerosis, inflammatory bowel disease and rheumatoid arthritis.

  5. The drama of the continuous increase in end-stage renal failure in patients with type II diabetes mellitus.

    Science.gov (United States)

    Rychlík, I; Miltenberger-Miltenyi, G; Ritz, E

    1998-01-01

    Type II diabetes mellitus has become the leading cause of end-stage renal failure in many countries of Western Europe. In all European countries, even in those with a relatively low prevalence of diabetic nephropathy, the number of patients with type II diabetes mellitus admitted for renal replacement therapy has recently increased continuously. Survival and medical rehabilitation of patients with type II diabetes on renal replacement therapy is significantly worse than in non-diabetic patients. It is obvious that in order to stem the tide, intense efforts are necessary (i) to inform the medical community about the renal risk of type II diabetes and the striking effectiveness of preventive measures, (ii) to provide better care for diabetic patients, and (iii) to reduce the high prevalence of diabetes in the population by modification of the Western life style.

  6. Mash1-expressing cells could differentiate to type III cells in adult mouse taste buds.

    Science.gov (United States)

    Takagi, Hiroki; Seta, Yuji; Kataoka, Shinji; Nakatomi, Mitsushiro; Toyono, Takashi; Kawamoto, Tatsuo

    2018-03-10

    The gustatory cells in taste buds have been identified as paraneuronal; they possess characteristics of both neuronal and epithelial cells. Like neurons, they form synapses, store and release transmitters, and are capable of generating an action potential. Like epithelial cells, taste cells have a limited life span and are regularly replaced throughout life. However, little is known about the molecular mechanisms that regulate taste cell genesis and differentiation. In the present study, to begin to understand these mechanisms, we investigated the role of Mash1-positive cells in regulating adult taste bud cell differentiation through the loss of Mash1-positive cells using the Cre-loxP system. We found that the cells expressing type III cell markers-aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase 4 (CA4), glutamate decarboxylase 67 (GAD67), neural cell adhesion molecule (NCAM), and synaptosomal-associated protein 25 (SNAP25)-were significantly reduced in the circumvallate taste buds after the administration of tamoxifen. However, gustducin and phospholipase C beta2 (PLC beta2)-markers of type II taste bud cells-were not significantly changed in the circumvallate taste buds after the administration of tamoxifen. These results suggest that Mash1-positive cells could be differentiated to type III cells, not type II cells in the taste buds.

  7. Relaxin affects cell organization and early and late stages of spermatogenesis in a coculture of rat testicular cells.

    Science.gov (United States)

    Pimenta, M T; Francisco, R A R; Silva, R P; Porto, C S; Lazari, M F M

    2015-07-01

    Relaxin and its receptor RXFP1 are co-expressed in Sertoli cells, and relaxin can stimulate proliferation of Sertoli cells. In this study, we investigated a role of relaxin in spermatogenesis, using a short-term culture of testicular cells of the rat that allowed differentiation of spermatogonia to spermatids. Sertoli, germ, and peritubular myoid cells were the predominant cell types in the culture. Sertoli and germ cells expressed RXFP1. Cultures were incubated without (control) or with 0.5% fetal bovine serum (FBS) or 100 ng/mL H2 relaxin (RLN) for 2 days. Cell organization, number, and differentiation were analyzed after 2 (D2), 5 (D5) or 8 (D8) days of culturing. Although the proportion of germ cells decayed from D2 to D5, the relative contribution of HC, 1C, 2C, and 4C germ cell populations remained constant in the control group during the whole culture. RLN did not affect the proportion of germ cell populations compared with control, but increased gene and/or protein expression of the undifferentiated and differentiated spermatogonia markers PLZF and c-KIT, and of the post-meiotic marker Odf2 in D5. RLN favored organization of cells in tubule-like structures, the arrangement of myoid cells around the tubules, arrangement of c-KIT-positive spermatogonia at the basal region of the tubules, and expression of the cell junction protein β-catenin close to the plasma membrane region. Knockdown of relaxin with small interfering RNA (siRNA) reduced expression of β-catenin at the cell junctions, and shifted its expression to the nucleus. We propose that relaxin may affect spermatogenesis by modulating spermatogonial self renewal and favoring cell contact. © 2015 American Society of Andrology and European Academy of Andrology.

  8. The effect of soy protein beverages on serum cell adhesion molecule concentrations in prehypertensive/stage 1 hypertensive individuals.

    Science.gov (United States)

    Dettmer, Michelle; Alekel, D Lee; Lasrado, Joanne A; Messina, Mark; Carriquiry, Alicia; Heiberger, Kevin; Stewart, Jeanne W; Franke, Warren

    2012-04-01

    Prehypertensive and hypertensive individuals are at increased risk of atherosclerotic cardiovascular disease (CVD), in part because hypertension contributes to endothelial dysfunction and increased cell adhesion molecule expression. Soy protein and isoflavones may favorably alter CVD risk factors, and hence the aim of this study was to determine whether intake of cow's milk compared with soy beverage prepared from whole soy bean (WSB) or soy protein isolate (SPI) would lower soluble cell adhesion molecule concentrations as a means of decreasing CVD risk. We enrolled healthy prehypertensive/stage 1 hypertensive men (n = 60; 18-63 years) and premenopausal women (n = 8; 20-48 years). Participants were randomized to 1 of 3 groups for 8 weeks: cow's milk (600 mL/d), SPI beverage (840 mL/d; 30.1 mg total isoflavones/d), or WSB beverage (840 mL/d; 91.4 mg total isoflavones/d). We measured soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and endothelial-leukocyte adhesion molecule-1 (E-selectin) concentrations at baseline and week 8. Soluble CAM concentrations were not altered by treatment and did not differ between prehypertensive and hypertensive participants. However, analysis of variance indicated a treatment × gender interaction (gender effect) for ICAM-1 (p = 0.0037) but not for E-selectin (p = 0.067) or VCAM-1 (p = 0.16). Men had higher concentrations of ICAM-1 and E-selectin, respectively, at baseline (p = 0.0071, p = 0.049) and week 8 (p = 0.0054, p = 0.038) than women did. Neither intake of cow's milk nor soy beverage for 8 weeks altered soluble CAM concentrations in prehypertensive/stage 1 hypertensive individuals, suggesting that neither type of beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals by way of improving circulating CAM concentrations.

  9. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  10. Substance P reduces apoptotic cell death possibly by modulating the immune response at the early stage after spinal cord injury.

    Science.gov (United States)

    Jiang, Mei Hua; Lim, Ji Eun; Chi, Guang Fan; Ahn, Woosung; Zhang, Mingzi; Chung, Eunkyung; Son, Youngsook

    2013-10-23

    Previously, we have reported that substance P (SP) enhanced functional recovery from spinal cord injury (SCI) possibly by the anti-inflammatory modulation associated with the induction of M2-type macrophages at the injured lesion. In this study, we explored the cytokine expression profiles and apoptotic cell death in the lesion site of the SCI after an immediate intravenous injection of SP. SP injection increased the levels of interleukin-4 (IL-4), IL-6, and IL-10 at day 1 after the SCI approximately by 2-, 9-, and 10-folds when compared with the control SCI, respectively. On the basis of double immunofluorescence staining with IL-10 and CD11b, activated macrophages or microglia expressing IL-10 appeared in the margin of the lesion site at day 1 only after the SP injection. This SP-mediated alteration in the lesion microenvironment was shown to be associated with the lower cell death of neuronal cells at day 1 and oligodendrocytes at day 5 by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which was also accompanied by a decrease in caspase-3 activation. These findings suggest that SP may reduce the inflammation-induced secondary cell death, possibly through immune modulation at an early stage after the SCI.

  11. Modern technology for the treatment of type 1 diabetes mellitus with end-stage renal failure

    OpenAIRE

    Julia Aleksandrovna Krupinova; Sergei Andreevich Martinov; Alexandra Mikhaylovna Glazunova; Evgeny Vladimirovich Tarasov

    2015-01-01

    This article describes the clinical case of a patient with early development of terminal complications of type 1 diabetes with chronic decompensated carbohydrate metabolism. For 1 year, the patient was treated with hemodialysis and she subsequently underwent successful kidney transplantation.

  12. Generation of male differentiated germ cells from various types of stem cells.

    Science.gov (United States)

    Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

    2014-06-01

    Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

  13. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  14. A Multi-stage Representation of Cell Proliferation as a Markov Process.

    Science.gov (United States)

    Yates, Christian A; Ford, Matthew J; Mort, Richard L

    2017-12-01

    The stochastic simulation algorithm commonly known as Gillespie's algorithm (originally derived for modelling well-mixed systems of chemical reactions) is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well-mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie's algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important (e.g. embryonic development, cancer formation) should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean.Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages, we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically as far as possible. We demonstrate the importance of employing the correct cell cycle time distribution by recapitulating the results from two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to the outcome of the models. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular

  15. Cell type-specific translational repression of Cyclin B during meiosis in males.

    Science.gov (United States)

    Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

    2015-10-01

    The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I. © 2015. Published by The Company of Biologists Ltd.

  16. A high parasite density environment induces transcriptional changes and cell death in Plasmodium falciparum blood stages.

    Science.gov (United States)

    Chou, Evelyn S; Abidi, Sabia Z; Teye, Marian; Leliwa-Sytek, Aleksandra; Rask, Thomas S; Cobbold, Simon A; Tonkin-Hill, Gerry Q; Subramaniam, Krishanthi S; Sexton, Anna E; Creek, Darren J; Daily, Johanna P; Duffy, Michael F; Day, Karen P

    2018-03-01

    Transient regulation of Plasmodium numbers below the density that induces fever has been observed in chronic malaria infections in humans. This species transcending control cannot be explained by immunity alone. Using an in vitro system we have observed density dependent regulation of malaria population size as a mechanism to possibly explain these in vivo observations. Specifically, Plasmodium falciparum blood stages from a high but not low-density environment exhibited unique phenotypic changes during the late trophozoite (LT) and schizont stages of the intraerythrocytic cycle. These included in order of appearance: failure of schizonts to mature and merozoites to replicate, apoptotic-like morphological changes including shrinking, loss of mitochondrial membrane potential, and blebbing with eventual release of aberrant parasites from infected erythrocytes. This unique death phenotype was triggered in a stage-specific manner by sensing of a high-density culture environment. Conditions of glucose starvation, nutrient depletion, and high lactate could not induce the phenotype. A high-density culture environment induced rapid global changes in the parasite transcriptome including differential expression of genes involved in cell remodeling, clonal antigenic variation, metabolism, and cell death pathways including an apoptosis-associated metacaspase gene. This transcriptional profile was also characterized by concomitant expression of asexual and sexual stage-specific genes. The data show strong evidence to support our hypothesis that density sensing exists in P. falciparum. They indicate that an apoptotic-like mechanism may play a role in P. falciparum density regulation, which, as in yeast, has features quite distinguishable from mammalian apoptosis. Gene expression data are available in the GEO databases under the accession number GSE91188. © 2017 Federation of European Biochemical Societies.

  17. The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

    Science.gov (United States)

    Ha, V L; Luong, A; Li, F; Casero, D; Malvar, J; Kim, Y M; Bhatia, R; Crooks, G M; Parekh, C

    2017-11-01

    The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

  18. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  19. The clinical results of stereotactic irradiation for stage IA non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Matsuura, Kanji; Kodama, Hisayuki; Murakami, Yuji; Kenjo, Masahiro; Kaneyasu, Yuko; Wadasaki, Koichi; Ito, Katsuhide; Kimura, Tomoki; Akagi, Yukio

    2006-01-01

    Discussed are the results in the title in authors' hospital. Subjects are 15 patients with the stage IA non-small cell lung cancer (10 males and 5 females; median age, 77 y; 11 cases of adenocarcinoma and 4 of squamous cell carcinoma), whose progress could be followed for 6 months or longer after the stereotactic irradiation during the period of July 1999 to 2006. The 8-9-gated irradiation therapy on the primary cancer alone was conducted with Varian Clinac 2300 (6MV-Xray) with the 3D planning equipment of PHILIPS Pinnacle. For some patients, the spirometer was used to monitor the voluntary breath-hold and body was fixed by vacuum fixer. Doses were 56 (4 Gy x 14) Gy in 3 cases, 60 (7.5 Gy x 8) Gy in 2, 50 (10 Gy x 5) Gy in 1 and 48 (12 Gy x 4) Gy in 9. Kaplan-Meier method was used for calculating the local control and survival rates. The former was 93% and the latter, 86% (1 year), 78% (2 y) and 39% (3 y). Three-year survival rate was 100% in 5 cases without other cancer and 18% in 10 with the cancers. Recurrence was seen in 3 cases and remote metastases, 7. Pneumonitis less than Grade 2 was in 11 cases. The stereotactic irradiation was thus found safe and effective in the stage IA non-small cell lung cancer. (T.I.)

  20. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

    Science.gov (United States)

    Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

    2017-09-15

    Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

    International Nuclear Information System (INIS)

    Furuta, Masaya; Hayakawa, Kazushige; Katano, Susumu

    1996-01-01

    Between 1976 and 1992, 32 patients aged 75 and older with stage I-II non-small cell lung cancer (NSCLC) were given definitive radiation therapy. These patients did not undergo surgery because of old age, poor cardiac/pulmonary condition, or refusal to give consent. The mean age was 79 years, and 11 patients were over 80 years old. The histologic type was squamous cell carcinoma in 25 patients and adenocarcinoma in 7. The clinical T and N stage was T1N0 in 4 patients, T2N0 in 9, and T2N0 in 19. The total dose of radiation therapy given to each patient exceeded 60 Gy using 10-MV X-rays. The treatment was completed in all 32 patients without treatment-related complications. The 2- and 5-year overall actuarial survival rates were 40% and 16%, respectively. Eleven intercurrent deaths occurred, including 7 patients who died of heart disease. The 2- and 5-year cause-specific survival rates were 57% and 36%, respectively. None of the patients developed severe pneumonitis requiring hospitalization. All but three patients received radiation therapy on an inpatient basis. The mean duration of the hospital stay for initial treatment was 56 days, and mean ratio to total survival period (mean 739 days) was 8%. Although many elderly patients have concurrent medical complications such as heart disease and chronic pulmonary disease, the present study showed that elderly patients with clinical stage I-II NSCLC can expert a realistic probability of long-term survival with definitive radiation therapy. (author)

  2. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  3. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  4. Cytokine-induced killer cells are type II natural killer T cells

    Directory of Open Access Journals (Sweden)

    Schmidt-Wolf, Ingo G.H.

    2007-09-01

    Full Text Available Background: Until now, cytokine-induced killer (CIK cells were assumed to be part of the type I natural killer T (NKT cell population, but it was not yet investigated if this is correct. Methods: For analysis, CIK cells were generated by various culture conditions. Human type I NKT cells express a T cell receptor (TCR composed of an invariant Vα24-JαQ chain combined with one of several Vβ chains. The Vα24 is a reliable marker for the presence of these TCRs. Results: While comparing cultures stimulated with different substances, we observed the lack of any Vα24 on the surface of CIK culture cells. Conclusion: We conclude that CIK cells do not belong to the type I NKT cells.

  5. Strain preservation of experimental animals: vitrification of two-cell stage embryos for multiple mouse strains.

    Science.gov (United States)

    Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu

    2015-04-01

    Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Gene expression profiling of dendritic cells in different physiological stages under Cordyceps sinensis treatment.

    Directory of Open Access Journals (Sweden)

    Chia-Yang Li

    Full Text Available Cordyceps sinensis (CS has been commonly used as herbal medicine and a health supplement in China for over two thousand years. Although previous studies have demonstrated that CS has benefits in immunoregulation and anti-inflammation, the precise mechanism by which CS affects immunomodulation is still unclear. In this study, we exploited duplicate sets of loop-design microarray experiments to examine two different batches of CS and analyze the effects of CS on dendritic cells (DCs, in different physiology stages: naïve stage and inflammatory stage. Immature DCs were treated with CS, lipopolysaccharide (LPS, or LPS plus CS (LPS/CS for two days, and the gene expression profiles were examined using cDNA microarrays. The results of two loop-design microarray experiments showed good intersection rates. The expression level of common genes found in both loop-design microarray experiments was consistent, and the correlation coefficients (Rs, were higher than 0.96. Through intersection analysis of microarray results, we identified 295 intersecting significantly differentially expressed (SDE genes of the three different treatments (CS, LPS, and LPS/CS, which participated mainly in the adjustment of immune response and the regulation of cell proliferation and death. Genes regulated uniquely by CS treatment were significantly involved in the regulation of focal adhesion pathway, ECM-receptor interaction pathway, and hematopoietic cell lineage pathway. Unique LPS regulated genes were significantly involved in the regulation of Toll-like receptor signaling pathway, systemic lupus erythematosus pathway, and complement and coagulation cascades pathway. Unique LPS/CS regulated genes were significantly involved in the regulation of oxidative phosphorylation pathway. These results could provide useful information in further study of the pharmacological mechanisms of CS. This study also demonstrates that with a rigorous experimental design, the biological effects

  7. Gene expression profiling of dendritic cells in different physiological stages under Cordyceps sinensis treatment.

    Science.gov (United States)

    Li, Chia-Yang; Chiang, Chi-Shiun; Cheng, Wei-Chung; Wang, Shu-Chi; Cheng, Hung-Tsu; Chen, Chaang-Ray; Shu, Wun-Yi; Tsai, Min-Lung; Hseu, Ruey-Shyang; Chang, Cheng-Wei; Huang, Chao-Ying; Fang, Shih-Hua; Hsu, Ian C

    2012-01-01

    Cordyceps sinensis (CS) has been commonly used as herbal medicine and a health supplement in China for over two thousand years. Although previous studies have demonstrated that CS has benefits in immunoregulation and anti-inflammation, the precise mechanism by which CS affects immunomodulation is still unclear. In this study, we exploited duplicate sets of loop-design microarray experiments to examine two different batches of CS and analyze the effects of CS on dendritic cells (DCs), in different physiology stages: naïve stage and inflammatory stage. Immature DCs were treated with CS, lipopolysaccharide (LPS), or LPS plus CS (LPS/CS) for two days, and the gene expression profiles were examined using cDNA microarrays. The results of two loop-design microarray experiments showed good intersection rates. The expression level of common genes found in both loop-design microarray experiments was consistent, and the correlation coefficients (Rs), were higher than 0.96. Through intersection analysis of microarray results, we identified 295 intersecting significantly differentially expressed (SDE) genes of the three different treatments (CS, LPS, and LPS/CS), which participated mainly in the adjustment of immune response and the regulation of cell proliferation and death. Genes regulated uniquely by CS treatment were significantly involved in the regulation of focal adhesion pathway, ECM-receptor interaction pathway, and hematopoietic cell lineage pathway. Unique LPS regulated genes were significantly involved in the regulation of Toll-like receptor signaling pathway, systemic lupus erythematosus pathway, and complement and coagulation cascades pathway. Unique LPS/CS regulated genes were significantly involved in the regulation of oxidative phosphorylation pathway. These results could provide useful information in further study of the pharmacological mechanisms of CS. This study also demonstrates that with a rigorous experimental design, the biological effects of a complex

  8. Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages.

