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Sample records for cells infiltrating central

  1. Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

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    Talita Maira Bueno da Silveira da Rocha

    2013-01-01

    Full Text Available OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7% patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5% patients of this cohort received rituximab as first-line treatment and nine (7.1% received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7% had parenchymal central nervous system involvement; seven (77.7% had stage III or IV disease; one (11.1% had bone marrow involvement; two (22.2% had received intrathecal chemoprophylaxis; and 3 (33.3% had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration

  2. Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system

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    Nielsen, Helle Hvilsted; Ladeby, Rune; Fenger, Christina;

    2009-01-01

    system. We investigated T-cell infiltration, myelin clearance, microglial activation, and phagocytic activity distal to sites of axonal transection through analysis of the perforant pathway deafferented dentate gyrus in SJL mice that had received T cells specific for myelin basic protein (TMBP...

  3. Neutrophils that infiltrate the central nervous system regulate T cell responses

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    Zehntner, Simone P; Brickman, Cristina; Bourbonnière, Lyne;

    2005-01-01

    Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1high......, and activated Gr-1high neutrophils within the target organ determines the outcome of inflammatory and potentially autoimmune T cell responses....

  4. Direct demonstration of the infiltration of murine central nervous system by Pgp-1/CD44high CD45RB(low) CD4+ T cells that induce experimental allergic encephalomyelitis

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    Zeine, R; Owens, T

    1992-01-01

    In experimental allergic encephalomyelitis (EAE), autoimmune T cells infiltrate the central nervous system (CNS) and initiate demyelinating pathology. We have used flow cytometry to directly analyse the migration to the CNS of MBP-reactive CD4+ T cells labelled with a lipophilic fluorescent dye (...

  5. Tumor infiltrating immune cells in gliomas and meningiomas.

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    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Miranda, David; Ruiz, Laura; Sousa, Pablo; Ciudad, Juana; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2016-03-01

    Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.

  6. Methylprednisolone inhibits IFN-γ and IL-17 expression and production by cells infiltrating central nervous system in experimental autoimmune encephalomyelitis

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    Mostarica-Stojković Marija

    2009-12-01

    Full Text Available Abstract Background Glucocorticoids have been shown to be effective in the treatment of autoimmune diseases of the CNS such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE. However, the mechanisms and the site of glucocorticoids' actions are still not completely defined. The aim of this study was to investigate the in vivo effect of the synthetic glucocorticoid methylprednisolone (MP on the expression and production of proinflammatory cytokines interferon (IFN-γ and interleukin (IL-17 by cells infiltrating CNS tissue. Methods Experimental autoimmune encephalomyelitis was induced in Dark Agouti (DA rats by immunization with rat spinal cord homogenate mixed with adjuvants. Commencing on the day when the first EAE signs appeared, DA rats were injected daily for 3 days with MP and/or RU486, an antagonist of glucocorticoid receptor. Cytokine production and gene expression in CNS-infiltrating cells and lymph node cells were measured using ELISA and real time PCR, respectively. Results Treatment of rats with MP ameliorated EAE, and the animals recovered without relapses. Further, MP inhibited IFN-γ and IL-17 expression and production in cells isolated from the CNS of DA rats with EAE after the last injection of MP. The observed effect of MP in vivo treatment was not mediated through depletion of CD4+ T cells among CNS infiltrating cells, or through induction of their apoptosis within the CNS. Finally, the glucocorticoid receptor-antagonist RU486 prevented the inhibitory effect of MP on IFN-γ and IL-17 production both in vitro and in vivo, thus indicating that the observed effects of MP were mediated through glucocorticoid receptor-dependent mechanisms. Conclusion Taken together, these results demonstrate that amelioration of EAE by exogenous glucocorticoids might be, at least partly, ascribed to the limitation of effector cell functions in the target tissue.

  7. Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis.

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    Wang, Liefeng; Du, Changsheng; Lv, Jie; Wei, Wei; Cui, Ye; Xie, Xin

    2011-09-01

    Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood-brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.

  8. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

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    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  9. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

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    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  10. Culture of graft-infiltrating cells from cryopreserved endomyocardial biopsies

    NARCIS (Netherlands)

    G.A. Patijn (G.); L.M.B. Vaessen (Leonard); W. Weimar (Willem); F.H.J. Claas (Frans); N.H.P.M. Jutte (Nicolet)

    1996-01-01

    textabstractGraft-infiltrating cells can be cultured from fresh endomyocardial biopsies (EMB) taken after heart transplantation to determine their growth patterns, phenotypic composition, and functional characteristics for clinical or scientific purposes. In this study we investigated whether graft-

  11. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis.

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    Rafik Menasria

    Full Text Available The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1 encephalitis (HSE. To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2 x 10(6 plaque forming units. Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P < 0.05 and "Ly6C hi" inflammatory monocytes (P < 0.001 significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P < 0.05 for inflammatory monocytes compared to non-infected controls to reach baseline levels on day 10 following infection. The percentage of "Ly6C low" patrolling monocytes significantly increased (P < 0.01 at a later time point (day 8, which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus

  12. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis

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    Menasria, Rafik; Canivet, Coraline; Piret, Jocelyne; Boivin, Guy

    2015-01-01

    The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE). To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2x106 plaque forming units). Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P<0.05) and «Ly6Chi» inflammatory monocytes (P<0.001) significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P<0.05 for inflammatory monocytes compared to non-infected controls) to reach baseline levels on day 10 following infection. The percentage of «Ly6Clow» patrolling monocytes significantly increased (P<0.01) at a later time point (day 8), which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus, our findings suggest

  13. Evaluation of two stormwater infiltration trenches in central Copenhagen after 15 years of operation

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    Bergman, Maria Kerstin; Hedegaard, Mathilde Jørgensen; Petersen, Mette Fjendbo;

    2011-01-01

    Two stormwater infiltration trenches were installed in 1993 in an area in central Copenhagen. The system was monitored continuously for almost three years after establishment, and a small reduction in performance over that time, possibly due to clogging, was noted. A new study was conducted in 2009...... to see whether the reduction in performance has continued and to determine how the system performs today. Water levels in the trenches were monitored for almost 4 months, and from this period seven events were selected to analyse the infiltration rate. A comparison with similar analyses on storm...... factors to consider when implementing stormwater infiltration trenches. © IWA Publishing 2011....

  14. Central nervous system fibrosis is associated with fibrocyte-like infiltrates.

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    Aldrich, Amy; Kielian, Tammy

    2011-12-01

    Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow-derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow-derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow-derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation.

  15. Asymptomatic leukemic-cell infiltration of the pancreas: US findings.

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    Collado, Laura; Dardanelli, Esteban; Sierre, Sergio; Moguillansky, Silvia; Lipsich, José

    2011-06-01

    Pancreatic infiltration of leukemic cells is a very rare manifestation at the onset of acute lymphoblastic leukemia (ALL) in childhood. Pancreatic enlargement in this situation is unusual and pancreatic involvement is often associated with biliary obstruction, cholestasis and pancreatitis. We report a 3-month-old girl who presented with asymptomatic leukemic infiltration of the pancreas, demonstrated by US with heterogeneous pancreatic enlargement associated with multiple hypoechogenic lesions, without cholestasis. Although these manifestations are rare, ALL should be considered a cause of pancreatic enlargement.

  16. Characterization of inflammatory cell infiltration in feline allergic skin disease.

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    Taglinger, K; Day, M J; Foster, A P

    2007-11-01

    Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.

  17. Hepatic failure caused by plasma cell infiltration in multiple Myeloma

    Institute of Scientific and Technical Information of China (English)

    Fadi E Rahhal; Robert R Schade; Asha Nayak; Teresa A Coleman

    2009-01-01

    Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage ?B. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction.Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

  18. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

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    Marios Giannakis

    2016-04-01

    Full Text Available Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs, memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

  19. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

    NARCIS (Netherlands)

    De Simone, M.; Arrigoni, A.; Rossetti, G.; Gruarin, P.; Ranzani, V.; Politano, C.; Bonnal, R.J.; Provasi, E.; Sarnicola, M.L.; Panzeri, I.; Moro, M.; Crosti, M.; Mazzara, S.; Vaira, V.; Bosari, S.; Palleschi, A.; Santambrogio, L.; Bovo, G.; Zucchini, N.; Totis, M.; Gianotti, L.; Cesana, G.; Perego, R.A.; Maroni, N.; Pisani Ceretti, A.; Opocher, E.; De Francesco, R.; Geginat, J.; Stunnenberg, H.; Abrignani, S.; Pagani, M.

    2016-01-01

    Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or

  20. Phenotypic characterisation of immune cell infiltrates in testicular germ cell neoplasia

    DEFF Research Database (Denmark)

    Hvarness, Tine; Nielsen, John E; Almstrup, Kristian

    2013-01-01

    and overt seminoma, in comparison to biopsies from infertile men without neoplasia. The composition of immune cells was similar across all the groups studied. Macrophages, CD8(+) and CD45R0(+) T lymphocytes constituted the majority of infiltrates, B lymphocytes were present in an intermediate proportion......Immune cells often infiltrate testicular germ cell neoplasms, including pre-invasive carcinoma in situ (CIS), but the significance of this phenomenon remains unknown. The composition and distribution of infiltrating immune cells were examined by immunohistochemistry in testis samples with CIS...... and very few CD4(+) and FoxP3(+) T cells were detected. HLA-I antigen was more abundant in Sertoli cells in tubules containing CIS than in those with normal spermatogenesis. This study showed a phenotypically comparable composition of infiltrating immune cells independently of the presence of neoplasia...

  1. CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

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    Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

    2009-01-01

    While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripher...

  2. Infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type: a case series

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    Pervez Shahid

    2007-09-01

    Full Text Available Abstract Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo. However on further histological work up and by using immunohistochemistry (IHC for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS comedo from invasive carcinoma with central necrosis.

  3. Selective enrichment of Th1 CD45RBlow CD4+ T cells in autoimmune infiltrates in experimental allergic encephalomyelitis

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    Renno, T; Zeine, R; Girard, J M;

    1994-01-01

    The cytokine effector status of CD4+ T cells from lymph nodes (LN) and the central nervous system (CNS) of SJL/J mice immunized with autoantigen in adjuvant for the induction of experimental allergic encephalomyelitis (EAE) was compared. CD4+ T cells were FACS sorted based on the levels of expres...... stained in perivascular infiltrates in frozen sections from the brains of animals with active EAE was 10-fold higher.(ABSTRACT TRUNCATED AT 250 WORDS)...

  4. Diagnostic biopsy does not commonly induce intratumoral CD8 T cell infiltration in Merkel cell carcinoma.

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    Shinichi Koba

    Full Text Available BACKGROUND: Merkel cell carcinoma is a polyomavirus-associated cancer that is strongly linked with T lymphocyte immune suppression in epidemiologic studies. CD8+ T cell infiltration into MCC tumors (intratumoral has recently been shown to be strongly predictive of improved survival. In contrast, the presence of CD8+ T cells at the border of the tumor (peritumoral had no independent prognostic value. Spontaneous regression has been reported for MCC approximately one thousand times more often than would be expected given the frequency of this cancer. Many of these events began shortly after biopsy, and in some cases lymphocytic infiltration was described. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether CD8+ lymphocyte infiltration in MCC tumors is commonly altered by biopsy.33 MCC patients who had microscopic confirmation of MCC on both an initial biopsy and a re-excision specimen were included in this study. Intratumoral and peritumoral CD8 lymphocyte infiltration was quantitated using immunohistochemistry and compared using the paired t-test in biopsy versus re-excision samples. There was a trend toward increased CD8 infiltration after biopsy in a peritumoral ('stalled' pattern (p = 0.08, however, biopsy was not associated with a significant increase in CD8 T cells in the clinically more important intratumoral location (p = 0.58. CONCLUSIONS/SIGNIFICANCE: The initial diagnostic biopsy for MCC does not commonly alter intratumoral CD8+ T cell infiltration, suggesting it does not directly induce immunologic recognition of this cancer. Because CD8 infiltration is typically stable after biopsy, this parameter may be useful to assess the efficacy of future immune therapies for this virus-associated, immunogenic, often-lethal cancer.

  5. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

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    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  6. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

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    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  7. Hydrologic behaviour of stormwater infiltration trenches in a central urban area during 2 3/4 years of operation

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    Warnaars, E.; Larsen, A.V.; Jacobsen, P.;

    1999-01-01

    Two infiltration trenches were constructed in a densely built-up area in central Copenhagen and equipped with on-line sensors measuring rain, runoff flow from the connected surfaces and water level in the trenches. The paper describes the field site, the measuring system and the results from an i...

  8. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

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    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  9. Blockade of CD47 ameliorates autoimmune inflammation in CNS by suppressing IL-1-triggered infiltration of pathogenic Th17 cells.

    Science.gov (United States)

    Gao, Qiangguo; Zhang, Yi; Han, Chaofeng; Hu, Xiang; Zhang, Hua; Xu, Xiongfei; Tian, Jun; Liu, Yiqi; Ding, Yuanyuan; Liu, Juan; Wang, Chunmei; Guo, Zhenhong; Yang, Yongguang; Cao, Xuetao

    2016-05-01

    The migration of Th17 cells into central nervous system (CNS) tissue is the key pathogenic step in experimental autoimmune encephalomyelitis (EAE) model. However, the mechanism underlying the pathogenic Th17 cell migration remains elusive. Here we report that blockade of CD47 with CD47-Fc fusion protein is effective in preventing and curing EAE by impairing infiltration of Th17 cells into CNS. However, CD47 deficiency does not directly impair the migration of Th17 cells. Mechanistic studies showed that CD47 deficiency inhibited degradation of inducible nitric oxide synthase (iNOS) in proteasome of macrophages by Src activation and led to the increased nitric oxide (NO) production. Then NO suppressed inflammasome activation-induced IL-1β production. This lower IL-1β reduces the expression of IL-1R1 and migration-related chemokine receptors on CD47(-/-) Th17 cells, inhibiting the ability of Th17 cells to infiltrate into the CNS of CD47(-/-) mice and therefore suppressing EAE development. In vivo administration of exogenous IL-1β indeed promoted the infiltration CD47(-/-) Th17 cells into CNS and antagonized the protective role of CD47 deficiency in EAE pathogenesis. Our results demonstrate a potential preventive and therapeutic application of CD47 blockade in controlling EAE development.

  10. Model for solid oxide fuel cell cathodes prepared by infiltration

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Hendriksen, Peter Vang

    2017-01-01

    A 1-dimensional model of a cathode has been developed in order to understand and predict the performance of cathodes prepared by infiltration of La0.6Sr0.4Co1.05O3-δ (LSC) into porous backbones of Ce0.9Gd0.1O1.95 (CGO). The model accounts for the mixed ionic and electronic conductivity of LSC......, ionic conductivity of CGO, gas transport in the porous cathode, and the oxygen reduction reaction at the surface of percolated LSC. Geometrical variations are applied to reflect a changing microstructure of LSC under varying firing temperatures. Using microstructural parameters obtained from detailed...... parameter variations are presented and discussed with the aim of presenting specific guidelines for optimizing the microstructure of cathodes prepared by infiltration....

  11. Mast cell infiltrates in vulvodynia represent secondary and idiopathic mast cell hyperplasias.

    Science.gov (United States)

    Regauer, Sigrid; Eberz, Barbara; Beham-Schmid, Christine

    2015-05-01

    Mast cell infiltrates in tissues of vulvodynia are common, but they have not been characterized for criteria of neoplastic mast cell disease or correlated with patient's concomitant diseases associated with increased mast cells. Formalin-fixed specimens of 35 patients with vulvodynia were evaluated immunohistochemically with antibodies to CD 3,4,8,20,117c and human mast cell tryptase, and for WHO-criteria of neoplastic mastocytosis (>25% spindled mast cell, CD25 expression, point mutations of the c-kit gene (D816V), and chronically elevated serum tryptase levels). Only 20/35 specimens showed a T-lymphocyte dominant inflammatory infiltrate on HE-stained sections, but all showed mast cells. 4/35 biopsies showed 60 mast cells/mm(2) (average 80/mm(2) ). Control tissue contained typically mast cell rich biopsies with >40 mast cells/mm(2) were classified as a secondary mast cell disorder reflecting an activated immune system in 75% of vulvodynia patients. Patients with increased mast cells may benefit from medical therapy targeting mast cells.

  12. Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor

    OpenAIRE

    2016-01-01

    Background Prognostic value of immune cells is not clear in testicular germ cell tumors (TGCTs). We aimed to investigate the prognostic value of tumor-infiltrating neutrophils in TGCTs. Methods A total of 102 patients who underwent orchiectomy for TGCT were investigated for CD66b positive tumor-infiltrating neutrophils (CD66b + TINs). Immmunostaining for CD66b was performed in 102 sections as described. Clinicopathological parameters as well as cancer specific survival and overall survival we...

  13. Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer.

    Science.gov (United States)

    Berntsson, Jonna; Nodin, Björn; Eberhard, Jakob; Micke, Patrick; Jirström, Karin

    2016-09-01

    Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p cells correlated significantly with an improved OS (HR = 0.53, 95% CI 0.36-0.78), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study.

  14. Immunohistochemical Analysis of Scarring Trachoma Indicates Infiltration by Natural Killer and Undefined CD45 Negative Cells.

    Directory of Open Access Journals (Sweden)

    Victor H Hu

    2016-05-01

    Full Text Available The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants.Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells, CD4 (helper T-cells, CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells, NCR1 (NK cells, CD20 (B-cells, CD45 (nucleated hematopoietic cells, CD56 (NK and T-cells, CD68 (macrophages/monocytes and CD83 (mature dendritic cells. The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres.Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring.These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work

  15. Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity.

    Science.gov (United States)

    Jochems, Caroline; Schlom, Jeffrey

    2011-05-01

    Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous groups. Analyses of immune infiltrate of several other carcinoma types also showed general correlations between immune infiltrate and prognosis, but with some conflicting results. This review will attempt to summarize the current state of this field and point out what factors may be responsible for some of the conflicting findings. Nonetheless, the breadth of reports drawing similar conclusions for some cancer cell types leads one to more seriously consider the link between immune cell infiltrate and tumor prognosis and/or response to therapy, and the potential for combining conventional cancer therapy with active immunotherapy employing therapeutic cancer vaccines.

  16. 山茱萸新苷对EAE中枢神经系统MCP-1表达及CD68阳性细胞浸润的影响%The Impact of Cornuside on the Expression of MCP-1 and the Infiltration of CD68 Positive Cells in the Central Nervous System in EAE

    Institute of Scientific and Technical Information of China (English)

    张荣博; 徐彬; 朱敏姿; 周未莹; 吴忧; 梁顺利; 章水晶; 李铮; 袁强

    2016-01-01

    [目的]研究山茱萸新苷对实验性自身免疫性脑脊髓炎( experimental autoimmune encephalomyelitis, EAE)大鼠中枢神经系统单核细胞趋化蛋白-1( monocyte chemoattractant protein-1,MCP-1)表达及CD68阳性细胞浸润的影响。[方法]制备豚鼠全脊髓匀浆免疫抗原,皮下注射至 Lewis大鼠,建立EAE模型。设正常对照组、EAE组、山茱萸新苷组、波尼松组,每天神经功能评分,待症状达到高峰处死实验动物,用RT-PCR、Western Blot法比较各组实验动物中枢神经系统MCP-1 mRNA及蛋白的表达,免疫组织化学染色法比较各组实验动物中枢神经系统 CD68阳性细胞浸润情况。[结果]正常对照组、EAE组、山茱萸新苷组、波尼松组大鼠MCP-1 mRNA的相对表达量分别为(11.265±2.928)、(401.373±55.398)、(124.987±20.244)、(75.465±7.766),MCP-1蛋白相对表达量分别为(7.458±2.570)、(24.155±1.420)、(19.568±0.863)、(17.458±1.630),CD68阳性指数分别为0%、(41.93±12.25)%、(16.08±8.70)%、(5.38±2.88)%。使用单因素方差分析法,MCP-1 mRNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数组间差异显著,均有统计学意义( F=199.734、66.081、35.565,均P=0.000)。山茱萸新苷组与EAE组在神经功能评分、MCP-1 mRNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数表达差异均有统计学意义( P=0.002、0.000、0.003、0.013)。[结论]山茱萸新苷可改善 EAE大鼠神经功能,抑制EAE大鼠中枢神经系统MCP-1表达及CD68阳性细胞浸润。%Objective] To explore the impact of cornuside on the expression of MCP-1 and the infiltration of CD68 positive cells in the central nervous system in EAE. [Methods] An EAE model was established by injecting the guinea pig spinal cord homogenate antigen in subcutaneous tissue of Lewis rats. The rats were randomly divided into normal control group, EAE

  17. Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma

    Science.gov (United States)

    Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

    2016-01-01

    Background: The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Aim: Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Materials and Methods: Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Result: Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. Conclusion: As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient. PMID:27688609

  18. Synthesis and Stability of a Nanoparticle-Infiltrated Solid OxideFuel Cell Electrode

    Energy Technology Data Exchange (ETDEWEB)

    Sholklapper, Tal Z.; Radmilovic, Velimir; Jacobson, Craig P.; Visco, Steven J.; De Jonghe, Lutgard C.

    2006-11-20

    Nanoparticulate catalysts infiltrated into SOFC (Solid OxideFUel Cell) electrodes can significantly enhance the cell performance, butthe stability of these electrodes has been an open issue. An infiltrationprocedure is reported that leads to a stable scandia-stablized zirconia(SSZ) cathode electrode performance.

  19. Inhibition of reactive astrocytosis in established experimental autoimmune encephalomyelitis favors infiltration by myeloid cells over T cells and enhances severity of disease

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Füchtbauer, Laila; Owens, Trevor

    2011-01-01

    encephalomyelitis (EAE), an animal model of multiple sclerosis. We made use of transgenic mice, which express herpes simplex virus-derived thymidine kinase under control of a glial fibrillary acidic protein promotor (GFAP HSV-TK mice). Treatment of these mice with ganciclovir leads to inhibition of reactive......Reactive astrocytosis, involving activation, hypertrophy, and proliferation of astrocytes, is a characteristic response to inflammation or injury of the central nervous system. We have investigated whether inhibition of reactive astrocytosis influences established experimental autoimmune...... by this treatment. Ganciclovir-treated GFAP HSV-TK mice with EAE had a 78% increase in the total number of infiltrating myeloid cells (mainly macrophages), whereas we did not find an increase in infiltrating T cells, using quantitative flow cytometry. Per cell expression of mRNA for the macrophage...

  20. Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance.

    Science.gov (United States)

    Doedens, Andrew L; Rubinstein, Mark P; Gross, Emilie T; Best, J Adam; Craig, David H; Baker, Megan K; Cole, David J; Bui, Jack D; Goldrath, Ananda W

    2016-09-02

    Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration. Probing of this poor responsiveness revealed that IL15cx only weakly activated intratumoral CD8(+) T cells, even though cells in the lung and spleen were activated and dramatically expanded. Tumor-infiltrating CD8(+) T cells exhibited cell-extrinsic and cell-intrinsic resistance to IL15. Our data showed that in the case of persistent viral or tumor antigen, single-agent systemic IL15cx treatment primarily expanded antigen-irrelevant or extratumoral CD8(+) T cells. We identified exhaustion, tissue-resident memory, and tumor-specific molecules expressed in tumor-infiltrating CD8(+) T cells, which may allow therapeutic targeting or programming of specific subsets to evade loss of function and cytokine resistance, and, in turn, increase the efficacy of IL2/15 adjuvant cytokine therapy. Cancer Immunol Res; 4(9); 799-811. ©2016 AACR.

  1. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    Science.gov (United States)

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

  2. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    Directory of Open Access Journals (Sweden)

    Julia Rodríguez-Castelán

    2015-01-01

    Full Text Available Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control n=6 and hypothyroid groups (n=6, methimazole, 0.02% in drinking water for 30 days. After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS or Masson’s Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.

  3. Assessment of Tumor Cells in a Mouse Model of Diffuse Infiltrative Glioma by Raman Spectroscopy

    Directory of Open Access Journals (Sweden)

    Kuniaki Tanahashi

    2014-01-01

    Full Text Available Glioma of infiltrative nature is challenging for surgeons to achieve tumor-specific and maximal resection. Raman spectroscopy provides structural information on the targeted materials as vibrational shifts. We utilized Raman spectroscopy to distinguish invasive tumors from normal tissues. Spectra obtained from replication-competent avian sarcoma-(RCAS- based infiltrative glioma cells and glioma tissues (resembling low-grade human glioma were compared with those obtained from normal mouse astrocytes and normal tissues. In cell analysis, the spectra at 950–1000, 1030, 1050–1100, 1120–1130, 1120–1200, 1200–1300, 1300–1350, and 1450 cm−1 were significantly higher in infiltrative glioma cells than in normal astrocytes. In brain tissue analysis, the spectra at 1030, 1050–1100, and 1200–1300 cm−1 were significantly higher in infiltrative glioma tissues than in normal brain tissues. These spectra reflect the structures of proteins, lipids, and DNA content. The sensitivity and specificity to predict glioma cells by distinguishing normal cells were 98.3% and 75.0%, respectively. Principal component analysis elucidated the significance of spectral difference between tumor tissues and normal tissues. It is possible to distinguish invasive tumors from normal tissues by using Raman spectroscopy.

  4. Antigen presentation for priming T cells in central system.

    Science.gov (United States)

    Dasgupta, Shaoni; Dasgupta, Subhajit

    2017-01-01

    Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system. The recent approach towards circulating B-lymphocytes is an important area in the context. Here, we analyze the existing findings on antigen presentation in the central nervous system. The aim is to visualize signaling events of myelin antigen presentation to T cells and lead to the strategy of future goals on immunotherapy research.

  5. [Malignant T-cell lymphoma with osteomyelitis-like bone infiltration].

    Science.gov (United States)

    Mittelmeier, H; Schmitt, O

    1980-01-01

    After a short review on the late literature, existing about various forms of acute lymphoblastic leucemias, it is reported on a rare case of malignant T-cell-Lymphoma with ostemyelitis-like, painfull bone infiltration. The clinical symptoms, as well as differential-diagnostic criterias to other leucemias are described.

  6. Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    A León-Suárez

    2016-12-01

    Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

  7. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC. A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B and other immunological markers (CD20, MHC class I and MHC class II. Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35 of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004. Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant

  8. Assessment of perineural infiltration and spread of oral squamous cell carcinoma: A clinicohistopathologic study

    Directory of Open Access Journals (Sweden)

    N A Agni

    2010-01-01

    Full Text Available Background : As the tumor spreads through the pathway of least resistance, the present study was carried out to evaluate the presence of perineural infiltration and spread of oral squamous cell carcinoma (OSCC along the perineural spaces in gingivobuccal sulcus tumors infiltrating into the mandible. AIMS and objectives : (1 To investigate the incidence of perineural invasion of OSCC along the inferior alveolar nerve and (2 to investigate the neurovascular bundle as a potential route of spread of OSCC. Materials and Methods : Twenty-six patients with histopathologically proven OSCC of the gingivobuccal sulcus with radiographic infiltration of the mandible were included. The surgical specimens were decalcified and serially sectioned. Each section was stained with hematoxylin and eosin and was screened for the presence of perineural invasion and spread. Results : Twenty-five specimens showed perineural infiltration but none of the cases showed perineural spread along the inferior alveolar canal. Also, not all cases showed any neurologic deficit. Follow-up of these cases showed early recurrence (6-8 months in the study group. Conclusion : Perineural infiltration is present in OSCC but perineural spread along the inferior alveolar canal is absent. It is a bad prognostic indicator.

  9. Preparation of big size open-cell aluminum foam board using infiltration casting

    Institute of Scientific and Technical Information of China (English)

    Wang Lucai; Chen Yuyong; Wang Fang; Wu Jianguo; You Xiaohong

    2008-01-01

    This paper presents an infiltration casting technique for manufacturing big size open-cell aluminum foam boards. The principle and key technologies of infiltration casting are also analyzed. Based on the previous practice of the small size aluminum foam production, the die for preparing big size aluminum foam boards is designed and manufactured. The experiments on aluminum boards of 300 mm×300 mm×(20-75) mm, with the pore size ranging from 1.0 to 3.2 mm and average porosity of 60%, have been performed. The experimental results show that a reliable infiltration process depends critically on the pouring temperature of the molten AI-alloy, the preheated temperature of the mould and salt particles and vacuum. Current research explores the possibility of large-scale manufacturing and application of the aluminum foams.

  10. Thermal aging stability of infiltrated solid oxide fuel cell electrode microstructures: A three-dimensional kinetic Monte Carlo simulation

    Science.gov (United States)

    Zhang, Yanxiang; Ni, Meng; Yan, Mufu; Chen, Fanglin

    2015-12-01

    Nanostructured electrodes are widely used for low temperature solid oxide fuel cells, due to their remarkably high activity. However, the industrial applications of the infiltrated electrodes are hindered by the durability issues, such as the microstructure stability against thermal aging. Few strategies are available to overcome this challenge due to the limited knowledge about the coarsening kinetics of the infiltrated electrodes and how the potentially important factors affect the stability. In this work, the generic thermal aging kinetics of the three-dimensional microstructures of the infiltrate electrodes is investigated by a kinetic Monte Carlo simulation model considering surface diffusion mechanism. Effects of temperature, infiltration loading, wettability, and electrode configuration are studied and the key geometric parameters are calculated such as the infiltrate particle size, the total and percolated quantities of three-phase boundary length and infiltrate surface area, and the tortuosity factor of infiltrate network. Through parametric study, several strategies to improve the thermal aging stability are proposed.

  11. Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Hidehito Saito

    2016-01-01

    Full Text Available Induced pluripotent stem cells (iPSCs derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs that express programmed cell death protein-1 (PD-1 are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy.