    Directory of Open Access Journals (Sweden)

    Jingxian Zhao

    2014-08-01

    Full Text Available Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg and conventional CD4 T cells (M133 Tconv in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN. Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.

  9. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

    Science.gov (United States)

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

  10. 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....

  11. Dynamic modeling of a three-stage low-temperature ethanol reformer for fuel cell application

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Vanesa M; Serra, Maria [Institut de Robotica i Informatica Industrial (CSIC-UPC), Llorens i Artigas 4-6, 08028 Barcelona (Spain); Lopez, Eduardo; Llorca, Jordi [Institut de Tecniques Energetiques, Universitat Politecnica de Catalunya, Diagonal 647, ed. ETSEIB, 08028 Barcelona (Spain)

    2009-07-01

    A low-temperature ethanol reformer based on a cobalt catalyst for the production of hydrogen has been designed aiming the feed of a fuel cell for an autonomous low-scale power production unit. The reformer comprises three stages: ethanol dehydrogenation to acetaldehyde and hydrogen over SnO{sub 2} followed by acetaldehyde steam reforming over Co(Fe)/ZnO catalyst and water gas shift reaction. Kinetic data have been obtained under different experimental conditions and a dynamic model has been developed for a tubular reformer loaded with catalytic monoliths for the production of the hydrogen required to feed a 1 kW PEMFC. (author)

  12. CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

    Directory of Open Access Journals (Sweden)

    Diana Rosa Fernández Ruiz

    2017-02-01

    Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

  13. Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

    Science.gov (United States)

    Oya, Ryohei; Takenaka, Yukinori; Takemura, Kazuya; Ashida, Naoki; Shimizu, Kotaro; Kitamura, Takahiro; Yamamoto, Yoshifumi; Uno, Atsuhiko

    2017-10-01

    External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.

  14. Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death

    Directory of Open Access Journals (Sweden)

    Naira F. Z. Schneider

    2018-03-01

    Full Text Available Cardiac glycosides (CGs are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.

  15. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Science.gov (United States)

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  16. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. The repair of damage to DNA in different cell types

    International Nuclear Information System (INIS)

    Karran, P.

    1974-01-01

    DNA single strand breaks induced by either X-ray irradiation or by methyl methanesulphonate (MMS) were studied in different lymphoid cell populations directly taken from the animal and maintained in tissue culture merely for the duration of the experiment. The results obtained from these cell populations were compared with those obtained with L5178Y cells maintained in tissue culture. All cell types studied were found to possess at least one class of enzymes required for repair of DNA damage, namely those enzymes involved in the rejoining of X-ray induced by MMS is different in each cell type. Repair replication was at much reduced levels and the endonucleolytic degradation was at much reduced levels and the endonucleolytic degradation was initiated at lower MMS concentration in the lymphoid cells as compared to L5178Y cells. It is suggested that the overall ''repair capacity'' of a population may be related to the number of cells in a cycle which, moreover, might be the only ones to have the ability to repair damage to DNA induced by MMS (G.G.)

  18. [TNF-α, diabetes type 1 and regulatory T cells].

    Science.gov (United States)

    Ryba, Monika; Myśliwska, Jolanta

    2010-01-01

    Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

  19. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2016-01-01

    Full Text Available Background. Proangiogenic Hematopoietic Cells (PHC which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4±7.40 yo preimplant NT proBNP level is 5124.5±4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87±0.41, 0.63±0.66, 99.00±2.60, and 3.22±3.79%, respectively. LVEF was improved (22±5.68 versus 26.8±7.93, p<0.001 during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

  20. Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes and Stage 3 Nephropathy

    NARCIS (Netherlands)

    Yamout, Hala; Perkovic, Vlado; Davies, Melanie; Woo, Vincent; de Zeeuw, Dick; Mayer, Cristiana; Vijapurkar, Ujjwala; Kline, Irina; Usiskin, Keith; Meininger, Gary; Bakris, George

    2014-01-01

    Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of >= 45 ml/mm/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT(2)

  1. Type IIIb glycogen storage disease associated with end-stage cirrhosis and hepatocellular carcinoma

    NARCIS (Netherlands)

    Haagsma, EB; Smit, GPA; NiezenKoning, KE; Gouw, ASH; Meerman, L; Slooff, MJH

    Type III glycogen storage disease (GSD) is a disorder of carbohydrate metabolism caused by a deficiency of debranching enzyme. Different subtypes with different clinical pictures have been recognized. During childhood and early adulthood, the symptoms generally regress, and normal adulthood appears

  2. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    International Nuclear Information System (INIS)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2015-01-01

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells

  3. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  4. Diffuse-type giant cell tumor of the subcutaneous thigh

    International Nuclear Information System (INIS)

    Sanghvi, D.A.; Purandare, N.C.; Jambhekar, N.A.; Agarwal, A.; Agarwal, M.G.

    2007-01-01

    Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms. (orig.)

  5. Photoluminescence due to early stage of oxygen precipitation in multicrystalline Si for solar cells

    Science.gov (United States)

    Higuchi, Fumito; Tajima, Michio; Ogura, Atsushi

    2017-07-01

    To analyze the early stage of oxygen precipitation in n-type multicrytalline Si, the spectral change of photoluminescence (PL) induced by thermal treatment at 450-650 °C was investigated in relation to the changes in excess donor and interstitial oxygen concentrations. We observed the characteristic PL bands in the near-band-edge region and sharp lines in the deep-level region in correspondence with the generation of thermal donors and new donors. The observed PL spectral variation is essentially the same as that in Czochralski-grown Si annealed at 450-650 °C.

  6. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition.

    Science.gov (United States)

    Gervin, Kristina; Page, Christian Magnus; Aass, Hans Christian D; Jansen, Michelle A; Fjeldstad, Heidi Elisabeth; Andreassen, Bettina Kulle; Duijts, Liesbeth; van Meurs, Joyce B; van Zelm, Menno C; Jaddoe, Vincent W; Nordeng, Hedvig; Knudsen, Gunn Peggy; Magnus, Per; Nystad, Wenche; Staff, Anne Cathrine; Felix, Janine F; Lyle, Robert

    2016-09-01

    Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood. The aim of this study was to generate a reference data set from cord blood to enable correct adjustment of the cell type composition in samples collected at birth. The purity of the isolated cell types was very high for all samples (>97.1%), and clustering analyses showed distinct grouping of the cell types according to hematopoietic lineage. We explored whether this cord blood and the adult peripheral blood reference data sets impact the estimation of cell type composition in cord blood samples from an independent birth cohort (MoBa, n = 1092). This revealed significant differences for all cell types. Importantly, comparison of the cell type estimates against matched cell counts both in the cord blood reference samples (n = 11) and in another independent birth cohort (Generation R, n = 195), demonstrated moderate to high correlation of the data. This is the first cord blood reference data set with a comprehensive examination of the downstream application of the data through validation of estimated cell types against matched cell counts.

  7. Update on Merkel Cell Carcinoma: Epidemiology, Etiopathogenesis, Clinical Features, Diagnosis, and Staging.

    Science.gov (United States)

    Llombart, B; Requena, C; Cruz, J

    2017-03-01

    Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer

    OpenAIRE

    Azzoli, Christopher G.; Giaccone, Giuseppe; Temin, Sarah

    2010-01-01

    ASCO published a guideline on use of chemotherapy in advanced stage non–small-cell lung cancer in 1997. The latest update covers treatment with chemotherapy and biologic agents and reviews literature from 2002 to 2009.

  9. Renal cell carcinoma in India demonstrates early age of onset & a late stage of presentation

    Directory of Open Access Journals (Sweden)

    Shalini Agnihotri

    2014-01-01

    Full Text Available Background & objectives: Clinical spectrum of most of the diseases in developing countries is different from the west. Similarly whether renal cell carcinomas (RCC in a developing country like India is seen in the same spectrum in relation to the age at presentation as in the west is not described in the literature. This study was carried out to investigate the spectrum of RCC in India with regards to age of onset, stage at presentation and survival. Methods: Patients with renal tumour, treated between January 2000 to December 2012 in a tertiary care hospital in north India, were analyzed for age at presentation, clinical features and histopathological characteristics. Clinical diagnosis was made by contrast enhanced computerized tomography (CECT scans and/or magnetic resonance imaging (MRI. Renal masses diagnosed as angiomyolipoma, infective masses and hydatid cysts were excluded from the analysis. Impact of various age groups on gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph node, inferior vena cava (IVC involvement and survival was analyzed. Patients were grouped in five age groups i.e. ≤39, 40-49, 50-59, 60-69 and more than 70 yr of age. Results: Of the total 617 patients with 617 renal tumours (2 patients had bilateral tumours but only the larger tumour was considered clinically suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non epithelial cell tumour. The mean tumour size was 8.08±3.5 cm (median 7, range 1-25 cm. Tumour of less than 4 cm size was present in only 10.4 per cent patients. The mean age at diagnosis was 55.15±13.34 (median 56, range 14-91 yr years. A total of 30.03 per cent of renal tumours presented in patients younger than 50 yr of age. Though there was no difference in stage, Fuhrman′s grade, IVC involvement and lymph nodal spread among various age groups, younger patients had higher proportion of non clear cell RCC and only 48.59 per cent of them presented

  10. Many-Objective Particle Swarm Optimization Using Two-Stage Strategy and Parallel Cell Coordinate System.

    Science.gov (United States)

    Hu, Wang; Yen, Gary G; Luo, Guangchun

    2017-06-01

    It is a daunting challenge to balance the convergence and diversity of an approximate Pareto front in a many-objective optimization evolutionary algorithm. A novel algorithm, named many-objective particle swarm optimization with the two-stage strategy and parallel cell coordinate system (PCCS), is proposed in this paper to improve the comprehensive performance in terms of the convergence and diversity. In the proposed two-stage strategy, the convergence and diversity are separately emphasized at different stages by a single-objective optimizer and a many-objective optimizer, respectively. A PCCS is exploited to manage the diversity, such as maintaining a diverse archive, identifying the dominance resistant solutions, and selecting the diversified solutions. In addition, a leader group is used for selecting the global best solutions to balance the exploitation and exploration of a population. The experimental results illustrate that the proposed algorithm outperforms six chosen state-of-the-art designs in terms of the inverted generational distance and hypervolume over the DTLZ test suite.

  11. 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.

  12. A manufacturing quality assessment model based-on two stages interval type-2 fuzzy logic

    Science.gov (United States)

    Purnomo, Muhammad Ridwan Andi; Helmi Shintya Dewi, Intan

    2016-01-01

    This paper presents the development of an assessment models for manufacturing quality using Interval Type-2 Fuzzy Logic (IT2-FL). The proposed model is developed based on one of building block in sustainable supply chain management (SSCM), which is benefit of SCM, and focuses more on quality. The proposed model can be used to predict the quality level of production chain in a company. The quality of production will affect to the quality of product. Practically, quality of production is unique for every type of production system. Hence, experts opinion will play major role in developing the assessment model. The model will become more complicated when the data contains ambiguity and uncertainty. In this study, IT2-FL is used to model the ambiguity and uncertainty. A case study taken from a company in Yogyakarta shows that the proposed manufacturing quality assessment model can work well in determining the quality level of production.

  13. Cell kinetics and genetic instabilities in differentiated type early gastric cancers with different mucin phenotype.

    Science.gov (United States)

    Shibata, Naomi; Watari, Jiro; Fujiya, Mikihiro; Tanno, Satoshi; Saitoh, Yusuke; Kohgo, Yutaka

    2003-01-01

    To clarify the biological impact and molecular pathogenesis of cellular phenotype in differentiated-type gastric cancers (DGCs), we investigated cell kinetics and genetic instabilities in early stage of DGCs. A total of 43 early gastric cancers (EGCs) were studied. EGCs were divided into 3 phenotypic categories: gastric (G type, n = 11), ordinary (O type, n = 20), and complete intestinal (CI type, n = 12) based on the combination of HGM, ConA, MUC2, and CD10. Proliferative index (PI), apoptotic index (AI), and p53 overexpression were investigated by immunohistochemical staining with anti-Ki-67, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method, and p53 antibody, respectively. Using a high-resolution fluorescent microsatellite analysis system, microsatellite instability (MSI) and loss of heterozygosity (LOH) were examined. Frameshift mutation analysis of transforming growth factor-beta type II receptor (TGF-betaRII) and bcl-2-associated X (BAX) in cancers with MSI was also performed. The mean AI/PI ratio values were 0.04 for G-type, 0.10 for O-type, and 0.13 for CI-type cancers--significantly lower in G type than in O and CI types (P = 0.02 and P = 0.001, respectively). No difference in the incidence of MSI and LOH was seen among the 3 cellular phenotypes. However, the major pattern of MSI, which showed drastic and widely dispersed changes and is related to an increased risk for cancer, was significantly higher in G and O types than in CI type (P cancers. These results indicate that G-type cancers are likely to show more aggressive behaviors than CI-type cancers, and that O-type cancers show the intermediate characteristics of both types. However, the molecular pathogenesis of each phenotypic cancer is not associated with microsatellite alterations. Copyright 2003, Elsevier Science (USA). All rights reserved.

  14. Effect of informing the diagnosis on depressive state in patients with non-small cell lung cancer of stage

    OpenAIRE

    Wei WANG; Ping CHEN; Xianglin PI; Anlan WANG; Xiaoping WEN; Dong HUANG

    2008-01-01

    Background and objective As other tumors, unresectabe lung cancer can cause many psychological problems to the patients, such as depression and anxiety. The present paper aims to evaluate the status of depression before and after knowing the state of illness in patients with non-small cell lung cancer of stage Ⅲ. Methods 43 casesof newly diagnosed non-small cell lung cancer (NSCLC) with stage Ⅲ were enrolled in the study. All the patients were distributed into three groups and given different...

  15. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    -renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

  16. Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

    International Nuclear Information System (INIS)

    Al-Mueilo, Samir H.

    2005-01-01

    Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

  17. Radiotherapy alone for elderly patients with stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Nakano, Kikuo; Hiramoto, Takehiko; Kanehara, Masasi; Doi, Mihoko; Furonaka, Osamu; Miyazu, Yuka; Hada, Yosihiro

    1999-01-01

    We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p=0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients. (author)

  18. Study on the mechanism of retinal ganglion cell apoptosis in early stage of diabetic rats

    Directory of Open Access Journals (Sweden)

    Rui-Dong Gu

    2014-03-01

    Full Text Available AIM: To investigate the mechanism of retinal ganglion cell apoptosis in early stage of streptozotocin(STZ-induced diabetic rats. METHODS: Sixty SD rats were randomly divided into two groups: control group(CONand diabetes mellitus group(DM. Diabetic rat model was produced by intraperitoneal injection of 1% STZ in 30 adult male SD rats. At 4, 8, 12wk,the rats were killed and eyeballs were enucleated for the HE staining, TUNEL staining, transmission electron microscopy detection respectively, and laser confocal microscope detection was used to detect the calcium ion concentration.RESULTS:At 8wk RGCs decreased gradually and appeared disordered arrangement and got worse at 12wk in DM group. In DM group, mitochondrial swelling was detected at 4wk., and became more obvious, more in number at 8wk with reduction in some cells' volume and the number of organelles decreased. In DM group, few TUNEL positive RGCs were seen at 4wk, and became more and more at 8 and 12wk. The apoptosis index was significantly higher in DM group compared with CON group in different time points(PPPCONCLUSION: The study suggested that RGCs apoptosis occurs in early stage of diabetes, the mechanism might be associated with increased intracellular calcium ion concentration.

  19. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; von der Maase, Hans; Sørensen, Flemming Brandt

    2002-01-01

    ; group 1, 23 patients with recurrent stage Ta (non-invasive) tumors; group 2, 22 patients presenting at their first admission with T2-4 (muscle invasive) tumors; group 3, 24 patients who experienced disease progression from Ta or T1 (invasive in connective tissue) to a higher stage......PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors.METHODS: The tissue material consisted of bladder tumors from three groups of patients......(kip1) ( P=0.03), Rb ( P=0.00002), and L-myc ( P=0.00000007) in muscle invasive tumors compared to noninvasive tumors. Tumors presenting as muscle invasive at first diagnosis had significantly lower levels of p16/CDKN2A ( P=0.01) when compared to muscle invasive tumors that followed Ta or T1 precursor...

  20. Islet β cell failure in type 2 diabetes

    Science.gov (United States)

    Prentki, Marc; Nolan, Christopher J.

    2006-01-01

    The major focus of this Review is on the mechanisms of islet β cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of β cell compensation for insulin resistance, consideration is also given to the mechanisms involved in the compensation process, including mechanisms for expansion of β cell mass and for enhanced β cell performance. The importance of genetic, intrauterine, and environmental factors in the determination of “susceptible” islets and overall risk for T2D is reviewed. The likely mechanisms of β cell failure are discussed within the two broad categories: those with initiation and those with progression roles. PMID:16823478

  1. Stage Presentation, Care Patterns, and Treatment Outcomes for Squamous Cell Carcinoma of the Penis

    Energy Technology Data Exchange (ETDEWEB)

    Burt, Lindsay M.; Shrieve, Dennis C.; Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu

    2014-01-01

    Purpose: Penile squamous cell carcinoma (SCC) is a rare entity, with few published series on outcomes. We evaluated the stage distributions and outcomes for surgery and radiation therapy in a U.S. population database. Methods and Materials: Subjects with SCC of the penis were identified using the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program database between 1988 and 2006. Descriptive statistics were performed, and cause-specific survival (CSS) was estimated using Kaplan-Meier analysis. Comparisons of treatment modalities were analyzed using multivariate Cox regression. Subjects were staged using American Joint Committee on Cancer, sixth edition, criteria. Results: There were 2458 subjects identified. The median age was 66.8 years (range, 17-102 years). Grade 2 disease was present in 94.5% of cases. T1, T2, T3, T4, and Tx disease was present in 64.8%, 17.1%, 9.5%, 2.1%, and 6.5% of cases, respectively. N0, N1, N2, N3, and Nx disease was noted in 61.6%, 6.9%, 4.0%, 3.7%, and 23.8% of cases, respectively. M1 disease was noted in 2.5% of subjects. Individuals of white ethnicity accounted for 85.1% of cases. Lymphadenectomy was performed in 16.7% of cases. The CSS for all patients at 5 and 10 years was 80.8% and 78.6%. By multivariable analysis grades 2 and 3 disease, T3 stage, and positive lymph nodes were adverse prognostic factors for CSS. Conclusion: SCC of the penis often presents as early-stage T1, N0, M0, grade 1, or grade 2 disease. The majority of patients identified were treated with surgery, and only a small fraction of patients received radiation therapy alone or as adjuvant therapy.

  2. Concurrent chemoradiation therapy in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Kim, I. A.; Choi, I. B.; Kang, K. M.; Jang, J. Y.; Song, J. S.; Lee, S. H.; Kuak, M. S.; Shinn, K. S.

    1997-01-01

    This study was tried to evaluate the potential benefits of concurrent chemoradiation therapy. Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Complete response rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group. In subgroup analyses for patients with good performance status, CRT group showed significantly higher overall survival rate compared with RT group. The prognostic factors affecting survival rate were performance status and pathologic subtype in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a prognostic factors. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity ahd no significant differences in between CRT group and RT group (16% vs. 6%). The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%). In analyses for relationship of field size and pulmonary toxicity, the patients who treated with field size beyond 200 cm 2 had significantly higher rates of pulmonary toxicities. The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group. Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term

  3. Comparative immune phenotypic analysis of cutaneous Squamous Cell Carcinoma and Intraepidermal Carcinoma in immune-competent individuals: proportional representation of CD8+ T-cells but not FoxP3+ Regulatory T-cells is associated with disease stage.

    Directory of Open Access Journals (Sweden)

    Andrew Freeman

    Full Text Available Squamous Cell Carcinoma (SCC is a type of non-melanoma skin cancer prevalent in immune-suppressed transplant recipients and older individuals with a history of chronic sun-exposure. SCC itself is believed to be a late-stage manifestation that can develop from premalignant lesions including Intraepidermal Carcinoma (IEC. Notably, while SCC regression is rare, IEC typically regresses in response to immune modifying topical treatments, however the underlying immunological reasons for these differential responses remain unclear. This study aimed to define whether IEC and SCC are associated with distinct immune profiles. We investigated the immune cell infiltrate of photo-damaged skin, IEC, and SCC tissue using 10-colour flow cytometry following fresh lesion digest. We found that IEC lesions contain higher percentages of CD3+ T-cells than photo-damaged skin, however, the abundance of CD3-CD56+ Natural Killer (NK cells, CD11c+HLA-DR+ conventional Dendritic Cells (cDC, BDCA-2+HLA-DR+ plasmacytoid DC (pDC, FoxP3+ Regulatory T-cells (T-reg, Vα24+Vβ11+ invariant NKT-cells, and γδ Tcells did not alter with disease stage. Within the total T-cell population, high percentages of CD4+ T-cells were associated with SCC, yet CD8+ T-cells were less abundant in SCC compared with IEC. Our study demonstrates that while IEC lesions contain a higher proportion of T-cells than SCC lesions in general, SCC lesions specifically display a lower abundance of CD8+ T-cells than IEC. We propose that differences in CD8+ T-cell abundance contribute critically to the different capacity of SCC and IEC to regress in response to immune modifying topical treatments. Our study also suggests that a high ratio of CD4+ T-cells to CD8+ T-cells may be a immunological diagnostic indicator of late-stage SCC development in immune-competent patients.

  4. Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

    Science.gov (United States)

    Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M

    2003-06-01

    We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P siblings of affected children.

  5. Sea urchin akt activity is Runx-dependent and required for post-cleavage stage cell division

    KAUST Repository

    Robertson, Anthony J.

    2013-03-25

    In animal development following the initial cleavage stage of embryogenesis, the cell cycle becomes dependent on intercellular signaling and controlled by the genomically encoded ontogenetic program. Runx transcription factors are critical regulators of metazoan developmental signaling, and we have shown that the sea urchin Runx gene runt-1, which is globally expressed during early embryogenesis, functions in support of blastula stage cell proliferation and expression of the mitogenic genes pkc1, cyclinD, and several wnts. To obtain a more comprehensive list of early runt-1 regulatory targets, we screened a Strongylocentrotus purpuratus microarray to identify genes mis-expressed in mid-blastula stage runt-1 morphants. This analysis showed that loss of Runx function perturbs the expression of multiple genes involved in cell division, including the pro-growth and survival kinase Akt (PKB), which is significantly underexpressed in runt-1 morphants. Further genomic analysis revealed that Akt is encoded by two genes in the S. purpuratus genome, akt-1 and akt-2, both of which contain numerous canonical Runx target sequences. The transcripts of both genes accumulate several fold during blastula stage, contingent on runt-1 expression. Inhibiting Akt expression or activity causes blastula stage cell cycle arrest, whereas overexpression of akt-1 mRNA rescues cell proliferation in runt-1 morphants. These results indicate that post-cleavage stage cell division requires Runx-dependent expression of akt.

  6. Sea urchin akt activity is Runx-dependent and required for post-cleavage stage cell division

    KAUST Repository

    Robertson, Anthony J.; Coluccio, Alison; Jensen, Sarah; Rydlizky, Katarina; Coffman, James A.

    2013-01-01

    In animal development following the initial cleavage stage of embryogenesis, the cell cycle becomes dependent on intercellular signaling and controlled by the genomically encoded ontogenetic program. Runx transcription factors are critical regulators of metazoan developmental signaling, and we have shown that the sea urchin Runx gene runt-1, which is globally expressed during early embryogenesis, functions in support of blastula stage cell proliferation and expression of the mitogenic genes pkc1, cyclinD, and several wnts. To obtain a more comprehensive list of early runt-1 regulatory targets, we screened a Strongylocentrotus purpuratus microarray to identify genes mis-expressed in mid-blastula stage runt-1 morphants. This analysis showed that loss of Runx function perturbs the expression of multiple genes involved in cell division, including the pro-growth and survival kinase Akt (PKB), which is significantly underexpressed in runt-1 morphants. Further genomic analysis revealed that Akt is encoded by two genes in the S. purpuratus genome, akt-1 and akt-2, both of which contain numerous canonical Runx target sequences. The transcripts of both genes accumulate several fold during blastula stage, contingent on runt-1 expression. Inhibiting Akt expression or activity causes blastula stage cell cycle arrest, whereas overexpression of akt-1 mRNA rescues cell proliferation in runt-1 morphants. These results indicate that post-cleavage stage cell division requires Runx-dependent expression of akt.

  7. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  8. A case of central type early stage lung cancer receiving 60Co high dose-rate postoperative endobronchial radiation

    International Nuclear Information System (INIS)

    Nakamori, Syouji; Kodama, Ken; Kurokawa, Eiji; Doi, Osamu; Terasawa, Toshio; Chatani, Masashi; Inoue, Toshihiko; Tateishi, Ryuhei

    1985-01-01

    Right middle-lower lobectomy and mediastinal lymph node dissection were performed for a case of central type early stage lung cancer. Tumor extended very closely to the line of incision margin of the resected specimen, appearing as carcinoma in situ. To inprove curativity, postoperative radiation therapy was performed with 60 Co high dose-rate endobronchial radiation by a remote afterloading system. A total dose of 40Gy was administered to the target area without any severe side effects. The patient is healthy and has no evidence of metastasis. This procedure is considered to be an effective treatment for postoperative lung cancer with possible residual malignancy. (author)

  9. Penile alterations at early stage of type 1 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Mingfang Tao

    Full Text Available ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.

  10. Revolution of Chinese architectural design at the new-type urbanization stage

    Directory of Open Access Journals (Sweden)

    Jianguo Wang

    2015-09-01

    Full Text Available Witnessing more than three decades of sustained and rapid economic growth, China has become a nation that enjoys the fastest rate of urbanization; the largest quantities of civil construction; the most obvious urban development to be “newer”, “bigger” and “higher”; and the most prosperous architectural design market worldwide. In terms of the construction industry, housing construction totals 31.3 billion square meters, occupying more than 70% of the floor area of the existing stock houses. It is safe to say that the construction industry significantly boosts GDP growth, expands the number of jobs, and improves the living conditions of the masses. Related to this is the need to end the architectural guidelines of the planned economy era economizing on food and clothing and instead step into a new historic stage allowing bold pursuit of architectural aesthetics and individuality. A group of architects who have social ideals, adhere faithfully to professional standards and pledge to pursue architectural innovation are active in China. Instead of simply converting the overwhelming opportunities brought to carry economic benefits, they dare to embrace the challenges imposed on enhancing architectural connotation and create a batch of high-level work that lives up to expectations of the era, marking the achievement of reform and rapid urbanization in China. Yet, as time goes on, the promotion of national development concepts, ideas of social consumption and the masses’ cultural level establishes new requirements for the architectural design industry, architects and architectural design works. An appeal is thus made against Chinese architects for a summary, reflection and proactive anticipation to respond to the new requirements of the era.

  11. A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

    Science.gov (United States)

    Murphy, Sean C.; Kas, Arnold; Stone, Brad C.; Bevan, Michael J.

    2013-01-01

    Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins. PMID:23530242

  12. Single-cell LEP-type cavity on measurement stand

    CERN Multimedia

    CERN PhotoLab

    1982-01-01

    A single-cell cavity, made of copper, with tapered connectors for impedance measurements. It was used as a model of LEP-type superconducting cavities, to investigate impedance and higher-order modes and operated at around 600 MHz (the LEP acceleration frequency was 352.2 MHz). See 8202500.

  13. Receptosecretory nature of type III cells in the taste bud.

    Science.gov (United States)

    Yoshie, Sumio

    2009-01-01

    Type III cells in taste buds form chemical synapses with intragemmal afferent nerve fibers and are characterized by the presence of membrane-bound vesicles in the cytoplasm. Although the vesicles differ in shape and size among species, they are primarily categorized into small clear (40 nm in diameter) and large dense-cored (90-200 nm) types. As such vesicles tend to be closely juxtaposed to the synaptic membrane of the cells, it is reasonable to consider that the vesicles include transmitter(s) towards the gustatory nerve. In the guinea-pig taste bud, stimulation with various taste substances (sucrose, sodium chloride, quinine hydrochloride, or monosodium L-glutamate) causes ultrastructural alterations of the type III cells. At the synapse, the presynaptic plasma membrane often displays invaginations of 90 nm in a mean diameter towards the cytoplasm, which indicates the dense-cored vesicles opening into the synaptic cleft by means of exocytosis. The vesicles are also exocytosed at the non-synaptic region into the intercellular space. These findings strongly suggest that the transmitters presumably contained in the vesicles are released to conduct the excitement of the type III cells to the nerves and also to exert their paracrine effects upon the surroundings, such as the Ebner's salivary gland, acting as local hormones.

  14. Automated cell type discovery and classification through knowledge transfer

    Science.gov (United States)

    Lee, Hao-Chih; Kosoy, Roman; Becker, Christine E.

    2017-01-01

    Abstract Motivation: Recent advances in mass cytometry allow simultaneous measurements of up to 50 markers at single-cell resolution. However, the high dimensionality of mass cytometry data introduces computational challenges for automated data analysis and hinders translation of new biological understanding into clinical applications. Previous studies have applied machine learning to facilitate processing of mass cytometry data. However, manual inspection is still inevitable and becoming the barrier to reliable large-scale analysis. Results: We present a new algorithm called Automated Cell-type Discovery and Classification (ACDC) that fully automates the classification of canonical cell populations and highlights novel cell types in mass cytometry data. Evaluations on real-world data show ACDC provides accurate and reliable estimations compared to manual gating results. Additionally, ACDC automatically classifies previously ambiguous cell types to facilitate discovery. Our findings suggest that ACDC substantially improves both reliability and interpretability of results obtained from high-dimensional mass cytometry profiling data. Availability and Implementation: A Python package (Python 3) and analysis scripts for reproducing the results are availability on https://bitbucket.org/dudleylab/acdc. Contact: brian.kidd@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28158442

  15. Radiotherapy alone for medically inoperable Stage I non-small-cell lung cancer: The Duke experience

    International Nuclear Information System (INIS)

    Sibley, Gregory S.; Jamieson, Timothy A.; Marks, Lawrence B.; Anscher, Mitchell S.; Prosnitz, Leonard R.

    1998-01-01

    Purpose: To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed. Methods: Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of ≥4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%). Results: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival

  16. The CD3-zeta chimeric antigen receptor overcomes TCR Hypo-responsiveness of human terminal late-stage T cells.

    Directory of Open Access Journals (Sweden)

    Gunter Rappl

    Full Text Available Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable efficacy in recent trials. Repetitive T cell receptor (TCR engagement of target antigen, however, inevitably ends up in hypo-responsive cells with terminally differentiated KLRG-1(+ CD57(+ CD7(- phenotype limiting their therapeutic efficacy. We here revealed that hypo-responsiveness of CMV-specific late-stage CD8(+ T cells is due to reduced TCR synapse formation compared to younger cells. Membrane anchoring of TCR components contributes to T cell hypo-responsiveness since dislocation of galectin-3 from the synapse by swainsonine restored both TCR synapse formation and T cell response. Transgenic expression of a CD3-zeta signaling chimeric antigen receptor (CAR recovered hypo-responsive T cells to full effector functions indicating that the defect is restricted to TCR membrane components while synapse formation of the transgenic CAR was not blocked. CAR engineered late-stage T cells released cytokines and mediated redirected cytotoxicity as efficiently as younger effector T cells. Our data provide a rationale for TCR independent, CAR mediated activation in the adoptive cell therapy to avoid hypo-responsiveness of late-stage T cells upon repetitive antigen encounter.

  17. Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene.

    Science.gov (United States)

    Preston, G A; Lang, J E; Maronpot, R R; Barrett, J C

    1994-08-01

    A cell culture model system has been used to study the susceptibility of cells to apoptotic cell death during different stages of neoplastic progression. This system consists of normal diploid Syrian hamster embryo (SHE) cells, two preneoplastic cell lines [tumor suppressor stage I (sup +I) and non-tumor suppressor stage II (sup -II)], and hamster tumor cell lines. Stage I preneoplastic cells are nontumorigenic immortal clones that suppress tumorigenicity when hybridized to tumor cells, whereas stage II cells have lost the ability to suppress tumorigenicity in cell hybrids. We refer to these two types of preneoplastic cells as sup +I and sup -II, respectively. Neoplastic progression is generally associated with cellular alterations in growth factor responsiveness. Therefore, to study the regulation of apoptosis in the system described above, cells were cultured in low serum (0.2%) as a means of withdrawing growth factors. In low serum, normal SHE cells were quiescent (labeling index of 0.2%), with little cell death. The sup +I cells showed a relatively low labeling index (1.6%) but, in contrast to the normal cells, died at a high rate (55% cell loss after 48 h) by apoptosis, as evidenced by morphology, DNA fragmentation, and in situ end-labeling of fragmented DNA. The apoptotic cells did not go through a replicative cycle while in low serum, implying that apoptosis was initiated in the G0/G1 phase of the cell cycle. The sup -II cell line showed a high labeling index (40%) after 48 h, but cell growth was balanced by cell death that occurred at approximately the same rate. The cells died, however, predominantly by necrosis. The tumor cell lines continued to proliferate in low serum, with high labeling indices (ranging from 27% to 43%) and a low level of apoptotic or necrotic cell death. To determine the relative ability of these cells to survive in vivo, normal SHE cells, sup +I cells, and sup -II cells were injected s.c. into nude mice. At 5 or 21 days after

  18. White blood cell subtypes and risk of type 2 diabetes.

    Science.gov (United States)

    Zhang, Hongmei; Yang, Zhen; Zhang, Weiwei; Niu, Yixin; Li, Xiaoyong; Qin, Li; Su, Qing

    2017-01-01

    It is reported that total white blood cell is associated with risk of diabetes mellitus. The present study is to investigate the relationship of white blood cell subsets with incidence of type 2 diabetes at baseline and 3year follow-up. We chose individuals without diabetes history as our study population; 8991 individuals were included at baseline. All of the participants underwent a 75-g OGTT at baseline. White blood cell count including all the subsets were measured along with all the other laboratory indices. The participants who were not diagnosed with type 2 diabetes according to the WHO 1999 diagnostic criteria underwent another 75-g OGTT at 3year follow-up. The total WBC count, neutrophil count, and lymphocyte count were significantly increased in subjects newly diagnosed with diabetes mellitus compared to non-DM subjects at baseline (all ptype 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

    Science.gov (United States)

    Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

    2015-10-01

    The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

  20. Analytic Bayesian solution of the two-stage poisson-type problem in probabilistic risk analysis

    International Nuclear Information System (INIS)

    Frohner, F.H.