  12. Highly durable anode supported solid oxide fuel cell with an infiltrated cathode

    Science.gov (United States)

    Samson, Alfred Junio; Hjalmarsson, Per; Søgaard, Martin; Hjelm, Johan; Bonanos, Nikolaos

    2012-10-01

    An anode supported solid oxide fuel cell with an La0.6Sr0.4Co1.05O3-δ (LSC) infiltrated-Ce0.9Gd0.1O1.95 (CGO) cathode that shows a stable performance has been developed. The cathode was prepared by screen printing a porous CGO backbone on top of a laminated and co-fired anode supported half cell, consisting of a Ni-yttria stabilized zirconia (YSZ) anode support, a Ni-scandia-doped yttria-stabilized zirconia (ScYSZ) anode, a ScYSZ electrolyte, and a CGO barrier layer. LSC was introduced into the CGO backbone by multiple infiltrations of an aqueous nitrate solution followed by firing. The cell was tested at 700 °C under a current density of 0.5 A cm-2 for 1500 h using air as oxidant and humidified hydrogen as fuel. The electrochemical performance of the cell was analyzed by impedance spectroscopy and current-voltage relationships. No measurable degradation in the cell voltage or increase in the resistance from the recorded impedance was observed during long term testing. The power density reached 0.79 W cm-2 at a cell voltage of 0.6 V at 750 °C. Post test analysis of the LSC infiltrated-CGO cathode by scanning electron microscopy revealed no significant micro-structural difference to that of a nominally identical untested counterpart.

  13. Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma.

    Science.gov (United States)

    Giavina-Bianchi, Mara; Giavina-Bianchi, Pedro; Sotto, Mirian Nacagami; Muzikansky, Alona; Kalil, Jorge; Festa-Neto, Cyro; Duncan, Lyn M

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  14. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mara Giavina-Bianchi

    2015-01-01

    Full Text Available NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79, rarely in in situ melanoma (1/10 and not in benign nevi (0/20. Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P=0.007 and inversely correlated with superficial spreading melanoma (P<0.02. NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P=0.017. When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P=0.010 or as isolated cells (P=0.002 than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  15. Highly durable anode supported solid oxide fuel cell with an infiltrated cathode

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Hjalmarsson, Per; Søgaard, Martin

    2012-01-01

    An anode supported solid oxide fuel cell with an La0.6Sr0.4Co1.05O3_δ (LSC) infiltrated-Ce0.9Gd0.1O1.95 (CGO) cathode that shows a stable performance has been developed. The cathode was prepared by screen printing a porous CGO backbone on top of a laminated and co-fired anode supported half cell...... in the resistance from the recorded impedance was observed during long term testing. The power density reached 0.79Wcm-2 at a cell voltage of 0.6 V at 750 deg. C. Post test analysis of the LSC infiltrated-CGO cathode by scanning electron microscopy revealed no significant micro-structural difference...

  16. Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection.

    Science.gov (United States)

    Sung, Jui-Min; Lee, Chien-Kuo; Wu-Hsieh, Betty A

    2012-01-01

    Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1(+) cells reduced cleaved caspase 3 and TUNEL(+) cells in the liver at day 1 after infection. CD8(+) T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL) exhibited cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL(+) cells were diminished in mice with TCRβ deficiency and in those depleted of CD8(+) T cells, respectively, at day 5 after infection. Moreover, intrahepatic CD8(+) T cells were like their splenic counterparts recognized DENV NS4B(99-107) peptide. Together, these results show that infiltrating NK and CD8(+) T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8(+) T cells were for later. CD8(+) T cells that recognize NS4B(99-107) constitute at least one of the major intrahepatic cytotoxic CD8(+) T cell populations.

  17. Intrahepatic infiltrating NK and CD8 T cells cause liver cell death in different phases of dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Jui-Min Sung

    Full Text Available Elevated liver enzyme level is an outstanding feature in patients with dengue. However, the pathogenic mechanism of liver injury has not been clearly demonstrated. In this study, employing a mouse model we aimed to investigate the immunopathogenic mechanism of dengue liver injury. Immunocompetent C57BL/6 mice were infected intravenously with dengue virus strain 16681. Infected mice had transient viremia, detectable viral capsid gene and cleaved caspase 3 in the liver. In the mean time, NK cell and T cell infiltrations peaked at days 1 and 5, respectively. Neutralizing CXCL10 or depletion of Asialo GM1(+ cells reduced cleaved caspase 3 and TUNEL(+ cells in the liver at day 1 after infection. CD8(+ T cells infiltrated into the liver at later time point and at which time intrahepatic leukocytes (IHL exhibited cytotoxicity against DENV-infected targets. Cleaved caspase 3 and TUNEL(+ cells were diminished in mice with TCRβ deficiency and in those depleted of CD8(+ T cells, respectively, at day 5 after infection. Moreover, intrahepatic CD8(+ T cells were like their splenic counterparts recognized DENV NS4B(99-107 peptide. Together, these results show that infiltrating NK and CD8(+ T cells cause liver cell death. While NK cells were responsible for cell death at early time point of infection, CD8(+ T cells were for later. CD8(+ T cells that recognize NS4B(99-107 constitute at least one of the major intrahepatic cytotoxic CD8(+ T cell populations.

  18. In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells

    DEFF Research Database (Denmark)

    Hald, J; Rasmussen, N; Claesson, Mogens Helweg

    1994-01-01

    A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their abi......A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well...... with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens......, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53...

  19. Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

    Directory of Open Access Journals (Sweden)

    Pelliccia Angela

    2007-10-01

    Full Text Available Abstract Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens

  20. Assessment of TCR-beta clonality in a diverse group of cutaneous T-Cell infiltrates.

    Science.gov (United States)

    Plaza, Jose Antonio; Morrison, Carl; Magro, Cynthia M

    2008-04-01

    While some unequivocally benign infiltrates are easy to distinguish from cutaneous T-cell lymphoma (CTCL), drug-associated lymphomatoid hypersensitivity reaction and cutaneous lesions of collagen vascular disease can show cytologic atypia, clonality and an immunophenotypic profile that closely simulates CTCL and cause diagnostics difficulties. Similar immunophenotypic and molecular abnormalities to those of malignant lymphoma can also be observed in pityriasis lichenoides chronica (PLC), large plaque parapsoriasis (LPP), pigmented purpuric dermatosis (PPD) and atypical lymphocytic lobular panniculitis leading one to consider these entities as forms of cutaneous lymphoid dyscrasia. The purpose of our study was to evaluate the distinction of these various subcategories of cutaneous T-cell infiltrates by assessment of T-cell receptor (TCR)-beta gene rearrangement. Formalin-fixed paraffin-embedded skin biopsies from 80 patients containing a T-cell dominant lymphocytic infiltrate were analyzed for TCR-beta gene rearrangement. Our findings indicate that monoclonality is a reliable characteristic of CTCL with polyclonality being very infrequent. However, some cases of drug associated lymphomatoid hypersensitivity, collagen vascular disease and the various cutaneous lymphoid dyscrasias (i.e. PLC, PPD and atypical lymphocytic lobular panniculitis) could manifest restricted molecular profiles in the context of an oligoclonal process or frank monoclonality.

  1. Influence of race on microsatellite instability and CD8+ T cell infiltration in colon cancer.

    Directory of Open Access Journals (Sweden)

    John M Carethers

    Full Text Available African American patients with colorectal cancer show higher mortality than their Caucasian counterparts. Biology might play a partial role, and prior studies suggest a higher prevalence for microsatellite instability (MSI among cancers from African Americans, albeit patients with MSI cancers have improved survival over patients with non-MSI cancers, counter to the outcome observed for African American patients. CD8+ T cell infiltration of colon cancer is postively correlated with MSI tumors, and is also related to improved outcome. Here, we utilized a 503-person, population-based colon cancer cohort comprising 45% African Americans to determine, under blinded conditions from all epidemiological data, the prevalence of MSI and associated CD8+ T cell infiltration within the cancers. Among Caucasian cancers, 14% were MSI, whereas African American cancers demonstrated 7% MSI (P = 0.009. Clinically, MSI cancers between races were similar; among microsatellite stable cancers, African American patients were younger, female, and with proximal cancers. CD8+ T cells were higher in MSI cancers (88.0 vs 30.4/hpf, P<0.0001, but was not different between races. Utilizing this population-based cohort, African American cancers show half the MSI prevalence of Caucasians without change in CD8+ T cell infiltration which may contribute towards their higher mortality from colon cancer.

  2. Autoimmune pancreatitis metachronously associated with retroperitoneal fibrosis with IgG4-positive plasma cell infiltration

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Pong Yui Chen; Yuyang Tu; Hitoshi Nakajima; Naoto Egawa

    2006-01-01

    Retroperitoneal fibrosis is an uncommon disorder characterized by the formation of a dense plaque of fibrous tissue in the retroperitoneum, and its etiology remains unknown. Autoimmune pancreatitis is a rare type of chronic pancreatitis characterized by fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis in the pancreas. We present a case of autoimmune pancreatitis that developed 10 mo after the occurrence of retroperitoneal fibrosis. Histological findings of the resected retroperitoneal mass were marked periureteral fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis.These findings suggest a common pathophysiological mechanism for retroperitoneal fibrosis and autoimmune pancreatitis in this case. Some cases of retroperitoneal fibrosis might be a retroperitoneal lesion of IgG4-related sclerosing disease.

  3. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

    Institute of Scientific and Technical Information of China (English)

    Takayoshi; Fujita; Takafumi; Ando; Masatoshi; Sakakibara; Waki; Hosoda; Hidemi; Goto

    2010-01-01

    We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

  4. Infiltrated carbon foam composites

    Science.gov (United States)

    Lucas, Rick D. (Inventor); Danford, Harry E. (Inventor); Plucinski, Janusz W. (Inventor); Merriman, Douglas J. (Inventor); Blacker, Jesse M. (Inventor)

    2012-01-01

    An infiltrated carbon foam composite and method for making the composite is described. The infiltrated carbon foam composite may include a carbonized carbon aerogel in cells of a carbon foam body and a resin is infiltrated into the carbon foam body filling the cells of the carbon foam body and spaces around the carbonized carbon aerogel. The infiltrated carbon foam composites may be useful for mid-density ablative thermal protection systems.

  5. Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.

    Science.gov (United States)

    Ohashi, Katsuyo; Sato, Yasushi; Iwata, Hiroshi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2007-12-01

    Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.

  6. Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology

    Energy Technology Data Exchange (ETDEWEB)

    Andrulis, Mindaugas [Institute of Pathology, University of Heidelberg, Heidelberg (Germany); Bäuerle, Tobias [Department of Diagnostic and Interventional Radiology, University of Hamburg, Hamburg (Germany); Goldschmidt, Hartmut [Department of Hematology and Oncology, University of Heidelberg, Heidelberg (Germany); Delorme, Stefan [Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Landgren, Ola [Multiple Myeloma Section, Metabolism Branch, National Cancer Institute, Bethesda (United States); Schirmacher, Peter [Institute of Pathology, University of Heidelberg, Heidelberg (Germany); Hillengass, Jens, E-mail: jens.hillengass@med.uni-heidelberg.de [Department of Hematology and Oncology, University of Heidelberg, Heidelberg (Germany); Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2014-06-15

    Objectives: To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. Methods: We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. Results: MRI revealed a minimal (n = 11, 22%), focal (n = 5, 10%), diffuse (n = 14, 28%) and mixed (n = 20, 40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with “focal component” (i.e. focal and mixed) were most common in symptomatic myeloma (p < 0.01). In histology an interstitial (n = 13, 26%), nodular (n = 23, 46%) and packed marrow (n = 14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. Conclusions: Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells.

  7. T-cell suppression mediated by regulatory T cells infiltrating hepatic tumors can be overcome by GITRL treatment

    NARCIS (Netherlands)

    A. Pedroza-Gonzalez (Alexander); J. Kwekkeboom (Jaap); D. Sprengers (Dave)

    2013-01-01

    textabstractRecently, we reported the accumulation of CD4+FOXP3+ regulatory T cells (Tregs) within the tumor mass of patients bearing liver cancer. Tumor-infiltrating Tregs (TiTreg) are active and potent suppressors of antitumor immunity. Importantly, treatment with GITR L reduced the immunosuppress

  8. Composite vascular grafts with high cell infiltration by co-electrospinning

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Zhikai, E-mail: tanzk@hnu.edu.cn; Wang, Hongjie; Gao, Xiangkai; Liu, Tong; Tan, Yongjun

    2016-10-01

    There is an increasing demand for functional small-diameter vascular grafts (diameter < 6 mm) to be used in clinical arterial replacement. An ideal vascular graft should have appropriate biomechanical properties and be biocompatible. Electrospinning has become a popular polymer processing technique for vascular tissue engineering, but the grafts fabricated by electrospinning often have relatively small pores and low porosity, which limit cell infiltration into scaffolds and hinder the regeneration and remodeling of grafts. In the present study, we aimed to develop an efficient method to prepare electrospun composite vascular grafts comprising natural and synthetic materials. We fabricated grafts made of polycaprolactone, gelatin, and polyvinyl alcohol (PVA) by co-electrospinning, and the scaffolds were further functionalized by immobilizing heparin on them. The PVA fibers degraded rapidly in vivo and generated electrospun scaffolds with high porosity, which significantly enhanced cell proliferation and infiltration. The mechanical properties of the grafts are suitable for use in artery replacement. Heparin functionalization of the grafts yielded a good antithrombogenic effect, which was demonstrated in platelet adhesion tests. Moreover, in vitro and in vivo results demonstrated that the heparin release from the grafts enhanced the growth of endothelial cells, which is important for the endothelium of implanted grafts. The results of this study indicate that our method is effective and controllable for the fabrication of vascular grafts that meet the clinical requirements for blood vessel transplantation. - Highlights: • This study indicate an effective method for the fabrication of vascular grafts that meet the clinical requirements. • Co-electrospinning were used to fabricate grafts made of polycaprolactone (PCL), gelatin (GT), and polyvinyl alcohol (PVA). • PVA was used to create large pores within the hybrid scaffolds, thereby enhancing cell infiltration

  9. Increased CD133+ cell infiltration in the rat brain following fluid percussion injury

    Institute of Scientific and Technical Information of China (English)

    Ming Wei; Ziwei Zhou; Shenghui Li; Chengwei Jing; Dashi Zhi; Jianning Zhang

    2012-01-01

    The prominin-1/CD133 epitope is expressed in undifferentiated cells. Studies have reported that craniocerebral trauma in animal models of fluid percussion injury induces production of a specific stem cell subgroup. It has been hypothesized that fluid percussion injury induces CD133+ cell infiltration in the brain tissue. The present study established a traumatic brain injury model through fluid percussion injury. Immunohistochemical staining showed significantly increased CD133 antigen expression in the rat brain following injury. CD133+ cells were mainly distributed in hippocampal CA1-3 regions, as well as the dentate gyrus and hilus, of the lesioned hemisphere. Occasional cells were also detected in the cortex. In addition, reverse transcription-PCR revealed that no change in CD133 mRNA expression in injured brain tissue. These results suggested that fluid percussion injury induced CD133 antigen expression in the brain tissues as a result of conformational epitope changes, but not transcriptional expression.

  10. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient's individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations...... therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  11. Dendritic cell and macrophage infiltration in microsatellite-unstable and microsatellite-stable colorectal cancer.

    Science.gov (United States)

    Bauer, Kathrin; Michel, Sara; Reuschenbach, Miriam; Nelius, Nina; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2011-09-01

    High level microsatellite instability (MSI-H) is a hallmark of Lynch syndrome-associated colorectal cancer (CRC). MSI-H CRC express immunogenic tumour antigens as a consequence of DNA mismatch repair deficiency-induced frameshift mutations. Consequently, frameshift antigen-specific immune responses are commonly observed in patients with Lynch syndrome-associated MSI-H CRC. Dendritic cells (DC) and macrophages play a crucial role in the induction and modulation of immune responses. We here analysed DC and macrophage infiltration in MSI-H and microsatellite-stable CRC. Sixty-nine CRC (MSI-H, n = 33; microsatellite-stable, n = 36) were examined for the density of tumour-infiltrating DC, Foxp3-positive regulatory T cells, and CD163-positive macrophages. In MSI-H lesions, S100-positive and CD163-positive cell counts were significantly higher compared to microsatellite-stable lesions (S100: epithelium P = 0.018, stroma P = 0.042; CD163: epithelium P < 0.001, stroma P = 0.046). Additionally, numbers of CD208-positive mature DC were significantly elevated in the epithelial compartment of MSI-H CRC (P = 0.027). High numbers of tumour-infiltrating Foxp3-positive T cells were detected in tumours showing a low proportion of CD208-positive, mature DC among the total number of S100-positive cells. Our study demonstrates that infiltration with DC, mature DC, and macrophages is elevated in MSI-H compared to microsatellite-stable CRC. The positive correlation of Foxp3-positive Treg cell density with a low proportion of mature DC suggests that impaired DC maturation may contribute to local immune evasion in CRC. Our results demonstrate that DC and macrophages in the tumour environment likely play an important role in the induction of antigen-specific immune responses in Lynch syndrome. Moreover, impaired DC maturation might contribute to local immune evasion in CRC.

  12. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes

    DEFF Research Database (Denmark)

    Donia, Marco; Ellebaek, Eva; Andersen, Mads Hald

    2012-01-01

    γδ T cells, including Vδ1 and Vδ2 T cells, can recognize tumor-associated ligands neglected by conventional αβ T cells in a MHC-independent manner. Little is known regarding the anticancer potential and the possibility to isolate and expand Vδ1 T cells to therapeutically relevant numbers....... In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T cells was found among the cell products from patients with an advanced disease stage. Vδ1 T cells...... displayed in vitro antitumor activities and sufficient proliferative potential to generate over 1 × 10(9) cells using current protocols for T cell transfer. Infusion of Vδ1 T cells together with high numbers of αβ TILs in a clinical trial was safe and well tolerated. These data suggest that Vδ1 T cells...

  13. γδ T cells and Foxp3(+) Treg cells infiltration in children with biliary atresia and its significance.

    Science.gov (United States)

    Li, Kang; Zhang, Xi; Tang, Shao-Tao; Yang, Li; Cao, Guo-Qing; Li, Shuai; Yang, De-Hua

    2015-01-01

    To investigate the changes in the proportion of γδ T cells and Foxp3(+) Treg cells in children with BA (biliary atresia). The distribution of γδ T cells in the liver tissues and the proportion of γδ T cells and Foxp3(+) Treg cells were observed and detected in BA Group (32 cases) and control group (CG) (12 cases) by using immunohistochemical methods and flow cytometry. The periportal bile duct of liver in BA Group was surrounded by a large number of γδ T cells and a certain degree of Foxp3(+) Treg cells infiltration. Additionally, the proportion of γδ T cells and Foxp3(+) Treg cells was significantly higher than that in CG (PTreg cells (PTreg cell proliferation in liver tissues of patients with biliary atresia exacerbated the progressive inflammatory injury of bile ducts.

  14. Using a Virtual Experiment to Analyze Infiltration Process from Point to Grid-cell Size Scale

    Science.gov (United States)

    Barrios, M. I.

    2013-12-01

    The hydrological science requires the emergence of a consistent theoretical corpus driving the relationships between dominant physical processes at different spatial and temporal scales. However, the strong spatial heterogeneities and non-linearities of these processes make difficult the development of multiscale conceptualizations. Therefore, scaling understanding is a key issue to advance this science. This work is focused on the use of virtual experiments to address the scaling of vertical infiltration from a physically based model at point scale to a simplified physically meaningful modeling approach at grid-cell scale. Numerical simulations have the advantage of deal with a wide range of boundary and initial conditions against field experimentation. The aim of the work was to show the utility of numerical simulations to discover relationships between the hydrological parameters at both scales, and to use this synthetic experience as a media to teach the complex nature of this hydrological process. The Green-Ampt model was used to represent vertical infiltration at point scale; and a conceptual storage model was employed to simulate the infiltration process at the grid-cell scale. Lognormal and beta probability distribution functions were assumed to represent the heterogeneity of soil hydraulic parameters at point scale. The linkages between point scale parameters and the grid-cell scale parameters were established by inverse simulations based on the mass balance equation and the averaging of the flow at the point scale. Results have shown numerical stability issues for particular conditions and have revealed the complex nature of the non-linear relationships between models' parameters at both scales and indicate that the parameterization of point scale processes at the coarser scale is governed by the amplification of non-linear effects. The findings of these simulations have been used by the students to identify potential research questions on scale issues

  15. Infiltration of hypertrophic esophageal smooth muscle by mast cells and basophils.

    Science.gov (United States)

    Tung, H N; Schulze-Delrieu, K; Shirazi, S

    1993-01-01

    Partial obstruction leads to chronic distension and muscular hypertrophy of the opossum esophagus. The smooth muscle cells of the circular muscle layer enlarge, become pleomorphic and are surrounded by an amorphous ground substance in the extracellular space. Here we describe the histological and ultrastructural features of a peculiar cellular infiltrate in the hypertrophic smooth muscle. The infiltrate consisted uniquely of mast cells and basophils. In per unit area, the number of mast cells increased from 0.9 +/- 0.1 cells in controls to 3.7 +/- 0.2 in hypertrophic smooth muscle; the corresponding numbers for basophils were 2.5 +/- 0.2 and 7.2 +/- 0.3 cells. Cells were seen primarily in the septal spaces of the circular muscle layer and at the interface of the circular and longitudinal muscle layer. The cytoplasm of basophils is normally packed with round and oval granules. The granules stain metachromatically and with varying intensity on Wright-Giemsa stains. On transmission electronmicroscopy, granules display a membrane and a great diversity in the structure of their luminal contents. In hypertrophic muscle, most granules were discharging their contents into the cytoplasm or extracellular space. The membranes of adjacent empty granules then fused to form a chain of vacuoles. Similar changes occurred also in the mast cells which differed from the basophil by their lack of nuclear lobulation and by the greater homogeneity of their cytoplasmic granules. It is possible that these inflammatory cells are involved in the reconstruction of the smooth muscle and its connective tissue which occur during esophageal distension and hypertrophy.

  16. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.

    Directory of Open Access Journals (Sweden)

    Ravid Shechter

    2009-07-01

    Full Text Available BACKGROUND: Although macrophages (MPhi are known as essential players in wound healing, their contribution to recovery from spinal cord injury (SCI is a subject of debate. The difficulties in distinguishing between different MPhi subpopulations at the lesion site have further contributed to the controversy and led to the common view of MPhi as functionally homogenous. Given the massive accumulation in the injured spinal cord of activated resident microglia, which are the native immune occupants of the central nervous system (CNS, the recruitment of additional infiltrating monocytes from the peripheral blood seems puzzling. A key question that remains is whether the infiltrating monocyte-derived MPhi contribute to repair, or represent an unavoidable detrimental response. The hypothesis of the current study is that a specific population of infiltrating monocyte-derived MPhi is functionally distinct from the inflammatory resident microglia and is essential for recovery from SCI. METHODS AND FINDINGS: We inflicted SCI in adult mice, and tested the effect of infiltrating monocyte-derived MPhi on the recovery process. Adoptive transfer experiments and bone marrow chimeras were used to functionally distinguish between the resident microglia and the infiltrating monocyte-derived MPhi. We followed the infiltration of the monocyte-derived MPhi to the injured site and characterized their spatial distribution and phenotype. Increasing the naïve monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Selective ablation of infiltrating monocyte-derived MPhi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte

  17. Macrophage-independent T cell infiltration to the site of injury-induced brain inflammation

    DEFF Research Database (Denmark)

    Fux, Michaela; van Rooijen, Nico; Owens, Trevor

    2008-01-01

    We have addressed the role of macrophages in glial response and T cell entry to the CNS after axonal injury, by using intravenous injection of clodronate-loaded mannosylated liposomes, in C57BL6 mice. As expected, clodronate-liposome treatment resulted in depletion of peripheral macrophages which...... was confirmed by F4/80(-) and MOMA-1(-) stainings in spleen. Sequential clodronate-liposome treatment 4, 2 and 0 days before axotomy resulted in significant reduction of infiltrating CD45(high) CD11b(+) macrophages in the hippocampus at 1, 2 and 3 days post-lesion, measured by flow cytometry. There was a slight...

  18. Classifying cancers based on T cell infiltration and PD-L1

    Science.gov (United States)

    Teng, Michele W. L.; Ngiow, Shin Foong; Ribas, Antoni; Smyth, Mark J.

    2015-01-01

    Cancer immunotherapy may become a major treatment backbone in many cancers over the next decade. There are numerous immune cell types found in cancers and many components of an immune reaction to cancer. Thus the tumor has many strategies to evade an immune response. It has been proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression. We review this stratification and the latest in a series of results that shed light on new approaches for rationally designing ideal combination cancer therapies based on tumor immunology. PMID:25977340

  19. Regulation of immune cell infiltration into the CNS by regional neural inputs explained by the gate theory.

    Science.gov (United States)

    Arima, Yasunobu; Kamimura, Daisuke; Sabharwal, Lavannya; Yamada, Moe; Bando, Hidenori; Ogura, Hideki; Atsumi, Toru; Murakami, Masaaki

    2013-01-01

    The central nervous system (CNS) is an immune-privileged environment protected by the blood-brain barrier (BBB), which consists of specific endothelial cells that are brought together by tight junctions and tight liner sheets formed by pericytes and astrocytic end-feet. Despite the BBB, various immune and tumor cells can infiltrate the CNS parenchyma, as seen in several autoimmune diseases like multiple sclerosis (MS), cancer metastasis, and virus infections. Aside from a mechanical disruption of the BBB like trauma, how and where these cells enter and accumulate in the CNS from the blood is a matter of debate. Recently, using experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we found a "gateway" at the fifth lumber cord where pathogenic autoreactive CD4+ T cells can cross the BBB. Interestingly, this gateway is regulated by regional neural stimulations that can be mechanistically explained by the gate theory. In this review, we also discuss this theory and its potential for treating human diseases.

  20. Composite vascular grafts with high cell infiltration by co-electrospinning.

    Science.gov (United States)

    Tan, Zhikai; Wang, Hongjie; Gao, Xiangkai; Liu, Tong; Tan, Yongjun

    2016-10-01

    There is an increasing demand for functional small-diameter vascular grafts (diameterElectrospinning has become a popular polymer processing technique for vascular tissue engineering, but the grafts fabricated by electrospinning often have relatively small pores and low porosity, which limit cell infiltration into scaffolds and hinder the regeneration and remodeling of grafts. In the present study, we aimed to develop an efficient method to prepare electrospun composite vascular grafts comprising natural and synthetic materials. We fabricated grafts made of polycaprolactone, gelatin, and polyvinyl alcohol (PVA) by co-electrospinning, and the scaffolds were further functionalized by immobilizing heparin on them. The PVA fibers degraded rapidly in vivo and generated electrospun scaffolds with high porosity, which significantly enhanced cell proliferation and infiltration. The mechanical properties of the grafts are suitable for use in artery replacement. Heparin functionalization of the grafts yielded a good antithrombogenic effect, which was demonstrated in platelet adhesion tests. Moreover, in vitro and in vivo results demonstrated that the heparin release from the grafts enhanced the growth of endothelial cells, which is important for the endothelium of implanted grafts. The results of this study indicate that our method is effective and controllable for the fabrication of vascular grafts that meet the clinical requirements for blood vessel transplantation.

  1. ROLE OF PANCREATIC STELLATE CELLS AND GALECTIN-3 ON PROLIFERATION AND INFILTRATION OF HUMAN PANCREATIC CANCER CELL LINE SW1990

    Institute of Scientific and Technical Information of China (English)

    JIANG Hai-biao; XU Ming; WANG Xing-peng

    2008-01-01

    Objective To investigate the role of pancreatic stellate cells (PSCs) and galectin-3 (GAL-3)on the proliferation and infiltration of pancreatic cancer cell line SW1990. Methods Human pancreatic cancercell line SW1990 and PSCs were cultured in vitro. Supernatant of cultured PSCs and SW1990 cells was collected.Expressions of GAL-3 in SW1990 cells and PSCs were detected by ELISA, RT-PCR and Western blot. Theproliferation of those cultured PSCs and SW1990 cells were measured by MTT assay and flowcytometry. Infiltrationof SW1990 cells was detected by cell infiltration kit. Results SW1990 cells expressed GAL-3 and the expressionwas up-regulated by the supernatant fluid of cultured PSCs. PSCs did not express GAL-3. SW1990 cells couldstimulate the proliferation of PSCs via GAL-3. GAL-3 antibody could inhibit SW1990 cells proliferation andinfiltration, which indicated that supernatant of PSCs might stimulate the proliferation of SW1990 cells through theinteraction with GAL-3 protein. The supernatant fluid of PSCs could enhance the invasiveness of SW1990 cellsthrough the interaction with GAL-3. Conclusion GAL-3 and PSCs was involved in the proliferation andinfiltration process of pancreatic cancer.

  2. Uncontrolled hypertension secondary to leukemic cell infiltration of kidneys in a hemodialysis patient

    Directory of Open Access Journals (Sweden)

    Kultigin Turkmen

    2010-06-01

    Full Text Available Kultigin Turkmen1, Lutfullah Altintepe2, Ibrahim Guney2, Ismet Aydogdu3, Osman Koc4, Mehmet Ali Erkut5, Halil Zeki Tonbul11Department of Nephrology, Meram School of Medicine, Selcuk University, 2Meram Training and Research Hospital, Selcuk University, 3Department of Hematology, Meram School of Medicine, Selcuk University, 4Department of Radiology, Meram School of Medicine, Selcuk University, 5Department of Hematology, Meram Training and Research Hospital, Selcuk UniversityAbstract: Leukemic infiltration of the kidney is usually silent, and the admission of the patients with renal dysfunction or acute kidney injury is uncommon. We present a 34-year old hemodialysis patient with new onset of uncontrolled hypertension, erythropoietin-resistant anemia, thrombocytopenia, and Bell’s palsy. On admission, his blood pressure (BP was 210/110 mmHg and he had petechiae and purpura at upper and lower extremities. Renal ultrasonography (USG showed bilaterally enlarged kidneys without hydronephrosis, unlike his previous USG, which determined bilaterally atrophic kidneys. Acute lymphoblastic leukemia, hypertensive crisis due to bilateral leukemic cell infiltration of kidneys, tumor lysis syndrome, and leukemic involvement of the facial nerve were diagnosed. Despite intense antihypertensive management, his BP was not controlled. After prednisolone, daunorubicine, and vincristine therapy, the size of kidneys diminished and his BP dropped under normal range. In conclusion, pathological findings such as uncontrolled hypertension, flank pain, skin rashes, and abnormal blood count should be considered carefully, even in patients with end-stage renal disease receiving renal replacement therapy.Keywords: leukemic cell infiltration, uncontrolled hypertension, hemodialysis

  3. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Verdegaal, Els M

    2014-01-01

    Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh...... review....

  4. Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.

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    Fabio Morandi

    Full Text Available Metastases in the bone marrow (BM are grim prognostic factors in patients with neuroblastoma (NB. In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes. Sixty-six Italian children over 18 months of age, diagnosed with stage 4 NB, were included in the study. Metastatic NB cells were freshly isolated from patients' BM by positive immunomagnetic bead manipulation using anti-GD2 monoclonal antibody. Gene expression profiles were compared with those obtained from archived NB primary tumors from patients with 5 y-follow-up. After validation by RT-qPCR, expression/secretion of the proteins encoded by the up-regulated genes in the BM-infiltrating NB cells was evaluated by flow cytometry and ELISA. Compared to primary tumor cells, BM-infiltrating NB cells down-modulated the expression of CX3CL1, AGT, ATP1A2 mRNAs, whereas they up-regulated several genes commonly expressed by various lineages of BM resident cells. BM-infiltrating NB cells expressed indeed the proteins encoded by the top-ranked genes, S100A8 and A9 (calprotectin, CD177 and CD3, and secreted the CXCL7 chemokine. BM-infiltrating NB cells also expressed CD271 and HLA-G. We have identified proteins specifically expressed by BM-infiltrating NB cells. Among them, calprotectin, a potent inflammatory protein, and HLA-G, endowed with tolerogenic properties facilitating tumor escape from host immune response, may represent novel biomarkers and/or targets for therapeutic intervention in high-risk NB patients.

  5. Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.

    Science.gov (United States)

    Kako, Shinichi; Kanda, Yoshinobu; Sato, Tomohiko; Goyama, Susumu; Noda, Naohiro; Shoda, Eriko; Oshima, Kumi; Inoue, Morihiro; Izutsu, Koji; Watanabe, Takuro; Motokura, Toru; Chiba, Shigeru; Fukayama, Masashi; Kurokawa, Mineo

    2007-05-01

    Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL.

  6. Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival.

    Science.gov (United States)

    Batal, Ibrahim; De Serres, Sacha A; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L; Iafrate, A John; Herter, Jan M; Lichtman, Andrew H; Mayadas, Tanya N; Guleria, Indira; Rennke, Helmut G; Najafian, Nader; Chandraker, Anil

    2015-12-01

    Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.

  7. Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Løbner, Morten; Cédile, Oriane

    2014-01-01

    BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells...... but detectable levels of all these cytokines. Transforming growth factor beta expression was similar in all three populations. Although CNS-resident and blood-derived CD11c+ cells showed equivalent ability to induce proliferation of myelin oligodendrocyte glycoprotein-immunised CD4+ T cells, CD11c+ microglia...

  8. TiO2 nanotubes infiltrated with nanoparticles for dye sensitized solar cells

    Science.gov (United States)

    Pan, Xuan; Chen, Changhong; Zhu, Kai; Fan, Zhaoyang

    2011-06-01

    We present a detailed study of the infiltration of titanium dioxide (TiO2) nanotubes (NTs) with TiO2 nanoparticles (NPs) for dye sensitized solar cells (DSSCs). The aim is to combine the merits of the NP's high dye loading and high light harvesting capability with the NT's straight carrier transport path and high electron collection efficiency to improve the DSSC performance. On infiltrating NTs with TiCl4 solution followed by hydrothermal synthesis, 10 nm size NPs were observed to form a conformal and dense layer on the NT walls. Compared with the bare NT structure, dye loading of this mixed NT and NP structure is more than doubled. The overall photon conversion efficiencies of the fabricated DSSCs are improved by 152%, 107%, and 49% for 8, 13, and 20 µm long NTs, respectively. Electron transport and recombination parameters were extracted based on electrochemical impedance spectroscopy measurements. Although a slight reduction of electron lifetime was observed in the mixed structures due to enhanced recombination with a larger surface area, the diffusion length is still significantly longer than the NT length used, suggesting that most electrons are collected. In addition to dye loading and hence photocurrent increment, the photovoltage and filling factor were also improved in the mixed structure due to a low serial resistance, leading to the enhancement of the overall efficiency.

  9. TiO{sub 2} nanotubes infiltrated with nanoparticles for dye sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Pan Xuan; Chen Changhong; Fan Zhaoyang [Department of Electrical and Computer Engineering and Nano Tech Center, Texas Tech University, PO Box 43102, Lubbock, TX, 79409-3102 (United States); Zhu Kai, E-mail: zhaoyang.fan@ttu.edu [National Renewable Energy Laboratory, Golden, CO 80401-3393 (United States)

    2011-06-10

    We present a detailed study of the infiltration of titanium dioxide (TiO{sub 2}) nanotubes (NTs) with TiO{sub 2} nanoparticles (NPs) for dye sensitized solar cells (DSSCs). The aim is to combine the merits of the NP's high dye loading and high light harvesting capability with the NT's straight carrier transport path and high electron collection efficiency to improve the DSSC performance. On infiltrating NTs with TiCl{sub 4} solution followed by hydrothermal synthesis, 10 nm size NPs were observed to form a conformal and dense layer on the NT walls. Compared with the bare NT structure, dye loading of this mixed NT and NP structure is more than doubled. The overall photon conversion efficiencies of the fabricated DSSCs are improved by 152%, 107%, and 49% for 8, 13, and 20 {mu}m long NTs, respectively. Electron transport and recombination parameters were extracted based on electrochemical impedance spectroscopy measurements. Although a slight reduction of electron lifetime was observed in the mixed structures due to enhanced recombination with a larger surface area, the diffusion length is still significantly longer than the NT length used, suggesting that most electrons are collected. In addition to dye loading and hence photocurrent increment, the photovoltage and filling factor were also improved in the mixed structure due to a low serial resistance, leading to the enhancement of the overall efficiency.

  10. Periocular Basal Cell Carcinoma Predictors for Recurrence and Infiltration of the Orbit

    Science.gov (United States)

    Furdova, Alena; Lukacko, Pavol

    2017-01-01

    Purpose: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the risk factors. Design: Retrospective, comparative, interventional case series. Methods: Data of all patients with BCC between 2008 and 2014 were reviewed for patient demographics, previous treatment options, tumor localization, and histopathologic subtype. Results: In group of 256 patients, orbital exenteration underwent 7 patients (2.7%). For 2 patients (5.1%), orbital exenteration was the first procedure performed. In the exenterated group, the most common tumor site was the medial cantus and lower eyelid, whereas in the overall group, it was the lower eyelid (P = 0.011). The proportion of patients initially treated with histopathologic result of infiltration of 1 margin was significantly higher in patients undergoing exenteration (P = 0.282). During the 7-year period observership, the authors have seen 13 recurrences (5.08%). In patients with recurrent BCC after surgery, the authors applied adjuvant high dose rate 192Ir brachytherapy. Neoadjuvant therapy with Vismodegib was effective in patient with biorbital infiltration after 1 side exenteration. Conclusions: Orbital invasion may be clinically silent. Recurrence rate of BCC in our group 5% corresponds to date in the literature. The exenteration for BCC may be significantly higher when the lesion involves a medial canthal location and lower eyelid and initial surgery does not include margin-controlled excision. PMID:27906855

  11. Long Term Stability Investigation of Solid Oxide Electrolysis Cell with Infiltrated Porous YSZ Air Electrode Under High Current

    DEFF Research Database (Denmark)

    Veltzé, Sune; Ovtar, Simona; Simonsen, Søren Bredmose

    2015-01-01

    activity, due to high surface area of catalyst nano particles. Advantage of infiltration is also separate production of electrolyte backbone structure with good ionic connectivity and mechanical properties. With this study we present the results of a solid oxide cell with infiltrated porous yttria...... and the backbone, and perovskite catalyst material. Cobalt doped lanthanum nickelate was used as the perovskite catalyst due to its excellent performance. The cell was tested in steam electrolysis for at least 2000h. This initial test indicate that a stable air electrode was formed, and that the cell performance...

  12. SPONGIOTIC DERMATITIS WITH A MIXED INFLAMMATORY INFILTRATE OF LYMPHOCYTES, ANTIGEN PRESENTING CELLS, IMMUNOGLOBULINS AND COMPLEMENT

    Directory of Open Access Journals (Sweden)

    Abreu Velez Ana Maria

    2011-04-01

    Full Text Available Background: The clinical and histological presentation of spongiotic dermatitis and its inflammatory infiltrates warrant further investigation. In this case documentation of a patient with cutaneous spongiotic reactivity, we aim to characterize antigen presenting cells, as well as the skin-specific cutaneous lymphocyte antigen population by multiple techniques. Case report: A 30 year old Caucasian female presented with a two week history of blistering and erosions around the vaginal, rectal and axillary areas. Material and Methods: We utilized hematoxylin and eosin histology, direct immunofluorescence, immunohistochemistry and confocal microscopy methods to evaluate the immune reaction patterns of the cutaneous inflammatory cells. Results: In the primary histologic areas of spongiotic dermatitis, a mixed population of B and T lymphocytes was seen. Ki-67 antigen proliferative index staining was accentuated in these areas, correlating with the presence of large numbers of epidermal and dermal antigen presenting cells. Among the antigen presenting cell population, we detected strong positivities with CD1a, Factor XIIIa, myeloid/hystoid antigen, S100, HAM-56, and CD68. Interestingly, immunoglobulins G, D and M and Complement factors C1q and C3 were also strongly expressed in antigen presenting cell areas, including positivity within the spongiotic epidermis and around dermal vessels. Conclusions: We document a heterogeneous population of B and T lymphocytes and the presence of multiple classes of antigen presenting cells, immunoglobulins and complement in and surrounding histologically spongiotic areas; these findings further correlated with increased levels of expression of Ki-67.

  13. Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Salman M Toor

    2016-12-01

    Full Text Available Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs, have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment of colorectal cancer (CRC patients, compared to blood from healthy donors (HDs and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of cells expressing myeloid markers and lacking the expression of MHC class II molecule HLA-DR in blood and tumor of CRC patients. Further analysis revealed that these cells were granulocytic and expressed Arginase 1 (ARG1, indicative of their suppressive phenotype. These expanded cells could be neutrophils or granulocytic MDSCs, and we refer to them as granulocytic myeloid cells (GMCs due to the phenotypical and functional overlap between these cell subsets. Interestingly, the expansion of peripheral GMCs correlated with higher stage and histological grade of cancer, thereby suggesting their role in cancer progression. Furthermore, an increase in CD33+CD11b+HLA-DR-CD14-CD15- immature myeloid cells (IMCs was also observed in CRC tumor tissue. Our work shows that GMCs are expanded in circulation and tumor microenvironment of CRC patients, which provides further insights for developing immunotherapeutic approaches targeting these cell subsets to enhance anti-tumor immune and clinical responses.

  14. Sequential metastases of colorectal cancer: Immunophenotypes and spatial distributions of infiltrating immune cells in relation to time and treatments.

    Science.gov (United States)

    Keim, Sophia; Zoernig, Inka; Spille, Anna; Lahrmann, Bernd; Brand, Karsten; Herpel, Esther; Grabe, Niels; Jäger, Dirk; Halama, Niels

    2012-08-01

    The role of the immune system in the course of colorectal cancer has been elucidated in the last decade. While quantification of immune cell infiltrates within the resected specimen at diagnosis has a clear power to estimate the prognosis of the patient, the role of infiltrating immune cells within the metastatic situation and especially within the metastatic lesion itself requires further detailed analyses. Recent analyses of infiltrates in colorectal cancer liver metastases revealed a role for the infiltrate density not only for prognosis but also in the prediction of treatment response. This not only broadens the view on these infiltrates and indicates a systematic role of the local immunological microenvironment, but also raises the question how these infiltrates change during repeated courses of treatment (i.e., resection, chemotherapy, etc.). To address this question, sequential lung or sequential liver metastases of colorectal cancer patients were analyzed using whole slide image quantification after immunohistochemical staining against CD3, CD8, FOXP3, CD68 and Granzyme B. The clinical data and interventions were associated with each individual patient and the metastatic lesions. The resulting cell densities reveal a heterogeneous profile: after successful treatment of a metastatic lesion, the recurrent lesion can still have the same immunophenotype with similar cell distributions. In a situation of a favorable immune cell profile, this profile can return and apparently convey a similar favorable course throughout the disease. But also the opposite was found: the recurrent metastatic lesion could have a different profile with alterations in specific immune cell subsets over time. Further analyses are required to elucidate the different patterns and their associations to the treatment, the tumor cell phenotype and other dynamic factors. However, it is clear from this data however, that there is an immune cell plasticity that needs to be analyzed for

  15. Tumor infiltrating lymphocytes in melanoma comprise high numbers of T-cell clonotypes that are lost during in vitro culture

    DEFF Research Database (Denmark)

    thor Straten, P; Kirkin, A F; Siim, E;

    2000-01-01

    Melanoma is generally accepted as being an antigenic tumor capable of eliciting T-cell responses that, however, in most cases are inadequate to control tumor growth. Tumor-infiltrating lymphocytes (TIL) in melanoma lesions comprise clonotypic T cells, indicating the in situ recognition of melanom...

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

    Science.gov (United States)

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

    2010-05-01

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

  17. Mesenchymal stem cells enhance ovarian cancer cell infiltration through IL6 secretion in an amniochorionic membrane based 3D model

    Directory of Open Access Journals (Sweden)

    Touboul Cyril

    2013-01-01

    Full Text Available Abstract Background The early peritoneal invasion of epithelial ovarian cancer (EOC by tumoral aggregates presents in ascites is a major concern. The role of the microenvironment seems to be important in this process but the lack of adequate models to study cellular interactions between cancer cells and stromal cells does not allow to uncover the molecular pathways involved. Our goal was to study the interactions between ovarian cancer cells (OCC and mesenchymal stem cells (MSC using a 3D model. Methods We used millimetric pieces of amniochorionic membrane - referred to as amniotic membrane scaffold (AMS - to create 3D peritoneal nodules mimicking EOC early invasion. We were able to measure the distribution and the depth of infiltration using confocal microsopy. We extracted MSC from the amniochorionic membrane using the markers CD34-, CD45-, CD73+, CD90+, CD105+ and CD29+ at the Fluorescence Activated Cell Sorting (FACS analysis. We used transwell and wound healing tests to test OCC migration and invasion in vitro. Results Here we show that OCC tumors were located in regions rich in MSC (70%. The tumors infiltrated deeper within AMS in regions rich in MSC (p Conclusions The use of tridimensional models using AMS could be a useful tool to decipher early molecular events in ovarian cancer metastasis. Cytokine inhibitors interrupting the cross-talk between OCCs and MSCs such as IL6 should be investigated as a new therapeutic approach in ovarian cancer.

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

    Directory of Open Access Journals (Sweden)

    MGS Vieira

    2002-10-01

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

  19. Myocardial collagen deposition and inflammatory cell infiltration in cats with pre-clinical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Khor, K H; Campbell, F E; Owen, H; Shiels, I A; Mills, P C

    2015-02-01

    The histological features of feline hypertrophic cardiomyopathy (HCM) have been well documented, but there are no reports describing the histological features in mild pre-clinical disease, since cats are rarely screened for the disease in the early stages before clinical signs are apparent. Histological changes at the early stage of the disease in pre-clinical cats could contribute to an improved understanding of disease aetiology or progression. The aim of this study was to evaluate the histological features of HCM in the left ventricular (LV) myocardium of cats diagnosed with pre-clinical HCM. Clinically healthy cats with normal (n = 11) and pre-clinical HCM (n = 6) were identified on the basis of echocardiography; LV free wall dimensions (LVFWd) and/or interventricular septal wall (IVSd) dimensions during diastole of 6-7 mm were defined as HCM, while equivalent dimensions <5.5 mm were defined as normal. LV myocardial sections were assessed and collagen content and inflammatory cell infiltrates were quantified objectively. Multifocal areas of inflammatory cell infiltration, predominantly lymphocytes, were observed frequently in the left myocardium of cats with pre-clinical HCM. Tissue from cats with pre-clinical HCM also had a higher number of neutrophils and a greater collagen content than the myocardium of normal cats. The myocardium variably demonstrated other features characteristic of HCM, including arteriolar mural hypertrophy and interstitial fibrosis and, to a lesser extent, myocardial fibre disarray and cardiomyocyte hypertrophy. These results suggest that an inflammatory process could contribute to increased collagen content and the myocardial fibrosis known to be associated with HCM.

  20. T cell receptor transgenic lymphocytes infiltrating murine tumors are not induced to express foxp3

    Directory of Open Access Journals (Sweden)

    Quatromoni Jon G

    2011-11-01

    Full Text Available Abstract Regulatory T cells (Treg that express the transcription factor Foxp3 are enriched within a broad range of murine and human solid tumors. The ontogeny of these Foxp3 Tregs - selective accumulation or proliferation of natural thymus-derived Treg (nTreg or induced Treg (iTreg converted in the periphery from naïve T cells - is not known. We used several strains of mice in which Foxp3 and EGFP are coordinately expressed to address this issue. We confirmed that Foxp3-positive CD4 T cells are enriched among tumor-infiltrating lymphocytes (TIL and splenocytes (SPL in B16 murine melanoma-bearing C57BL/6 Foxp3EGFP mice. OT-II Foxp3EGFP mice are essentially devoid of nTreg, having transgenic CD4 T cells that recognize a class II-restricted epitope derived from ovalbumin; Foxp3 expression could not be detected in TIL or SPL in these mice when implanted with ovalbumin-transfected B16 tumor (B16-OVA. Likewise, TIL isolated from B16 tumors implanted in Pmel-1 Foxp3EGFP mice, whose CD8 T cells recognize a class I-restricted gp100 epitope, were not induced to express Foxp3. All of these T cell populations - wild-type CD4, pmel CD8 and OTII CD4 - could be induced in vitro to express Foxp3 by engagement of their T cell receptor (TCR and exposure to transforming growth factor β (TGFβ. B16 melanoma produces TGFβ and both pmel CD8 and OTII CD4 express TCR that should be engaged within B16 and B16-OVA respectively. Thus, CD8 and CD4 transgenic T cells in these animal models failed to undergo peripheral induction of Foxp3 in a tumor microenvironment.

  1. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  2. Identification of immune cell infiltration in hematoxylin-eosin stained breast cancer samples: texture-based classification of tissue morphologies

    Science.gov (United States)

    Turkki, Riku; Linder, Nina; Kovanen, Panu E.; Pellinen, Teijo; Lundin, Johan

    2016-03-01

    The characteristics of immune cells in the tumor microenvironment of breast cancer capture clinically important information. Despite the heterogeneity of tumor-infiltrating immune cells, it has been shown that the degree of infiltration assessed by visual evaluation of hematoxylin-eosin (H and E) stained samples has prognostic and possibly predictive value. However, quantification of the infiltration in H and E-stained tissue samples is currently dependent on visual scoring by an expert. Computer vision enables automated characterization of the components of the tumor microenvironment, and texture-based methods have successfully been used to discriminate between different tissue morphologies and cell phenotypes. In this study, we evaluate whether local binary pattern texture features with superpixel segmentation and classification with support vector machine can be utilized to identify immune cell infiltration in H and E-stained breast cancer samples. Guided with the pan-leukocyte CD45 marker, we annotated training and test sets from 20 primary breast cancer samples. In the training set of arbitrary sized image regions (n=1,116) a 3-fold cross-validation resulted in 98% accuracy and an area under the receiver-operating characteristic curve (AUC) of 0.98 to discriminate between immune cell -rich and - poor areas. In the test set (n=204), we achieved an accuracy of 96% and AUC of 0.99 to label cropped tissue regions correctly into immune cell -rich and -poor categories. The obtained results demonstrate strong discrimination between immune cell -rich and -poor tissue morphologies. The proposed method can provide a quantitative measurement of the degree of immune cell infiltration and applied to digitally scanned H and E-stained breast cancer samples for diagnostic purposes.

  3. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    1997-01-01

    In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE...

  4. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology.

  5. Progressive renal failure due to renal infiltration by BK polyomavirus and leukaemic cells: which is the culprit?

    Science.gov (United States)

    Sangala, Nicholas; Dewdney, Alex; Marley, Nicholas; Cranfield, Tanya; Venkat-Raman, Gopalakrishnan

    2011-02-01

    Renal infiltration with leukaemic cells is a common finding in patients suffering with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft failure in renal transplant recipients but rarely causes significant disease in native kidneys. In the few reports where leukaemic infiltration of the kidney has led to significant renal impairment, the pathological process causing renal dysfunction is not identified on biopsy. In these cases, it is unclear whether BK polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual pathologies in a patient with Binet stage C CLL and deteriorating renal function where renal biopsy reveals leukaemic infiltration of the kidney occurring alongside BKV nephropathy. The relative importance of each pathology in relation to the rapid decline to end-stage renal failure remains unclear, but the presence of both pathologies appears to impart a poor prognosis. Additionally, we describe the novel histological finding of loss of tubular integrity resulting in tubular infiltration and occlusion by leukaemic cells. It is possible that the patient with advanced CLL is at particular risk of BK activation, and the presence of BK nephropathy may compromise tubular integrity allowing leukaemic cell infiltration and obstruction of tubules. This case bares remarkable resemblance to the first and only other report of its kind in the literature. It is not clear how available immunocytochemistry for polyoma infection is outside transplant centres, and it is possible that BK nephropathy is being under-diagnosed in patients with CLL in the context of declining renal function. At present, the combination of BKV nephropathy and leukaemic infiltration represents a management conundrum and the prognosis is poor. Further research is required in order to better understand the pathological process and therefore develop management strategies.

  6. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection

  7. Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Dongxian; Liu, Yalan; Wang, Hao; Wang, Haixing; Song, Qi; Sujie, Akesu; Huang, Jie; Xu, Yifan; Zeng, Haiying; Tan, Lijie; Hou, Yingyong; Xu, Chen

    2017-03-21

    We undertook a study of tumour infiltrating lymphocytes (TILs) in a large and relatively homogeneous group of patients with completely resected esophageal squamous cell carcinoma (ESCC). Hematoxylin and eosin-stained sections of 235 ESCC tumours were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Foxp3+, CD4+, and CD8+ T cells in tumoural and stromal areas were evaluated by immunohistochemistry. Of the 235 tumours, high sTIL (>10%), and iTIL (>10%) were observed in 101 (43.0%) and 98 (41.7%), respectively. The median follow-up period was 36.0 months (95% CI 29.929-42.071). Univariate analysis revealed that sTIL (>10%), iTIL (>20%), vessels involvement, lymph node metastasis, and clinical stage were significantly associated with postoperative outcome. In multivariate analysis, high sTIL (HR: 0.664, P = 0.019 for Disease free survival; HR: 0.608, P = 0.005 for Overall survival) was identified as independent better prognostic factor. Further analysis, sTIL was identified as independently prognostic factor in Stage III-IVa disease, which was not found in Stage I-II disease. Our study demonstrated that sTIL was associated with better ESCC patients' survival, especially in Stage III-IVa disease. Assessment of sTIL could be useful to discriminate biological behavior for ESCC patients.

  8. Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Kazutaka Kurokohchi; Shigeki Kuriyama; Tsutomu Masaki; Takashi Himoto; Akihiro Deguchi; Seiji Nakai; Asahiro Morishita; Hirohito Yoneyama; Yasuhiko Kimura; Seishiro Watanabe

    2006-01-01

    AIM: Although the pathogenic mechanism underlying autoimmune hepatitis (AIH) remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses. Analysis of costimulatory molecule expressed on mononuclear cells from the patients with AIH may give us insight into the pathogenic mechanism of hepatocellular damage in AIH.METHODS: Peripheral blood mononuclear cells (PBMC)were taken from the patients with AIH (34 cases) and healthy controls (25 cases). Liver infiltrating mononuclear cells (LIMCs) were taken from the patients with AIH (18 cases), the patient with chronic hepatitis C (CH-C) (13 cases) and the patients with fatty liver (2 cases).Using flow cytometry, the cells were analyzed for the expression of costimulatory molecules, such as CD80,CD86, and CD152 (CTLA-4). The results were compared with clinical data such as the level of gammaglobulin,histological grade, presence or absence of corticosteroids administration and the response to corticosteroids.RESULTS: The levels of CD80+, CD86+ and CD152+PBMC were significantly reduced in the patients with AIH as compared with healthy controls. By contrast,those cells were significantly higher in LTMC than in PBMC of the patients with AIH. Especially, the level of CD86+ LIMC showed a marked increase irrespective of the degree of disease activity in the patients with ATH,although CD86+ cells were rarely present in PBMC. The levels of CD86+ cells were present in significantly higher frequency in patients with AIH than in the patients with CH-C. Furthermore, the patients with AIH with high levels of CD86+ LIMC showed good responses to corticosteroids, whereas 2 cases of AIH with low levels of CD86+ LIMC did not respond well

  9. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  10. Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Han-qiu CHEN; Jian ZHENG

    2004-01-01

    AIM: To investigate the ability of proteinase inhibitors to modulate nucleated cell infiltration into the peritoneum of mice induced by tryptase and chymase. METHODS: Human lung tryptase and skin chymase were purified by a similar procedure involving high salt extraction, heparin agarose affinity chromatography followed by S-200 Sephacryl gel filtration chromatography. The actions of proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation were examined with a mouse peritoneum model. RESULTS: A selective chymase inhibitor Z-Ile-GluPro-Phe-CO2Me (ZIGPPF) was able to inhibit approximately 90% neutrophil, 73% eosinophil, 87% lymphocyte and 60% macrophage accumulation induced by chymase at 16 h following injection. Soy bean trypsin inhibitor (SBTI), chymostatin, and α1-antitrypsin showed slightly less potency than ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors tested were able to inhibit neutrophil, eosinophil, and macrophage accumulation provoked by tryptase at 16 h following injection, only leupeptin, APC366, and aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation. The inhibitiors of tryptase tested were also able to inhibit tryptase induced neutrophil and eosinophil accumulation at 6 h following injection. When being injected alone, all inhibitors of chymase and tryptase at the concentrations tested by themselves had no significant effect on the accumulation of nucleated cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase inhibitors significantly inhibited tryptase and chymase-induced nucleated cell accumulation in vivo, and therefore they are likely to be developed as a novel class of anti-inflammatory drugs.

  11. Clinical significance of tumor-infiltrating immune cells focusing on BTLA and Cbl-b in patients with gallbladder cancer.

    Science.gov (United States)

    Oguro, Seiji; Ino, Yoshinori; Shimada, Kazuaki; Hatanaka, Yutaka; Matsuno, Yoshihiro; Esaki, Minoru; Nara, Satoshi; Kishi, Yoji; Kosuge, Tomoo; Hiraoka, Nobuyoshi

    2015-12-01

    The host immune system plays a significant role in tumor control, although most cancers escape immune surveillance through a variety of mechanisms. The aim of the present study was to evaluate the clinicopathological significance of a novel co-inhibitory receptor, B and T lymphocyte attenuator (BTLA), the anergy cell marker Casitas-B-lineage lymphoma protein-b (Cbl-b), and clinical implications of tumor-infiltrating immune cells in gallbladder cancer (GBC) tissues. We investigated 211 cases of GBC, 21 cases of chronic cholecystitis (CC), and 11 cases of xanthogranulomatous cholecystitis (XGC) using immunohistochemistry to detect tissue-infiltrating immune cells and their expression of BTLA and Cbl-b, and carried out correlation and survival analyses. The density of infiltrating T cells was significantly higher in CC and XGC than in GBC. The density ratio of BTLA(+) cells to CD8(+) T cells (BTLA/CD8) and that of Cbl-b(+) cells to CD8(+) T cells (Cbl-b/CD8) were significantly higher in GBC than in CC and XGC. The FOXP3/CD4, BTLA/CD8, and Cbl-b/CD8 ratios were significantly correlated with each other, and also with malignant phenotypes. Survival analyses revealed that a lower density of tumor-infiltrating CD8(+) cells, and higher Foxp3/CD4, BTLA/CD8, and Cbl-b/CD8 ratios were significantly associated with shorter overall survival and disease-free survival in GBC patients. Multivariate analyses showed that M factor, perineural invasion, BTLA/CD8, and Cbl-b/CD8 were closely associated with shorter overall survival. These findings suggest that higher ratios of BTLA/CD8 and Cbl-b/CD8 are independent indicators of unfavorable outcome in GBC patients, and that upregulation of BTLA in cancer tissues is involved in inhibition of antitumor immunity.

  12. Gamma Delta T-Cells Regulate Inflammatory Cell Infiltration of the Lung after Trauma-Hemorrhage

    Science.gov (United States)

    2015-06-01

    propose that resident +% T cells regulate the influx of !" T cells and MDSCs, which are the primary effector cells of the inflammatory and healing ...Choudhry MA, Schwacha MG: T cells of the gammadelta T-cell receptor lineage play an important role in the postburn wound healing process. J Burn Care Res...Schock BC, Okamoto T, McGrew GM, Last JA: Susceptibility to ozone -induced acute lung injury in iNOS-deficient mice. Am J Physiol Lung Cell Mol Physiol 282

  13. A comparative study of psoriasis and psoriasiform lesion on basis of CD4 and CD8 cell infiltration

    OpenAIRE

    2012-01-01

    Introduction: Psoriasis is a chronic inflammatory skin disorder with immunological factors playing an important role in its pathogenesis. It is now regarded as a T cell mediated disorder in which lymphocytic infiltrates, mainly CD4 and CD 8 cells which provide a major contribution in the initiation and maintenance of psoriatic lesions.Methods: Skin biopsies from both psoriatic and psoriasiform lesions were stained with monoclonal antibodies against CD4 and CD8 and their percentage was calcula...

  14. Giant cell arteritis mimicking infiltrative leptomeningeal disease of the optic nerves.

    Science.gov (United States)

    Kornberg, Michael D; Ratchford, John N; Subramaniam, Rathan M; Probasco, John C

    2015-04-09

    A 67-year-old man presented with several days of progressive, painless left eye vision loss. He reported mild jaw claudication but denied headache, scalp tenderness or constitutional symptoms. Examination revealed palpable temporal arteries, blurring of the left optic disc, and 20/100 vision in the left eye with mild relative afferent pupillary defect. Inflammatory markers were sent, and methylprednisolone was initiated for presumptive giant cell arteritis (GCA). Erythrocyte sedimentation rate was normal, however, and C reactive protein was only mildly elevated, prompting further investigation. Orbital MRI revealed nodular enhancement of the optic nerve sheaths bilaterally from optic nerve head to chiasm, raising concern for an infiltrative leptomeningeal process such as sarcoidosis or lymphoma. Methylprednisolone was temporarily stopped while a broad work up for inflammatory and neoplastic causes was pursued. Fluorodeoxyglucose-positron emission tomography ultimately revealed hypermetabolism in the temporal, ophthalmic and occipital arteries suggesting GCA, which was confirmed by temporal artery biopsy. Steroids were restarted, and the patient's vision stabilised.