    1985-01-01

    The basic purpose of probabilistic risk analysis is to make inferences about the probabilities of various postulated events, with an account of all relevant information such as prior knowledge and operating experience with the specific system under study, as well as experience with other similar systems. Estimation of the failure rate of a Poisson-type system leads to an especially simple Bayesian solution in closed form if the prior probabilty implied by the invariance properties of the problem is properly taken into account. This basic simplicity persists if a more realistic prior, representing order of magnitude knowledge of the rate parameter, is employed instead. Moreover, the more realistic prior allows direct incorporation of experience gained from other similar systems, without need to postulate a statistical model for an underlying ensemble. The analytic formalism is applied to actual nuclear reactor data

  1. Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation.

    Science.gov (United States)

    Nair, Shiny; Boddupalli, Chandra Sekhar; Verma, Rakesh; Liu, Jun; Yang, Ruhua; Pastores, Gregory M; Mistry, Pramod K; Dhodapkar, Madhav V

    2015-02-19

    Chronic inflammation including B-cell activation is commonly observed in both inherited (Gaucher disease [GD]) and acquired disorders of lipid metabolism. However, the cellular mechanisms underlying B-cell activation in these settings remain to be elucidated. Here, we report that β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), 2 major sphingolipids accumulated in GD, can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells. Human βGL1-22- and LGL1-reactive CD1d tetramer-positive T cells have a distinct T-cell receptor usage and genomic and cytokine profiles compared with the classical type I NKT cells. In contrast to type I NKT cells, βGL1-22- and LGL1-specific NKT cells constitutively express T-follicular helper (TFH) phenotype. Injection of these lipids leads to an increase in respective lipid-specific type II NKT cells in vivo and downstream induction of germinal center B cells, hypergammaglobulinemia, and production of antilipid antibodies. Human βGL1-22- and LGL1-specific NKT cells can provide efficient cognate help to B cells in vitro. Frequency of LGL1-specific T cells in GD mouse models and patients correlates with disease activity and therapeutic response. Our studies identify a novel type II NKT-mediated pathway for glucosphingolipid-mediated dysregulation of humoral immunity and increased risk of B-cell malignancy observed in metabolic lipid disorders. © 2015 by The American Society of Hematology.

  2. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.

    Science.gov (United States)

    Wang, Xiaofang; Lazorchak, Adam S; Song, Li; Li, Enqin; Zhang, Zhenwu; Jiang, Bin; Xu, Ren-He

    2016-02-01

    Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNγ. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies. © 2015 AlphaMed Press.

  3. Selective enrichment and biochemical characterization of seven human skin fibroblasts cell types in vitro

    International Nuclear Information System (INIS)

    Rodemann, H.P.; Bayreuther, K.; Francz, P.I.; Dittmann, K.; Albiez, M.

    1989-01-01

    The mitotic and postmitotic populations of the human skin fibroblast cell line HH-8 are heterogeneous when studied in vitro. There are reproducible changes in the frequencies of the mitotic fibroblasts (MF), MF I, MF II, MF III, and the postmitotic fibroblasts (PMF), PMF IV, PMF V, PMF VI, and PMF VII. For biochemical characterization, methods for selective enrichment of homogeneous populations of these seven fibroblast cell types have been established. Clonal populations with 95% purity for the mitotic fibroblasts MF I, MF II, and MF III can be raised in uniform clone types of fibroblasts (CTF) CTF I, CTF II, and CTF III. Pure clonal subpopulations of MF I type cells are present in mass populations in the range of 1-20 cumulative population doublings (CPD). Populations of mitotic fibroblasts represent nearly homogeneous populations of MF II (75-85% purity) in the range of 28-34 CPD and MF III (73-86% purity) in the range of 48-53 CPD. These populations can be easily expanded to up to 10(7)-10(8) cells. The spontaneous transition of MF III to PMF VI takes 140-180 days. In order to shorten this period and increase the proportion of distinct postmitotic types, mitotic fibroblast mass populations (CPD 30-32, MF II: 75-85% purity) have been induced by uv-irradiation to differentiate to nearly homogeneous populations of PMF IV, PMF V, PMF VI, and PMF VII within 4 to 36 days of culture. Using this method, 10(7) cells of one differentiation stage can be obtained. Spontaneously arising and experimentally selected or induced homogeneous clonal and mass populations of MF I, MF II, MF III, PMF IV, PMF V, PMF VI, and PMF VII express an identical differentiation-dependent and cell-type-specific [35S]methionine-labeled polypeptide pattern

  4. Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma.

    Science.gov (United States)

    Zhang, Guqin; Nie, Hanxiang; Yang, Jiong; Ding, Xuhong; Huang, Yi; Yu, Hongying; Li, Ruyou; Yuan, Zhuqing; Hu, Suping

    2011-12-01

    Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

  5. Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block

    Directory of Open Access Journals (Sweden)

    Jun Sung Moon

    2015-02-01

    Full Text Available Type 2 diabetes (T2D has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from α-cell has languished whereas β-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant α-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted α-cell suppression. During hypoglycemia, insufficient counter-regulation response is also observed in advanced T2D. Though many debates still remained for exact mechanisms behind the dysregulation of α-cell in T2D, it is clear that the blockade of glucagon receptor or suppression of glucagon secretion from α-cell would be novel therapeutic targets for control of hyperglycemia. Whereas there have not been remarkable advances in developing new class of drugs, currently available glucagon-like peptide-1 and dipeptidyl peptidase-IV inhibitors could be options for treatment of hyperglucagonemia. In this review, we focus on α-cell dysfunction and therapeutic potentials of targeting α-cell in T2D.

  6. A nomogram to predict the survival of stage IIIA-N2 non-small cell lung cancer after surgery.

    Science.gov (United States)

    Mao, Qixing; Xia, Wenjie; Dong, Gaochao; Chen, Shuqi; Wang, Anpeng; Jin, Guangfu; Jiang, Feng; Xu, Lin

    2018-04-01

    Postoperative survival of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) is highly heterogeneous. Here, we aimed to identify variables associated with postoperative survival and develop a tool for survival prediction. A retrospective review was performed in the Surveillance, Epidemiology, and End Results database from January 2004 to December 2009. Significant variables were selected by use of the backward stepwise method. The nomogram was constructed with multivariable Cox regression. The model's performance was evaluated by concordance index and calibration curve. The model was validated via an independent cohort from the Jiangsu Cancer Hospital Lung Cancer Center. A total of 1809 patients with stage IIIA-N2 NSCLC who underwent surgery were included in the training cohort. Age, sex, grade, histology, tumor size, visceral pleural invasion, positive lymph nodes, lymph nodes examined, and surgery type (lobectomy vs pneumonectomy) were identified as significant prognostic variables using backward stepwise method. A nomogram was developed from the training cohort and validated using an independent Chinese cohort. The concordance index of the model was 0.673 (95% confidence interval, 0.654-0.692) in training cohort and 0.664 in validation cohort (95% confidence interval, 0.614-0.714). The calibration plot showed optimal consistency between nomogram predicted survival and observed survival. Survival analyses demonstrated significant differences between different subgroups stratified by prognostic scores. This nomogram provided the individual survival prediction for patients with stage IIIA-N2 NSCLC after surgery, which might benefit survival counseling for patients and clinicians, clinical trial design and follow-up, as well as postoperative strategy-making. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Relation between clinical findings and progression of cerebral cortical pathology in MM1-type sporadic Creutzfeldt-Jakob disease: proposed staging of cerebral cortical pathology.

    Science.gov (United States)

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Hashizume, Yoshio; Yoshida, Mari

    2014-06-15

    In our pathologic observation of the cerebral cortex including the neocortex, hippocampus, and limbic cortex in 43 Japanese patients with MM1-type sporadic Creutzfeldt-Jakob disease, the earliest pathologic finding was spongiform change and next was gliosis. Subsequently, neuropil rarefaction appeared, followed by neuron loss. On the basis of these observations, we propose the following cortical pathologic staging: Stage I, spongiform change; Stage II, hypertrophic astrocytosis; Stage III, neuropil rarefaction; Stage IV, neuron loss; Stage V, status spongiosus; and Stage VI, large cavity formation. We also suggest a more simple staging classification: Stages I and II, mild; Stages III and IV, moderate; and Stages V and VI, severe involvement. Based on statistical analysis of the cases, strong correlation coefficients were obtained between the neocortical and limbic pathologic stage and both total disease duration and brain weight. We estimated that the first observation times of cortical hyperintensity on diffusion-weighted images of magnetic resonance imaging, myoclonus, and periodic sharp wave complexes on the electroencephalogram approximately correspond to the early phase of Stage II of the neocortex. The time to reach the akinetic mutism state approximately corresponds to the middle phase of Stage II of the neocortex. Therefore, we think that approximate clinical manifestations at death, total disease duration, and brain weight can be estimated according to the pathologic stage of the neocortex or limbic cortex. Panencephalopathic-type pathology appeared approximately 12 months after disease onset, and this time approximately corresponds to the middle phase of Stage III of the neocortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. [Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas].

    Science.gov (United States)

    Asaturova, A V; Ezhova, L S; Faizullina, N M; Adamyan, L V; Khabas, G N; Sannikova, M V

    to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (pepithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (pepithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC. SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly

  9. A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

    Science.gov (United States)

    He, Xiao-Shun; Fu, Shun-Jun; Zhao, Qiang; Zhu, Xiao-Feng; Wang, Dong-Ping; Han, Ming; Ju, Wei-Qiang; Ma, Yi; Jiao, Xing-Yuan; Yuan, Xiao-Peng; Hu, An-Bin; Guo, Zhi-Yong

    2017-09-01

    In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  10. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  11. Stage-dependent alterations of progenitor cell proliferation and neurogenesis in an animal model of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Vetreno, Ryan P; Klintsova, Anna; Savage, Lisa M

    2011-05-19

    Alcohol-induced Wernicke-Korsakoff syndrome (WKS) culminates in bilateral diencephalic lesion and severe amnesia. Using the pyrithiamine-induced thiamine deficiency (PTD) animal paradigm of WKS, our laboratory has demonstrated hippocampal dysfunction in the absence of gross anatomical pathology. Extensive literature has revealed reduced hippocampal neurogenesis following a neuropathological insult, which might contribute to hippocampus-based learning and memory impairments. Thus, the current investigation was conducted to determine whether PTD treatment altered hippocampal neurogenesis in a stage-dependent fashion. Male Sprague-Dawley rats were assigned to one of 4 stages of thiamine deficiency based on behavioral symptoms: pre-symptomatic stage, ataxic stage, early post-opisthotonus stage, or the late post-opisthotonus stage. The S-phase mitotic marker 5'-bromo-2'-deoxyuridine (BrdU) was administered at the conclusion of each stage following thiamine restoration and subjects were perfused 24 hours or 28 days after BrdU to assess cellular proliferation or neurogenesis and survival, respectively. Dorsal hippocampal sections were immunostained for BrdU (proliferating cell marker), NeuN (neurons), GFAP (astrocytes), Iba-1 (microglia), and O4 (oligodendrocytes). The PTD treatment increased progenitor cell proliferation and survival during the early post-opisthotonus stage. However, levels of neurogenesis were reduced during this stage as well as the late post-opisthotonus stage where there was also an increase in astrocytogenesis. The diminished numbers of newly generated neurons (BrdU/NeuN co-localization) was paralleled by increased BrdU cells that did not co-localize with any of the phenotypic markers during these later stages. These data demonstrate that long-term alterations in neurogenesis and gliogenesis might contribute to the observed hippocampal dysfunction in the PTD model and human WKS. Published by Elsevier B.V.

  12. Application of multi-stage, multi-disk type downhole seismic source; Tadanshiki taso enbangata koseinai shingen no tekiyosei

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, N [Japan National Oil Corp., Tokyo (Japan); Shoji, Y [Oyo Corp., Tokyo (Japan)

    1997-05-27

    A multi-stage, multi-disk type seismic source was developed as a downhole seismic source. The seismic source is an improved version of the downhole seismic source of a system in which an elastic wave is generated by a weight accelerated by restitutive force of a spring striking the upper part of a laminated structure consisted of metal disks and elastic bodies installed in water in a well. Enhancing the vibration exciting efficiency requires impedance radiated from the disks to be increased. The multi-disk structure was adopted because of restrictions on the disk area under the limiting condition of being inside the well. Further limitation has still existed, which led to finally structuring the multi-disk type to a multi-stage construction to increase the radiated impedance. In order to increase average velocity on the radiation surface, mass relationship between the hammer and the anvil was sought so that the maximum velocity is achieved at the process of converting motion energies among the hammer, anvil and disks. The anvil mass may sufficiently be 50% to 100% of the hammer mass. The equipment was installed in an actual oil well for testing. This seismic source was verified to have sufficient applicability in the cross hole measurement. 5 refs., 7 figs., 1 tab.

  13. Radiation therapy alone for early stage non-small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2002-01-01

    To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy along and define the optimal radiotherapeutic regimen for these patients. A retrospective review was performed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 69 Gy. No patients were lost to follow-up. The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and 21%, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and 25%, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was 43%. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented 78% of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm (0% vs 36%). Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70

  14. Study of cell cycle parameters of man lymphocytes irradiated at various stages using differential coloring of sister chromatides

    International Nuclear Information System (INIS)

    Poryadkova, N.A.

    1984-01-01

    Parameters of the cell cycle of human lymphocytes are specified, radiation effect applied at various stages of mitotic cycle on the kinetics of cell advance in the cycle is also investigated. It is shown that increasing mitotic index occurs only due to the introduction of cells into the first mitosis. It is not excluded that cells ready to enter the second mitosis died with greater probability as after second synthesis they contained two-fold amount of BDU (5-brominedesoxiuridine) than cells of the first mitosis. In all cases with irradiation of cells of the third mitosis were not found

  15. Quality improvement for integrated management of patients with type 2 diabetes (PRIHTA project stage 1).

    Science.gov (United States)

    Paccagnella, Agostino; Mauri, Alessandra; Spinella, Nello

    2012-01-01

    The purpose of the study was to show how a different collaborative relationship with family doctors and increasingly specialized diabetologists could lead to a 50% reduction in recurrent appointments due to procedural errors and a 50% reduction in the average waiting times for a specialist medical visit. A qualitative and quantitative definition of the problem was made using the Lean Six Sigma method: (Define); process indicators were observed that might interfere with the objectives of this study (Measure); descriptive statistics were used to confirm the validity and significance of the results (Analyze); and finally strategies were established to intervene on these variables (Improve). Four groups of action led to optimization of the objectives: (1) establishing clinical protocols for primary care physicians for treating hospitalized patients with type 2 diabetes and hyperglycemia; (2) increasing the autonomy of nursing care staff; (3) reorganizing the appointments booking office; and (4) making diabetes clinics more specialized. Thanks to this project, primary care physicians have rediscovered their role and defined their diagnostic-therapeutic function under a shared scientific protocol. The model presented in this study provides scope for reflection on the role of the diabetologist, proposing an "alternative" that concerns only the care of patients with metabolic decompensation.

  16. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  17. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  18. The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment.

    Science.gov (United States)

    Lundgren, Sebastian; Warfvinge, Carl Fredrik; Elebro, Jacob; Heby, Margareta; Nodin, Björn; Krzyzanowska, Agnieszka; Bjartell, Anders; Leandersson, Karin; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers.

  19. Germ cell tumors in patients with disorders of sex development: Risk factors, initial developmental stages and targets for early diagnosis

    NARCIS (Netherlands)

    M.B.C.M. Cools (Martine)

    2006-01-01

    textabstractThis thesis describes the origin, identification and correct diagnosis of the earliest stages of malignant germ cell tumors, i.e. intra tubular germ cell neoplasia unclassified (ITGNU) and gonadoblastoma, in patients with disorders of sex development. Special attention is given to the

  20. Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Witkiewicz, Agnieszka; Raghunath, Puthiyaveettil; Wasik, Agnieszka

    2007-01-01

    Cutaneous T-cell lymphoma (CTCL) comprises distinct and often progressive stages of skin involvement by patches, plaques, and tumors. We have previously demonstrated that CTCL-derived malignant T-cell lines display loss of a tumor suppressor SHP-1 tyrosine phosphatase because of epigenetic...

  1. Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

    International Nuclear Information System (INIS)

    Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro

    1996-01-01

    The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P=0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P=0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P=0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P=0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy. (author)

  2. Characterization of tissue plasminogen activator binding proteins isolated from endothelial cells and other cell types

    International Nuclear Information System (INIS)

    Beebe, D.P.; Wood, L.L.; Moos, M.