  15. Three-dimensional cellulose sponge: Fabrication, characterization, biomimetic mineralization, and in vitro cell infiltration.

    Science.gov (United States)

    Joshi, Mahesh Kumar; Pant, Hem Raj; Tiwari, Arjun Prasad; Maharjan, Bikendra; Liao, Nina; Kim, Han Joo; Park, Chan Hee; Kim, Cheol Sang

    2016-01-20

    In this study, cellulose based scaffolds were produced by electrospinning of cellulose acetate (CA) solution followed by its saponification with NaOH/ethanol system for 24h. The resulting nonwoven cellulose mat was treated with sodium borohydride (SB) solution. In situ hydrolysis of SB solution into the pores of the membrane produced hydrogen gas resulting a three-dimensional (3D) cellulose sponge. SEM images demonstrated an open porous and loosely packed fibrous mesh compared to the tightly packed single-layered structure of the conventional electrospun membrane. 3D cellulose sponge showed admirable ability to nucleate bioactive calcium phosphate (Ca-P) crystals in simulated body fluid (SBF) solution. SEM-EDX and X-ray diffraction studies revealed that the minerals deposited on the nanofibers have the nonstoichiometric composition similar to that of hydroxyapatite, the mineralized component of the bone. 3D cellulose sponge exhibited the better cell infiltration, spreading and proliferation compared to 2D cellulose mat. Therefore, a facile fabrication of 3D cellulose sponge with improved mineralization represents an innovative strategy for the bone tissue engineering applications.

  16. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.

    Science.gov (United States)

    Smid, Marcel; Rodríguez-González, F Germán; Sieuwerts, Anieta M; Salgado, Roberto; Prager-Van der Smissen, Wendy J C; Vlugt-Daane, Michelle van der; van Galen, Anne; Nik-Zainal, Serena; Staaf, Johan; Brinkman, Arie B; van de Vijver, Marc J; Richardson, Andrea L; Fatima, Aquila; Berentsen, Kim; Butler, Adam; Martin, Sancha; Davies, Helen R; Debets, Reno; Gelder, Marion E Meijer-Van; van Deurzen, Carolien H M; MacGrogan, Gaëtan; Van den Eynden, Gert G G M; Purdie, Colin; Thompson, Alastair M; Caldas, Carlos; Span, Paul N; Simpson, Peter T; Lakhani, Sunil R; Van Laere, Steven; Desmedt, Christine; Ringnér, Markus; Tommasi, Stefania; Eyford, Jorunn; Broeks, Annegien; Vincent-Salomon, Anne; Futreal, P Andrew; Knappskog, Stian; King, Tari; Thomas, Gilles; Viari, Alain; Langerød, Anita; Børresen-Dale, Anne-Lise; Birney, Ewan; Stunnenberg, Hendrik G; Stratton, Mike; Foekens, John A; Martens, John W M

    2016-09-26

    A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.

  17. Fabrication and characterization of protonic-ceramic fuel cells and electrolysis cells utilizing infiltrated lanthanum nickelate electrodes

    Science.gov (United States)

    Babiniec, Sean M.

    High-temperature protonic ceramics (HTPCs) have gained interest as fuel cell and electrolysis cell electrolytes, as well as hydrogen separation membranes. The transport of hydrogen as opposed to oxygen results in several benefits and applications, including higher fuel efficiency, dehydrogenation of fuel streams, and hydrogen-based chemical synthesis. However, limited work has been done in the development of air/steam electrodes for these devices. This work presents the characterization of lanthanum nickelate, La 2NiO4+delta (LN), as a potential air/steam electrode material for use with BaCe0.2Zr0.7Y0.1O3-delta (BCZY27) HTPC electrolytes fabricated by the solid-state reactive sintering technique. Two types of devices were made; a symmetric cell used for electrode characterization, and a full fuel cell/electrolysis cell used for device performance characterization. The symmetric cell consists of a 1 mm thick BCZY27 substrate with identical air/steam electrodes on both sides. Air/steam electrodes were made by infiltrating ˜ 50 nm lanthanum nickelate nanoparticles into a BCZY27 porous backbone. The fuel cell/electrolysis cell consists of a 1mm thick Ni/BCZY27 anode support, a 25 mum thick BCZY27 electrolyte, and a 50 mum thick porous BCZY27 backbone infiltrated with lanthanum nickelate. Through symmetric cell testing, it was found that the electrode polarization resistance decreases with increasing oxygen content, indicating good oxygen reduction reaction characteristics. A minimum polarization resistance was found as 2.58 Ohm-cm2 in 3% humidied oxygen at 700 °C. Full cell testing revealed a peak power density of 27 mW-cm-2 at 700 °C. Hydrogen flux measurements were also taken in the both galvanic/post-galvanic and electrolytic operation. Galvanic/post-galvanic fluxes exhibit a very high faradaic efficiency. However, electrolytic hydrogen fluxes were much lower than the calculated hydrogen faradaic flux, indicating a different charge carrier other than protons is

  18. The RhoA/ROCK Pathway Ameliorates Adhesion and Inflammatory Infiltration Induced by AGEs in Glomerular Endothelial Cells.

    Science.gov (United States)

    Rao, Jialing; Ye, Zengchun; Tang, Hua; Wang, Cheng; Peng, Hui; Lai, Weiyan; Li, Yin; Huang, Wanbing; Lou, Tanqi

    2017-01-05

    A recent study demonstrated that advanced glycation end products (AGEs) play a role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular endothelial cells (rGECs) were cultured with AGEs (80 μg/ml) in vitro. The ROCK inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK. We investigated levels of the intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein1 (MCP-1) in rGECs. Db/db mice were used as a diabetes model and received Fasudil (10 mg/kg/d, n = 6) via intraperitoneal injection for 12 weeks. We found that AGEs increased the expression of ICAM-1 and MCP-1 in rGECs, and the RhoA/ROCK pathway inhibitor Y27632 depressed the release of adhesion molecules. Moreover, blocking the RhoA/ROCK pathway ameliorated macrophage transfer to the endothelium. Reduced expression of adhesion molecules and amelioration of inflammatory cell infiltration in the glomerulus were observed in db/db mice treated with Fasudil. The RhoA/ROCK pathway plays a role in adhesion molecule expression and inflammatory cell infiltration in glomerular endothelial cells induced by AGEs.

  19. TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Renno, T; Krakowski, M; Piccirillo, C

    1995-01-01

    , the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m......RNA. Therefore, TNF-alpha is made by both CNS-resident microglia and infiltrating macrophages during EAE, and this production is tightly controlled by cytokines secreted by infiltrating CD4+ T cells.......The inflammatory cytokines IFN-gamma and TNF-alpha have been demonstrated in various autoimmune diseases, and are thought to participate in the induction and pathogenesis of disease. TFN-alpha is a cytopathic cytokine that is cytotoxic for oligodendrocytes in vitro and has been implicated...

  20. Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration

    Directory of Open Access Journals (Sweden)

    Ana P. Berbegall

    2014-06-01

    Full Text Available Neuroblastoma (NB is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years formed part of the cohort. We performed single nucleotide polymorphism arrays, immunohistochemistry for immune markers (CD4, CD8, CD20, CD11b, CD11c, and CD68, and ATRX protein expression. Assorted genetic profiles were found with a predominant presence of a segmental chromosome aberration (SCA profile. Preadolescent and adolescent NB tumors showed a higher number of SCA, including 17q gain and 11q deletion. There was also a marked infiltration of immune cells, mainly high and heterogeneous, in young and middle-aged adult tumors. ATRX negative expression was present in the tumors. The characteristics of preadolescent, adolescent, young adult, and middle-aged adult NB tumors are different, not only from childhood NB tumors but also from each other. Similar examinations of a larger number of such tumor tissues from cooperative groups should lead to a better older age–dependent tumor pattern and to innovative, individual risk-adapted therapeutic approaches for these patients.

  1. Meningeal infiltration of the spinal cord by non-classically activated B cells is associated with chronic disease course in a spontaneous B cell-dependent model of CNS autoimmune disease

    Directory of Open Access Journals (Sweden)

    Amy K Dang

    2015-09-01

    Full Text Available We characterized B cell infiltration of the spinal cord in a B cell-dependent, spontaneous model of central nervous system (CNS autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein (MOG. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4+ T cell infiltration was pervasive throughout the white and in some cases grey matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis (MS. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35+ follicular dendritic cells (FDCs, or germinal centers (GCs. The majority of cluster B cells were IgD+ with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38hi CD95lo phenotype. Nevertheless, they were CD62Llo and CD80hi compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.

  2. Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.

    Science.gov (United States)

    Dang, Amy K; Tesfagiorgis, Yodit; Jain, Rajiv W; Craig, Heather C; Kerfoot, Steven M

    2015-01-01

    We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4(+) T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers. The majority of cluster B cells were IgD(+) with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38(hi) CD95(lo) phenotype. Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.

  3. Sensitivity Analysis of Centralized Dynamic Cell Selection

    DEFF Research Database (Denmark)

    Lopez, Victor Fernandez; Alvarez, Beatriz Soret; Pedersen, Klaus I.;

    2016-01-01

    mechanism and solutions involving cell switching in general. Simulation results show that such solutions can greatly benefit from the use of receivers with interference suppression capabilities and a larger number of antennas, with a maximum data rate gain of 120%. High performance gains are observed...... with two different traffic models, and it is not necessary to be able to connect to a large number of cells in order to reap most of the benefits of the centralized dynamic cell selection....

  4. Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH Tissues via Modulation of CCL5 Secretion

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2014-01-01

    Full Text Available Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5α-dihydrotestosterone (DHT exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP were divided into 2 groups: (1 no medication history; (2 administration of 5α-reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry. In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif Ligand 5 (CCL5 mRNA in BPH-1 cells and chemokine (C-C motif receptor 5 (CCR5 mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR. CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

  5. Correlation between CD4, CD8 cell infiltration in gastric mucosa,Helicobacter pylori infection and symptoms in patients with chronic gastritis

    Institute of Scientific and Technical Information of China (English)

    Ai-Ping Lu; Sheng-Sheng Zhang; Qing-Lin Zha; Da-Hong Ju; Hao Wu; Hong-Wei Jia; Cheng Xiao; Shao Li; Hui Jian

    2005-01-01

    AIM: To evaluate the correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori(H pylori)infection and symptoms or the assemblage of symptoms in cases with chronic gastritis.METHODS: Biopsy samples at the gastric antrum were obtained from 62 patients with chronic gastritis. CD4 and CD8 cell infiltration was evaluated by immunohistochemical assays on frozen sections of the biopsy samples. Fifteen symptoms referring to digestion-related activity and nondigestion related activity were observed. The correlation between lymphocyte infiltration and each symptom or symptom assemblage was analyzed by logistic regression and K-mean cluster methods.RESULTS: CD4 cell infiltrations in gastric mucosa were much more in patients with H pylori infection, while CD8 cell infiltrations were similar in patients with or without H pylori infection. Logistic regression analysis showed that the symptoms including heavy feeling in head or body (t= 2.563), and thirst (t= 2.478) were significantly related with CD4 cell infiltration in gastric mucosa (P<0.05), and cool limbs with aversion to cold were related with CD8cell infiltration (t = 2.872, P<0.05). Further analysis showed that non-digestive related symptom assemblage could increase the predicted percentage of CD4 and CD8cell infiltration in gastric mucosa, including lower CD4infiltration by 12.5%, higher CD8 infiltration by 33.3%,and also non-H pylori infection by 23.6%.K-means cluster analysis of all symptoms and CD4 and CD8 cell infiltration in gastric mucosa showed a similar tendency to increase the predicted percentage of CD4, CD8 cell infiltration and H pylori infection.CONCLUSION: Based on correlation between the gastric mucosa lymphocyte infiltration, H pylori infection and clinical symptoms, symptoms or symptomatic assemblages play an important role in making further classification of chronic gastritis, which might help find a more specific therapy for chronic gastritis.

  6. Limited T-cell receptor diversity in liver-infiltrating lymphocytes from patients with primary biliary cirrhosis.

    Science.gov (United States)

    Diu, A; Moebius, U; Ferradini, L; Genevée, C; Roman-Roman, S; Claudon, M; Delorme, D; Meuer, S; Hercend, T; Praz, F

    1993-10-01

    Primary biliary cirrhosis is associated with the presence of high-titer anti-mitochondrial autoantibodies as well as T-cell infiltration of the liver, suggesting the involvement of autoimmune mechanisms. We have studied here the sequences of T-cell receptor alpha and beta chains expressed by T-cell clones derived from liver-infiltrating lymphocytes of two patients with primary biliary cirrhosis. Among the eight clones studied from the first patient, four expressed the same member of the V beta 6 subfamily, associated with either V alpha 4 (three clones) or V alpha 21 (one clone) gene segment. Two other clones expressed an identical V beta 12 transcript, and two in-frame alpha chain transcripts, involving V alpha 2 and V alpha 7 gene segments. From the second patient, eight out of the nine clones were found to rearrange V beta 17-J beta 2.1 and V alpha 3 gene segments. The remaining clone expressed distinct T-cell receptor chains, involving V beta 9 and V alpha 11 gene segments. As deduced from the analysis of their junctional regions, the eight T-cell clones expressing V beta 17/V alpha 3 gene segments derived from only three different T cells. Furthermore, conserved amino acid motifs were found to be encoded in both the alpha and the beta-chain junctional regions. Together, these data show a local amplification of unique T lymphocytes in both patients. The use of identical V beta J beta and V alpha gene segments with similar junctional sequences by three different cells, evidenced in one of the two cases, strengthens the view that liver-infiltrating T lymphocytes are selected locally by autoantigens in PBC.

  7. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

    Directory of Open Access Journals (Sweden)

    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  8. Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

    Science.gov (United States)

    Howson, Lauren J; Morris, Katrina M; Kobayashi, Takumi; Tovar, Cesar; Kreiss, Alexandre; Papenfuss, Anthony T; Corcoran, Lynn; Belov, Katherine; Woods, Gregory M

    2014-05-01

    The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration.

  9. Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a novel murine model of palladium-induced metal allergy.

    Directory of Open Access Journals (Sweden)

    Hiroshi Kobayashi

    Full Text Available Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is characterized by the recruitment of lymphocytes into sites of allergic inflammation. Because of the unavailability of suitable animal models for metal allergy, the role of T cells in the pathogenesis of metal allergy has not been explored. Thus, we developed a novel mouse model for metal allergy associated with infiltration of T cells by multiple injections of palladium (Pd plus lipopolysaccharide into the footpad. Using this model, we characterized footpad-infiltrating T cells in terms of phenotypic markers, T cell receptor (TCR repertoires and cytokine expression. CD3+ CD4+ T cells accumulated in the allergic footpads 7 days after Pd challenge. The expression levels of CD25, interleukin-2, interferon-γ and tumor necrosis factor, but not interleukin-4 and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T helper 1 (Th1 cells locally expanded in response to Pd. Infiltrated T cells in the footpads frequently expressed AV18-1 and BV8-2 T cell receptor (TCR chains compared with T cells in the lymph nodes and exhibited oligoclonality. T-cell clones identified from Pd-allergic mouse footpads shared identical CDR3 sequences containing AV18-1 and BV8-2. These results suggest that TCR AV18-1 and BV8-2 play dominant and critical parts in the antigen specificity of Pd-specific Th1 cells.

  10. Infiltrative Cardiomyopathies

    Science.gov (United States)

    Bejar, David; Colombo, Paolo C; Latif, Farhana; Yuzefpolskaya, Melana

    2015-01-01

    Infiltrative cardiomyopathies can result from a wide spectrum of both inherited and acquired conditions with varying systemic manifestations. They portend an adverse prognosis, with only a few exceptions (ie, glycogen storage disease), where early diagnosis can result in potentially curative treatment. The extent of cardiac abnormalities varies based on the degree of infiltration and results in increased ventricular wall thickness, chamber dilatation, and disruption of the conduction system. These changes often lead to the development of heart failure, atrioventricular (AV) block, and ventricular arrhythmia. Because these diseases are relatively rare, a high degree of clinical suspicion is important for diagnosis. Electrocardiography and echocardiography are helpful, but advanced techniques including cardiac magnetic resonance (CMR) and nuclear imaging are increasingly preferred. Treatment is dependent on the etiology and extent of the disease and involves medications, device therapy, and, in some cases, organ transplantation. Cardiac amyloid is the archetype of the infiltrative cardiomyopathies and is discussed in great detail in this review. PMID:26244036

  11. A Mushroom Extract Piwep from Phellinus igniarius Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Immune Cell Infiltration in the Spinal Cord

    Directory of Open Access Journals (Sweden)

    Lan Li

    2014-01-01

    Full Text Available The present study aimed to evaluate the therapeutic potential of a mushroom extract from Phellinus igniarius in an animal model of multiple sclerosis. The medicinal mushroom, Phellinus igniarius, contains biologically active compounds that modulate the human immune system. Experimental autoimmune encephalomyelitis (EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG 35–55 in C57BL/6 female mice. A water-ethanol extract of Phellinus igniarius (Piwep was delivered intraperitoneally every other day for the entire experimental course. Three weeks after the initial immunization, demyelination and immune cell infiltration in the spinal cord were examined. Piwep injection profoundly decreased the daily incidence rate and clinical score of EAE. The Piwep-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination and infiltration of encephalitogenic immune cells including CD4+ T cells, CD8+ T cells, macrophages, and B cells in the spinal cord. Piwep reduced expression of vascular cell adhesion molecule-1 (VCAM-1 in the spinal cord and integrin-α4 in the lymph node of EAE mice. Piwep also inhibited proliferation of lymphocytes and secretion of interferon-γ in the lymph node of EAE mice. The results suggest that a mushroom extract, Piwep, may have a high therapeutic potential for ameliorating multiple sclerosis progression.

  12. Renal cell carcinoma-infiltrating natural killer cells express differential repertoires of activating and inhibitory receptors and are inhibited by specific HLA class I allotypes.

    Science.gov (United States)

    Schleypen, Julia S; Von Geldern, Marion; Weiss, Elisabeth H; Kotzias, Nicole; Rohrmann, Karl; Schendel, Dolores J; Falk, Christine S; Pohla, Heike

    2003-10-10

    Among tumor-infiltrating lymphocytes (TILs) directly isolated from renal cell carcinomas (RCCs), we found substantial numbers of natural killer (NK) cells in most tumor tissues. They could be identified reliably in situ with an antibody directed against the activating receptor (AR) NKp46 that is exclusively expressed by all NK cells. NK-enriched TILs (NK-TILs) showed cytotoxicity against major histocompatibility complex (MHC) class I-negative cell lines. The ability to detect lysis of target cells was dependent on the percentage of NK cells within the TILs, and cytotoxicity was only observed after overnight activation with low-dose interleukin-2 (IL-2). Infiltrating NK cells were found to express various inhibitory receptors (IRs); among these the CD94/NKG2A receptor complex was overrepresented compared to the autologous peripheral blood mononuclear cell (PBMC) population. Other IRs were underrepresented, indicating that NK subpopulations vary in their tumor-infiltrating capacity. IRs expressed by NK-TILs are functional since receptor engagement with MHC class I ligands presented by human leukocyte antigen (HLA)-transfected target cell lines was able to inhibit NK-mediated cytotoxicity. NK-TILs were also able to lyse autologous or allogeneic tumor cell lines in vitro. This activity correlated with low HLA class I surface expression since lysis could be inhibited by interferon (IFN)-gamma-expressing RCC transductants that displayed a higher surface density of HLA class I molecules. Therefore, NK cells infiltrating tumor tissues have an inherent ability to recognize transformed cells, but they require cytokine activation and are sensitive to inhibition by IR ligands.

  13. Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

    Directory of Open Access Journals (Sweden)

    Liliana Germán-Castelán

    2014-01-01

    Full Text Available Progesterone (P4 promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4 and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL, P4 (1 mg, RU486 (5 mg, or P4 + RU486 (1 mg and 5 mg, resp. for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4 significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4 effects. All rats treated with P4 showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4 + RU486, respectively, presented it. Our data suggest that P4 promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor.

  14. Electrodes for solid oxide fuel cells based on infiltration of Co-based materials

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Bonanos, Nikolaos

    2012-01-01

    The electrochemical performance of cathodes produced by infiltration of nitrates corresponding to the nominal compositions Co3O4, LaCoO3, and La0.6Sr0.4Co1.05O3−δ into porous backbones of Ce0.9Gd0.1O1.95 has been studied. Characterization by electrochemical impedance spectroscopy at 600◦C in air ...... at the nanoscale and raise questions on the necessity of Sr doping if the electrocatalyst is formed as nanoparticles using the infiltration technique. ©2012 The Electrochemical Society......The electrochemical performance of cathodes produced by infiltration of nitrates corresponding to the nominal compositions Co3O4, LaCoO3, and La0.6Sr0.4Co1.05O3−δ into porous backbones of Ce0.9Gd0.1O1.95 has been studied. Characterization by electrochemical impedance spectroscopy at 600◦C in air...

  15. IFN-{gamma} gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Rabinovitch, A.; Suarez-Pinzon, W.L.; Sorensen, O. [Univ. of Alberta, Edmonton (Canada)] [and others

    1995-05-01

    Insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice results from selective destruction of pancreatic islet {beta}-cells following islet filtration by mononuclear leukocytes. Cytokines produced by islet-infiltrating mononuclear cells may be involved in {beta}-cell destruction. Therefore, we analyzed cytokine mRNA expression, by reverse-transcriptase PCR (RT-PCR) assay, in mononuclear leukocytes isolated from pancreatic islets of four groups of mice: diabetes-prone female NOD mice; female NOD mice protected from diabetes by injection of CFA at an early age; male NOD mice with a low diabetes incidence; and female BALB/c mice that do not develop diabetes. We found that mRNA levels of IL-1{beta}, IL-2, IL-4, IL-10, and IFN-{gamma} in mononuclear cells from islets of diabetes-prone female NOD mice increased progressively as these cells infiltrated the islets from age 5 wk to diabetes onset (>13 wk). However, only IFN-{gamma} mRNA levels were significantly higher in islet mononuclear cells from 12-wk-old diabetes-prone female NOD mice than from less diabetes-prone NOD mice (CFA-treated females, and males) and normal mice (BALB/c). In contrast, IL-4 mRNA levels were lower in islet mononuclear cells from diabetes-prone female NOD mice than from NOD mice with low diabetes incidence (CFA-treated females and males). Splenic cell mRNA levels of IFN-{gamma} and IL-4 were not different in the four groups of mice. These results suggest that islet {beta}-cell destruction and diabetes in female NOD mice are dependent upon intra-islet IFN-{gamma} production by mononuclear cells, and that CFA-treated female NOD mice and male NOD mice may be protected from diabetes development by down-regulation of IFN-{gamma} production in the islets. 56 refs., 4 figs., 3 tabs.

  16. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available BACKGROUND: When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. METHODOLOGY AND PRINCIPAL FINDINGS: In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294]. SIGNIFICANCE: Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  17. FTY720, Sphingosine 1-Phosphate Receptor Modulator, Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibition of T Cell Infiltration

    Institute of Scientific and Technical Information of China (English)

    Hirotoshi Kataoka; Kunio Sugahara; Kyoko Shimano; Koji Teshima; Mamoru Koyama; Atsushi Fukunari; Kenji Chiba

    2005-01-01

    FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, (S)-enantiomer of FTY720-phosphate [(S)-FTY720-P] on experimental autoimmune encephalomyelitis (EAE) in rats and mice.Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE,and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4+ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and (S)-FTY720-P. When FTY720 or (S)-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4+ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4+ T cells into the inflammation site.

  18. Metastatic spread in patients with non-small cell lung cancer is associated with a reduced density of tumor-infiltrating T cells.

    Science.gov (United States)

    Müller, Philipp; Rothschild, Sacha I; Arnold, Walter; Hirschmann, Petra; Horvath, Lukas; Bubendorf, Lukas; Savic, Spasenija; Zippelius, Alfred

    2016-01-01

    Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site.

  19. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    OpenAIRE

    Mara Giavina-Bianchi; Pedro Giavina-Bianchi; Mirian Nacagami Sotto; Alona Muzikansky; Jorge Kalil; Cyro Festa-Neto; Duncan, Lyn M.

    2015-01-01

    NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. N...

  20. Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

    Science.gov (United States)

    Konturek, S J; Brzozowski, T; Stachura, J; Dembinski, A; Majka, J

    1994-01-01

    Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration, significant reduction in gastric blood flow, and almost complete suppression of biosynthesis of prostaglandins. After rechallenge with aspirin, the mucosal damage became smaller and progressively declined with repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a significant rise in gastric blood flow, reduction in both blood neutrophilia and mucosal neutrophil infiltration, and a remarkable increase in mucosal cell regeneration and mucosal content of epidermal growth factor. Salivectomy, which reduced the mucosal content of epidermal growth factor, aggravated the initial mucosal damage induced by the first exposure to acidified aspirin but did not prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperaemic response to repeated aspirin but did not abolish the development of adaptation to aspirin showing that the maintenance of the gastric blood flow plays little part in this adaptation. In conclusion, the stomach adapts readily to repeated aspirin insults and this is accompanied by a considerable reduction in blood neutrophilia and the severity of neutrophil infiltration and by an extensive proliferation of mucosal cells possibly involving epidermal growth factor. PMID:7525421

  1. A versatile complementation assay for cell-to-cell and long distance movements by cucumber mosaic virus based agro-infiltration.

    Science.gov (United States)

    Shen, Yan; Zhao, Xiaohui; Yao, Min; Li, Chun; Miriam, Karwitha; Zhang, Xue; Tao, Xiaorong

    2014-09-22

    Microinjection, bombardment or tobamovirus and potexvirus based assay has been developed to identify the putative movement protein (MP) or to characterize plasmodesma-mediated macromolecular transport. In this study, we developed a versatile complementation assay for the cell-to-cell and long distance movements of macromolecules by agro-infiltration based on the infectious clones of cucumber mosaic virus (CMV). The movement-deficient CMV reporter was constructed by replacing the MP on RNA 3 with ER targeted GFP. The ectopic expression of CMV MP was able to efficiently move the RNA3-MP::erGFP reporter from the original cell to neighboring cells, whereas CMV MP-M5 mutant was unable to initiate the movement. Importantly, the presence of CMV RNA1 and RNA2 can dramatically amplify the movement signals once the RNA3-MP::erGFP reporter moves out of the original cell. The appropriate observation time for this movement complementation assay was at 48-72 hours post infiltration (hpi), whereas the optimal incubation temperature was between 25 and 28 °C. The ectopic co-expression of MPs from other virus genera, NSm from tomato spotted wilt tospovirus (TSWV) or NSvc4 from rice stripe tenuivirus (RSV), could also facilitate the movement of the RNA3::erGFP reporter from the original cell into other cells. The chimeric mutant virus created by substituting the MP of CMV RNA3 with NSm from TSWV or NSvc4 from RSV move systemically in Nicotiana benthamiana plants by agro-infiltration. This agro-infiltration complementation assay is simple, efficient and reliable. Our approach provides an alternative and powerful tool with great potentials in identifying putative movement protein and characterizing macromolecular trafficking.

  2. Gene expression profile correlates with T cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy

    Science.gov (United States)

    Prins, Robert M.; Soto, Horacio; Konkankit, Vera; Odesa, Sylvia K.; Eskin, Ascia; Yong, William H.; Nelson, Stanley F.; Liau, Linda M.

    2010-01-01

    Purpose To assess the feasibility, safety, and toxicity of autologous tumor lysate-pulsed dendritic cell (DC) vaccination and toll-like receptor (TLR) agonists in patients with newly diagnosed and recurrent glioblastoma. Clinical and immune responses were monitored and correlated with tumor gene expression profiles. Experimental Design Twenty-three patients with glioblastoma (WHO grade IV) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every three months until tumor progression. Gene expression profiling, IHC, FACS, and cytokine bead arrays were performed on patient tumors and PBMC. Results DC vaccinations are safe and not associated with any dose-limiting toxicity. The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months, with a one-, two-, and three-year survival rate of 91%, 55% and 47%, respectively. Patients whose tumors had mesenchymal gene expression signatures exhibited increased survival following DC vaccination compared to historical controls of the same genetic subtype. Tumor samples with a mesenchymal gene expression signature had a higher number of CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) compared with glioblastomas of other gene expression signatures (p = 0.006). Conclusion Autologous tumor lysate-pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients. Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies. PMID:21135147

  3. Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in mice with Sjogren's-like disease.

    Directory of Open Access Journals (Sweden)

    Saeed Khalili

    Full Text Available BACKGROUND: Non-obese diabetic (NOD mice develop Sjögren's-like disease (SS-like with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs. There are recent reports using multipotent mesenchymal stromal cells (MSCs as a therapeutic strategy for autoimmune diseases due to their anti-inflammatory and immunomodulatory capabilities. This paper proposed a combined immuno- and cell-based therapy consisting of: A an injection of complete Freund's adjuvant (CFA to eradicate autoreactive T lymphocytes, and B transplantations of MSCs to reselect lymphocytes. The objective of this was to test the effectiveness of CD45(-/TER119(- cells (MSCs in re-establishing salivary function and in reducing the number of lymphocytic infiltrates (foci in SGs. The second objective was to study if the mechanisms underlying a decrease in inflammation (focus score was due to CFA, MSCs, or CFA+MSCs combined. METHODOLOGY/PRINCIPAL FINDINGS: Donor MSCs were isolated from bones of male transgenic eGFP mice. Eight week-old female NOD mice received one of the following treatments: insulin, CFA, MSC, or CFA+MSC (combined therapy. Mice were followed for 14 weeks post-therapy. CD45(-/TER119(- cells demonstrated characteristics of MSCs as they were positive for Sca-1, CD106, CD105, CD73, CD29, CD44, negative for CD45, TER119, CD11b, had high number of CFU-F, and differentiated into osteocytes, chondrocytes and adipocytes. Both MSC and MSC+CFA groups prevented loss of saliva flow and reduced lymphocytic infiltrations in SGs. Moreover, the influx of T and B cells decreased in all foci in MSC and MSC+CFA groups, while the frequency of Foxp3(+ (T(reg cell was increased. MSC-therapy alone reduced inflammation (TNF-α, TGF-β, but the combination of MSC+CFA reduced inflammation and increased the regenerative potential of SGs (FGF-2, EGF. CONCLUSIONS/SIGNIFICANCE: The combined use of MSC+CFA was effective in both preventing saliva secretion loss and reducing

  4. Analysis of T cell receptor alpha beta variability in lymphocytes infiltrating melanoma primary tumours and metastatic lesions

    DEFF Research Database (Denmark)

    Schøller, J; thor Straten, P; Jakobsen, Annette Birck;

    1994-01-01

    The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reverse-transcription-couple......The T cell receptor (TCR) alpha beta variable (V) gene family usage of tumour-infiltrating lymphocytes (TIL) in four different primary human malignant melanomas and their corresponding metastatic lesions was characterized using a recently developed method based on the reverse...... usage of the TCR V gene families V alpha 4, V alpha 5, V alpha 22 and V beta 8, whereas the V beta 3 gene family appeared to be expressed together with HLA-A1. Other highly expressed V gene families, apparently not restricted to either HLA-A1 or -A2, were V alpha 1 (expressed in three of four primary...... tumours) and V alpha 21 (expressed in two of four tumours). We found no evidence suggesting any correlations between the haplotypes HLA-A1 and -A2 and preferential V gene family expression in the metastatic lesions, and the only common feature was V alpha 8, which was found to be highly expressed in two...