    1990-01-01

    Human tissue plasminogen activator (t-PA) was shown to bind specifically to human osteosarcoma cells (HOS), and human epidermoid carcinoma cells (A-431 cells). Crosslinking studies with DTSSP demonstrated high molecular weight complexes (130,000) between 125 I-t-PA and cell membrane protein on human umbilical vein endothelial cells (HUVEC), HOS, and A-431 cells. A 48-65,000 molecular weight complex was demonstrated after crosslinking t-PA peptide (res. 7-20) to cells. Ligand blotting of cell lysates which had been passed over a t-PA affinity column revealed binding of t-PA to 54,000 and 95,000 molecular weight proteins. Several t-PA binding proteins were identified in immunopurified cell lysates, including tubulin beta chain, plasminogen activator inhibitor type 1 and single chain urokinase

  3. Hematopoietic cell crisis: An early stage of evolving myeloid leukemia following radiation exposure

    International Nuclear Information System (INIS)

    Seed, T.M.

    1990-01-01

    Under select radiological conditions, chronic radiation exposure elicits a high incidence of myeloproliferative disease, principally myeloid leukemia (ML), in beagles. Previously we demonstrated that for full ML expression, a four-stage preclinical sequence is required, namely (1) suppression, (2) recovery, (3) accommodation, and (4) preleukemic transition. Within this pathological sequence, a critical early event has been identified as the acquisition of radioresistance by hematopoietic progenitors that serves to mediate a newfound regenerative hematopoietic capacity. As such, this event ''sets the stage'' for preleukemic progression by initiating progression from preclinical phase 1 to 2. Due to the nature of target cell suppression, the induction of crisis, and the outgrowth of progenitors with altered phenotypes, this preleukemic event resembles the ''immortalization'' step of the in vitro transformation sequence following induction with either physical and chemical carcinogens. The radiological, temporal, and biological dictates governing this event have been extensively evaluated and will be discussed in light of their role in the induction and progression of chronic radiation leukemia. 35 refs., 2 tabs

  4. Whole-genome analysis of a patient with early-stage small-cell lung cancer.

    Science.gov (United States)

    Han, J-Y; Lee, Y-S; Kim, B C; Lee, G K; Lee, S; Kim, E-H; Kim, H-M; Bhak, J

    2014-12-01

    We performed whole-genome sequencing (WGS) of a case of early-stage small-cell lung cancer (SCLC) to analyze the genomic features. WGS revealed a lot of single-nucleotide variations (SNVs), small insertion/deletions and chromosomal abnormality. Chromosomes 4p, 5q, 13q, 15q, 17p and 22q contained many block deletions. Especially, copy loss was observed in tumor suppressor genes RB1 and TP53, and copy gain in oncogene hTERT. Somatic mutations were found in TP53 and CREBBP. Novel nonsynonymous (ns) SNVs in C6ORF103 and SLC5A4 genes were also found. Sanger sequencing of the SLC5A4 gene in 23 independent SCLC samples showed another nsSNV in the SLC5A4 gene, indicating that nsSNVs in the SLC5A4 gene are recurrent in SCLC. WGS of an early-stage SCLC identified novel recurrent mutations and validated known variations, including copy number variations. These findings provide insight into the genomic landscape contributing to SCLC development.

  5. Hematopoietic cell crisis: An early stage of evolving myeloid leukemia following radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1990-01-01

    Under select radiological conditions, chronic radiation exposure elicits a high incidence of myeloproliferative disease, principally myeloid leukemia (ML), in beagles. Previously we demonstrated that for full ML expression, a four-stage preclinical sequence is required, namely (1) suppression, (2) recovery, (3) accommodation, and (4) preleukemic transition. Within this pathological sequence, a critical early event has been identified as the acquisition of radioresistance by hematopoietic progenitors that serves to mediate a newfound regenerative hematopoietic capacity. As such, this event sets the stage'' for preleukemic progression by initiating progression from preclinical phase 1 to 2. Due to the nature of target cell suppression, the induction of crisis, and the outgrowth of progenitors with altered phenotypes, this preleukemic event resembles the immortalization'' step of the in vitro transformation sequence following induction with either physical and chemical carcinogens. The radiological, temporal, and biological dictates governing this event have been extensively evaluated and will be discussed in light of their role in the induction and progression of chronic radiation leukemia. 35 refs., 2 tabs.

  6. Micrometastasis in non-small-cell lung cancer: Detection and staging

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri

    2012-01-01

    Full Text Available Background: The clinical relevance of bone marrow micrometastasis (BMM in non-small-cell lung cancer is undetermined, and the value of such analyses in advanced stage patients has not been clearly assessed previously. This study was conducted to estimate the accuracy of both polymerase chain reaction (PCR and immunohistochemistry (IHC in micrometastases detection and determine the best site for bone marrow biopsy in order to find micrometastasis. Methods: This prospective cross-sectional study was performed in the Department of Thoracic Surgery, Alzahra University Hospital from September 2008 to June 2009. To evaluate the bone marrow, a 3-cm rib segment and an aspirated specimen from the iliac bone prior to tumor resection were taken. PCR and IHC were performed for each specimen to find micrometastasis. Results: Of 41 patients, 14 (34% were positive for BMM by PCR compared with two positive IHC (4.8%. All BMMs were diagnosed in rib segments, and iliac specimens were all free from metastatic lesion. Our data showed no significant association between variables such as age, sex, histology, tumor location, side of tumor, involved lobe, smoking, or weight loss and presence of BMM. Conclusion: PCR could use as a promising method for BMM detection. BMM in a sanctuary site (rib is not associated with advanced stages of lung cancer. In addition, when predictor variables such as age, sex, histology, tumor location, smoking, or weight loss are analyzed, no correlation can be found between micrometastasis prevalence and any of those variables.

  7. Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192

    International Nuclear Information System (INIS)

    Piedbois, P.; Mazeron, J.J.; Haddad, E.; Coste, A.; Martin, M.; Levy, C.; Raynal, M.; Pavlovitch, J.M.; Peynegre, R.; Perquin, B.; Bourgeois, J.P. le

    1991-01-01

    This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive brachytherapy. Minimum follow-up is 3 years. Treatment of the neck was chosen by a multidisciplinary team, according to age, medical status and availability for follow-up. One hundred and ten patients (47 percent) underwent elective neck dissection (END), 28 (25 percent) had positive nodes and received neck irradiation post-operatively. One hundred and twenty-three patients (53 percent) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17 percent): 12/60 (20 percent) in patients with mobile tongue carcinoma and 7/50 (14 percent) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13-21 (62 percent) cases. Ten-year survival is 37 percent for the END-group and 31 percent for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p<0.04). (author). 30 refs.; 2 figs.; 7 tabs

  8. Proton-Based Stereotactic Ablative Radiotherapy in Early-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jonathan D. Grant

    2014-01-01

    Full Text Available Stereotactic ablative radiotherapy (SABR, a recent implementation in the practice of radiation oncology, has been shown to confer high rates of local control in the treatment of early stage non-small-cell lung cancer (NSCLC. This technique, which involves limited invasive procedures and reduced treatment intervals, offers definitive treatment for patients unable or unwilling to undergo an operation. The use of protons in SABR delivery confers the added physical advantage of normal tissue sparing due to the absence of collateral radiation dose delivered to regions distal to the target. This may translate into clinical benefit and a decreased risk of clinical toxicity in patients with nearby critical structures or limited pulmonary reserve. In this review, we present the rationale for proton-based SABR, principles relating to the delivery and planning of this modality, and a summary of published clinical studies.

  9. Computed tomography contribution to the staging of supraglottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Monte Aragao Junior, Antonio Gilson; Rapoport, Abrao; Souza, Ricardo Pires de

    2007-01-01

    Objective: The present study was aimed at evaluating the role of computed tomography in the local clinical staging of supraglottic tumors according to the TNM classification, as well as the interobserver agreement on the detection of the tumor extent. Materials and methods: Thirty-nine dossiers of inpatients of Hospital Heliopolis with supraglottic squamous cell carcinoma in the period between 1988 and 1998 were retrospectively evaluated. CT studies were individually analyzed by two radiologists. The kappa test was utilized for evaluating the interobserver agreement. Results: Computed tomography has played a decisive role in the upstaging of 38.5% of cases, as a result of a deep tumor extent undetected at clinical examination. Conclusion: Interobserver agreement was considered as excellent for vocal folds and subglottis; good for supraglottic, paraglottic and preepiglottic spaces, thyroid and cricoid cartilages and for extralaryngeal tumor extension; and regular for the base of the tongue. (author)

  10. Radioimmunoassay of type D oncovirus from continuous J-96 cells

    International Nuclear Information System (INIS)

    Vlasenkova, N.K.; Altshtejn, A.D.; Zhdanov, V.M.; Kitsak, V.Ya.

    1978-01-01

    The radioimmunoassay of the J-96 virus and an extract of J-96 cells in the homologous and heterologous systems aimed at detecting antigenic determinants of p25 of Mason-Pfizer virus and group-specific and interspecies antigenic determinants p30 of Rauscher leukaemia virus demonstrated that (1) J-96 virus contains a major internal protein immunologically identical with p25 protein of Mason-Pfizer virus based on the antigenic determinants detectable by the radioimmunoassay used; and (2) no interspecies antigenic determinants characteristic of the major internal protein of mammalian type C viruses were detectable in the J-96 virus or the J-96 cell extract. (author)

  11. INTEGRATED PET-CT SCAN IN THE STAGING OF NON SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    I Made Ngurah Agus Surya Negara S

    2013-09-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Lung cancer is a common disease and is a leading cause of death in many countries. The most kind of lung cancer was Non Small Cell Lung Cancer. The management of lung cancer is directed by an optimal staging of the tumour. On 1998, integrated positron emission tomography (PET-computed tomography (CT was published. PET-CT is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. There wasbetter results for PET/CT in the staging of non small cell lung cancer in comparison with CT nor PET alone. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  12. Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, Kristin [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Chino, Junzo P [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Marks, Lawrence B [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States); Ready, Neal [Department of Medicine, Division of Medical Oncology, Duke University of Medical Center, Durham, NC (United States); D' Amico, Thomas A [Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University of Medical Center, Durham, NC (United States); Clough, Robert W; Kelsey, Chris R [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States)

    2009-12-01

    Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

  13. Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Higgins, Kristin; Chino, Junzo P.; Marks, Lawrence B.; Ready, Neal; D'Amico, Thomas A.; Clough, Robert W.; Kelsey, Chris R.

    2009-01-01

    Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

  14. Study of oil palm root architecture with variation of crop stage and soil type vulnerable to drought

    Science.gov (United States)

    Safitri, Lisma; Suryanti, Sri; Kautsar, Valensi; Kurniawan, Agung; Santiabudi, Fajar

    2018-03-01

    Root arhitecture is affected by watertable level, characteristic of soil, organic matter and also the crop stages. Root architecture spread horizontally and vertically which each consist of primary, secondary, tertiary and quaternary downward root. The oil palm root observation with variation of crop stage and soil type showed that the root of oil palm plant year 2008 on spodosols soil spread along 650 cm horizontally from the trunk and penetrate downward in range of 9-28 cm vertically. Planted in the same type of soil, the root of oil palm plant year 2004 spread along 650 cm horizontally and reached to downward in a larger range from 3 to 57 cm vertically. As a comparison, the root architecture of oil palm on inceptisols soil established the range much greater vertically than the previous. The root of oil palm plant year 2008 spread along 640 cm horizontally and penetrate downward in range of 52-90 cm vertically. With the variation of crop age, the root of oil palm plant year 2003 spread along 650 cm horizontally and reached to downward in a larger range from 150 to 200 cm vertically. Based on this study, root architecture of oil palm was varied and need to be detailed. The precise root architecture of oil palm allows a better understanding on hydrological properties of oil palm root particularly which is cultivated on soil type vulnerable to drought. Referring to this root architecture, it was enable to develop the study on early drought detection of oil palm to optimise production and towards oil palm sustainability.

  15. Delicate balance among three types of T cells in concurrent regulation of tumor immunity

    Science.gov (United States)

    Izhak, Liat; Ambrosino, Elena; Kato, Shingo; Parish, Stanley T.; O’Konek, Jessica J.; Weber, Hannah; Xia, Zheng; Venzon, David; Berzofsky, Jay A.; Terabe, Masaki

    2013-01-01

    The nature of the regulatory cell types that dominate in any given tumor is not understood at present. Here we addressed this question for Tregs and type II NKT cells in syngeneic models of colorectal and renal cancer. In mice with both type I and type II NKT cells, or in mice with neither type of NKT cell, Treg depletion was sufficient to protect against tumor outgrowth. Surprisingly, in mice lacking only type I NKT cells, Treg blockade was insufficient for protection. Thus, we hypothesized that type II NKT cells may be neutralized by type I NKT cells, leaving Treg cells as the primary suppressor, whereas in mice lacking type I NKT cells, unopposed type II NKT cells could suppress tumor immunity even when Tregs were blocked. We confirmed this hypothesis in three ways by reconstituting type I NKT cells as well as selectively blocking or activating type II NKT cells with antibody or the agonist sulfatide, respectively. In this manner, we demonstrated that blockade of both type II NKT cells and Tregs is necessary to abrogate suppression of tumor immunity, but a third cell, the type I NKT cell, determines the balance between these regulatory mechanisms. As cancer patients often have deficient type I NKT cell function, managing this delicate balance among three T cell subsets may be critical for the success of immunotherapy of human cancer. PMID:23319803

  16. Optimal topotactic conversion of layered octosilicate to RWR-type zeolite by separating the formation stages of interlayer condensation and elimination of organic guest molecules.

    Science.gov (United States)

    Asakura, Yusuke; Osada, Shimon; Hosaka, Nami; Terasawa, Taichi; Kuroda, Kazuyuki

    2014-07-21

    We demonstrate that the separation of two stages of interlayer condensation under refluxing and elimination of organic guests provides the optimal conditions for the formation of RWR-type zeolite from layered octosilicate. The obtained RWR-type zeolite has higher quality than any other RWR-type zeolite reported previously.

  17. Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Weir, Jacquelyn M; De Souza, David Peter

    2016-01-01

    as methionine deficits were detected in the pre-type 1 diabetic mice. Additionally higher lysophosphatidylinositol levels and low phosphatidylglycerol levels where novel findings in the pre-type 1 diabetic mice. These observations suggest that metabolomic disturbances precede the onset of T1D.......The early mechanisms regulating progression towards beta cell failure in type 1 diabetes (T1D) are poorly understood, but it is generally acknowledged that genetic and environmental components are involved. The metabolomic phenotype is sensitive to minor variations in both, and accordingly reflects...... changes that may lead to the development of T1D. We used two different extraction methods in combination with both liquid- and gas chromatographic techniques coupled to mass spectrometry to profile the metabolites in a transgenic non-diabetes prone C57BL/6 mouse expressing CD154 under the control...

  18. Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development.

    Directory of Open Access Journals (Sweden)

    Alain Bordon

    Full Text Available OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow: a first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Transcriptome analysis identified genes deregulated in these mice and Id2 and Id3, two known negative regulators of B cell differentiation, were found to be upregulated in the EPLM and preB cells of the transgenic mice. Furthermore, the Id2 and Id3 promoters contain octamer-like sites, to which OBF1 can bind. These results provide evidence that tight regulation of OBF1 expression in early B cells is essential to allow efficient B lymphocyte differentiation.

  19. Operating method of molten carbonate type fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Tsuneo

    1988-12-06

    Molten carbonate type fuel cell involves a problem of oxidation of anode while the unit is stopped. Although there is a method proposed wherein an inactive gas is supplied to anode during the stoppage, the market-available inactive gas contains a slight amount of oxygen which makes it difficult to prevent the deterioration of the anode. In this invention, at the start and the stop other than the normal operation, a protective gas mixture of an inactive gas with a small amount of hydrogen is supplied to the anode. The inactive gas is a commercial type nitrogen, argon or helium; hydrogen is mixed in amount 0.5 - 2.0% of the inactive gas. By this method, oxygen in air which comes in from the gas-sealed portion of the cell is reduced by hydrogen in the protective gas and is discharged in the form of water. 2 figs.

  20. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2014-09-01

    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  1. Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center

    International Nuclear Information System (INIS)

    Mac Manus, Michael P.; Wong, Kevin; Hicks, Rodney J.; Matthews, Jane P.; Wirth, Andrew; Ball, David L.

    2002-01-01

    Purpose: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. Methods and Materials: Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I-III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. Results: Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p=0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. Conclusion: Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging

  2. Delicate balance among three types of T cells in concurrent regulation of tumor immunity.

    Science.gov (United States)

    Izhak, Liat; Ambrosino, Elena; Kato, Shingo; Parish, Stanley T; O'Konek, Jessica J; Weber, Hannah; Xia, Zheng; Venzon, David; Berzofsky, Jay A; Terabe, Masaki

    2013-03-01

    The nature of the regulatory cell types that dominate in any given tumor is not understood at present. Here, we addressed this question for regulatory T cells (Treg) and type II natural killer T (NKT) cells in syngeneic models of colorectal and renal cancer. In mice with both type I and II NKT cells, or in mice with neither type of NKT cell, Treg depletion was sufficient to protect against tumor outgrowth. Surprisingly, in mice lacking only type I NKT cells, Treg blockade was insufficient for protection. Thus, we hypothesized that type II NKT cells may be neutralized by type I NKT cells, leaving Tregs as the primary suppressor, whereas in mice lacking type I NKT cells, unopposed type II NKT cells could suppress tumor immunity even when Tregs were blocked. We confirmed this hypothesis in 3 ways by reconstituting type I NKT cells as well as selectively blocking or activating type II NKT cells with antibody or the agonist sulfatide, respectively. In this manner, we showed that blockade of both type II NKT cells and Tregs is necessary to abrogate suppression of tumor immunity, but a third cell, the type I NKT cell, determines the balance between these regulatory mechanisms. As patients with cancer often have deficient type I NKT cell function, managing this delicate balance among 3 T-cell subsets may be critical for the success of immunotherapy for human cancer. ©2012 AACR.

  3. Trophic significance of solitary cells of the prymnesiophyte Phaeocystis globosa depends on cell type

    DEFF Research Database (Denmark)

    Dutz, Jörg; Koski, Marja

    2006-01-01

    With the use of five different isolates of Phaeocystis globosa solitary cells from the North Sea, we conducted experiments to reveal whether grazing and development of the nauplii of the calanoid copepod Temora longicornis varies in response to the cell type. Two P. globosa strains representing n...

  4. Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

    Directory of Open Access Journals (Sweden)

    Ian A Cockburn

    2010-05-01

    Full Text Available Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

  5. Allogeneic MSCs and Recycled Autologous Chondrons Mixed in a One-Stage Cartilage Cell Transplantion: A First-in-Man Trial in 35 Patients.

    Science.gov (United States)

    de Windt, Tommy S; Vonk, Lucienne A; Slaper-Cortenbach, Ineke C M; Nizak, Razmara; van Rijen, Mattie H P; Saris, Daniel B F

    2017-08-01

    MSCs are known as multipotent mesenchymal stem cells that have been found capable of differentiating into various lineages including cartilage. However, recent studies suggest MSCs are pericytes that stimulate tissue repair through trophic signaling. Aimed at articular cartilage repair in a one-stage cell transplantation, this study provides first clinical evidence that MSCs stimulate autologous cartilage repair in the knee without engrafting in the host tissue. A phase I (first-in-man) clinical trial studied the one-stage application of allogeneic MSCs mixed with 10% or 20% recycled defect derived autologous chondrons for the treatment of cartilage defects in 35 patients. No treatment-related serious adverse events were found and statistically significant improvement in clinical outcome shown. Magnetic resonance imaging and second-look arthroscopies showed consistent newly formed cartilage tissue. A biopsy taken from the center of the repair tissue was found to have hyaline-like features with a high concentration of proteoglycans and type II collagen. DNA short tandem repeat analysis delivered unique proof that the regenerated tissue contained patient-DNA only. These findings support the hypothesis that allogeneic MSCs stimulate a regenerative host response. This first-in-man trial supports a paradigm shift in which MSCs are applied as augmentations or "signaling cells" rather than differentiating stem cells and opens doors for other applications. Stem Cells 2017;35:1984-1993. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  6. Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

    Science.gov (United States)

    Iakovakis, Dimitrios; Hadjidimitriou, Stelios; Charisis, Vasileios; Bostantzopoulou, Sevasti; Katsarou, Zoe; Hadjileontiadis, Leontios J

    2018-05-16

    Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

  7. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    International Nuclear Information System (INIS)

    Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  8. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  9. New type of cells with multiple chromosome rearrangements

    International Nuclear Information System (INIS)

    Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

    2008-01-01

    Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

  10. Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Ryuji; Takada, Yoshiki; Obayashi, Kayoko; Kado, Tetsuji; Yamamoto, Hiroyuki; Hirota, Saeko; Soejima, Toshinori; Suzuki, Yasushi; Mimura, Fumitoshi [Hyogo Medical Center for Adult Disease, Akashi (Japan)

    1994-12-01

    In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m{sup 2}) on day 1 and vindesine (3mg/m{sup 2}) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author).

  11. Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Inoue, Ryuji; Takada, Yoshiki; Obayashi, Kayoko; Kado, Tetsuji; Yamamoto, Hiroyuki; Hirota, Saeko; Soejima, Toshinori; Suzuki, Yasushi; Mimura, Fumitoshi

    1994-01-01

    In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m 2 ) on day 1 and vindesine (3mg/m 2 ) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author)

  12. Clinical outcome of stage III non-small-cell lung cancer patients after definitive radiotherapy.

    Science.gov (United States)

    Nakamura, Tatsuya; Fuwa, Nobukazu; Kodaira, Takeshi; Tachibana, Hiroyuki; Tomoda, Takuya; Nakahara, Rie; Inokuchi, Haruo

    2008-01-01

    Primarily combined radiotherapy and chemotherapy are used to treat unresectable non-small-cell lung cancer; however, the results are not satisfactory. In this study treatment results were retrospectively analyzed and the prognostic factors related to survival were identified. From March 1999 to January 2004, 102 patients with stage IIIA/IIIB non-small-cell lung cancer received definitive radiotherapy with or without chemotherapy. Radiotherapy involved a daily dose of 1.8-2.0 Gy five times a week; 60 Gy was set as the total dose. Maximal chemotherapy was given to patients with normal kidney, liver, and bone marrow functions. The 5-year overall survival rate was 22.2%; the median survival was 18 months. The median follow-up of surviving patients was 53 months. The complete or partial response rate was 85%. At the time of the last follow-up, 21 patients were alive and 81 patients had died, including 5 patients who had died due to radiation pneumonitis. There were significant differences in survival and in the fatal radiation pneumonitis rate between patients with superior lobe lesions and those with middle or inferior lobe lesions. Patients whose primary tumor is located in the superior lobe appear to have a better clinical outcome.

  13. Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal.

    Science.gov (United States)

    Masetto, Sergio; Zampini, Valeria; Zucca, Giampiero; Valli, Paolo

    2005-11-01

    Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

  14. The Functions of Type I and Type II Natural Killer T (NKT) Cells in Inflammatory Bowel Diseases

    Science.gov (United States)

    Liao, Chia-Min; Zimmer, Michael I.; Wang, Chyung-Ru

    2013-01-01

    CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines upon activation and play a critical role in regulating various immune responses. NKT cells are classified into two groups based on differences in T cell receptor (TCR) usage. Type I NKT cells have an invariant TCRα-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. Type II NKT cells have a more diverse TCR repertoire and cannot be directly identified. Both types of NKT cells as well as multiple CD1d-expressing cell types are present in the intestine and their interactions are likely to be modulated by pathogenic and commensal microbes, which in turn contribute to the intestinal immune responses in health and disease. Indeed, in several animal models of inflammatory bowel disease (IBD), Type I NKT cells have been shown to make both protective and pathogenic contributions to disease. In contrast, in human patients suffering from ulcerative colitis (UC), and a mouse model in which both CD1d expression and the frequency of Type II NKT cells are increased, Type II NKT cells appear to promote intestinal inflammation. In this review, we summarize present knowledge on the antigen recognition, activation and function of NKT cells with a particular focus on their role in IBD, and discuss factors that may influence the functional outcome of NKT cell responses in intestinal inflammation. PMID:23518808

  15. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition

    NARCIS (Netherlands)

    Gervin, K. (Kristina); Page, C.M. (Christian Magnus); H.C.D. Aass (Hans Christian Dalsbotten); M.A.E. Jansen (Michelle); Fjeldstad, H.E. (Heidi Elisabeth); B.K. Andreassen (Bettina Kulle); L. Duijts (Liesbeth); J.B.J. van Meurs (Joyce); M.C. van Zelm (Menno); V.W.V. Jaddoe (Vincent); Nordeng, H. (Hedvig); Knudsen, G.P. (Gunn Peggy); P. Magnus (Per); W. Nystad (Wenche); Staff, A.C. (Anne Cathrine); J.F. Felix (Janine); R. Lyle (Robert)

    2016-01-01

    textabstractEpigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused

  16. Role of Nutritional Factors at the Early Life Stages in the Pathogenesis and Clinical Course of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Yukiko Kagohashi

    2015-01-01

    Full Text Available Nutrition has been suggested as an important environmental factor other than viruses and chemicals in the pathogenesis of type 1 diabetes (T1D. Whereas various maternal dietary nutritional elements have been suggested and examined in T1D of both humans and experimental animals, the results largely remain controversial. In a series of studies using T1D model nonobese diabetic (NOD mice, maternal dietary n-6/n-3 essential fatty acid ratio during pregnancy and lactation period, that is, early life stages of the offspring, has been shown to affect pathogenesis of insulitis and strongly prevent overt T1D of the offspring, which is consistent with its preventive effects on other allergic diseases.

  17. Evaluation of the effectiveness of diabetic nephropathy stage III in patients with type 2 diabetes mellitus therapy with sulodexide

    Directory of Open Access Journals (Sweden)

    V. G. Kadzharyan

    2013-08-01

    Full Text Available Introduction. Diabetes mellitus (DM - takes the main place in the structure of endocrine diseases, and the third after cardiovascular and cancer pathology. In Ukraine 1.2 million of people suffer from diabetes and type 2 diabetes occurs in 85-90% of them. In 2004, 3.4 million of people died from diabetes complications. Diabetic nephropathy (DN is a serious chronic complication of diabetes that leads to the formation of nodular or diffuse glomerulosclerosis. It is the most frequent cause of terminal chronic renal failure (CRF in the world, accounting for over 25% of all cases of CRF. The generally accepted classification is Moggensen`s classification (1983, WHO, according to which five stages of diabetic nephropathy are identified, the first two stages of them are preclinical. Leading role in the pathogenesis of DN takes hyperglycemia, which is implemented by the phenomenon of glucosetoxicity. A lot of facts underscore the importance of inflammatory mechanisms triggered by cytokines. There's immune and non-immune theory of DN. The basis of non-immune theory is a violation of the synthesis of glycosaminoglycans (GAGs that are a major component of the glomerular basement membrane (GMB. GAGs create its negative charge, which prevents the passage through the renal filter small negatively charged molecules, including albumin. In hemodynamic regulation leading role belongs to the renin-angiotensin-aldosterone system (RAAS. The blockade of the RAAS system with ACE inhibitors is the basis of a treatment strategy of DN. All mentioned above became a reason for study of the possibility of a new direction in the treatment of DN using the drug sulodexid, which is a natural mixture of GAGs. Objective of the research. Evaluating the effectiveness of sulodexide therapy of DN stage III in patients with type 2 diabetes. Materials and methods. The patients were divided into 2 groups. Group I consisted of 24 patients aged 40 to 68 years. 5 of them were women and 19

  18. Cell- and stage-specific chromatin structure across the Complement receptor 2 (CR2/CD21) promoter coincide with CBF1 and C/EBP-beta binding in B cells.

    Science.gov (United States)

    Cruickshank, Mark N; Fenwick, Emily; Karimi, Mahdad; Abraham, Lawrence J; Ulgiati, Daniela

    2009-08-01

    Stringent developmental transcription requires multiple transcription factor (TF) binding sites, cell-specific expression of signaling molecules, TFs and co-regulators and appropriate chromatin structure. During B-lymphopoiesis, human Complement receptor 2 (CR2/CD21) is detected on immature and mature B cells but not on B cell precursors and plasma cells. We examined cell- and stage-specific human CR2 gene regulation using cell lines modeling B-lymphopoiesis. Chromatin accessibility assays revealed a region between -409 and -262 with enhanced accessibility in mature B cells and pre-B cells, compared to either non-lymphoid or plasma cell-types, however, accessibility near the transcription start site (TSS) was elevated only in CR2-expressing B cells. A correlation between histone acetylation and CR2 expression was observed, while histone H3K4 dimethylation was enriched near the TSS in both CR2-expressing B cells and non-expressing pre-B cells. Candidate sites within the CR2 promoter were identified which could regulate chromatin, including a matrix attachment region associated with CDP, SATB1/BRIGHT and CEBP-beta sites as well as two CBF1 sites. ChIP assays verified that both CBF1 and C/EBP-beta bind the CR2 promoter in B cells raising the possibility that these factors facilitate or respond to alterations in chromatin structure to control the timing and/or level of CR2 transcription.

  19. Aortic superoxide production at the early hyperglycemic stage in a rat type 2 diabetes model and the effects of pravastatin.

    Science.gov (United States)

    Kikuchi, Chigusa; Kajikuri, Junko; Hori, Eisei; Nagami, Chie; Matsunaga, Tamihide; Kimura, Kazunori; Itoh, Takeo

    2014-01-01

    Endothelium-derived superoxide induces vascular dysfunctions. The aim of this study was to examine the activity of protein kinase C (PKC) isoforms and endothelial nitric oxide synthase (eNOS), which leads to vascular superoxide production in type 2 diabetes, in addition to the effects of pravastatin. We studied these mechanisms in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycemic stage (vs. non-diabetic Long-Evans Tokushima Otsuka [LETO] rats). Superoxide production and catalase activity were measured in aortas, as were the protein expressions of PKCδ and phospho-Ser(1177) eNOS. Superoxide production was increased in OLETF rats, and this increase was inhibited by the selective conventional PKC (cPKC) inhibitor Gö6976 and by the non-selective cPKC and novel PKC inhibitor GF109203X. Phospho-Ser(1177) eNOS was significantly increased in OLETF rats, whereas the protein expressions of PKCδ and phosopho-Thr(505) PKCδ and catalase activity were all greatly reduced. Pravastatin administration to OLETF rats in vivo had normalizing effects on all of these variables. The increment in superoxide production seen in OLETF rats (but not the production in pravastatin-treated OLETF rats) was abolished by high concentration of N(ω)-nitro-L-arginine methyl ester (electron transport inhibitor of eNOS), by sepiapterin (precursor of tetrahydrobiopterin), and by LY294002 (phosphatidylinositol 3-kinase [PI3-kinase] inhibitor). In OLETF rats at the early hyperglycemic stage, aortic superoxide production is increased owing to activation of uncoupled eNOS through phosphorylation by PI3-kinase/Akt. This may be related to the observed reduction in PKCδ/catalase activities. Pravastatin inhibited endothelial superoxide production via normalization of PKCδ/catalase activities.

  20. One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Creemers, L.B.; Tsuchida, A.I.; van Rijen, M.H.P.; Custers, R.J.H.; Dhert, W.J.A.; Saris, Daniël B.F.

    2013-01-01

    Objective The combination of chondrocytes and mononuclear fraction (MNF) cells might solve the expansion induced dedifferentiation problem of reimplanted cells in autologous chondrocytes implantation as sufficient cells would be available for direct, one-stage, implantation. Earlier in vitro work

  1. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  2. Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.

    Science.gov (United States)

    Bao, Zhiyao; Han, Xuelin; Chen, Fangyan; Jia, Xiaodong; Zhao, Jingya; Zhang, Changjian; Yong, Chen; Tian, Shuguang; Zhou, Xin; Han, Li

    2015-08-13

    The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. β-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.

  3. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  4. Sourcing of an alternative pericyte-like cell type from peripheral blood in clinically relevant numbers for therapeutic angiogenic applications.

    Science.gov (United States)

    Blocki, Anna; Wang, Yingting; Koch, Maria; Goralczyk, Anna; Beyer, Sebastian; Agarwal, Nikita; Lee, Michelle; Moonshi, Shehzahdi; Dewavrin, Jean-Yves; Peh, Priscilla; Schwarz, Herbert; Bhakoo, Kishore; Raghunath, Michael

    2015-03-01

    Autologous cells hold great potential for personalized cell therapy, reducing immunological and risk of infections. However, low cell counts at harvest with subsequently long expansion times with associated cell function loss currently impede the advancement of autologous cell therapy approaches. Here, we aimed to source clinically relevant numbers of proangiogenic cells from an easy accessible cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a biotechnological platform, we derived a novel cell type from peripheral blood that is generated within 5 days in large numbers (10-40 million cells per 100 ml of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin, but exhibits pericyte markers PDGFR-β and NG2 and demonstrates strong angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings suggest that BDACs represent an alternative pericyte-like cell population of hematopoietic origin that is involved in promoting early stages of microvasculature formation. As a proof of principle of BDAC efficacy in an ischemic disease model, BDAC injection rescued affected tissues in a murine hind limb ischemia model by accelerating and enhancing revascularization. Derived from a renewable tissue that is easy to collect, BDACs overcome current short-comings of autologous cell therapy, in particular for tissue repair strategies.

  5. Theoretical and experimental investigations on the cooling capacity distributions at the stages in the thermally-coupled two-stage Stirling-type pulse tube cryocooler without external precooling

    Science.gov (United States)

    Tan, Jun; Dang, Haizheng

    2017-03-01

    The two-stage Stirling-type pulse tube cryocooler (SPTC) has advantages in simultaneously providing the cooling powers at two different temperatures, and the capacity in distributing these cooling capacities between the stages is significant to its practical applications. In this paper, a theoretical model of the thermally-coupled two-stage SPTC without external precooling is established based on the electric circuit analogy with considering real gas effects, and the simulations of both the cooling performances and PV power distribution between stages are conducted. The results indicate that the PV power is inversely proportional to the acoustic impedance of each stage, and the cooling capacity distribution is determined by the cold finger cooling efficiency and the PV power into each stage together. The design methods of the cold fingers to achieve both the desired PV power and the cooling capacity distribution between the stages are summarized. The two-stage SPTC is developed and tested based on the above theoretical investigations, and the experimental results show that it can simultaneously achieve 0.69 W at 30 K and 3.1 W at 85 K with an electric input power of 330 W and a reject temperature of 300 K. The consistency between the simulated and the experimental results is observed and the theoretical investigations are experimentally verified.

  6. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Directory of Open Access Journals (Sweden)

    Joseph L Baker

    2013-04-01

    Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

  7. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Science.gov (United States)

    Baker, Joseph L; Biais, Nicolas; Tama, Florence

    2013-04-01

    Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P) from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD) simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon stretching.

  8. Quality of Life After Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Voort van Zyp, Noelle C. van der; Prevost, Jean-Briac; Holt, Bronno van der; Braat, Cora; Klaveren, Robertus J. van; Pattynama, Peter M.; Levendag, Peter C.; Nuyttens, Joost J.

    2010-01-01

    Purpose: To determine the impact of stereotactic radiotherapy on the quality of life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Overall survival, local tumor control, and toxicity were also evaluated in this prospective study. Methods and Materials: From January 2006 to February 2008, quality of life, overall survival, and local tumor control were assessed in 39 patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were treated with stereotactic radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ LC13 lung cancer-specific questionnaire were used to investigate changes in quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4, 6, 9, and 12 months after treatment, until death or progressive disease. Toxicity was evaluated using common terminology criteria for adverse events version 3.0. Results: Emotional functioning improved significantly after treatment. Other function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and coughing) showed no significant changes. The overall 2-year survival rate was 62%. After a median follow-up of 17 months, 1 patient had a local recurrence (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity consisted of thoracic pain, which occurred in 1 patient within 4 months of treatment, while it occurred thereafter in 2 patients. Conclusions: Quality of life was maintained, and emotional functioning improved significantly after stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local tumor control was high, and toxicity was low.