  5. Fatal respiratory failure caused by pulmonary infiltration by pseudo-Gaucher cells

    NARCIS (Netherlands)

    Links, T P; Karrenbeld, A; Steensma, J T; Weits, J; van der Jagt, E J; Postmus, P E

    1992-01-01

    Pseudo-Gaucher cells are reticuloendothelial cells that are found in several diseases. We report a case of pulmonary tuberculosis in which extensive pulmonary involvement with these cells resulted in fatal respiratory failure.

  6. FATAL RESPIRATORY-FAILURE CAUSED BY PULMONARY INFILTRATION BY PSEUDOGAUCHER CELLS

    NARCIS (Netherlands)

    LINKS, TP; KARRENBELD, A; STEENSMA, JT; WEITS, J; VANDERJAGT, EJ; POSTMUS, PE

    1992-01-01

    Pseudo-Gaucher cells are reticuloendothelial cells that are found in several diseases. We report a case of pulmonary tuberculosis in which extensive pulmonary involvement with these cells resulted in fatal respiratory failure.

  7. Transforming Growth Factor-Beta and Matrix Metalloproteinases: Functional Interactions in Tumor Stroma-Infiltrating Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Jelena Krstic

    2014-01-01

    Full Text Available Transforming growth factor-beta (TGF-β is a pleiotropic factor with several different roles in health and disease. In tumorigenesis, it may act as a protumorigenic factor and have a profound impact on the regulation of the immune system response. Matrix metalloproteinases (MMPs are a family that comprises more than 25 members, which have recently been proposed as important regulators acting in tumor stroma by regulating the response of noncellular and cellular microenvironment. Tumor stroma consists of several types of resident cells and infiltrating cells derived from bone marrow, which together play crucial roles in the promotion of tumor growth and metastasis. In cancer cells, TGF-β regulates MMPs expression, while MMPs, produced by either cancer cells or residents’ stroma cells, activate latent TGF-β in the extracellular matrix, together facilitating the enhancement of tumor progression. In this review we will focus on the compartment of myeloid stroma cells, such as tumor-associated macrophages, neutrophils, and dendritic and mast cells, which are potently regulated by TGF-β and produce large amounts of MMPs. Their interplay and mutual implications in the generation of pro-tumorigenic cancer microenvironment will be analyzed.

  8. Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression.

    Science.gov (United States)

    Ren, Jun; Liu, Zhenjie; Wang, Qiwei; Giles, Jasmine; Greenberg, Jason; Sheibani, Nader; Kent, K Craig; Liu, Bo

    2016-01-01

    Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB-mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms.

  9. Rapid copper acquisition by developing murine mesothelioma: decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration.

    Directory of Open Access Journals (Sweden)

    Andrew Crowe

    Full Text Available Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF. Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4(+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes.

  10. Assessment of expression of selected Bcl-2 family proteins in lymphoid infiltration in patients with B-cell chronic lymphocytic leukaemia treated with nucleoside analogues.

    Directory of Open Access Journals (Sweden)

    Janusz Kłoczko

    2008-12-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL is characterized by clonal growth and accumulation of mature lymphoid cells due to disturbance in genetically regulated form of cell death called apoptosis. The intrinsic mechanism of apoptosis is controlled by Bcl-2 family proteins. Purine nucleoside analogues induce the apoptosis in cells in a state of quiescence. The aim of the study was to assess expression of selected Bcl-2 family proteins in neoplastic infiltration in bone marrow in patients with B-CLL treated with nucleoside analogues. The study comprised examination of bone marrow obtained routinely by trephine biopsy from 18 patients with B-CLL diagnosed before administration of purine nucleoside analogues treatment and after its completion. Expression of Bcl-2, Bcl-x and Bax proteins was examined. Lymphoid cells in bone marrow were present in all patients before administration of treatment. After treatment in two patients bone marrow was infiltrated in diffuse pattern, whereas other patients presented nodular pattern of infiltration. The difference between stage of infiltration before and after treatment was statistically significant (p<0.002. High percentage of infiltration cells with positive anti Bcl-2 reaction from 42.0% in one patient to 85.33+/-3.06% in four patients before treatment was observed. After treatment percentage of infiltration cells with positive anti Bcl-2 antibody reaction was from 33.0+/-18.38% in two patients to 99.0% in one patient. Positive correlation between stage of infiltration and expression of Bcl-2 protein was confirmed before and after treatment. Such correlations were not observed in case of Bax and Bcl-x. Strong staining of immunohistochemical reaction of cells in lymphoid infiltration with Bcl-2 antibody was confirmed. There was a difference between Bcl-/Bax ratio before and after treatment. Immunohistochemical assessment of expression of Bcl-2 family proteins in cells of lymphoid infiltration in bone

  11. Carbon deposition behaviour in metal-infiltrated gadolinia doped ceria electrodes for simulated biogas upgrading in solid oxide electrolysis cells

    Science.gov (United States)

    Duboviks, V.; Lomberg, M.; Maher, R. C.; Cohen, L. F.; Brandon, N. P.; Offer, G. J.

    2015-10-01

    One of the attractive applications for reversible Solid Oxide Cells (SOCs) is to convert CO2 into CO via high temperature electrolysis, which is particularly important for biogas upgrading. To improve biogas utility, the CO2 component can be converted into fuel via electrolysis. A significant issue for SOC operation on biogas is carbon-induced catalyst deactivation. Nickel is widely used in SOC electrodes for reasons of cost and performance, but it has a low tolerance to carbon deposition. Two different modes of carbon formation on Ni-based electrodes are proposed in the present work based on ex-situ Raman measurements which are in agreement with previous studies. While copper is known to be resistant towards carbon formation, two significant issues have prevented its application in SOC electrodes - namely its relatively low melting temperature, inhibiting high temperature sintering, and low catalytic activity for hydrogen oxidation. In this study, the electrodes were prepared through a low temperature metal infiltration technique. Since the metal infiltration technique avoids high sintering temperatures, Cu-Ce0.9Gd0.1O2-δ (Cu-CGO) electrodes were fabricated and tested as an alternative to Ni-CGO electrodes. We demonstrate that the performance of Cu-CGO electrodes is equivalent to Ni-CGO electrodes, whilst carbon formation is fully suppressed when operated on biogas mixture.

  12. Neuronal influence behind the central nervous system regulation of the immune cells

    Directory of Open Access Journals (Sweden)

    ANAHI eCHAVARRIA

    2013-09-01

    Full Text Available Central nervous system has a highly specialized microenvironment, and despite being initially considered an immune privileged site, this immune status is far from absolute because it varies with age and brain topography. The brain monitors immune responses by several means that act in parallel; one pathway involves afferent nerves (vagal nerve and the other resident cells (neurons and glia. These cell populations exert a strong role in the regulation of the immune system, favoring an immune-modulatory environment in the CNS. Neurons control glial cell and infiltrated T-cells by contact-dependent and -independent mechanisms. Contact-dependent mechanisms are provided by several membrane immune modulating molecules such as Sema-7A, CD95L, CD22, CD200, CD47, NCAM, ICAM-5 and cadherins; which can inhibit the expression of microglial inflammatory cytokines, induce apoptosis or inactivate infiltrated T-cells. On the other hand, soluble neuronal factors like Sema-3A, cytokines, neurotrophins, neuropeptides, and neurotransmitters attenuate microglial and/or T-cell activation. In this review, we focused on all known mechanism driven only by neurons in order to control the local immune cells.

  13. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes.

    Science.gov (United States)

    Jourdan, Tony; Godlewski, Grzegorz; Cinar, Resat; Bertola, Adeline; Szanda, Gergő; Liu, Jie; Tam, Joseph; Han, Tiffany; Mukhopadhyay, Bani; Skarulis, Monica C; Ju, Cynthia; Aouadi, Myriam; Czech, Michael P; Kunos, George

    2013-09-01

    Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to beta cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat. The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and beta cell failure. Endocannabinoids contribute to insulin resistance through activation of peripheral CB1 receptors (CB₁Rs) and also promote beta cell failure. Here we show that beta cell failure in adult ZDF rats is not associated with CB₁R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. These effects are replicated in vitro by incubating wild-type human or rodent macrophages, but not macrophages from CB₁R-deficient (Cnr1(-/-)) or Nlrp3(-/-) mice, with the endocannabinoid anandamide. Peripheral CB₁R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB₁R reverses or prevents these changes and restores normoglycemia and glucose-induced insulin secretion. These findings implicate endocannabinoids and inflammasome activation in beta cell failure and identify macrophage-expressed CB₁R as a therapeutic target in T2DM.

  14. In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium

    Science.gov (United States)

    Alfonso, J. C. L.; Schaadt, N. S.; Schönmeyer, R.; Brieu, N.; Forestier, G.; Wemmert, C.; Feuerhake, F.; Hatzikirou, H.

    2016-09-01

    Scattered inflammatory cells are commonly observed in mammary gland tissue, most likely in response to normal cell turnover by proliferation and apoptosis, or as part of immunosurveillance. In contrast, lymphocytic lobulitis (LLO) is a recurrent inflammation pattern, characterized by lymphoid cells infiltrating lobular structures, that has been associated with increased familial breast cancer risk and immune responses to clinically manifest cancer. The mechanisms and pathogenic implications related to the inflammatory microenvironment in breast tissue are still poorly understood. Currently, the definition of inflammation is mainly descriptive, not allowing a clear distinction of LLO from physiological immunological responses and its role in oncogenesis remains unclear. To gain insights into the prognostic potential of inflammation, we developed an agent-based model of immune and epithelial cell interactions in breast lobular epithelium. Physiological parameters were calibrated from breast tissue samples of women who underwent reduction mammoplasty due to orthopedic or cosmetic reasons. The model allowed to investigate the impact of menstrual cycle length and hormone status on inflammatory responses to cell turnover in the breast tissue. Our findings suggested that the immunological context, defined by the immune cell density, functional orientation and spatial distribution, contains prognostic information previously not captured by conventional diagnostic approaches.

  15. CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Wagner, Steffen; Wittekindt, Claus; Reuschenbach, Miriam; Hennig, Ben; Thevarajah, Mauran; Würdemann, Nora; Prigge, Elena-Sophie; von Knebel Doeberitz, Magnus; Dreyer, Thomas; Gattenlöhner, Stefan; Klussmann, Jens Peter

    2016-05-01

    Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead-based hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD56+) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p = 0.004 and p = 0.002). For the entire cohort presence of CD56+ cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p = 0.002; Cox regression: p = 0.042). Presence of CD56+ cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption ≤ 2 standard drinks per day (Kaplan-Meier: p = 0.05 and p = 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD56+ cells and coexpression of CD16 and CD56 suggests that detected CD56+ cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p = 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.

  16. Water filtration rate and infiltration/accumulation of low density lipoproteins in 3 different modes of endothelial/smooth muscle cell co-cultures.

    Science.gov (United States)

    Ding, ZuFeng; Fan, YuBo; Deng, XiaoYan

    2009-11-01

    Using different endothelial/smooth muscle cell co-culture modes to simulate the intimal structure of blood vessels, the water filtration rate and the infiltration/accumulation of LDL of the cultured cell layers were studied. The three cell culture modes of the study were: (i) The endothelial cell monolayer (EC/Phi); (ii) endothelial cells directly co-cultured on the smooth muscle cell monolayer (EC-SMC); (iii) endothelial cells and smooth muscle cells cultured on different sides of a Millicell-CM membrane (EC/SMC). It was found that under the same condition, the water filtration rate was the lowest for the EC/SMC mode and the highest for the EC/Phi mode, while the infiltration/accumulation of DiI-LDLs was the lowest in the EC/Phi mode and the highest in the EC-SMC mode. It was also found that DiI-LDL infiltration/accumulation in the cultured cell layers increased with the increasing water filtration rate. The results from the in vitro model study therefore suggest that the infiltration/accumulation of the lipids within the arterial wall is positively correlated with concentration polarization of atherogenic lipids, and the integrity of the endothelium plays an important role in the penetration and accumulation of atherogenic lipids in blood vessel walls.

  17. Water filtration rate and infiltration/accumulation of low density lipoproteins in 3 different modes of endothelial/smooth muscle cell co-cultures

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Using different endothelial/smooth muscle cell co-culture modes to simulate the intimal structure of blood vessels, the water filtration rate and the infiltration/accumulation of LDL of the cultured cell layers were studied. The three cell culture modes of the study were: (i) The endothelial cell monolayer (EC/Φ); (ii) endothelial cells directly co-cultured on the smooth muscle cell monolayer (EC-SMC); (iii) endothelial cells and smooth muscle cells cultured on different sides of a Millicell-CM membrane (EC/SMC). It was found that under the same condition, the water filtration rate was the lowest for the EC/SMC mode and the highest for the EC/Φ mode, while the infiltration/accumulation of DiI-LDLs was the lowest in the EC/Φ mode and the highest in the EC-SMC mode. It was also found that DiI-LDL infiltration/accumulation in the cultured cell layers increased with the increasing water filtration rate. The results from the in vitro model study therefore suggest that the infiltration/accumulation of the lipids within the arterial wall is positively correlated with concentration polarization of atherogenic lipids, and the integrity of the endothelium plays an important role in the penetration and accumulation of atherogenic lipids in blood vessel walls.

  18. Mast cells infiltration and decreased E-cadherin expression in ketamine-induced cystitis

    Directory of Open Access Journals (Sweden)

    Mengqiang Li

    2015-01-01

    Conclusions: Increased mast cells in bladder wall and downregulated expression of E-cadherin junction protein in epithelial cells were probably associated with interstitial inflammation and fissures in mucosa. It implied that ketamine induced an interstitial cystitis.

  19. Locally-Delivered T-Cell-Derived Cellular Vehicles Efficiently Track and Deliver Adenovirus Delta24-RGD to Infiltrating Glioma

    Directory of Open Access Journals (Sweden)

    Rutger K. Balvers

    2014-08-01

    Full Text Available Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs, which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007. Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement.

  20. A mycosis fungoides d'emblee showing morphological change in infiltrating lymphoid cells after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tabata, Hideyuki; Ishikawa, Osamu; Ishikawa, Hidekazu (Gunma Univ., Maebashi (Japan). School of Medicine)

    1992-11-01

    A 67-year-old woman was treated with electron beam irradiation for Mycosis fungoides d'emblee. Blast-like cells were remarkably increased after irradiation, which replaced mycosis cells. Morphological analysis showed that these cells were similar to those observed in cases of classic mycosis fungoides. Such a noticeable increase of blast-like cells seemed be attributable not only to the aggravation of the underlying disease but also to the involvement of electron beam irradiation. (N.K.).

  1. Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

    Energy Technology Data Exchange (ETDEWEB)

    Paone, Gaetano; Itti, Emmanuel; Lin, Chieh; Meignan, Michel [Universite Paris 12, Department of Nuclear Medicine, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP), Creteil (France); Haioun, Corinne; Dupuis, Jehan [Universite Paris 12, Department of Clinical Haematology, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP), Creteil (France); Gaulard, Philippe [Universite Paris 12, Department of Pathology, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP), Creteil (France); Universite Paris 12, INSERM U841, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP), Creteil (France)

    2009-05-15

    To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

  2. Encenicline, an α7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice

    DEFF Research Database (Denmark)

    Salaga, M; Blomster, L V; Piechota-Polańczyk, A;

    2016-01-01

    as myeloperoxidase (MPO) activity were recorded. Immunohistochemistry (IHC) was used to measure the infiltration of immune cells in the colon. Furthermore, we employed flow cytometry to determine the effect of encenicline on frequencies of FoxP3(+) and interleukin (IL)-17A(+) T cells in the mouse colon. Encenicline...

  3. Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II.

    Directory of Open Access Journals (Sweden)

    Weici Zhang

    Full Text Available Hepatosplenic T cell lymphoma (HSTCL is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFβRII (dnTGFβRII under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFβRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4(-CD8(-TCRβ(+NK1.1(+ or CD8(+TCRβ(+NK1.1(- T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2×10(4 isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFβRII is critical for development of lymphoma-like T cell infiltration.

  4. IL-17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival.

    Science.gov (United States)

    Lu, Lin; Pan, Ke; Zheng, Hai-Xia; Li, Jian-Jun; Qiu, Hui-Juan; Zhao, Jing-Jing; Weng, De-Sheng; Pan, Qiu-Zhong; Wang, Dan-Dan; Jiang, Shan-Shan; Chang, Alfred E; Li, Qiao; Xia, Jian-Chuan

    2013-10-01

    We previously reported that tumor-infiltrating interleukin (IL)-17A-producing cells play a protective role in human esophageal squamous cell carcinoma (ESCC). However, the potential mechanisms involved remain unclear. In the present study, we investigated the effects of IL-17A on immune cell recruitment and function in ESCC. In vitro chemotaxis assays using the ESCC cell lines EC109 and KYSE30 demonstrated that although IL-17A showed no significant direct effects on the migration of T cells, natural killer (NK) cells as well as dendritic cells (DCs), it could induce ESCC tumor cells to produce inflammatory chemokines, for example, CXCL9, CXCL10 and CCL2, CCL20, which are associated with the migration of T cells, NK cells, and DCs, respectively. In addition, IL-17A enhanced the cytotoxic effects of NK cells against tumor cells by augmenting the expression of cytotoxic molecules, for example, tumor necrosis factor-α, interferon-γ, Perforin, and Granzyme B and activation receptors, for example, NKp46, NKp44, NTB-A, and NKG2D on NK cells. Furthermore, immunohistochemical analysis revealed that the density of IL-17A-producing cells was positively and significantly associated with the density of CD1a DCs in tumor tissues. With the analyses of 181 ESCC patients, we found a correlation of higher number of tumor-infiltrating CD1a DCs with significantly improved overall survival of patients with ESCC. This study provides further understanding of the roles of Th17 cells in ESCC, which may contribute to the development of novel cancer immunotherapy strategies.

  5. Expression of ICAM-1 and acute inflammatory cell infiltration in the early phase of radiation colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Yuji; Ito, Masahiro; Matsuu, Mutsumi; Shichijo, Kazuko; Fukuda, Eiichiro; Nakayama, Toshiyuki; Nakashima, Masahiro; Naito, Shinji; Sekine, Ichiro [Nagasaki Univ. (Japan). Atomic Bomb Disease Inst.

    2000-09-01

    Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting, ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer. (author)

  6. Gastric infiltration of diffuse large B-cell lymphoma: Endoscopic diagnosis and improvement of lesions after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of the non-Hodgkin's lymphoma (NHL) accounting for about 40% of all NHLs. This is a case report about the endoscopic appearance of a DLBCL with infiltration to the stomach in a 39-year-old female. She had a 6-me history of lumbar and left upper quadrant pain with intermittent episodes of melena. A computer tomograghy (CT) scan showed mural thickening of the gastric antrum. Endoscopic examination revealed multiple gastric ulcers. Definite diagnosis could be made by endoscopic biopsies and the patient had a good response to chemotherapy. This response correlated well with a further endoscopic follow-up. A follow-up endoscopic examination could be considered to evaluate a good response to chemotherapy in DLBCL patients with secondary gastric dissemination.

  7. Experimental infection with non-cytopathic bovine viral diarrhea virus 1 in mice induces inflammatory cell infiltration in the spleen.

    Science.gov (United States)

    Han, Yu-Jung; Kwon, Young-Je; Lee, Kyung-Hyun; Choi, Eun-Jin; Choi, Kyoung-Seong

    2016-09-01

    Previously, our study showed that oral inoculation of mice with cytopathic (cp) bovine viral diarrhea virus (BVDV) led to lymphocyte depletion and increased numbers of megakaryocytes in the spleen as well as thrombocytopenia and lymphopenia. In the present study, to investigate the possible differences in the detection of viral antigen, histopathological lesions, and hematologic changes between non-cytopathic (ncp) BVDV1 and cp BVDV1, mice were orally administered low and high doses of ncp BVDV1 and were necropsied at days 0, 2, 5, and 9 postinfection (pi). None of the ncp BVDV1-infected mice exhibited clinical signs of illness, unlike those infected with cp BVDV1. Statistically significant thrombocytopenia was observed during ncp BVDV1 infection, and lymphopenia was found only in mice infected with a high dose at day 9 pi. Interestingly, ncp BVDV1 infection increased the numbers of basophils, eosinophils, neutrophils, and monocytes in some infected mice. Viral antigen was detected in the lymphocytes of the spleen, mesenteric lymph nodes, Peyer's patches, and bone marrow by immunohistochemistry. Lymphoid depletion was evident in the mesenteric lymph nodes of mice infected with a high dose and also found in the Peyer's patches of some infected mice. Infiltration of inflammatory cells, including neutrophils and monocytes, and an increased number of megakaryocytes were seen in the spleen. These results suggest that the distribution of viral antigens is not associated with the presence of histopathological lesions. Inflammatory cell infiltration was observed in the spleens as a result of viral replication and may be attributable to the host reaction to ncp BVDV1 infection. Together, these findings support the possibility that mice can be used as an animal model for BVDV infection.

  8. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  9. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Löfdahl Claes-Göran

    2011-10-01

    Full Text Available Abstract Background Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF and idiopathic pulmonary fibrosis (IPF has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients, IPF (21 regions; 7 patients and controls (16 regions; 8 subjects. In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β. Results In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-β, correlated negatively with patient lung function. Conclusions The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further

  10. Transfection of Tumor-Infiltrating T Cells with mRNA Encoding CXCR2

    DEFF Research Database (Denmark)

    Idorn, Manja; Thor Straten, Per; Svane, Inge Marie

    2016-01-01

    Adoptive T-cell therapy based on the infusion of patient's own immune cells after ex vivo culturing is among the most potent forms of personalized treatment among recent clinical developments for the treatment of cancer. However, despite high rates of successful initial clinical responses, only...... infused T cells migrating to the tumor and the clinical response, but also that only a small fraction of adoptively transferred T cells reach the tumor site. In this chapter, we describe a protocol for transfection of TILs with mRNA encoding the chemokine receptor CXCR2 transiently redirecting...

  11. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Ramiro Diz

    Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

  12. Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease

    Directory of Open Access Journals (Sweden)

    Ma Qing

    2006-07-01

    Full Text Available Abstract Background We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. Here, we examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes. Methods Expression patterns of selected inflammatory genes were mined from our previously published data base. Bilateral pelvic peritoneal and subjacent stromal specimens were obtained from 20 women with EOC and 7 women with benign pelvic conditions. Sections were first stained by indirect immunoperoxidase and numbers of monocytes/macrophages (MO/MA, T cells, B cells, and NK cells counted. Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A2 [pcPLA2], which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence. Results MO/MA were present on both sides of the pelvic peritoneum in EOC patients, with infiltration of the subjacent stroma and mesothelium. CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. NK cells, B cells, and granulocytes were rare. CXCL8 (IL-8 and the chemokine receptor CCR1 were coexpressed more frequently on MO/MA than on CD3+ cells contrasting with CD68+/CD163+ cells that coexpressed CXCL8 less often. An important activated enzyme in the eicosanoid pathway, pcPLA2, was highly expressed on both CD68+ and CD163+ cells. The adherence molecule Vascular Cell Adhesion Molecule-1 (VCAM1 was expressed on CD31+ endothelial cells and on a proportion of CD68+ MO/MA but rarely on CD3+ cells. Conclusion The pelvic peritoneum in EOC exhibits a general pattern of chronic inflammation, represented primarily by differentiated MO/MA, and distinct from that in benign

  13. Maternal microchimerism: increased in the insulin positive compartment of type 1 diabetes pancreas but not in infiltrating immune cells or replicating islet cells.

    Directory of Open Access Journals (Sweden)

    Jody Ye

    Full Text Available Maternal microchimeric cells (MMc transfer across the placenta during pregnancy. Increased levels of MMc have been observed in several autoimmune diseases including type 1 diabetes but their role is unknown. It has been suggested that MMc are 1 effector cells of the immune response, 2 targets of the autoimmune response or 3 play a role in tissue repair. The aim of this study was to define the cellular phenotype of MMc in control (n = 14 and type 1 diabetes pancreas (n = 8.Using sex chromosome-based fluorescence in-situ hybridization, MMc were identified in male pancreas and their phenotype determined by concomitant immunofluorescence.In normal pancreas, MMc positive for endocrine, exocrine, duct and acinar markers were identified suggesting that these cells are derived from maternal progenitors. Increased frequencies of MMc were observed in type 1 diabetes pancreas (p = 0.03 with particular enrichment in the insulin positive fraction (p = 0.01. MMc did not contribute to infiltrating immune cells or Ki67+ islet cell populations in type 1 diabetes.These studies provide support for the hypothesis that MMc in human pancreas are derived from pancreatic precursors. Increased frequencies of MMc beta cells may contribute to the initiation of autoimmunity or to tissue repair but do not infiltrate islets in type 1 diabetes.

  14. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg

    1995-01-01

    , the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells...

  15. Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

    2002-07-01

    Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

  16. A 25-Year-Old Man with Exudative Retinal Detachments and Infiltrates without Hematological or Neurological Findings Found to Have Relapsed Precursor T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Jordan S. Johnson

    2015-09-01

    Full Text Available Background: Precursor T-cell acute lymphoblastic leukemia (pre-T-ALL may cause ocular pathologies such as cotton-wool spots, retinal hemorrhage, and less commonly, retinal detachment or leukemic infiltration of the retina itself. However, these findings are typically accompanied by the pathognomonic hematological signs of acute leukemia. CasePresentation: In this case report and review of the literature, we describe a particularly unusual case of a 25-year-old man who presented to our hospital with bilateral exudative retinal detachments associated with posterior pole thickening without any hematological or neurological findings. The patient, who had a history of previously treated pre-T-ALL in complete remission, was found to have leukemia cell infiltration on retinal biopsy. Conclusion: Our case underscores the fact that the ophthalmologist may be the first provider to detect the relapse of previously treated leukemia, and that ophthalmic evaluation is critical for detecting malignant ocular infiltrates.

  17. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

    Directory of Open Access Journals (Sweden)

    Kazuko Ino

    Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

  18. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration.

    Science.gov (United States)

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-04-24

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors.

  19. Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri.

    Science.gov (United States)

    Sugino, Toshiya; Mikami, Takeshi; Akiyama, Yukinori; Wanibuchi, Masahiko; Hasegawa, Tadashi; Mikuni, Nobuhiro

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.

  20. Carbon and Redox Tolerant Infiltrated Oxide Fuel-Electrodes for Solid Oxide Cells

    DEFF Research Database (Denmark)

    Skafte, Theis Løye; Sudireddy, Bhaskar Reddy; Blennow, P.

    2016-01-01

    To solve issues of coking and redox instability related to the presence of nickel in typical fuel electrodes in solid oxide cells,Gd-doped CeO2 (CGO) electrodes were studied using symmetriccells. These electrodes showed high electro-catalytic activity, butlow electronic conductivity. When...

  1. Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer

    Science.gov (United States)

    2011-03-01

    thymicmaturation and is molded continuously by the clonal expansion of antigen responsive cells in the periphery (Nikolich-Zugich et al. 2004; Harty...Ann. Rheum . Dis. 67: 917–925. 17. Stasi, R., G. Del Poeta, E. Stipa, M. L. Evangelista, M. M. Trawinska, N. Cooper, and S. Amadori. 2007. Response to B

  2. Effective improvement of interface modified strontium titanate based solid oxide fuel cell anodes by infiltration with nano-sized palladium and gadolinium-doped cerium oxide

    DEFF Research Database (Denmark)

    Abdul Jabbar, Mohammed Hussain; Høgh, Jens Valdemar Thorvald; Zhang, Wei

    2013-01-01

    The development of low temperature solid oxide fuel cell (SOFC) anodes by infiltration of Pd/Gd-doped cerium oxide (CGO) electrocatalysts in Nb-doped SrTiO3 (STN) backbones has been investigated. Modification of the electrode/electrolyte interface by thin layer of spin-coated CGO (400-500 nm...

  3. A Preliminary Study on WO3Infiltrated W–Cu–ScYSZ Anodes for Low Temperature Solid Oxide Fuel Cells

    DEFF Research Database (Denmark)

    Abdul Jabbar, Mohammed Hussain; Reddy Sudireddy, Bhaskar; Høgh, Jens Valdemar Thorvald

    2012-01-01

    Preparation and electrochemical characterization of WO3‐infiltrated 0.48W–0.52Cu–ScYSZ (WCS) anode for solid oxide fuel cell are reported. The DC conductivity of a WO3 ceramic was 1,200 and 24 S cm–1 in reducing and oxidizing atmospheres, respectively, at 650 °C. WCS porous backbones in the form ...

  4. The relation between serum sex steroid levels and plasma cell infiltrates in endometritis.

    Science.gov (United States)

    Punnonen, R; Lehtinen, M; Teisala, K; Aine, R; Rantala, I; Heinonen, P K; Miettinen, A; Laine, S; Paavonen, J

    1989-01-01

    We measured serum levels of progesterone and estradiol among 35 patients with endometritis confirmed by endometrial biopsy. The onset of symptoms took place predominantly in the proliferative phase of the cycle. A negative correlation was found between the serum progesterone levels and the histopathologic severity of plasma cell endometritis. Our results suggest that the hormonal status contributes to the immune response and susceptibility to endometrial infection.

  5. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection.

    Science.gov (United States)

    Huang, Zhen; Gan, Jingjing; Long, Ziyan; Guo, Guangxing; Shi, Xiafei; Wang, Chunming; Zang, Yuhui; Ding, Zhi; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

    2016-06-01

    Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let-7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy.

  6. Functional Characterization of Shape Memory CuZnAl Open-Cell Foams by Molten Metal Infiltration

    Science.gov (United States)

    Arnaboldi, S.; Bassani, P.; Passaretti, F.; Redaelli, A.; Tuissi, A.

    2011-07-01

    In the recent years, the research for novel materials with tailored mechanical properties, as well as functional properties, has encouraged the study of porous and cellular materials. Our previous work proposed and reported about the possibility to manufacture open-cell metal foams of CuZnAl shape memory alloy by liquid infiltration in a leachable bed of silica-gel particles. This innovative methodology is based on cheap commercial consumables and a simple technology, focusing on intermediate-density low-cost foams with interesting cost/benefits ratio. Microstructural analyses on foamed specimens showed uniform microstructure of ligaments and a very regular and well reproducible open-cell morphology. Moreover, calorimetric analysis detected a thermo-elastic martensitic transformation in the foamed material. In this study, a CuZnAl shape memory alloy was considered and tested to clarify possible effects of the foaming process on the functional properties of the material. Morphological, calorimetric, and thermo-mechanical analyses were carried out. The results show that it is possible to produce metal foams of CuZnAl shape memory alloy with different functional properties and able to recover mono-axial compressive strains up to 3%.

  7. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Hjelmborg, J v B; Christensen, Per B

    2003-01-01

    clinical course, with significantly higher 5-year survival, p=0.046, independent of the Dukes stage and age. Our results have implications for tumour immunology; colorectal cancer cells might be a target for cytotoxic T-lymphocytes, however the tumour cells are not able to initiate an immune response......The purpose of this study was to clarify whether HLA-DR expression of colorectal tumour cells or the CD4+/CD8+ ratio of the tumour infiltrating lymphocytes is significantly associated with the prognosis of colorectal cancer. Using flow cytometry, we studied the tumour cell expression of the HLA...... class II in 70 enzymatically dissociated colorectal cancers and the phenotype of tumour infiltrating lymphocytes (TILs) in 41 cases. There was no trend in 5-year survival between three levels (low, medium, high) of HLA-DR expression on the tumour cells. Patients with low CD4+/CD8+ ratios had a better...

  8. The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

    Science.gov (United States)

    Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

    2014-06-01

    To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process.

  9. Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

    Directory of Open Access Journals (Sweden)

    JA DeQuach

    2012-06-01

    Full Text Available Peripheral artery disease (PAD currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI, which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold’s degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week post-injury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

  10. Objective Quantification of Immune Cell Infiltrates and Epidermal Proliferation in Psoriatic Skin

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Nielsen, Ole H; Skak, Kresten;

    2015-01-01

    research. Published data of manual cell counts in psoriatic skin samples were in this study reevaluated using the digital image analysis (DIA) software. Whole slides immunohistochemically stained for CD3, CD4, CD8, CD45R0, and Ki-67 were scanned and quantitatively evaluated using simple threshold analysis......Digital pathology and image analysis have developed extensively during the last couple of years. Especially the advance in whole-slide scanning, software, and computer processing makes it possible to apply these methods in tissue-based research. Today this task is dominated by tedious manual...

  11. Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer

    Science.gov (United States)

    2010-03-01

    plates ( MSIP , Millipore) were pre-coated overnight with 10 μg/ml anti-IFN-γ capture antibody (mAb 1-D1K, Mabtech) and then blocked for 2 h at 37 °Cwith...Alt FW. 2004. Unraveling V(D)J recombination: Insights into gene regulation. Cell 116: 299–311. Krangel MS . 2003. Gene segment selection in V(D)J...and tumor necrosis factor-alpha. Blood 104: 487-494. 28. Badr G, Bedard N, Abdel-Hakeem MS , Trautmann L, Willems B, et al. (2008) Early interferon

  12. Detailed impedance characterization of a well performing and durable Ni:CGO infiltrated cermet anode for metal-supported solid oxide fuel cells

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Klemensø, Trine; Blennow Tullmar, Peter

    2012-01-01

    Further knowledge of the novel, well performing and durable Ni:CGO infiltrated cermet anode for metal supported fuel cells has been acquired by means of a detailed impedance spectroscopy study. The anode impedance was shown to consist of three arcs. Porous electrode theory (PET) represented...... as a transmission line response could account for the intermediate frequency arc. The PET model enabled a detailed insight into the effect of adding minor amounts of Ni into the infiltrated CGO and allowed an estimation of important characteristics such as the electrochemical utilization thickness of the anode...... of the infiltrated submicron sized particles was surprisingly robust. TEM analysis revealed the nano sized Ni particles to be trapped within the CGO matrix, which along the self limiting grain growth of the CGO seem to be able to stabilize the submicron structured anode....

  13. Electrochemical characterization of infiltrated Bi2V0.9Cu0.1O5.35 cathodes for use in low temperature solid oxide fuel cells

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Bonanos, Nikolaos

    2012-01-01

    nitrate solutions followed by firing. The polarization resistance at 500 °C in air, measured using electrochemical impedance spectroscopy on symmetrical cells of BICUVOX backbones infiltrated with LSC, was approximately 100 times higher than the one obtained for a CGO backbone subjected to the same LSC......The electrochemical performance of porous Bi2V0.9Cu0.1O5.35 (BICUVOX) and BICUVOX-Ce0.9Gd0.1O1.95 (CGO) composite backbones infiltrated with La0.6Sr0.4Co1.05O3-δ (LSC) has been evaluated. LSC was introduced into the screen printed and sintered porous backbones by multiple infiltrations of aqueous...

  14. Three-dimensional polycaprolactone scaffold via needleless electrospinning promotes cell proliferation and infiltration.

    Science.gov (United States)

    Li, Dawei; Wu, Tong; He, Nanfei; Wang, Jing; Chen, Weiming; He, Liping; Huang, Chen; Ei-Hamshary, Hany A; Al-Deyab, Salem S; Ke, Qinfei; Mo, Xiumei

    2014-09-01

    Electrospinning has been widely used in fabrication of tissue engineering scaffolds. Currently, most of the electrospun nanofibers performed like a conventional two-dimensional (2D) membrane, which hindered their further applications. Moreover, the low production rate of the traditional needle-electrospinning (NE) also limited the commercialization. In this article, disc-electrospinning (DE) was utilized to fabricate a three-dimensional (3D) scaffold consisting of porous macro/nanoscale fibers. The morphology of the porous structure was investigated by scanning electron microscopy images, which showed irregular pores of nanoscale spreading on the surface of DE polycaprolactone (PCL) fibers. Protein adsorption assessment illustrated the porous structure could significantly enhance proteins pickup, which was 55% higher than that of solid fiber scaffolds. Fibroblasts were cultured on the scaffold. The results demonstrated that DE fiber scaffold could enhance initial cell attachment. In the 7 days of culture, fibroblasts grew faster on DE fiber scaffold in comparison with solid fiber, solvent cast (SC) film and TCP. Fibroblasts on DE fibers showed a stretched shape and integrated with the porous surface tightly. Cells were also found to migrate into the DE scaffold up to 800μm. Results supported the use of DE PCL fibers as a 3D tissue engineering scaffold in soft tissue regeneration.

  15. A Rare Case of Gastric Variceal Hemorrhage Secondary to Infiltrative B-Cell Lymphoma

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    Adrienne Lenhart

    2016-10-01

    Full Text Available Portal hypertension commonly arises in the setting of advanced liver cirrhosis and is the consequence of increased resistance within the portal vasculature. Less commonly, left-sided noncirrhotic portal hypertension can develop in a patient secondary to isolated obstruction of the splenic vein. We present a rare case of left-sided portal hypertension and isolated gastric varices in a patient with large B-cell lymphoma, who was treated with splenic artery embolization. The patient is a 73-year-old male with no previous history of liver disease, who presented with coffee ground emesis and melena. On admission to hospital, he was found to have a hemoglobin level of 3.4 g/l. Emergent esophagogastroduodenoscopy showed isolated bleeding gastric varices (IGV1 by Sarin classification in the fundus and cardia with subsequent argon plasma coagulation injection. He was transferred to our tertiary center where work-up revealed normal liver function tests, and abdominal ultrasound showed patent hepatic/portal vasculature without cirrhosis. MRI demonstrated a large heterogeneously enhancing mass in the pancreatic tail, with invasion into the spleen and associated splenic vein thrombosis. Surgery consultation was obtained, but urgent splenectomy was not recommended. The patient instead underwent splenic artery embolization to prevent future bleeding from his known gastric varices. Pathology from a CT-guided biopsy was consistent with diffuse large B-cell lymphoma. PET imaging showed uptake in the splenic hilum/pancreatic tail region with no additional metastatic involvement. He was evaluated by the Hematology Department to initiate R-CHOP chemotherapy. During his outpatient follow-up, he reported no further episodes of melena or hematemesis. To the best of our knowledge, there have only been two published case reports of large B-cell lymphoma causing upper gastrointestinal bleeding from isolated gastric varices. These cases were treated with splenectomy or

  16. Inverse relationship of tumors and mononuclear cell leukemia infiltration in the lungs of F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Griffith, W.C.; Hahn, F.F.

    1995-12-01

    In 1970 and F344 rat, along with the B6C3F{sub 1} mouse, were selected as the standard rodents for the National Cancer Institute Carcinogenic Bioassay program for studies of potentially carcinogenic chemicals. The F344 rat has also been used in a variety of other carcinogenesis studies, including numerous studies at ITRI. A major concern to be considered in evaluating carcinogenic bioassay studies using the F344 rat is the relatively high background incidence of mononuclear cell leukemia (MCL) (also referred to as large granular lymphocytic leukemia, Fischer rat leukemia, or monocytic leukemia). Incidences of MCL ranging from 10 to 72% in male F344 rats to 6 to 31% in female F344 rats have been reported. Gaining the understanding of the mechanisms involved in the negative correlations noted should enhance our understanding of the mechanisms involved in the development of lung cancer.

  17. Evaluation of the Reactive T-Cell Infiltrate in Uveitis and Intraocular Lymphoma with Flow Cytometry of Vitreous Fluid (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Davis, Janet L.; Ruiz, Philip; Shah, Milan; Mandelcorn, Efrem D.

    2012-01-01

    Purpose: To describe the reactive T-cell infiltrate in uveitis and intraocular lymphoma using flow cytometry of clinical intraocular specimens acquired during diagnostic pars plana vitrectomy. Methods: This was a retrospective review of diagnostic vitreous specimens (1992–2011) obtained at a university-based, tertiary care center. Seventy-eight patients with uveitis or lymphoma undergoing pars plana vitrectomy were selected for intraocular testing based on clinical diagnostic uncertainty. Pars plana vitrectomy with flow cytometry, gene rearrangement studies, and cytology was performed. Results: T-cell infiltrates were found in all diagnostic categories with limited power to discriminate between uveitis and T-lymphocyte reactive infiltrates in response to intraocular lymphoma. Statistically significant differences by two-sample test of means between group means were found between 35 uveitis and 35 B-cell lymphoma cases for T-cell markers CD2, 3, 4, 5, and 7, but not for CD8. The CD4:CD8 ratio had a higher mean value in the uveitis group (P=.0113), and 8 T-cell lymphomas had a statistically greater number of CD3+ lymphocytes compared to uveitis (P=.0199) by two-sample test of means. Likelihood ratios were highest for CD2, CD5, CD7, CD4:CD8 ratio, CD20, and CD22. Conclusions: Discrimination between uveitis and lymphoma based on cell identification by flow cytometry was limited because of the prevalence of T lymphocytes in all diagnostic categories, emphasizing the importance of a reactive T-cell infiltrate in B-cell lymphomas, which may impede diagnosis. Flow cytometry may allow identification of more cases of T-cell lymphoma than reported when it is combined with gene rearrangement and cytology. PMID:23818738

  18. Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.

    Science.gov (United States)

    Surmann, Eva-Maria; Voigt, Anita Y; Michel, Sara; Bauer, Kathrin; Reuschenbach, Miriam; Ferrone, Soldano; von Knebel Doeberitz, Magnus; Kloor, Matthias

    2015-03-01

    Besides being expressed on professional antigen-presenting cells, HLA class II antigens are expressed on various tumors of non-lymphoid origin, including a subset of colorectal cancers (CRC). Information about the regulation of HLA class II antigen expression is important for a better understanding of their role in the interactions between tumor and immune cells. Whether lack of HLA class II antigen expression in tumors reflects the selective immune destruction of HLA class II antigen-expressing tumor cells is unknown. To address this question, we tested whether lack of HLA class II antigen expression in CRC was associated with immune cell infiltration. We selected microsatellite-unstable (MSI-H) CRC, because they show pronounced tumor antigen-specific immune responses and, in a subset of tumors, lack of HLA class II antigen expression due to mutations inactivating HLA class II-regulatory genes. We examined HLA class II antigen expression, mutations in regulatory genes, and CD4-positive T cell infiltration in 69 MSI-H CRC lesions. Mutations in RFX5, CIITA, and RFXAP were found in 13 (28.9%), 3 (6.7%), and 1 (2.2%) out of 45 HLA class II antigen-negative tumors. CD4-positive tumor-infiltrating lymphocyte counts were significantly higher in HLA class II antigen-negative tumors harboring mutations in HLA class II-regulatory genes (107.4 T cells per 0.25 mm(2)) compared to tumors without mutations (55.5 T cells per 0.25 mm(2), p = 0.008). Our results suggest that the outgrowth of tumor cells lacking HLA class II antigen expression due to mutations of regulatory genes is favored in an environment of dense CD4-positive T cell infiltration.

  19. Fermented Brown Rice and Rice Bran with Aspergillus oryzae (FBRA Prevents Inflammation-Related Carcinogenesis in Mice, through Inhibition of Inflammatory Cell Infiltration

    Directory of Open Access Journals (Sweden)

    Kunishige Onuma

    2015-12-01

    Full Text Available We have established an inflammation-related carcinogenesis model in mouse, in which regressive QR-32 cells subcutaneously co-implanted with a foreign body—gelatin sponge—convert themselves into lethal tumors due to massive infiltration of inflammatory cells into the sponge. Animals were fed with a diet containing 5% or 10% fermented brown rice and rice bran with Aspergillus oryzae (FBRA. In 5% and 10% FBRA diet groups, tumor incidences were lower (35% and 20%, respectively than in the non-treated group (70%. We found that FBRA reduced the number of inflammatory cells infiltrating into the sponge. FBRA administration did not cause myelosuppression, which indicated that the anti-inflammatory effects of FBRA took place at the inflammatory lesion. FBRA did not have antitumor effects on the implanted QRsP-11 tumor cells, which is a tumorigenic cell line established from a tumor arisen after co-implantation of QR-32 cells with sponge. FBRA did not reduce formation of 8-hydroxy-2′-deoxyguanine adducts, a marker of oxidative DNA damage in the inflammatory lesion; however, it reduced expression of inflammation-related genes such as TNF-α, Mac-1, CCL3 and CXCL2. These results suggest that FBRA will be an effective chemopreventive agent against inflammation-related carcinogenesis that acts by inhibiting inflammatory cell infiltration into inflammatory lesions.

  20. Chronic diarrhea associated with high serum level of immunoglobulin A and diffuse infiltration of plasma cell in small intestine

    Science.gov (United States)

    Yang, Junwen; Chen, Shuijiao; Chen, Linlin; Ouyang, Miao; Li, Fujun

    2017-01-01

    Abstract Rationale: Chronic diarrhea in adult patients due to various causes is very common in clinic, but patient suffering with mal-absorption due to immunoproliferative small intestinal disease was rarely reported in China. Patient concerns and Diagnoses: A 35-year-old female presented with more than three years history of chronic diarrhea, rickets, high serum value of immunoglobulin A protein, and anemia. Bone marrow aspiration suggested that the patient was in a sideropenic and megalobastic anemia stage. Duodenal and ileac biopsies revealed atrophy and blunting villi. The bowel lamina propria was infiltrated with slightly increased intraepithelial lymphocytes and mainly with diffuse plasma cells. The following enzyme labeling immunohistochemistry results were strongly positive to alpha-heavy-chain. Computed tomography manifested she had diffuse thickening of small intestine wall. At last a diagnosis of immunoproliferative small intestinal disease was made. Interventions and Outcomes: On the first month, the patient was treated with vitamin D supplements, calcium, magnesium, potassium, iron, folic acid, mecobalamin replacements and microflora probiotics. The patient frequency of water diarrhea alleviated slightly, but her weight loss, anxiety neurosis and other disorders were still severe. After taking with prednisone (40 mg per day, and gradually reduced to the lowest dose) for another month, the symptoms was gradually subsided. Lessons: The study shows that immunohistochemical staining for alpha-heavy chain proteins should be completed on small intestine biopsy specimens if the patient is suspected a diagnosis of immunoproliferative small intestinal disease. PMID:28151917

  1. High performance air electrode for solid oxide regenerative fuel cells fabricated by infiltration of nano-catalysts

    Science.gov (United States)

    Lee, Sung-il; Kim, Jeonghee; Son, Ji-Won; Lee, Jong-Ho; Kim, Byung-Kook; Je, Hae-June; Lee, Hae-Weon; Song, Huesup; Yoon, Kyung Joong

    2014-03-01

    A high performance air electrode fabricated by infiltration of highly active nano-catalysts into a porous scaffold is demonstrated for high-temperature solid oxide regenerative fuel cells (SORFCs). The nitrate precursor solution for Sm0.5Sr0.5CoO3 (SSC) catalyst is impregnated into a porous La0.6Sr0.4Co0.2Fe0.8O3 (LSCF)-gadolinia-doped ceria (GDC) composite backbone, and extremely fine SSC nano-particles are uniformly synthesized by in-situ crystallization at the initial stage of SORFC operation via homogeneous nucleation induced by urea decomposition. The SSC nano-catalysts are in the size range of 40-80 nm and stable against coarsening upon the SORFC operation at 750 °C. The electrochemical performance is significantly improved by incorporation of SSC nano-catalysts in both power generation and hydrogen production modes. Systematic analysis on the impedance spectra reveals that the surface modification of the air electrode with nano-catalysts remarkably accelerates the chemical surface exchange reactions for both O2 reduction and O2- oxidation, which are the major limiting processes for SORFC performance.

  2. Attenuation fluctuations and local dermal reflectivity are indicators of immune cell infiltrate and epidermal hyperplasia in skin inflammation

    Science.gov (United States)

    Phillips, Kevin G.; Wang, Yun; Choudhury, Niloy; Levitz, David; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven

    2012-02-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.

  3. Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF).

    Science.gov (United States)

    Mammoto, Tadanori; Higashiyama, Shigeki; Mukai, Mutsuko; Mammoto, Akiko; Ayaki, Masako; Mashimo, Takashi; Hayashi, Yukio; Kishi, Yoshihiko; Nakamura, Hiroyuki; Akedo, Hitoshi

    2002-09-01

    Although the mechanism is unknown, infiltration anesthetics are believed to have membrane-stabilizing action. We report here that such a most commonly used anesthetic, lidocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5-20 mM). Ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) from the cell surface plays an important role in invasion by HT1080 cells. Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. The anesthetic action of lidocaine (sodium channel blocking ability) did not contribute to this anti-invasive action. In addition, lidocaine (5-30 mM), infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo. These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations.

  4. Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma.

    Science.gov (United States)

    Bosisio, Francesca; Boi, Sebastiana; Caputo, Valentina; Chiarelli, Concetta; Oliver, Fergus; Ricci, Roberto; Cerroni, Lorenzo

    2015-02-01

    Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by panniculitic infiltrates that may be difficult to distinguish from inflammatory disorders, particularly lupus erythematosus profundus (LEP). We report on 11 patients (M:F=5:6; median age: 49 y; range: 20 to 75 y) presenting with lobular panniculitic infiltrates showing histopathologic features of both SPTCL and LEP in different parts of the same biopsy specimen. The areas showing aspects of SPTCL revealed dense infiltrates of small and medium-sized, atypical α/β T-cytotoxic lymphocytes with focal rimming of the adipocytes and high proliferation. In other areas the infiltrate was composed of nodules of B lymphocytes arranged characteristically at the periphery of the fat lobules and in the septa and showing a low proliferation rate. CD123-positive plasmocytoid dendritic cells arranged in small clusters could be observed in 3 cases. Our observation raises an important question concerning the relationship between SPTCL and LEP. A simple chance overlap of 2 unrelated pathologies seems unlikely, as we could observe these unusual features in 11 cases, much more than mere chance would justify. Three other hypotheses may explain the features observed in our patients: (1) these are examples of SPTCL with focal histologic features mimicking those of LEP; (2) these are examples of LEP with focal atypical histologic features mimicking those of SPTCL; (3) SPTCL and LEP may represent 2 ends of a spectrum, a hypothesis that may be supported by the frequent association of the 2 diseases.

  5. Central Nervous System Involvement of T-cell Prolymphocytic Leukemia Diagnosed with Stereotactic Brain Biopsy: Case Report

    Directory of Open Access Journals (Sweden)

    Selçuk Göçmen

    2014-03-01

    Full Text Available Prolymphocytic leukemia (PLL is a generalized malignancy of the lymphoid tissue characterized by the accumulation of monoclonal lymphocytes, usually of B cell type. Involvement of the central nervous system (CNS is an extremely rare complication of T-cell prolymphocytic leukemia (T-PLL. We describe a case of T-PLL presenting with symptomatic infiltration of the brain that was histopathologically proven by stereotactic brain biopsy. We emphasize the importance of rapid diagnosis and immediate treatment for patients presenting with CNS involvement and a history of leukemia or lymphoma.

  6. High-throughput sequencing of islet-infiltrating memory CD4+ T cells reveals a similar pattern of TCR Vβ usage in prediabetic and diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Idania Marrero

    Full Text Available Autoreactive memory CD4(+ T cells play a critical role in the development of type 1 diabetes, but it is not yet known how the clonotypic composition and TCRβ repertoire of the memory CD4(+ T cell compartment changes during the transition from prediabetes to diabetes. In this study, we used high-throughput sequencing to analyze the TCRβ repertoire of sorted islet-infiltrating memory CD4(+CD44(high T cells in 10-week-old prediabetic and recently diabetic NOD mice. We show that most clonotypes of islet-infiltrating CD4(+CD44(high T cells were rare, but high-frequency clonotypes were significantly more common in diabetic than in prediabetic mice. Moreover, although the CD4(+CD44(high TCRβ repertoires were highly diverse at both stages of disease development, dominant use of TRBV1 (Vβ2, TRBV13-3 (Vβ8.1, and TRBV19 (Vβ6 was evident in both prediabetic and diabetic mice. Our findings strongly suggest that therapeutic targeting of cells specifically expressing the dominant TCRβ might reduce pancreatic infiltration in prediabetic mice and attenuate the progression to diabetes.

  7. Diffuse alopecia areata is associated with intense inflammatory infiltration and CD8+ T cells in hair loss regions and an increase in serum IgE level

    Directory of Open Access Journals (Sweden)

    Ying Zhao

    2012-01-01

    Full Text Available Background: Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA remains unclear. Aims: To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. Methods: Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher′s exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. Results: The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. Conclusions: Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.

  8. The utility of the in situ detection of T-cell receptor Beta rearrangements in cutaneous T-cell-dominant infiltrates.

    Science.gov (United States)

    Magro, Cynthia M; Nuovo, Gerard J; Crowson, A Neil

    2003-09-01

    The diagnostic assessment of cutaneous T-cell infiltrates is problematic for dermatopathologists. A variety of conditions, including lymphomatoid hypersensitivity reactions and lymphomatoid lupus erythematosus, can demonstrate lymphoid atypia and phenotypic changes that can mimic cutaneous T-cell lymphoma (CTCL). A similar issue revolves around lymphoid dyscrasias, which includes parapsoriasis, atypical pigmentary purpura, pityriasis lichenoides chronica, indeterminate lymphocytic lobular panniculitis, and lymphomatoid papulosis, which can progress to CTCL. A reverse transcription (RT) in situ PCR assay for T-cell receptor beta rearrangements (TCRbeta) was used to assess T-cell clonality in formalin-fixed, paraffin-embedded tissues. In 7 of 8 cases of classic CTCL, the RT in situ PCR assay for TCRbeta rearrangement showed monoclonality; the other was biclonal. Further, in cases with multiple lesions over time, the same T-cell clone could be detected including in those patients whose biopsies showed large-cell transformation. Monoclonality was also demonstrated in each of 2 cases of cutaneous lymphomatoid papulosis. Demonstration of oligoclonality (and one case of biclonality) by RT in situ PCR was confined to those cases that either represented prelymphomatous conditions such as large plaque parapsoriasis or pityriasis lichenoides or lesions of drug-induced lymphomatoid hypersensitivity that all demonstrated clinical regression. In conclusion, RT in situ PCR for TCRbeta, which can be done on formalin-fixed biopsies and allows direct correlation of the molecular data with the histology, is a useful adjunctive test in the differentiation of CTCL from its mimics.

  9. Neuronal chemokines : Versatile messengers in central nervous system cell interaction

    NARCIS (Netherlands)

    de Haas, A. H.; van Weering, H. R. J.; de Jong, E. K.; Boddeke, H. W. G. M.; Biber, K. P. H.

    2007-01-01

    Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemoki

  10. Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract

    Institute of Scientific and Technical Information of China (English)

    Masashi Taguchi; Gentaro Aridome; Shintaro Abe; Keiichiro Kume; Mitsuo Tashiro; Mitsuyoshi Yamamoto; Yasuyuki Kihara; Hayato Nakamura; Makoto Otsuki

    2005-01-01

    A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain.Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows: total protein 90 g/L with γ-globulin of 37.3% (33 g/L), total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L, γ-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated (18 900 mg/L). Computed tomography (CT) showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis (AIP) with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

  11. Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jamie L. Harden

    2015-08-01

    Full Text Available It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR have suggested there are expanded T-cell receptor (TCR clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire αβ- and γδ- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique β- and γ- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the αβ- and γδ- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low amounts of shared β-chain sequences between different patient samples, there was significantly increased sequence sharing of the γ-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular γδ- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire αβ- and γδ- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse αβ- and γδ- T-cell populations.

  12. Increased percentage of CD8 CD28– suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas

    Directory of Open Access Journals (Sweden)

    Donata Urbaniak-Kujda

    2009-07-01

    Full Text Available Introduction: T cells with the CD8 CD28– phenotype are CD8 lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8 CD28– lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL has not yet been described. The aim of the study was to determine their levels in these patients’ peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease.Material/Methods: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8 CD28– lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates.Results: The percentage of CD8 CD28– lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8 CD28– lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8 CD28– lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8 CD28– T cells in the skin infiltrates correlated positively with age and clinical stage of the disease.Conclusions: These data suggest that CD8 CD28– lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma.

  13. Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Fernando Antonio Fierro

    2015-10-01

    Full Text Available Many therapies using mesenchymal stem cells (MSC rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR. We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1 and induce transwell migration of CD34+ hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1 antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

  14. Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells

    DEFF Research Database (Denmark)

    Yang, Q.; Goding, S.; Hagenaars, M.;

    2006-01-01

    We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell....... Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components...

  15. Expression of calreticulin is associated with infiltration of T-cells in stage ⅢB colon cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the correlation between expression of calreticulin and infiltration of lymphocytes in stage ⅢB colon cancer. METHODS: Sixty-eight pathologically-confirmed speci-mens were obtained from stage ⅢB (T3N1M0) colon cancer patients who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University, Guangzhou, China. Immuno-histochemical analysis was performed to show infiltration of lymphocytes and expression of calreticulin in colon cancer. Associa...

  16. Intraepithelial macrophage infiltration is related to a high number of regulatory T cells and promotes a progressive course of HPV-induced vulvar neoplasia.

    Science.gov (United States)

    van Esch, Edith M G; van Poelgeest, Mariette I E; Trimbos, J Baptist M Z; Fleuren, Gert Jan; Jordanova, Ekaterina S; van der Burg, Sjoerd H

    2015-02-15

    Human papilloma virus (HPV)-induced usual-type vulvar intraepithelial neoplasia (uVIN) is infiltrated by myeloid cells but the type and role of these cells is unclear. We used triple immunofluorescent confocal microscopy to locate, identify and quantify myeloid cells based on their staining pattern for CD14, CD33 and CD163 in a cohort of 43 primary and 20 recurrent uVIN lesions, 21 carcinomas and 26 normal vulvar tissues. The progressive course of uVIN is characterized by an increase in both intraepithelial and stromal mature M1 and M2 macrophages. While the M2 macrophages outnumber M1 macrophages in healthy controls and uVIN, they are matched in number by M1 macrophages in cancer. Importantly, uVIN patients with a dense intraepithelial infiltration with mature CD14+ macrophages (irrespective of M1 or M2 type) displayed approximately a six times higher risk to develop a recurrence and a high number of these cells constituted an independent prognostic factor for recurrence. In addition, a dense intraepithelial CD14+ cell infiltration was associated with high numbers of intraepithelial CD4+ Tregs and low numbers of stromal CD8+TIM3+ T cells. Patients with low numbers of intraepithelial CD14+ cells and high numbers of stromal CD8+TIM3+ cells showed the best recurrence-free survival. These data clearly show the importance of the local immune response in HPV-induced vulvar neoplasia and may be of help in predicting the prognosis of patients or their response to immunotherapy.

  17. Cholesterol, the central lipid of mammalian cells

    NARCIS (Netherlands)

    Maxfield, F. R.; van Meer, G.

    2010-01-01

    Despite its importance for mammalian cell biology and human health, there are many basic aspects of cholesterol homeostasis that are not well understood. Even for the well-characterized delivery of cholesterol to cells via lipoproteins, a novel regulatory mechanism has been discovered recently, invo

  18. CD8 T cells are involved in skeletal muscle regeneration through facilitating MCP-1 secretion and Gr1(high) macrophage infiltration.

    Science.gov (United States)

    Zhang, Jing; Xiao, Zhicheng; Qu, Chao; Cui, Wei; Wang, Xiaonan; Du, Jie

    2014-11-15

    Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8α-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8α-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8α deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8α-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8α-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.