  9. Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zuliani, Antonio Carlos; Cunha, Maercio de Oliveira, E-mail: aczo.rt@gmail.co [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Esteves, Sergio C.B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Secao de Radioterapia; Teixeira, Julio Cesar [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Tocoginecologia

    2010-07-01

    Objective: to compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. Methods: between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. Results: the five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. Conclusion: patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups. (author)

  10. Consequences of Late-Stage Non-Small-Cell Lung Cancer Cachexia on Muscle Metabolic Processes.

    Science.gov (United States)

    Murton, Andrew J; Maddocks, Matthew; Stephens, Francis B; Marimuthu, Kanagaraj; England, Ruth; Wilcock, Andrew

    2017-01-01

    The loss of muscle is common in patients with advanced non-small-cell lung cancer (NSCLC) and contributes to the high morbidity and mortality of this group. The exact mechanisms behind the muscle loss are unclear. To investigate this, 4 patients with stage IV NSCLC who met the clinical definitions for sarcopenia and cachexia were recruited, along with 4 age-matched healthy volunteers. After an overnight fast, biopsy specimens were obtained from the vastus lateralis, and the key components associated with inflammation and the control of muscle protein, carbohydrate, and fat metabolism were assessed. Compared with the healthy volunteers, significant increases in mRNA levels for interleukin-6 and NF-κB signaling and lower intramyocellular lipid content in slow-twitch fibers were observed in NSCLC patients. Although a significant decrease in phosphorylation of the mechanistic target of rapamycin (mTOR) signaling protein 4E-BP1 (Ser 65 ) was observed, along with a trend toward reduced p70 S6K (Thr 389 ) phosphorylation (P = .06), no difference was found between groups for the mRNA levels of MAFbx (muscle atrophy F box) and MuRF1 (muscle ring finger protein 1), chymotrypsin-like activity of the proteasome, or protein levels of multiple proteasome subunits. Moreover, despite decreases in intramyocellular lipid content, no robust changes in mRNA levels for key proteins involved in insulin signaling, glycolysis, oxidative metabolism, or fat metabolism were observed. These findings suggest that examining the contribution of suppressed mTOR signaling in the loss of muscle mass in late-stage NSCLC patients is warranted and reinforces our need to understand the potential contribution of impaired fat metabolism and muscle protein synthesis in the etiology of cancer cachexia. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Fluorodeoxyglucose positron emission tomography in the initial staging of germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hain, S.F.; O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospitals, London (United Kingdom); Timothy, A.R.; Leslie, M.D.; Partridge, S.E. [Dept. of Clinical Oncology, Guy' s and St Thomas' Hospitals, London (United Kingdom); Huddart, R.A. [Dept. of Radiotherapy and Oncology, Royal Marsden, Surrey (United Kingdom)

    2000-05-01

    Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease. (orig.)

  12. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    Science.gov (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Langendijk, Johannes A.; Aaronson, Neil K.; Jong, Jos M.A. de; Velde, Guul P.M. ten; Muller, Martin J.; Slotman, Ben J.; Wouters, Emiel F.M.

    2002-01-01

    Purpose: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. Patients and Methods: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. Results: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. Conclusions: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence

  14. The Role of Postoperative Radiotherapy on Stage N2 Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fangfang DU

    2009-11-01

    Full Text Available Background and objective The clinical value of postoperative radiotherapy (PORT in stage N2 nonsmall-cell lung cancer (NSCLC is controversy. The aim of this study is to analyze the efficacy of PORT in subgroup of stage N2 NSCLC, which can help clinicians to choose proper patients for PORT. Methods Clinical data of 359 patients with stage N2 NSCLC treated with radical surgery between Mar. 2000 and Jul. 2005 were retrospectively reviewed. Two hundred and seven patients received adjuvant chemotherapy and one hundred and four patients received adjuvant radiotherapy. First, the group of patients were analyzed to evaluate the factors affecting the overall survival. The all patients were divided based on tumor size and the number of lymph node metastasis station (single station or multiple station so as to evaluate the role of PORT. The endpoint was overall survival (OS and local recurrence-free survival (LRFS. Kaplan-Meier method was used to calculate the OS, LRFS and Log-rank was used to compare the difference in OS and LRFS between different groups. Results The median duration of follow-up was 2.3 years. 224 patients died. The median survival was 1.5 years and 1, 3, 5-year survival were 78%, 38% and 26%. Univariate analysis showed tumor size, the number of lymph node metastasis station and PORT were correlated with OS. Among patients, 5-year survival rates in PORT and non-PORT were 29% and 24% (P=0.047 respectively. In subgroups, PORT was related with high survival in patients with multiple station N2 compared to non-PORT: 36% vs 20% (P=0.013 and 33% vs 15% (P=0.002 in patients in patients with tumor size > 3 cm. Also, it was related with low local recurrence compared to non-PORT: 65% vs 48% (P=0.006 and 62% vs 48% (P=0.033. Conclusion PORT can improve overall survival for N2 NSCLC, especially the patients with the factors as follows: tumor size > 3 cm and multiple station N2 can benefit from PORT more or less.

  15. Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Simone, Charles B. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gajjar, Sameer R. [Baylor College of Medicine, Houston, Texas (United States); Shah, Chirag [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Zhen, Weining [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Harkenrider, Matthew M. [Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois (United States); Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Jabbour, Salma K. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey (United States); Matthiesen, Chance L. [Department of Radiation Oncology, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma (United States); Braunstein, Steve E. [Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, California (United States); Lee, Percy [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Allen, Bryan G. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Nichols, Elizabeth M. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); and others

    2017-02-01

    Purpose: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. Methods and Materials: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. Results: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and “elsewhere lung” (20.8%). The median time to each was 5 to 7 months. Conclusions: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50

  16. Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

    Science.gov (United States)

    Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

    2015-01-01

    Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

  17. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    International Nuclear Information System (INIS)

    Rades, Dirk; Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-01-01

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin ≥12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin ≥12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p 1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results

  18. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  19. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    International Nuclear Information System (INIS)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki

    2015-01-01

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture

  20. Endogenous Jaagsiekte Sheep Retrovirus RNA is expressed by different cell types in ovine foetus and placenta

    Directory of Open Access Journals (Sweden)

    E Sanna

    2010-01-01

    Full Text Available The endogenous retroviruses are inherited elements transmitted trough the germline of most animal species and their biological role is still controversial. Ovine Pulmonary Carcinoma (OPC represents a good model for studying the interactions of endogenous retroviruses with their exogenous counterparts. The type D exogenous retrovirus known as Jaagsiekte Sheep Retro-Virus (JSRV is necessary and sufficient to cause OPC in domestic and wild sheep, but both affected and unaffected animals host in their genome 15 to 20 copies of related endogenous retroviruses named endogenous JSRV (enJSRV. In this study we evaluated the expression of enJSRV gag sequences in ovine foetal and placental tissues. RNA in situ hybridisation was performed on tissue sections of thymi, lymph nodes and lungs from ovine foetuses and related placentas, taken at a late stage of development. Reverse transcriptase- in situ polymerase chain reactions were also carried out on placental samples to better define the involved cells. In foetal tissues, specific signals were observed in the thymus medulla, lymph nodes and, at a lesser extent, in foetal bronchiolar cells. In the placental tissues, positive areas were detected in various cell types in the sincythium-and cyto-trophoblast. These data demonstrate that en JSRV RNA is largely expressed in a broad spectrum of cells including tissues which are critical for the development of the immune system.

  1. SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C; Yin, Y [Shandong Cancer Hospital, Jinan, Shandong (China)

    2014-06-01

    Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters were derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.

  2. Milk losses associated with somatic cell counts by parity and stage of lactation.

    Science.gov (United States)

    Gonçalves, Juliano L; Cue, Roger I; Botaro, Bruno G; Horst, José A; Valloto, Altair A; Santos, Marcos V

    2018-05-01

    The reduction of milk production caused by subclinical mastitis in dairy cows was evaluated through the regression of test-day milk yield on log-transformed somatic cell counts (LnSCC). Official test-day records (n = 1,688,054) of Holstein cows (n = 87,695) were obtained from 719 herds from January 2010 to December 2015. Editing was performed to ensure both reliability and consistency for the statistical analysis, and the final data set comprised 232,937 test-day records from 31,692 Holstein cows in 243 herds. A segmented regression was fitted to estimate the cutoff point in the LnSCC scale where milk yield started to be affected by mastitis. The statistical model used to explain daily milk yield included the effect of herd as a random effect and days in milk and LnSCC as fixed effects regressions, and analyses were performed by parity and stage of lactation. The cutoff point where milk yield starts to be affected by changes in LnSCC was estimated to be around 2.52 (the average of all estimates of approximately 12,400 cells/mL) for Holsteins cows from Brazilian herds. For first-lactation cows, milk losses per unit increase of LnSCC had estimates around 0.68 kg/d in the beginning of the lactation [5 to 19 d in milk (DIM)], 0.55 kg/d in mid-lactation (110 to 124 DIM), and 0.97 kg/d at the end of the lactation (289 to 304 DIM). For second-lactation cows, milk losses per unit increase of LnSCC had estimates around 1.47 kg/d in the beginning of the lactation (5 to 19 DIM), 1.09 kg/d in mid-lactation (110 to 124 DIM), and 2.45 kg/d at the end of the lactation (289 to 304 DIM). For third-lactation cows, milk losses per unit increase of LnSCC had estimates around 2.22 kg/d in the beginning of the lactation (5 to 19 DIM), 1.13 kg/d in mid-lactation (140 to 154 DIM), and 2.65 kg/d at the end of the lactation (289 to 304 DIM). Daily milk losses caused by increased LnSCC were dependent on parity and stage of lactation, and these factors should be considered when estimating

  3. [Experimental-morphological study of morphogenetic potencies of homogeneous aggregates of different types of cells from the freshwater sponge Ephydatia fluviatilis (L.)].

    Science.gov (United States)

    Nikitin, N S

    1977-01-01

    The morphogenetic potencies of somatic cells of the fresh-water sponge Ephydatia fluviatilis in the developing aggregates depend on their initial specialization and the number of cells in the aggregate. The aggregates of nucleolar amoebocytes consisting of 500 or more cells have the highest morphogenetic potencies. All main cell types can arise in the developing homogeneous aggregates of nucleolar amoebocytes. The fine structure of nucleolar amoebocytes at different stages of development of the homogeneous aggregates was studied by means of electron microscopy. The structural rearrangements are described which accompany the process of redifferentiation of the nucleolar amoebocytes in other cell types.

  4. The prognostic effect of subpleural lesions in early stage non-small cell lung cancer: preliminary report

    International Nuclear Information System (INIS)

    Lee, Ho Jun; Lee, Hyung Sik; Hur, Won Joo; Lee, Ki Nam; Choi, Pill Jo

    1998-01-01

    We retrospectively analyzed the impact of subpleural lesions of early stage non-small cell lung cancer on the patterns of failure to support selection of postoperative adjuvant therapy. The study included 91 patients who underwent surgery for early stage non-small cell lung cancer at Donga University hospital from Dec 1990 to Sep 1996. Twenty five patients were excluded due to postoperative mortality (four patients, 4.4%) and stage III (21 patients). Of 66 patients, 22 patients were subpleural lesions (15 patients in stage I, and seven patients in stage II). Postoperative adjuvant radiation therapy was given to seven patients with T2N1 disease. The median follow-up duration was 29.5 months (range; 8-84 months). The overall survival rate was 69.5% at 3 years. For all patients who presented with (22 patients) and without (44 patients) subpleural lesions, 3-year overall survival rates were 35.5% and 84.6%, respectively (p=0.0017). For stage I patients who presented with (15 patients) and without (29 patients) subpleural lesions, 3-year overall survival rates were 33.1% and 92.3%, respectively (p=0.001). For stage II patients who presented with (7 patients) and without (15 patients) subpleural lesions, 3-year overall survival rates were 53.3% and 45.7%, respectively (p=0.911). For patients with T2NO disease (34 patients) who presented with (11 patients) and without (23 patients) subpleural lesions, 3-year overall survival rates were 27.3% and 90.3%,respectively (p=0.009).These observations suggest that the subpleural lesion play an important role as a prognostic factor for early stage non-small cell lung cancer. Especially for T2NO disease, patients with subpleural lesions showed significantly lower survival rate than those without that

  5. The social determinants of health for people with type 1 diabetes that progress to end-stage renal disease.

    Science.gov (United States)

    Hill, Kathleen E; Gleadle, Jonathan M; Pulvirenti, Mariastella; McNaughton, Darlene A

    2015-12-01

    Self-management of type 1 diabetes over a lifetime is complex and challenging even in the best of circumstances, and the social environment can be a powerful determinant of health behaviours and outcomes. The aim of this study was to identify how social determinants of health can impact on the capacity of young people to manage their glycaemic control. The findings emerged from a constructivist grounded theory approach through an in-depth examination of life course events that were recounted through qualitative interviews. The rich descriptive detail obtained from this enquiry locates common experiences and the context in which concordance with therapies occurs and health behaviours develop. This qualitative study of young people with type 1 diabetes who have developed end-stage renal disease demonstrates that there are many factors beyond individual control that can contribute to health outcomes. The social determinants of childhood environment, education, socio-economic status, gender and the culture of public health can contribute to disengagement from treatment regimens and the health-care system and to the development of microvascular complications at a comparatively young age. These findings challenge the assumptions of health-care practitioners about individual responsibility and highlight the importance of considering how social determinants can shape lives, behaviours and health. © 2014 John Wiley & Sons Ltd.

  6. Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

    Science.gov (United States)

    Boysen, Anders Kindberg; Wettergren, Yvonne; Sorensen, Boe Sandahl; Taflin, Helena; Gustavson, Bengt; Spindler, Karen-Lise Garm

    2017-11-01

    Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

  7. Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

    Science.gov (United States)

    Augustyniak, J; Lenart, J; Zychowicz, M; Lipka, G; Gaj, P; Kolanowska, M; Stepien, P P; Buzanska, L

    2017-12-01

    Pyrroloquinoline quinone (PQQ) is a factor influencing on the mitochondrial biogenesis. In this study the PQQ effect on viability, total cell number, antioxidant capacity, mitochondrial biogenesis and differentiation potential was investigated in human induced Pluripotent Stem Cells (iPSC) - derived: neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP). Here we demonstrated that sensitivity to PQQ is dependent upon its dose and neural stage of development. Induction of the mitochondrial biogenesis by PQQ at three stages of neural differentiation was evaluated at mtDNA, mRNA and protein level. Changes in NRF1, TFAM and PPARGC1A gene expression were observed at all developmental stages, but only at eNP were correlated with the statistically significant increase in the mtDNA copy numbers and enhancement of SDHA, COX-1 protein level. Thus, the "developmental window" of eNP for PQQ-evoked mitochondrial biogenesis is proposed. This effect was independent of high antioxidant capacity of PQQ, which was confirmed in all tested cell populations, regardless of the stage of hiPSC neural differentiation. Furthermore, a strong induction of GFAP, with down regulation of MAP2 gene expression upon PQQ treatment was observed. This indicates a possibility of shifting the balance of cell differentiation in the favor of astroglia, but more research is needed at this point. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney

    2010-10-01

    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  9. Two-sided effect of Cordyceps sinensis on dendritic cells in different physiological stages.

    Science.gov (United States)

    Li, Chia-Yang; Chiang, Chi-Shiun; Tsai, Min-Lung; Hseu, Ruey-Shyang; Shu, Wun-Yi; Chuang, Chun-Yu; Sun, Yuh-Chang; Chang, Yuan-Shiun; Lin, Jaung-Geng; Chen, Chih-Sheng; Huang, Ching-Lung; Hsu, Ian C

    2009-06-01

    Cordyceps sinensis (CS), a Chinese tonifying herb, has been widely used for centuries in Asian countries as a medicine and a health supplement. Although ample evidence indicates that CS can modulate immune responses, the functional effect of CS on dendritic cells (DCs) is still unclear. This study examines how CS affects human monocyte-derived DCs in two physiological states: naïve and LPS-induced inflammatory. Our experimental results demonstrate that CS acts as an activator and maturation inducer of immature DCs by stimulating the expression of costimulatory molecules and proinflammatory cytokines by DCs, enhancing the DC-induced, allogeneic T cell proliferation, and reducing the endocytic ability of DCs. In contrast, CS suppresses the LPS-induced, inflammatory response by decreasing the LPS-induced expression of costimulatory molecules and proinflammatory cytokines by DCs. CS also suppresses the LPS-induced, DC-elicited, allogeneic T cell proliferation and shifts the LPS-activated, DC-driven Th1 response toward a Th2 response. These results demonstrate that CS differentially regulates the DC activities according to the presence or absence of the inflammatory signs. Restated, with the lack of an ongoing inflammatory environment, CS primes DCs toward a Th1-type immunity, whereas in a potential inflammatory reaction, CS balances the over-reactivity of elicited Th1 immunity. This investigation illustrates the Yin-Yang balancing effects of CS as a medicine and a health supplement.