  19. [Microglial cells and development of the embryonic central nervous system].

    Science.gov (United States)

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  20. Atypical Herpes simplex keratitis (HSK presenting as a perforated corneal ulcer with a large infiltrate in a contact lens wearer: multinucleated giant cells in the Giemsa smear offered a clue to the diagnosis

    Directory of Open Access Journals (Sweden)

    Vemuganti Geeta K

    2001-04-01

    Full Text Available Abstract Purpose To report a case of atypical herpes simplex keratitis initially diagnosed as bacterial keratitis, in a contact lens wearer. Results Case report of an 18-year-old woman using contact lenses who presented with pain, redness and gradual decrease in vision in the right eye. Examination revealed a paracentral large stromal infiltrate with a central 2-mm perforation. Corneal and conjunctival scrapings were collected for microbiological investigations. Corneal tissue was obtained following penetrating keratoplasty. Corneal scraping revealed no microorganisms. Giemsa stained smear showed multinucleated giant cells. Conjunctival, corneal scrapings and tissue were positive for herpes simplex virus - 1 (HSV antigen. Corneal tissue was positive for HSV DNA by PCR. Conclusions Atypical HSV keratitis can occur in contact lens wearers. A simple investigation like Giemsa stain may offer a clue to the diagnosis.

  1. Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

    Institute of Scientific and Technical Information of China (English)

    Sung-Hsin Kuo; Jaw-Town Lin; Ann-Lii Cheng; Li-Tzong Chen; Chi-Long Chen; Shin-Lian Doong; Kun-Huei Yeh; Ming-Shiang Wu; Tsui-Lien Mao; Hui-Chen Hsu; Hsiu-Po Wang

    2005-01-01

    AIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori(H pylori)-dependent. However,unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict Hpylori-dependent status of high-grade gastric MALT lymphoma.METHODS: Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade Ⅱ or less after H pylorieradication were classified as H pyloridependent; others were classified as H pylori-independent.The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry.RESULTS: There were 16 H pylori-dependent and 10H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 Hpyiori-dependent cases but in none of 10 Hpylori-independent cases (P = 0.001).H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+)NK cells compared to CD86-negative cases (2.9±1.1% vs1.4±1.3%; P= 0.005).CONCLUSION: These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT

  2. MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

    Directory of Open Access Journals (Sweden)

    Kamraan Z Gill

    Full Text Available Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80% showed centroblastic morphology, and 12 (20% displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69% cases had a non-germinal center B-cell and 18 (31% had a germinal center B-cell cell-of-origin (COO phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%. Forty-three cases (73% showed MYC overexpression (≥ 40%, and 35 (60% showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%; however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply

  3. Cell fate control in the developing central nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

    2014-02-01

    The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

  4. Practical diagnostic approaches to composite plasma cell neoplasm and low grade B-cell lymphoma/clonal infiltrates in the bone marrow.

    Science.gov (United States)

    Hussein, Shafinaz; Gill, Kamraan; Baer, Lea N; Hoehn, Daniela; Mansukhani, Mahesh; Jobanputra, Vaidehi; Bhagat, Govind; Alobeid, Bachir

    2015-03-01

    Composite plasma cell neoplasm (PCN) and low grade B-cell lymphoma (B-NHL) in the bone marrow are uncommon and raise the differential diagnosis of B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. This can be a challenging differential diagnosis, and the distinctions are important because of differences in management. We report five cases of composite PCN with B-NHL or clonal B-cell infiltrates involving the bone marrow. By using multiple different diagnostic modalities, including immunophenotyping by flow cytometry and immunohistochemistry, cytogenetic analysis and IGH gene rearrangement studies by polymerase chain reaction, we were able to distinguish two distinct clonally unrelated neoplasms in all cases. We describe the utility and pitfalls of these different diagnostic modalities. Flow cytometric analysis with a panel of antibodies that includes CD19, CD56, CD138, CD45 and other aberrant markers commonly expressed by PCN will allow identification of clonally unrelated PCN and B-NHL in a composite neoplasm, and distinguish them from B-NHL with plasmacytic differentiation and PCN with lymphoplasmacytic morphology. Cytogenetic and molecular analyses can give false-negative or false-positive results. In summary, a multimodal approach utilizing these different tools, including clinical data, should be used to arrive at the correct diagnosis.

  5. Migration of bone marrow-derived cells into the central nervous system in models of neurodegeneration.

    Science.gov (United States)

    Lampron, Antoine; Pimentel-Coelho, Pedro M; Rivest, Serge

    2013-12-01

    Microglia are the brain-resident macrophages tasked with the defense and maintenance of the central nervous system (CNS). The hematopoietic origin of microglia has warranted a therapeutic potential for the hematopoietic system in treating diseases of the CNS. However, migration of bone marrow-derived cells (BMDC) into the CNS is a marginal event under normal, healthy conditions. A busulfan-based chemotherapy regimen was used for bone marrow transplantation in wild-type mice before subjecting them to a hypoxic-ischemic brain injury or in APP/PS1 mice prior to the formation of amyloid plaques. The cells were tracked and analyzed throughout the development of the pathology. The efficacy of a preventive macrophage colony-stimulating factor (M-CSF) treatment was also studied to highlight the effects of circulating monocytes in hypoxic-ischemic brain injury. Such an injury induces a strong migration of BMDC into the CNS, without the need for irradiation. These migrating cells do not replace the entire microglial pool but rather are confined to the sites of injury for several weeks, suggesting that they could perform specific functions. M-CSF showed neuroprotective effects as a preventive treatment. In APP/PS1 mice, the formation of amyloid plaques was sufficient to induce the entry of cells into the parenchyma, though in low numbers. This study confirms that BMDC infiltrate the CNS in animal models for stroke and Alzheimer's disease and that peripheral cells can be targeted to treat affected regions of the CNS.

  6. Intratumoral interleukin-21 increases antitumor immunity, tumor-infiltrating CD8+ T-cell density and activity, and enlarges draining lymph nodes

    DEFF Research Database (Denmark)

    Søndergaard, Henrik; Galsgaard, Elisabeth D; Bartholomaeussen, Monica

    2010-01-01

    Interleukin (IL)-21 is a novel cytokine in clinical development for the treatment of cancer. In this study, we have compared the efficacy of subcutaneous and intratumoral (IT) administration of IL-21 protein in two syngeneic mouse tumor models, RenCa renal cell carcinoma and B16 melanoma, and inv......Interleukin (IL)-21 is a novel cytokine in clinical development for the treatment of cancer. In this study, we have compared the efficacy of subcutaneous and intratumoral (IT) administration of IL-21 protein in two syngeneic mouse tumor models, RenCa renal cell carcinoma and B16 melanoma......, and investigated the mechanisms by which IL-21 enhances CD8 T-cell-mediated antitumor immunity. We found that in comparison to subcutaneous administration, IT administration of IL-21 more potently inhibited tumor growth and increased survival. This correlated with increased densities of tumor-infiltrating CD8...... microenvironment and activates tumor-draining LNs. Overall, our data suggest that IL-21 augments CD8 T-cell-mediated antitumor immunity through increased proliferation and effector function and acts both on tumor-infiltrating CD8 T cells as well as on the draining LNs. IT administration led to superior CD8 T...

  7. Frequent infiltration of S-100 protein+ CCR5+ immature dendritic cells in damaged bile ducts of primary biliary cirrhosis compared to cholangiocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Mitsui H

    2013-04-01

    Full Text Available Hiroko Mitsui,1,2 Hiroya Ohtake,1 Rintaro Ohe,1 Mitsunori Yamakawa1 1Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan Abstract: Dendritic cells (DCs are professional antigen presenting cells that initiate immune responses. We evaluated the relationship between DC infiltration, chemokines/chemokine receptors, and bile duct damage in primary biliary cirrhosis (PBC, compared to cases of cholangiocellular carcinoma arising from the bile duct. Immunohistochemistry revealed significantly more S-100 protein+ DCs infiltrating the epithelial layer of bile ducts in PBC than in chronic hepatitis C or control neonatal livers. Furthermore, a higher number of S-100 protein+ DCs, but not fascin+ or DC lysosomal associated membrane protein+ mature DCs, were found in the epithelial layer of the damaged bile ducts of the PBC liver. CC-chemokine receptor (CCR 5+ immature DCs frequently accumulated in the portal area in PBC. CCR5 mRNA was also detected in liver tissues from PBC patients by reverse transcription polymerase chain reaction. In situ hybridization revealed the expression of macrophage inflammatory protein (MIP-1α and MIP-1ß mRNA in the epithelial cells of damaged bile ducts. However, no CD1a+ immature DCs were found in any of the PBC or chronic hepatitis C specimens or in neonatal liver, whereas they occurred frequently in the cancer nests of cholangiocellular carcinoma, which expressed MIP-3α and were frequently infiltrated by CCR6+ DCs. These results indicate that bile ducts damaged by PBC secrete MIP-1α and MIP-1ß, while neoplastic ones secrete MIP-3α. They also suggest that CCR5+ immature DCs attracted by MIP-1α and MIP-1ß may play an important role in the pathogenesis of chronic nonsuppurative destructive cholangitis in PBC. Keywords: chemokines, cholangiocellular carcinoma, chronic nonsuppurative destructive cholangitis, dendritic cell, primary biliary

  8. Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues.

    Science.gov (United States)

    Nteeba, J; Ortinau, L C; Perfield, J W; Keating, A F

    2013-11-01

    Dysregulation of immune cells and/or altered inflammatory signaling have been implicated with reproductive dysfunction. Physiological changes leading to perturbations in the profile of immune cells and/or pro-inflammatory cytokines in or around female reproductive tissue could potentially have profound effects on ovarian function. Obesity is associated with chronic low-grade inflammation due, in part, to increased immune cell infiltration and inflammation in visceral adipose depots. This study investigated the impact of diet-induced obesity on immune cell infiltration and inflammation in peri-ovarian adipose tissue and mRNA expression of key inflammatory markers and microRNAs (miRs) in ovarian tissue. Six-week-old female C57Bl/6J mice were fed a standard chow or high-fat diet (HFD; 60% kcal fat) for approximately 7 months, at which time peri-ovarian adipose tissue and ovarian tissues were collected. Histological analysis of peri-ovarian adipose tissue from obese mice revealed increased (P adipose tissue, along with increases (P tissue (P adipose depot, potentially negatively affecting ovarian function.

  9. Electrochemical performance and stability of Sr-doped LaMnO3-infiltrated yttria stabilized zirconia oxygen electrode for reversible solid oxide fuel cells

    Institute of Scientific and Technical Information of China (English)

    Hui Fan; Minfang Han

    2014-01-01

    Porous Sr-doped lanthanum manganite–yttria stabilized zirconia (LSM–YSZ) oxygen electrode is prepared by an infiltration process for a reversible solid oxide fuel cell (RSOFC). X-ray diffraction and SEM analysis display that perovskite phase LSM submicro particles are evenly distributed in the porous YSZ matrix. Polarization curves and electrochemical impedance spectra are conducted for the RSOFC at 800 and 850 ?C under both SOFC and SOEC modes. At 850 ?C, the single cell has the maximum power density of*726 mW/cm2 under SOFC mode, and electrolysis voltage of 1.35 V at 1 A/cm2 under SOEC mode. Fuel cell/water electrolysis cycle shows the cell has good performance stability during 6 cycles, which exhibits the LSM–YSZ oxygen electrode has high electrochemical performance and good stability. The results suggest that network-like LSM–YSZ electrode made by infiltration process could be a promising oxygen electrode for high temperature RSOFCs.

  10. Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor.

    Science.gov (United States)

    Rodríguez-Castelán, J; Corona-Pérez, A; Nicolás-Toledo, L; Martínez-Gómez, M; Castelán, F; Cuevas-Romero, E

    2017-03-01

    Hypothyroidism is associated with the development of non-alcoholic steatohepatitis, but cellular mechanisms have been scarcely analyzed. Thyroid hormones regulate the synthesis and secretion of bile acids that are endogenous ligands of the farnesoid receptor (FXRα), which have been involved in the development of non-alcoholic steatohepatitis. However, the relationship between thyroid hormones and FXRα expression in the liver is yet unknown. Control (n=6) and methimazole-induced hypothyroid (n=6) female rabbits were used to evaluate the amount of lipids and glycogen, vascularization, hepatocytes proliferation, immune cells infiltration, and expression of FXRα. Student-t or Mann-Whitney U tests were carried out to determine significant differences. Hypothyroidism induced steatosis, glycogen loss, fibrosis, and a minor vascularization in the liver. In contrast, hypothyroidism increased the proliferation of hepatocytes and the infiltration of mast cells, but did not modify the number of immune cells into sinusoids. These changes were associated with a minor anti-FXRα immunoreactivity of periportal hepatocytes and pericentral immune cells. Our results suggest that hypothyroidism induces a moderate non-alcoholic steatohepatitis, alllowing the hepatic regeneration. The FXRα may be involved in the development of non-alcoholic steatohepatitis in hypothyroid subjects.

  11. Decreased infiltration of macrophage scavenger receptor-positive cells in initial negative biopsy specimens is correlated with positive repeat biopsies of the prostate.

    Science.gov (United States)

    Nonomura, Norio; Takayama, Hitoshi; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Tsujimura, Akira; Nishimura, Kazuo; Aozasa, Katsuyuki; Okuyama, Akihiko

    2010-06-01

    Macrophage scavenger receptor (MSR)-positive inflammatory cells and tumor-associated macrophages (TAMs) have been reported to regulate the growth of various cancers. In this study, the infiltration of MSR-positive cells and TAMs was analyzed to predict the outcome of repeat biopsy in men diagnosed as having no malignancy at the first prostate biopsy. Repeat biopsy of the prostate was carried out in 92 patients who were diagnosed as having no malignancy at the first biopsy. Of these, 30 patients (32.6%) were positive for prostate cancer at the repeat biopsy. Tumor-associated macrophages and MSR-positive cells were immunohistochemically stained with mAbs CD68 and CD204, respectively. Six ocular measuring fields were chosen randomly under a microscope at x400 power in the initial negative biopsy specimens, and the mean TAM and MSR counts for each case were determined. No difference in TAM count was found between the cases with or without prostate cancer. By contrast, the MSR count in patients with cancer was significantly lower than that in patients without cancer at the repeat biopsy (P biopsies, or TAM count. Decreased infiltration of MSR-positive cells in negative first biopsy specimens was correlated with positive findings in the repeat biopsy. The MSR count might be a good indicator for avoiding unnecessary repeat biopsies.

  12. Antibody-supervised deep learning for quantification of tumor-infiltrating immune cells in hematoxylin and eosin stained breast cancer samples

    Directory of Open Access Journals (Sweden)

    Riku Turkki

    2016-01-01

    Full Text Available Background: Immune cell infiltration in tumor is an emerging prognostic biomarker in breast cancer. The gold standard for quantification of immune cells in tissue sections is visual assessment through a microscope, which is subjective and semi-quantitative. In this study, we propose and evaluate an approach based on antibody-guided annotation and deep learning to quantify immune cell-rich areas in hematoxylin and eosin (H&E stained samples. Methods: Consecutive sections of formalin-fixed parafin-embedded samples obtained from the primary tumor of twenty breast cancer patients were cut and stained with H&E and the pan-leukocyte CD45 antibody. The stained slides were digitally scanned, and a training set of immune cell-rich and cell-poor tissue regions was annotated in H&E whole-slide images using the CD45-expression as a guide. In analysis, the images were divided into small homogenous regions, superpixels, from which features were extracted using a pretrained convolutional neural network (CNN and classified with a support of vector machine. The CNN approach was compared to texture-based classification and to visual assessments performed by two pathologists. Results: In a set of 123,442 labeled superpixels, the CNN approach achieved an F-score of 0.94 (range: 0.92-0.94 in discrimination of immune cell-rich and cell-poor regions, as compared to an F-score of 0.88 (range: 0.87-0.89 obtained with the texture-based classification. When compared to visual assessment of 200 images, an agreement of 90% (k = 0.79 to quantify immune infiltration with the CNN approach was achieved while the inter-observer agreement between pathologists was 90% (k = 0.78. Conclusions: Our findings indicate that deep learning can be applied to quantify immune cell infiltration in breast cancer samples using a basic morphology staining only. A good discrimination of immune cell-rich areas was achieved, well in concordance with both leukocyte antigen expression and

  13. T cells infiltrate the liver and kill hepatocytes in HLA-B(∗)57:01-associated floxacillin-induced liver injury.

    Science.gov (United States)

    Wuillemin, Natascha; Terracciano, Luigi; Beltraminelli, Helmut; Schlapbach, Christoph; Fontana, Stefano; Krähenbühl, Stephan; Pichler, Werner J; Yerly, Daniel

    2014-06-01

    Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.

  14. Cell replacement therapy for central nervous system diseases

    Institute of Scientific and Technical Information of China (English)

    Danju Tso; Randall D. McKinnon

    2015-01-01

    The brain and spinal cord can not replace neurons or supporting glia that are lost through trau-matic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this ifeld needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate pa-tient-speciifc replacement cells is to reprogram autologous cells such as ifbroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms ifbroblasts into the ifnal graft-able cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efifciency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain.

  15. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Heon, Elise K. [University of Maryland Medical Center, Baltimore, MD 21201 (United States); Wulan, Hasi [Department of Plastic and Reconstructive Surgery, PLA General Hospital, Beijing, 100853 (China); Macdonald, Loch P.; Malek, Adel O.; Braunstein, Glenn H.; Eaves, Connie G.; Schattner, Mark D. [Brown University, Providence, RI 02912 (United States); Allen, Peter M.; Alexander, Michael O.; Hawkins, Cynthia A.; McGovern, Dermot W.; Freeman, Richard L. [University of Wisconsin, Madison, WI 53706 (United States); Amir, Eitan P.; Huse, Jason D. [University of Illinois, Chicago, IL 60607 (United States); Zaltzman, Jeffrey S.; Kauff, Noah P.; Meyers, Paul G. [University of Texas, Austin, TX 78712 (United States); Gleason, Michelle H., E-mail: GleasonM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Overholtzer, Michael G., E-mail: OverholtzerM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Wiseman, Sam S. [Ohio State University, Columbus, OH 43210 (United States); and others

    2015-08-14

    IL-15 has pivotal roles in the control of CD8{sup +} memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. - Highlights: • We explored the effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells of breast cancer. • IL-15

  16. Intracranial Injection of Dengue Virus Induces Interferon Stimulated Genes and CD8+ T Cell Infiltration by Sphingosine Kinase 1 Independent Pathways.

    Science.gov (United States)

    Al-Shujairi, Wisam H; Clarke, Jennifer N; Davies, Lorena T; Alsharifi, Mohammed; Pitson, Stuart M; Carr, Jillian M

    2017-01-01

    We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain. Body weight loss and DENV RNA level tended to be greater in SK1-/- compared with wildtype (WT) mice. Brain infection with DENV-2 is associated with the induction of interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression including viperin, Ifi27l2a, IRF7, and CXCL10 without any significant differences between WT and SK1-/- mice. The SK2 and sphingosine-1-phosphate (S1P) levels in the brain were unchanged by DENV infection or the lack of SK1. Histological analysis demonstrated the presence of a cellular infiltrate in DENV-infected brain with a significant increase in mRNA for CD8 but not CD4 suggesting this infiltrate is likely CD8+ but not CD4+ T-lymphocytes. This increase in T-cell infiltration was not affected by the lack of SK1. Overall, DENV-infection in the brain induces IFN and T-cell responses but does not influence the SK/S1P axis. In contrast to our observations in vitro, SK1 has no major influence on these responses following DENV-infection in the mouse brain.

  17. Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord

    Science.gov (United States)

    Chechneva, Olga V.; Mayrhofer, Florian; Daugherty, Daniel J.; Pleasure, David E.; Hong, Jau-Shyong; Deng, Wenbin

    2011-01-01

    Dextromethorphan (DM) is a dextrorotary morphinan and a widely used component of cough medicine. Relatively high doses of DM in combination with quinidine are used for the treatment of mood disorders for patients with multiple sclerosis (MS). However, at lower doses, morphinans exert anti-inflammatory activities through the inhibition of NOX2-dependent superoxide production in activated microglia. Here we investigated the effects of high (10 mg/kg, i.p., “DM-10”) and low (0.1 mg/kg, i.p., “DM-0.1”) doses of DM on the development and progression of mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We found no protection by high dose DM treatment. Interestingly, a minor late attenuation by low dose DM treatment was seen in severe EAE that was characterized by a chronic disease course and a massive spinal cord infiltration of CD45+ cells including T-lymphocytes, macrophages and neutrophils. Furthermore, in a less severe form of EAE, where lower levels of CD4+ and CD8+ T-cells, Iba1+ microglia/macrophages and no significant infiltration of neutrophils were seen in the spinal cord, the treatment with DM-0.1 was remarkably more beneficial. The effect was the most significant at the peak of disease and was associated with an inhibition of NOX2 expression and a decrease in infiltration of monocytes and lymphocytes into the spinal cord. In addition, chronic treatment with low dose DM resulted in decreased demyelination and reduced axonal loss in the lumbar spinal cord. Our study is the first report to show that low dose DM is effective in treating EAE of moderate severity. Our findings reveal that low dose morphinan DM treatment may represent a new promising protective strategy for treating MS. PMID:21704706

  18. Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy

    Science.gov (United States)

    Choi, Jung-Eun; Lee, Hae Ri; Ohn, Jung Hun; Moon, Min Kyong; Park, Juri; Lee, Seong Jin; Choi, Moon-Gi; Yoo, Hyung Joon; Kim, Jung Han

    2014-01-01

    We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated. PMID:25309800

  19. Classical activation of microglia in CD200-deficient mice is a consequence of blood brain barrier permeability and infiltration of peripheral cells.

    Science.gov (United States)

    Denieffe, Stephanie; Kelly, Ronan J; McDonald, Claire; Lyons, Anthony; Lynch, Marina A

    2013-11-01

    The interaction between CD200, expressed on several cell types, and its receptor CD200R, expressed on cells of the myeloid lineage, has been shown to be an important factor in modulating inflammation in macrophage function in several conditions including colitis and arthritis. More recently its modulatory effect on microglial activation has been identified and CD200-deficiency has been associated with increased microglial activation accompanied by increased production of inflammatory cytokines. The response of glia prepared from CD200-deficient mice to stimuli like lipopolysaccharide (LPS) is markedly greater than the response of cells prepared from wildtype mice and, consistent with this, is the recent observation that expression of Toll-like receptor (TLR)4 and signalling through NFκB are increased in microglia prepared from CD200-deficient mice. Here we show that glia from CD200-deficient mice are also more responsive to interferon-γ (IFNγ) which triggers classical activation of microglia. We investigated the effects of CD200-deficiency in vivo and report that there is an increase in expression of several markers of microglial activation including tumor necrosis factor (TNF)-α, which is a hallmark of classically-activated microglia. These changes are accompanied by increased IFNγ, and the evidence suggests that this is produced by infiltrating cells including T cells and macrophages. We propose that these cells enter the brain as a consequence of increased blood brain barrier (BBB) permeability in CD200-deficient mice and that infiltration is assisted by increased expression of the chemokines, monocyte chemotactic protein-1 (MCP-1), IFNγ-induced protein-10 (IP-10) and RANTES. This may have implications in neurodegenerative diseases where BBB permeability is compromised.

  20. Infiltrating macrophages are key to the development of seizures following virus infection.

    Science.gov (United States)

    Cusick, Matthew F; Libbey, Jane E; Patel, Dipan C; Doty, Daniel J; Fujinami, Robert S

    2013-02-01

    Viral infections of the central nervous system (CNS) can trigger an antiviral immune response, which initiates an inflammatory cascade to control viral replication and dissemination. The extent of the proinflammatory response in the CNS and the timing of the release of proinflammatory cytokines can lead to neuronal excitability. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), two proinflammatory cytokines, have been linked to the development of acute seizures in Theiler's murine encephalomyelitis virus-induced encephalitis. It is unclear the extent to which the infiltrating macrophages versus resident CNS cells, such as microglia, contribute to acute seizures, as both cell types produce TNF-α and IL-6. In this study, we show that following infection a significantly higher number of microglia produced TNF-α than did infiltrating macrophages. In contrast, infiltrating macrophages produced significantly more IL-6. Mice treated with minocycline or wogonin, both of which limit infiltration of immune cells into the CNS and their activation, had significantly fewer macrophages infiltrating the brain, and significantly fewer mice had seizures. Therefore, our studies implicate infiltrating macrophages as an important source of IL-6 that contributes to the development of acute seizures.

  1. Pathologic and imunohistochemical characterization of tumoral inflammatory cell infiltrate in invasive penile squamous cell carcinomas: Fox-P3 expression is an independent predictor of recurrence.

    Science.gov (United States)

    Vassallo, José; Rodrigues, André Fellipe Freitas; Campos, Antonio Hugo J F M; Rocha, Rafael Malagoli; da Cunha, Isabela Werneck; Zequi, Stênio Cássio; Guimarães, Gustavo Cardoso; da Fonseca, Francisco Paulo; Lopes, Ademar; Cubilla, Antonio; Soares, Fernando Augusto

    2015-04-01

    Penile carcinomas (PeCa) are relatively rare, but devastating neoplasms, more frequent among people of underprivileged socioeconomic status. There is mounting evidence that immune cells may trigger various mechanisms that enhance tumor growth and metastasis, but no data on the peritumoral inflammation is available for PeCa. The objectives of the present study are to evaluate the immunohistomorphology of tumoral inflammation in PeCa, and to correlate it with clinicopathological parameters, which could contribute to the prognostic evaluation. One hundred and twenty-two patients with the diagnosis of usual-type squamous cell penile carcinoma were included. Paraffin-embedded tissue was submitted to immunohistochemical evaluation of p16 protein, CD3, CD4, CD8, CD20, CD68, CD138, granzyme B, and Fox-P3. The Fisher's exact test was employed for comparison between histological variables and parameters, and the Kaplan-Meier method for the analysis of survival. Improved 5-year overall survival was significantly associated to age ≤60 years, stage I + II, tumor size T1 + T2, lymph node status N0, and absent perineural invasion. In a multivariate analysis age ≥60 years, presence of lymph node metastasis, urethral invasion, and high histologic grade retained a significantly more unfavorable outcome. Improved 5-year failure free survival was associated to stage of the disease I + II, lymph node status N0, absence of perineural, vascular, and urethral invasion, and Fox-P3 expression. In a multivariate analysis, presence of lymph node metastasis, perineural and vascular invasion, and of Fox-P3-positive lymphocytes together with low inflammatory infiltrate retained a significantly more unfavorable outcome. These results support the prognostic value of determining the levels of Fox-P3-positive lymphocytes by immunohistochemistry in PeCa, as this parameter adds value to the traditional clinicopathological features.

  2. Enhancing Sulfur Tolerance of Ni-Based Cermet Anodes of Solid Oxide Fuel Cells by Ytterbium-Doped Barium Cerate Infiltration.

    Science.gov (United States)

    Li, Meng; Hua, Bin; Luo, Jing-Li; Jiang, San Ping; Pu, Jian; Chi, Bo; Li, Jian

    2016-04-27

    Conventional anode materials for solid oxide fuel cells (SOFCs) are Ni-based cermets, which are highly susceptible to deactivation by contaminants in hydrocarbon fuels. Hydrogen sulfide is one of the commonly existed contaminants in readily available natural gas and gasification product gases of pyrolysis of biomasses. Development of sulfur tolerant anode materials is thus one of the critical challenges for commercial viability and practical application of SOFC technologies. Here we report a viable approach to enhance substantially the sulfur poisoning resistance of a Ni-gadolinia-doped ceria (Ni-GDC) anode through impregnation of proton conducting perovskite BaCe0.9Yb0.1O3-δ (BCYb). The impregnation of BCYb nanoparticles improves the electrochemical performance of the Ni-GDC anode in both H2 and H2S containing fuels. Moreover, more importantly, the enhanced stability is observed in 500 ppm of H2S/H2. The SEM and XPS analysis indicate that the infiltrated BCYb fine particles inhibit the adsorption of sulfur and facilitate sulfur removal from active sites, thus preventing the detrimental interaction between sulfur and Ni-GDC and the formation of cerium sulfide. The preliminary results of the cell with the BCYb+Ni-GDC anode in methane fuel containing 5000 ppm of H2S show the promising potential of the BCYb infiltration approach in the development of highly active and stable Ni-GDC-based anodes fed with hydrocarbon fuels containing a high concentration of sulfur compounds.

  3. Improvement of dye-sensitized solar cell performance through infiltration of TiO{sub 2} nanoparticles between mesoporous TiO{sub 2} particles

    Energy Technology Data Exchange (ETDEWEB)

    Park, Su-Bin [Department of Chemistry, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Chung, Il Jun; Woo, Ji Won; Kim, Tae Hun [Baekyoung High School, Anyang 461-070 (Korea, Republic of); Li, Zhenghua; Jin, Mingshi [Department of Chemistry, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Lee, Duk Jae [Baekyoung High School, Anyang 461-070 (Korea, Republic of); Kim, Ji Man, E-mail: jimankim@skku.edu [Department of Chemistry, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2014-10-15

    Highlights: • Spherical mesoporous TiO{sub 2} materials were obtained by a simple sol–gel method. • Physical mixture of TiO{sub 2} nanoparticle and mesoporous TiO{sub 2} was utilized for solar cell electrode. • Mixed electrode system exhibited higher DSSC performance. - Abstract: There are two factors on the efficiency of dye-sensitized solar cell (DSSC): one is the amount of dye adsorbed, and the other is contact resistance. In this study, TiO{sub 2} nanoparticles (nano-TiO{sub 2}, about 20 nm particle size) were infiltrated between mesoporous TiO{sub 2} (meso-TiO{sub 2}) particles with about 300 nm particle sizes, in order to reduce the contact resistance of TiO{sub 2} electrodes. The infiltrated nano-TiO{sub 2} can facilitate electron transfer between meso-TiO{sub 2} particles by filling the empty volume of DSSC electrodes. As a result, the TiO{sub 2} electrode containing 65 wt% of meso-TiO{sub 2} and 35 wt% of nano-TiO{sub 2} exhibited the highest performance of DSSC.

  4. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  5. Rat acute GvHD is Th1-driven and characterized by predominant donor CD4(+) T cell infiltration of skin and gut.

    Science.gov (United States)

    Boieri, Margherita; Shah, Pranali; Jalapothu, Dasaradha; Zaitseva, Olena; Walter, Lutz; Rolstad, Bent; Naper, Christian; Dressel, Ralf; Inngjerdingen, Marit

    2017-02-23

    Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of allo-activated donor T cells primarily into the gastrointestinal tract and skin. While cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete immunoregulatory cytokines. Acute GvHD is thought to be primarily initiated by Th1 cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T cell subsets to aGvHD in the rat. Acute GvHD was induced by transplanting irradiated rats with T-cell depleted MHC-mismatched bone marrow, followed two weeks later by donor lymphocyte infusion. Near complete donor T cell chimerism was achieved in the blood and lymphatic tissues, in contrast to mixed chimerism in the skin and gut. Skin and gut donor T cells were predominantly CD4(+), in contrast to T cells in blood and lymphatic tissues. Genes associated with Th1 cells were up-regulated in gut, liver, lung, and skin tissues affected by aGvHD. Increased serum levels of CXCL10 and IL-18 preceded symptoms of aGvHD, accompanied by increased responsiveness to CXCL10 by blood CD4(+) T cells. No changes in expression of Th2- or Th17-associated genes were observed, indicating that aGvHD in this rat model is mainly Th1-driven. The rat model of aGvHD could be instrumental for further investigations of donor T cell subsets in the skin and gut, and for exploring therapeutic options to ameliorate symptoms of aGvHD.

  6. Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fuchs Mary

    2012-08-01

    Full Text Available Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.

  7. Immunophenotyping of inflammatory cells associated with Schmallenberg virus infection of the central nervous system of ruminants.

    Directory of Open Access Journals (Sweden)

    Vanessa Herder

    Full Text Available Schmallenberg virus (SBV is a recently discovered Bunyavirus associated mainly with abortions, stillbirths and malformations of the skeletal and central nervous system (CNS in newborn ruminants. In this study, a detailed immunophenotyping of the inflammatory cells of the CNS of affected animals was carried out in order to increase our understanding of SBV pathogenesis. A total of 82 SBV-polymerase chain reaction (PCR positive neonatal ruminants (46 sheep lambs, 34 calves and 2 goat kids were investigated for the presence of inflammation in the brain and spinal cord. The study focused on 15 out of 82 animals (18.3% showing inflammation in the CNS. All 15 neonates displayed lymphohistiocytic meningoencephalomyelitis affecting most frequently the mesencephalon and the parietal and temporal lobes. The majority of infiltrating cells were CD3-positive T cells, followed by CD79α-positive B cells and CD68-positive microglia/macrophages. Malformations like por- and hydranencephaly, frequently found in the temporal lobe, showed associated demyelination and axonal loss. SBV antigen was detected in 37 out of 82 (45.1% neonatal brains by immunohistochemistry. In particular, SBV antigen was found in 93.3% (14 out of 15 ruminants and 32.8% (22 out of 67 ruminants of animals with and without encephalitis, respectively. Highest amounts of virus-protein expression levels were found in the temporal lobe. Our findings suggest that: (i different brain regions display differential susceptibility to SBV infection; (ii inflammatory cells in the CNS are found only in a minority of virus infected animals; (iii malformations occur in association with and without inflammation in the CNS; and (iv viral antigen is strongly associated with the presence of inflammation in naturally infected animals. Further studies are required to explore the cell tropism and pathogenesis of SBV infection in ruminants.

  8. Immunophenotyping of Inflammatory Cells Associated with Schmallenberg Virus Infection of the Central Nervous System of Ruminants

    Science.gov (United States)

    Herder, Vanessa; Hansmann, Florian; Wohlsein, Peter; Peters, Martin; Varela, Mariana; Palmarini, Massimo; Baumgärtner, Wolfgang

    2013-01-01

    Schmallenberg virus (SBV) is a recently discovered Bunyavirus associated mainly with abortions, stillbirths and malformations of the skeletal and central nervous system (CNS) in newborn ruminants. In this study, a detailed immunophenotyping of the inflammatory cells of the CNS of affected animals was carried out in order to increase our understanding of SBV pathogenesis. A total of 82 SBV-polymerase chain reaction (PCR) positive neonatal ruminants (46 sheep lambs, 34 calves and 2 goat kids) were investigated for the presence of inflammation in the brain and spinal cord. The study focused on 15 out of 82 animals (18.3%) showing inflammation in the CNS. All 15 neonates displayed lymphohistiocytic meningoencephalomyelitis affecting most frequently the mesencephalon and the parietal and temporal lobes. The majority of infiltrating cells were CD3-positive T cells, followed by CD79α-positive B cells and CD68-positive microglia/macrophages. Malformations like por- and hydranencephaly, frequently found in the temporal lobe, showed associated demyelination and axonal loss. SBV antigen was detected in 37 out of 82 (45.1%) neonatal brains by immunohistochemistry. In particular, SBV antigen was found in 93.3% (14 out of 15 ruminants) and 32.8% (22 out of 67 ruminants) of animals with and without encephalitis, respectively. Highest amounts of virus-protein expression levels were found in the temporal lobe. Our findings suggest that: (i) different brain regions display differential susceptibility to SBV infection; (ii) inflammatory cells in the CNS are found only in a minority of virus infected animals; (iii) malformations occur in association with and without inflammation in the CNS; and (iv) viral antigen is strongly associated with the presence of inflammation in naturally infected animals. Further studies are required to explore the cell tropism and pathogenesis of SBV infection in ruminants. PMID:23667545

  9. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.

    Science.gov (United States)

    Matsuzaki, Junko; Gnjatic, Sacha; Mhawech-Fauceglia, Paulette; Beck, Amy; Miller, Austin; Tsuji, Takemasa; Eppolito, Cheryl; Qian, Feng; Lele, Shashikant; Shrikant, Protul; Old, Lloyd J; Odunsi, Kunle

    2010-04-27

    NY-ESO-1 is a "cancer-testis" antigen frequently expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs), tumor-infiltrating lymphocytes (TILs), and tumor-associated lymphocytes (TALs) of EOC patients with NY-ESO-1-expressing tumors, with or without humoral immunity to NY-ESO-1. Whereas NY-ESO-1-specific CD8(+) T cells were readily detectable ex vivo with tetramers in TILs and TALs of seropositive patients, they were only detectable in PBLs following in vitro stimulation. Compared with PBLs, tumor-derived NY-ESO-1-specific CD8(+) T cells demonstrated impaired effector function, preferential usage of dominant T-cell receptor, and enriched coexpression of inhibitory molecules LAG-3 and PD-1. Expression of LAG-3 and PD-1 on CD8(+) T cells was up-regulated by IL-10, IL-6 (cytokines found in tumor ascites), and tumor-derived antigen-presenting cells. Functionally, CD8(+)LAG-3(+)PD-1(+) T cells were more impaired in IFN-gamma/TNF-alpha production compared with LAG-3(+)PD-1(-) or LAG-3(-)PD-1(-) subsets. Dual blockade of LAG-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1-specific CD8(+) T cells, indicating that antitumor function of NY-ESO-1-specific CD8(+) T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.

  10. Effect of Co3O4 and Co3O4/CeO2 infiltration on the catalytic and electro-catalytic activity of LSM15/CGO10 porous cells stacks for oxidation of propene

    DEFF Research Database (Denmark)

    Ippolito, Davide; Kammer Hansen, Kent

    2015-01-01

    The objective of this work was to study the effect of Co3O4 and Co3O4/CeO2 infiltration on the propene oxidation catalytic activity of a La0.85Sr0.15MnO3/Ce0.9Gd0.1O1.95 electrochemical porous cell stack (11 layers, 5 single cells in series). The effect of the infiltration of Co3O4 and Co3O4/CeO2...... on the electrochemical properties of the porous cell stack was also investigated by electrochemical impedance spectroscopy (EIS). Co3O4 and Co3O4/CeO2 exhibited high catalytic activity for propene oxidation. The increase of propene oxidation rate with +4 V (0.8 V/cell) polarization reached 10% for the Co3O4 infiltrated...... reactor and 48% of efficiency at 300 °C. The Co3O4/CeO2 co-infiltration decreased the reactor polarization resistance, while Co3O4 infiltration had negligible effect on reactor electrochemical performance. The beneficial effect of CeO2 on the electrode activity was attributed to the increased...

  11. 肾组织浸润细胞在新月体肾炎患者中的分布特点及意义%The distribution and significance of renal infiltrating cells in patients with diffuse crescentic glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    唐政; 吴燕; 胡伟新; 姚小丹; 周红; 陈惠萍; 刘志红; 黎磊石

    2001-01-01

    Objective To study the significance and distribution of renal infiltrating cells, including monocytes (CD68+ cells), proliferative cell nuclear antigen positive cells (PCNA+ cells), CD4+ and CD8+ cells in diffuse crescent glomerulonephritis (DCGN). Methods Fifty-six patients with DCGN were studied, including 10 cases of anti-glomerular basement membrane (GBM)-type Ⅰ DCGN, 26 immune complex-type Ⅱ DCGN, and 20 cases of pauci-immune-type Ⅲ DCGN. Glomerular and interstitial infiltrates of CD68+ and PCNA+ cells, and interstitial infiltrates of CD4+ and CD8+ cells were detected by using four-layer PAP methods. Results There was a significant increase of renal infiltrating CD68+, PCNA+, CD4+ and CD8+ cells in patients with DCGN compared with that in normal controls. In patients with type Ⅰ DCGN, there was a higher number of renal infiltrating CD68+ and PCNA+ cells than that in patients with type Ⅱ and Ⅲ DCGN. A glomerular infiltrates of CD68+ and PCNA+ cells correlated with the interstitial infiltrates of CD4+ cells in type Ⅰ or Ⅲ DCGN patients. In lupus DCGN patients, the numbers of renal infiltrating CD68+ and PCNA+ cells were similar to vasculitis or type Ⅲ DCGN patients.Conclusion These findings demonstrate that the renal infiltrates of CD68+ and PCNA+ cells play an important role in patients with DCGN, that the infiltrates of CD4+ cells correlate with the infiltrates of CD68+ and PCNA+ cells may be an active marker of DCGN, and that cell-mediated immunity may contribute to crescent formation in lupus DCGN patients.%目的研究肾组织各种浸润细胞在各类新月体肾炎发生发展中的发病机制。方法分析56例各类新月体肾炎患者肾组织中单核细胞(CD68+)及增殖细胞核抗原阳性细胞(PCNA+)的分布特点,并就它们与肾组织中淋巴细胞亚群CD4+及CD8+细胞浸润的关系进行分析探讨。结果本组新月体患者肾组织中CD68+、PCNA+、CD4+及CD8+细胞均明显高于正常供肾组织。

  12. Exploring Variation and Predictors of Residential Fine Particulate Matter Infiltration

    Directory of Open Access Journals (Sweden)

    Amanda J. Wheeler

    2010-08-01

    Full Text Available Although individuals spend the majority of their time indoors, most epidemiological studies estimate personal air pollution exposures based on outdoor levels. This almost certainly results in exposure misclassification as pollutant infiltration varies between homes. However, it is often not possible to collect detailed measures of infiltration for individual homes in large-scale epidemiological studies and thus there is currently a need to develop models that can be used to predict these values. To address this need, we examined infiltration of fine particulate matter (PM2.5 and identified determinants of infiltration for 46 residential homes in Toronto, Canada. Infiltration was estimated using the indoor/outdoor sulphur ratio and information on hypothesized predictors of infiltration were collected using questionnaires and publicly available databases. Multiple linear regression was used to develop the models. Mean infiltration was 0.52 ± 0.21 with no significant difference across heating and non-heating seasons. Predictors of infiltration were air exchange, presence of central air conditioning, and forced air heating. These variables accounted for 38% of the variability in infiltration. Without air exchange, the model accounted for 26% of the variability. Effective modelling of infiltration in individual homes remains difficult, although key variables such as use of central air conditioning show potential as an easily attainable indicator of infiltration.

  13. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis

    DEFF Research Database (Denmark)

    Holst, P J; Orskov, C; Qvortrup, K;

    2007-01-01

    CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed...... tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis....... One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5(-/-), CXCR3(-/-), and CCR5/CXCR3(-/-) mice with regard to virus-induced liver...

  14. Biophysical characteristics of successful oilseed embryo cryoprotection and cryopreservation using vacuum infiltration vitrification: an innovation in plant cell preservation.

    Directory of Open Access Journals (Sweden)

    Jayanthi Nadarajan

    Full Text Available Heterogeneity in morphology, physiology and cellular chemistry of plant tissues can compromise successful cryoprotection and cryopreservation. Cryoprotection is a function of exposure time × temperature × permeability for the chosen protectant and diffusion pathway length, as determined by specimen geometry, to provide sufficient dehydration whilst avoiding excessive chemical toxicity. We have developed an innovative method of vacuum infiltration vitrification (VIV at 381 mm (15 in Hg (50 kPa that ensures the rapid (5 min, uniform permeation of Plant Vitrification Solution 2 (PVS2 cryoprotectant into plant embryos and their successful cryopreservation, as judged by regrowth in vitro. This method was validated on zygotic embryos/embryonic axes of three species (Carica papaya, Passiflora edulis and Laurus nobilis up to 1.6 mg dry mass and 5.6 mm in length, with varying physiology (desiccation tolerances and 80 °C variation in lipid thermal profiles, i.e., visco-elasticity properties, as determined by differential scanning calorimetry. Comparisons between the melting features of cryoprotected embryos and embryo regrowth indicated an optimal internal PVS2 concentration of about 60% of full strength. The physiological vigour of surviving embryos was directly related to the proportion of survivors. Compared with conventional vitrification, VIV-cryopreservation offered a ∼ 10-fold reduction in PVS2 exposure times, higher embryo viability and regrowth and greater effectiveness at two pre-treatment temperatures (0 °C and 25 °C. VIV-cryopreservation may form the basis of a generic, high throughput technology for the ex situ conservation of plant genetic resources, aiding food security and protection of species from diverse habitats and at risk of extinction.

  15. Biophysical characteristics of successful oilseed embryo cryoprotection and cryopreservation using vacuum infiltration vitrification: an innovation in plant cell preservation.

    Science.gov (United States)

    Nadarajan, Jayanthi; Pritchard, Hugh W

    2014-01-01

    Heterogeneity in morphology, physiology and cellular chemistry of plant tissues can compromise successful cryoprotection and cryopreservation. Cryoprotection is a function of exposure time × temperature × permeability for the chosen protectant and diffusion pathway length, as determined by specimen geometry, to provide sufficient dehydration whilst avoiding excessive chemical toxicity. We have developed an innovative method of vacuum infiltration vitrification (VIV) at 381 mm (15 in) Hg (50 kPa) that ensures the rapid (5 min), uniform permeation of Plant Vitrification Solution 2 (PVS2) cryoprotectant into plant embryos and their successful cryopreservation, as judged by regrowth in vitro. This method was validated on zygotic embryos/embryonic axes of three species (Carica papaya, Passiflora edulis and Laurus nobilis) up to 1.6 mg dry mass and 5.6 mm in length, with varying physiology (desiccation tolerances) and 80 °C variation in lipid thermal profiles, i.e., visco-elasticity properties, as determined by differential scanning calorimetry. Comparisons between the melting features of cryoprotected embryos and embryo regrowth indicated an optimal internal PVS2 concentration of about 60% of full strength. The physiological vigour of surviving embryos was directly related to the proportion of survivors. Compared with conventional vitrification, VIV-cryopreservation offered a ∼ 10-fold reduction in PVS2 exposure times, higher embryo viability and regrowth and greater effectiveness at two pre-treatment temperatures (0 °C and 25 °C). VIV-cryopreservation may form the basis of a generic, high throughput technology for the ex situ conservation of plant genetic resources, aiding food security and protection of species from diverse habitats and at risk of extinction.

  16. CENTRAL GIANT CELL GRANULOMA OF THE MANDIBLE: A RARE PRESENTATION

    Directory of Open Access Journals (Sweden)

    Virendra SINGH

    2012-06-01

    Full Text Available Central giant cell granuloma (CGCG is an intra-osseous lesion consisting of cellular fibrosis tissue containing multiple foci of hemorrhage, multinucleated giant cells and trabecules of woven bone. This lesion accounts for less than 7% of all benign jaw tumours. Jaffe considered it as a locally reparative reaction of bone, which can be possibly due to either an inflammatory response, hemorrhage or local trauma. Females are affected more frequently than males. It occurs over a wide age range.It has been reported that this lesion is diagnosed during the first two decades of life in approximately 48% of cases, and 60% of cases are evident before the age of 30. It is considerably more common in the mandible than in the maxilla. Most lesions occur in the molar and premolar area, some of these extending up to the ascending ramus. The presence of giant cell granuloma in the mandibular body area, the entire ramus, condyle and coronoid represents a therapeutic challenge for the oral and maxillofacial surgeons. The aim of this report is to describe an unusual presentation of central giant cell granuloma involving the mandibular body, ramus, condylar and coronoid processes, and to discuss the differentiated diagnosis, the radiographic presentation and the management of this lesion.

  17. Tumor infiltrating lymphocytes in melanoma comprise high numbers of T-cell clonotypes that are lost during in vitro culture

    DEFF Research Database (Denmark)

    thor Straten, P; Kirkin, A F; Siim, E;

    2000-01-01

    -associated peptide epitopes. Cultured TIL have been studied in order to unveil characteristics of TIL and the interactions of TIL and melanoma cells. Whether in vitro cultured TIL mirrors the in situ situation has, however, been questioned. In the present study we have taken advantage of T-cell receptor clonotype...... mapping methodology to conduct a full and detailed analysis of the T-cell clonotypes in melanoma lesions and in corresponding lines of TIL established in vitro. All melanoma lesions and the corresponding TIL cultures comprised high numbers of T-cell clonotypes, typically in the range of 40 to more than 60...... that in situ T-cell clonotypes in melanoma are not readily expanded in vitro and that the majority of T-cell clonotypes present in cultured TIL are not present in situ....

  18. Immunotherapy Expands and Maintains the Function of High-Affinity Tumor-Infiltrating CD8 T Cells In Situ.

    Science.gov (United States)

    Moran, Amy E; Polesso, Fanny; Weinberg, Andrew D

    2016-09-15

    Cancer cells harbor high-affinity tumor-associated Ags capable of eliciting potent antitumor T cell responses, yet detecting these polyclonal T cells is challenging. Therefore, surrogate markers of T cell activation such as CD69, CD44, and programmed death-1 (PD-1) have been used. We report in this study that in mice, expression of activation markers including PD-1 is insufficient in the tumor microenvironment to identify tumor Ag-specific T cells. Using the Nur77GFP T cell affinity reporter mouse, we highlight that PD-1 expression can be induced independent of TCR ligation within the tumor. Given this, we characterized the utility of the Nur77GFP model system in elucidating mechanisms of action of immunotherapies independent of PD-1 expression. Coexpression of Nur77GFP and OX40 identifies a polyclonal population of high-affinity tumor-associated Ag-specific CD8(+) T cells, which produce more IFN-γ in situ than OX40 negative and doubles in quantity with anti-OX40 and anti-CTLA4 mAb therapy but not with anti-PD-1 or programmed death ligand-1. Moreover, expansion of these high-affinity CD8 T cells prolongs survival of tumor-bearing animals. Upon chronic stimulation in tumors and after adoptive cell therapy, CD8 TCR signaling and Nur77GFP induction is impaired, and tumors progress. However, this can be reversed and overall survival significantly enhanced after adoptive cell therapy with agonist OX40 immunotherapy. Therefore, we propose that OX40 agonist immunotherapy can maintain functional TCR signaling of chronically stimulated tumor-resident CD8 T cells, thereby increasing the frequency of cytotoxic, high-affinity, tumor-associated Ag-specific cells.

  19. Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

    Science.gov (United States)

    Chen, Michael; Deng, April; Crowson, A Neil; Srinivasan, Mythily; Yearsley, Kurtis H; Jewell, Scott; Morrison, Carl; Long, Susan; Werling, Robert; Magro, Cynthia

    2004-12-01

    Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

  20. Whole-body MRI in the detection of bone marrow infiltration in patients with plasma cell neoplasms in comparison to the radiological skeletal survey

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Nadir; Lohrmann, Christian; Pache, Gregor; Uhl, Markus; Saueressig, Ulrich; Kotter, Elmar; Langer, Mathias [University Hospital Freiburg, Department of Diagnostic Radiology, Freiburg (Germany); Engelhardt, Monika [University Hospital Freiburg, Department of Hematology and Oncology, Freiburg (Germany)

    2006-05-15

    To compare the diagnostic value of whole-body MRI versus radiological skeletal survey (RSS) in staging patients with plasma cell neoplasms (PCN) and to evaluate the possible therapeutic impact of the replacement of RSS by whole-body MRI. Fifty-four patients with PCN [multiple myeloma (MM), n=47; monoclonal gammopathy of unknown significance (MGUS), n=7] were studied by whole-body MRI and RSS in a monocenter prospective analysis from August 2002 to May 2004. The MRIs were performed using a rolling table platform ''AngioSURF'' for unlimited field of view with a 1.5-T system (Magnetom Sonata/Maestro Class, Siemens Medical Solutions, Erlangen, Germany). A coronal STIR sequence (TR5500-4230/TE102-94/TI160) was used for imaging of the different body regions, including the head, neck, thorax, abdomen, pelvis and upper and lower extremities. The RSS consisted of eight different projections of the axial and appendicular skeleton. In 41/54 (74%) patients, the results of the whole-body MRI and RSS were concordant. In 11/54 (20%) patients, both imaging techniques were negative. Bone involvement was observed in 30/54 (55%) patients; however, whole-body MRI revealed this more extensively than the RSS in 27/30 (90%) patients with concordant positive imaging findings. In 3/30 (10%) patients, both imaging techniques demonstrated a similar extent of bone marrow infiltration. In 10/54 (19%) patients, the whole-body MRI was superior to RSS in detecting bone marrow infiltration, whereas the RSS was negative. In 3/54 (6%) patients, the RSS was proven to be false positive by the clinical course, whereas the whole-body MRI was truly negative. Whole-body MRI is a fast and highly effective method for staging PCN patients by the use of a rolling table platform. Moreover, it is more sensitive and specific than RSS and reveals bone marrow infiltration and extensive disease more reliably. Therefore, whole-body MRI should be performed as an additional method of exactly

  1. Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

    Science.gov (United States)

    Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

    2016-05-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

  2. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  3. Central granular cell odontogenic tumor: Report of an unusual case

    Directory of Open Access Journals (Sweden)

    Mani Madan

    2016-01-01

    Full Text Available Central granular cell odontogenic tumor (CGCOT is an unusual benign odontogenic neoplasm characterized by the presence of granular cells associated with apparently inactive odontogenic epithelium. These tumors tend to occur in the posterior mandible and usually present as well-defined unilocular or multilocular radiolucent lesions. So far, only <40 cases of CGCOT have been described in the literature under various terminologies. Though these tumors were not considered as distinct entity in the recent WHO classification of odontogenic tumors, long-term follow-up is recommended as malignant counterpart of CGCOT has already been reported. The main aim of this article is to report an additional case of CGCOT to the literature, occurring in a 73-year-old male.

  4. Urban Stormwater Infiltration Perspectives

    DEFF Research Database (Denmark)

    Geldof, Govert; Jacobsen, Per; Fujita, Shoichi

    1994-01-01

    water management. This paper focuses on the possibilities for urban stormwater infiltration. The results of three studies are presented. The first study concerns the flooding of the Shirako River in Tokyo. It is shown that with the help of stormwater infiltration the floods can be reduced remarkably......In urban areas there are many problems with water management: combined sewer overflows, peak flows, man-induced droughts, consolidation of the soil, damage from frost penetration, etc. It is preferable to look at all these problems in relation to each other, according the concept of integrated...... shows the impact of urban stormwater infiltration on the groundwater flux in an area in the south of the Netherlands. To relate the different results from the three studies an analogy is introduced with the human body. The combination of problems results in a so-called urban hang-over. It is shown...

  5. Approach to cutaneous lymphoid infiltrates: When to consider lymphoma?

    Directory of Open Access Journals (Sweden)

    Yann Vincent Charli-Joseph

    2016-01-01

    Full Text Available Cutaneous lymphoid infiltrates (CLIs are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1 Superficial dermal T-cell infiltrates (2 superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3 pan-dermal diffuse T-cell infiltrates (4 panniculitic T-cell infiltrates (5 small cell predominant B-cell infiltrates, and (6 large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.

  6. Approach to Cutaneous Lymphoid Infiltrates: When to Consider Lymphoma?

    Science.gov (United States)

    Charli-Joseph, Yann Vincent; Gatica-Torres, Michelle; Pincus, Laura Beth

    2016-01-01

    Cutaneous lymphoid infiltrates (CLIs) are common in routine dermatopathology. However, differentiating a reactive CLI from a malignant lymphocytic infiltrate is often a significant challenge since many inflammatory dermatoses can clinically and/or histopathologically mimic cutaneous lymphomas, coined pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma, cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs and the most common differential imitators of lymphoma is discussed herein based on six predominant morphologic and immunophenotypic, histopathologic patterns: (1) Superficial dermal T-cell infiltrates (2) superficial and deep dermal perivascular and/or nodular natural killer/T-cell infiltrates (3) pan-dermal diffuse T-cell infiltrates (4) panniculitic T-cell infiltrates (5) small cell predominant B-cell infiltrates, and (6) large-cell predominant B-cell infiltrates. Since no single histopathological feature is sufficient to discern between a benign and a malignant CLI, the overall balance of clinical, histopathological, immunophenotypic, and molecular features should be considered carefully to establish a diagnosis. Despite advances in ancillary studies such as immunohistochemistry and molecular clonality, these studies often display specificity and sensitivity limitations. Therefore, proper clinicopathological correlation still remains the gold standard for the precise diagnosis of CLIs.

  7. Ultrastructural studies of allergic contact dermatitis in man. Infiltrating cells at the earliest phase of spongiotic bulla formation.

    Science.gov (United States)

    Komura, J; Oguchi, M; Aoshima, T; Ofuji, S

    1980-01-01

    The kind and fine structure of mononuclear cells appearing in the epidermis at about 6 h of allergic contact dermatitis were examined by electron microscopy. They were monocytes and lymphocytes, the number being about equal. The ultrastructure of monocytes was that described for normal ones in blood, and apparently actively moving, streching the intercellular connections of the keratinocytes. Lymphocytes displayed a round or oval nucleus with some electron-dense cytoplasm which contained ribosomes and polysomes but only occasional mitochondria and Golgi complexes.

  8. Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft.

    Science.gov (United States)

    Xie, Jingxin; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, Sifeng

    2016-08-01

    Renal transplantation is the treatment of choice for end-stage renal failure. Although acute rejection is not a major issue anymore, chronic rejection, especially vascular rejection, is still a major factor that might lead to allograft dysfunction on the long term. The role of the local immune-regulating cytokine interleukin-10 (IL-10) in chronic renal allograft is unclear. Many clinical observations showed that local IL-10 level was negatively related to kidney allograft function. It is unknown this negative relationship was the result of immunostimulatory property or insufficient immunosuppression property of local IL-10. We performed ex vivo transduction before transplantation through artery of the renal allograft using adeno-associated viral vectors carrying IL-10 gene. Twelve weeks after transplantation, we found intrarenal IL-10 gene transduction significantly inhibited arterial neointimal proliferation, the number of occluded intrarenal artery, interstitial fibrosis, peritubular capillary congestion and glomerular inflammation in renal allografts compared to control allografts receiving PBS or vectors carrying YFP. IL-10 transduction increased serum IL-10 level at 4 weeks but not at 8 and 12 weeks. Renal IL-10 level increased while serum creatinine decreased significantly in IL-10 group at 12 weeks compared to PBS or YFP controls. Immunohistochemical staining showed unchanged total T cells (CD3) and B cells (CD45R/B220), decreased cytotoxic T cells (CD8), macrophages (CD68) and increased CD4+ and FoxP3+ cells in IL-10 group. In summary, intrarenal IL-10 inhibited the allograft rejection while modulated immune response.

  9. The Promoting Effect of the Extracellular Matrix Peptide TNIIIA2 Derived from Tenascin-C in Colon Cancer Cell Infiltration

    Science.gov (United States)

    Suzuki, Hideo; Sasada, Manabu; Kamiya, Sadahiro; Ito, Yuka; Watanabe, Hikaru; Okada, Yuko; Ishibashi, Kazuma; Iyoda, Takuya; Yanaka, Akinori; Fukai, Fumio

    2017-01-01

    The extracellular matrix (ECM) molecule tenascin C (TNC) is known to be highly expressed under various pathological conditions such as inflammation and cancer. It has been reported that the expression of TNC is correlated with the malignant potential of cancer. In our laboratory, it was found that the peptide derived from the alternative splicing domain A2 in TNC, termed TNIIIA2, has been shown to influence a variety of cellular processes, such as survival, proliferation, migration, and differentiation. In this study, we investigated the effect of TNC/TNIIIA2 on the invasion and metastasis of colon cancer cells, Colon26-M3.1, or PMF-Ko14, using an in vitro and in vivo experimental system. The degree of cell invasion was increased by the addition of TNC and TNIIIA2 in a dose-dependent manner. The invasion by TNC and TNIIIA2 were suppressed by an MMP inhibitor or TNIIIA2-blocking antibody. In an in vivo experiment, pulmonary metastasis was promoted conspicuously by the addition of TNIIIA2. In this study, we found that colon cancer cell invasion and metastasis was accelerated by TNC/TNIIIA2 via MMP induction. This result suggests the possibility of a new strategy targeting TNC/TNIIIA2 for colon cancer. PMID:28106752

  10. Atrial natriuretic peptide (ANP) inhibits DMBA/croton oil induced skin tumor growth by modulating NF-κB, MMPs, and infiltrating mast cells in swiss albino mice.

    Science.gov (United States)

    Subramanian, Vimala; Vellaichamy, Elangovan

    2014-10-01

    Cardiac hormone atrial natriuretic peptide (ANP) and its receptor, natriuretic peptide receptor-A (NPR-A) are implicated as a vital regulator of cancer cell growth and tumor progression. However, the underlying mechanism by which ANP opposes the cancer growth in in-vivo remains unknown. Herein, we investigated the anti-cancer activity of ANP on 7, 