  10. Sapanisertib and Osimertinib in Treating Patients With Stage IV EGFR Mutation Positive Non-small Cell Lung Cancer After Progression on a Previous EGFR Tyrosine Kinase Inhibitor

    Science.gov (United States)

    2018-04-25

    EGFR Activating Mutation; EGFR Exon 19 Deletion Mutation; EGFR NP_005219.2:p.G719X; EGFR NP_005219.2:p.L858R; EGFR NP_005219.2:p.L861Q; EGFR T790M Mutation Negative; Recurrent Non-Small Cell Lung Carcinoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

  11. High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

    Science.gov (United States)

    de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

    2018-05-09

    Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  12. ER Stress and β-Cell Pathogenesis of Type 1 and Type 2 Diabetes and Islet Transplantation

    OpenAIRE

    Kataoka, Hitomi Usui; Noguchi, Hirofumi

    2013-01-01

    Endoplasmic reticulum (ER) stress affects the pathogenesis of diabetes. ER stress plays important roles, both in type 1 and type 2 diabetes, because pancreatic β-cells possess highly developed ER for insulin secretion. This review summarizes the relationship between ER stress and the pathogenesis of type 1 and type 2 diabetes. In addition, the association between islet transplantation and ER stress is discussed.

  13. Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Rubenstein, James H.; Dosoretz, Daniel E.; Katin, Michael J.; Blitzer, Peter H.; Salenius, Sharon A.; Floody, Patrick A.; Harwin, William N.; Teufel, Thomas E.; Raymond, Michael G.; Reeves, James A.; Hart, Lowell L.; McCleod, Michael J.; Pizarro, Alejandro; Gabarda, Antonio L.; Rana, Van G.

    1995-01-01

    Purpose: Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. Methods and Materials: One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. Results: Patients receiving PCI exhibited brain failure in 15%, while 38% of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS ≥ 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). Conclusion: In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials

  14. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  15. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Cell-type-specific gene delivery into neuronal cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Parveen, Zahida; Mukhtar, Muhammad; Rafi, Mohammed; Wenger, David A.; Siddiqui, Khwaja M.; Siler, Catherine A.; Dietzschold, Bernhard; Pomerantz, Roger J.; Schnell, Matthias J.; Dornburg, Ralph

    2003-01-01

    The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain

  17. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  18. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  19. Advances in the staging of renal cell carcinoma with high-resolution imaging

    International Nuclear Information System (INIS)

    Hallscheidt, P.; Noeldge, G.; Schawo, S.; Kauffmann, G.; Palmowski, M.; Bartling, S.; Pfitzenmaier, J.

    2007-01-01

    Modern imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) allow high-resolution imaging of the abdomen. Modern scanners made high temporal as well as high spatial resolution available. Therapeutic approaches to the treatment of renal cell carcinoma have been improved over the recent years. Besides conventional and open laparoscopic tumor nephrectomy and nephron sparing, surgical approaches such as local tumor cryotherapy and radiofrequency ablation (RF) are ablative modalities and are used increasingly. Improved anesthesiological methods and new surgical approaches also allow curative treatment in extended tumors. Prerequisites for preoperative imaging modalities include visualization of the kidney tumor as well as its staging. Tumor-related infiltration of the renal pelvis or invasion of the perinephric fat and the renal hilus has to be excluded prior to nephron sparing surgery. In cases with extended tumors with infiltration of the inferior vena cava, it is necessary to visualize the exact extension of the tumor growth towards the right atrium in the vena cava. The radiologist should be informed about the diagnostic possibilities and limitations of the imaging modalities of CT and MRI in order to support the urologist in the planning and performance of surgical therapeutical approaches. (orig.)

  20. Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

    International Nuclear Information System (INIS)

    Giuliani, Meredith E.; Lindsay, Patricia E.; Sun, Alexander; Bezjak, Andrea; Le, Lisa W.; Brade, Anthony; Cho, John; Leighl, Natasha B.; Shepherd, Frances A.; Hope, Andrew J.

    2012-01-01

    Purpose: To determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent. Methods: From 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure. The cumulative LR failure (LRF) rate was calculated. Distant failure-free survival (FFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Volumetric images of LR failures were delineated and registered with the original radiation treatment plans if available. Dosimetric parameters for the delineated failure volumes were calculated from the original treatment information. Results: The median follow-up was 19 months. The site of first failure was LR in 34, distant in 80 and simultaneous LR and distant in 31 patients. The cumulative LRF rate was 29% and 38% at 2 and 5 years. OS was 44% at 2 years. Seventy patients had electronically archived treatment plans of which there were 16 LR failures (7 local and 39 regional failure volumes). Of the local and regional failure volumes 29% and 31% were in-field, respectively. Conclusions: The predominant pattern of LR failure was marginal or out-of-field. LR failures may be preventable with improved radiotherapy target definition.

  1. Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

    Directory of Open Access Journals (Sweden)

    Gazzinelli R.T.

    1998-01-01

    Full Text Available Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host. Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

  2. White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type.

    Science.gov (United States)

    Rajmohan, Ravi; Anderson, Ronald C; Fang, Dan; Meyer, Austin G; Laengvejkal, Pavis; Julayanont, Parunyou; Hannabas, Greg; Linton, Kitten; Culberson, John; Khan, Hafiz M R; De Toledo, John; Reddy, P Hemachandra; O'Boyle, Michael

    2017-01-01

    In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC). We hypothesized that such activity would reflect an increased reliance on these structures to compensate for on-going neuronal loss in frontoparietal regions due to the disease. We used diffusion tensor imaging (DTI) to determine if white matter (WM) damage had occurred in frontoparietal regions as well. CDDAT participants had similar behavioral performance and no differences were observed in brain activity or connectivity patterns within the amygdalae or r-ACC. Decreased fractional anisotropy (FA) values were noted, however, for the bilateral superior longitudinal fasciculi and posterior cingulate cortex (PCC). We interpret these findings to suggest that emotional valence determination and non-verbal skill sets are largely intact at this stage of the disease, but signs foreshadowing future decline were revealed by possible WM deterioration. Understanding how non-verbal skill sets are altered, while remaining largely intact, offers new insights into how non-verbal communication may be more successfully implemented in the care of AD patients and highlights the potential role of DTI as a presymptomatic biomarker.

  3. Comparison of sample types and diagnostic methods for in vivo detection of Mycoplasma hyopneumoniae during early stages of infection.

    Science.gov (United States)

    Pieters, Maria; Daniels, Jason; Rovira, Albert

    2017-05-01

    Detection of Mycoplasma hyopneumoniae in live pigs during the early stages of infection is critical for timely implementation of control measures, but is technically challenging. This study compared the sensitivity of various sample types and diagnostic methods for detection of M. hyopneumoniae during the first 28days after experimental exposure. Twenty-one 8-week old pigs were intra-tracheally inoculated on day 0 with M. hyopneumoniae strain 232. Two age matched pigs were mock inoculated and maintained as negative controls. On post-inoculation days 0, 2, 5, 9, 14, 21 and 28, nasal swabs, laryngeal swabs, tracheobronchial lavage fluid, and blood samples were obtained from each pig and oral fluid samples were obtained from each room in which pigs were housed. Serum samples were assayed by ELISA for IgM and IgG M. hyopneumoniae antibodies and C-reactive protein. All other samples were tested for M. hyopneumoniae DNA by species-specific real-time PCR. Serum antibodies (IgG) to M. hyopneumoniae were detected in challenge-inoculated pigs on days 21 and 28. M. hyopneumoniae DNA was detected in samples from experimentally inoculated pigs beginning at 5days post-inoculation. Laryngeal swabs at all samplings beginning on day 5 showed the highest sensitivity for M. hyopneumoniae DNA Detection, while oral fluids showed the lowest sensitivity. Although laryngeal swabs are not considered the typical M. hyopneumoniae diagnostic sample, under the conditions of this study laryngeal swabs tested by PCR proved to be a practical and reliable diagnostic sample for M. hyopneumoniae detection in vivo during early-stage infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Dissecting engineered cell types and enhancing cell fate conversion via CellNet

    Science.gov (United States)

    Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

    2014-01-01

    SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

  5. Basal Cell Carcinoma in Type 2 Segmental Dariers Disease

    International Nuclear Information System (INIS)

    Robertson, L.; Sauder, M. B.

    2012-01-01

    Dariers disease (DD), also known as Keratosis Follicularis or Dariers-White disease, is a rare disorder of keratinisation. DD can present as a generalized autosomal dominant condition as well as a localized or segmental post zygotic condition (Vasquez et al., 2002). Clinical features of DD include greasy, warty papules and plaques on seborrhoeic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Dariers disease with only 8 previous cases reported to date. In addition, non melanoma skin cancer (NMSC) arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  6. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  7. An inhibitor of polyamine synthesis arrests cells at an earlier stage of G1 than does calcium deprivation.

    OpenAIRE

    Cheetham, B F

    1983-01-01

    Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation.

  8. An inhibitor of polyamine synthesis arrests cells at an earlier stage of G1 than does calcium deprivation.

    Science.gov (United States)

    Cheetham, B F

    1983-01-01

    Methylglyoxal bis(guanylhydrazone) completely inhibits the induction of thymidine kinase after serum stimulation of quiescent fibroblasts only if added within 3 h after serum, whereas calcium deprivation blocks this induction up to 12 h after serum stimulation. Experiments in which one of these blocks was imposed as the other was released confirmed that cells blocked by methylglyoxal bis(guanylhydrazone) are arrested at an earlier stage in G1 than cells blocked by calcium deprivation. PMID:6843551

  9. Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Finkle, Joshua H.; Jo, Stephanie Y.; Yuan, Cindy; Pu, Yonglin [University of Chicago, Department of Radiology, Chicago, IL (United States); Ferguson, Mark K. [University of Chicago, Department of Surgery, Chicago, IL (United States); Liu, Hai-Yan [First Hospital of Shanxi Medical University, Department of Nuclear Medicine, Taiyuan, Shanxi (China); Zhang, Chenpeng [Shanghai Jiao Tong University, Department of Nuclear Medicine, RenJi Hospital, School of Medicine, Shanghai (China); Zhu, Xuee [Nanjing Medical University, Department of Radiology, BenQ Medical Center, Nanjing, Jiangsu Province (China)

    2017-08-15

    Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTV{sub WB}) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTV{sub WB} to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTV{sub WB}, MTV{sub WB} may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTV{sub WB} in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTV{sub WB}, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTV{sub WB}. The optimal MTV{sub WB} cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTV{sub WB} cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTV{sub WB} (below 29.2 mL) and the stage IIIA patients with high MTV{sub WB} (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTV{sub WB} stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTV{sub WB} stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTV{sub WB} was observed in a large range of cutoff values from 15 to 55 mL in

  10. [Application of lateral malleolus hook-plate in treatment of stage II supination-adduction type medial malleolus fracture].

    Science.gov (United States)

    Chen, Yu; Zhang, Hui; Huang, Fuguo; Xiang, Zhuo; Fang, Yue; Liu, Lei; Cen, Shiqiang

    2014-09-01

    To investigate the application of lateral malleolus hook-plate for the treatment of stage II supination-adduction type medial malleolus fractures. Between January 2011 and June 2013, 21 patients with stage II supination-adduction type ankle fractures were treated with lateral malleolus hook-plate, including 12 males and 9 females with an average age of 55.5 years (range, 27-65 years). The injury causes were sprain in 17 cases and traffic accident in 4 cases. The mean time between injury and admission was 12.4 hours (range, 2-72 hours). The tibial distal medial articular surface collapse was found in 7 cases by CT examination and in 3 cases by X-ray film. Of 21 cases, there were 12 cases of low transverse fractures of lateral malleolus, 7 cases of short oblique fractures of lateral malleolus, and 2 cases of ankle joint lateral collateral ligament injury without fractures of lateral malleolus. After operation, the clinical outcome was evaluated according to the talus-leg angle, the recovery of Coin-sign continuity, inside-outside and top ankle gap, talus slope, American Orthopedic Foot and Ankle Society (AOFAS) score, Olerud-Molander score, Kofoed evaluation standards, and patient satisfaction. Seventeen cases were followed up 18.7 months on average (range, 12-25 months). Primary healing was obtained in 16 cases except 1 case of delayed healing. Fracture healed at an average of 14.6 weeks (range, 12-16 weeks). All cases achieved anatomical reduction, the continuity of Coin-sign, and consistency of inside and outside joint gap; no talus tilt occurred. There was no complication of reduction loss, loosening or breakage of internal fixation, or osteoarthritis during follow-up. The talus-leg angle of the affected side was significantly improved to (83.4 ± 1.8)° at 1 week after operation from preoperative (74.8 ± 7.1)° (t = 5.370, P = 0.000), but no significant difference was found when compared with normal side (83.8 ± 2.3)° (t = 0.676, P = 0.509). The AOFAS score

  11. Stages of change for physical activity and dietary habits in persons with type 2 diabetes included in a mobile health intervention: the Norwegian study in RENEWING HEALTH.

    Science.gov (United States)

    Holmen, Heidi; Wahl, Astrid; Torbjørnsen, Astrid; Jenum, Anne Karen; Småstuen, Milada Cvancarova; Ribu, Lis

    2016-01-01

    The aim of this study was to investigate stages of change for physical activity and dietary habits using baseline data from persons with type 2 diabetes included in a mobile health intervention. We examined the associations between stages of change for physical activity change and dietary change, and between stages of change for each behavior and individual characteristics, health-related quality of life, self-management, depressive symptoms, and lifestyle. We examined 151 persons with type 2 diabetes with an glycated hemoglobin (HbA1c) level ≥7.1%, aged ≥18 years at baseline of a randomized controlled trial, before testing a mobile app with or without health counseling. Stages of change were dichotomized into 'pre-action' and 'action'. Self-management was measured using the Health Education Impact Questionnaire (heiQ) where a higher score reflects increased self-management, and health-related quality of life was measured with the Short-Form-36 (SF-36). Logistic regression modeling was performed. The median HbA1c level was 7.9% (7.1-12.4), 90% were overweight or obese, and 20% had ≥3 comorbidities. 58% were in the preaction stage for physical activity change and 79% in the preaction stage for dietary change. Higher scores of self-management were associated with an increased chance of being in the action stage for both dietary change and physical activity change. Higher body mass index was associated with an 8% reduced chance of being in the action stage for physical activity change (OR 0.92, 95% CI 0.86 to 0.99). Being in the action stage was associated with higher scores of self-management, crucial for type 2 diabetes. Over half of the participants were in the preaction stage for physical activity and dietary change, and many had a high disease burden with comorbidities and overweight. NCT01315756.

  12. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Current treatments for advanced stage non-small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2009-04-15

    Lung cancer remains the leading cause of cancer mortality in the United States, and the majority of patients will have non-small cell lung cancer (NSCLC) and will present with locally advanced or metastatic disease. In the United States, the most common histology is adenocarcinoma, followed by squamous cell, large cell, and not otherwise specified. For patients with a preserved performance status (PS), double agent platinum-based therapy extends survival, improves quality of life (Qol), and reduces disease-related symptoms. The addition of a third cytotoxic agent increases toxicity without any clinical benefit. However, the addition of a targeted agent (bevacizumab, an antiangioegenesis agent, or cetuximab, an antibody against the epidermal growth factor receptor [EGFR]) to platinum-based therapy has yielded an improvement in survival compared with platinum-based therapy alone. To receive bevacizumab, patients are required to have nonsquamous histology, a PS of 0 or 1, and no evidence of brain metastases, hemoptysis, uncontrolled hypertension, and no need for therapeutic anticoagulation. The benefits of chemotherapy for patients with a poor performance status are less well defined, and the current recommendations are for treatment with single-agent chemotherapy. Elderly patients (defined as age > or = 70 yr) derive a survival and Qol benefit from chemotherapy treatment, and for the majority of elderly patients single-agent chemotherapy is the standard. However, elderly patients with a good performance status and without co-morbidities can tolerate platinum-based therapy without excessive toxicity and appear to derive a survival benefit similar to that in younger patients. Recently, a separate population of patients defined by a light or never-smoking history has been identified. This patient population appears to have unique clinical and molecular characteristics, and may benefit from initial therapy with an EGFR tyrosine kinase inhibitor. Once patients have

  14. Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Hung-Yuan Li

    Full Text Available Diabetes is the leading cause of end-stage renal disease (ESRD worldwide. Vascular adhesion protein-1 (VAP-1 participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD, and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects.In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay.Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001. Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01 for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%. We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively.In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to

  15. Value of 18F-FDG PET in Clinical Staging of Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Suwen Liu; Jinming Yu; Ligang Xing

    2005-01-01

    OBJECTIVE To evaluate the feasibility of 18F-deoxyglucose positron emission tomography (18F-FDG PET) in the staging of non-small cell lung cancer(NSCLC).METHODS 105 patients with NSCLC had been examined by 18F-FDG PET before radiotherapy. The results of the 18F-FDG PET examination were compared with those of CT:RESULTS The staging was changed in 38 patients because of 18F-FDG PET findings, with PET resulting in upstaging in 31 patients and downstaging in seven patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the seven downstaged patients underwent radical surgery, among which the PET findings were concordant with the pathological findings in five patients. Distant metastasis detected by PET elevated the pre-PET stage: at stage 110.0% (2/20), stage Ⅱ 14.3% (3/21 ) and stage Ⅲ 25.0% (16/64), respectively.CONCLUSION 18F-FDG PET, by changing clinical staging in 36.2% (38/105)of NSCLC patients, has an impact on treatment strategy in NSCLC patients.

  16. A patient perspective on shared decision making in stage I non-small cell lung cancer: a mixed methods study

    NARCIS (Netherlands)

    Hopmans, W.; Damman, O.C.; Senan, S.; Hartemink, K.J.; Smit, E.F.; Timmermans, D.R.M.

    2015-01-01

    Background: Surgery and stereotactic ablative radiotherapy (SABR) are both curative treatment options for patients with a stage I non-small cell lung cancer (NSCLC). Consequently, there is growing interest in studying the role of patients in treatment decision making. We studied how patients with

  17. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell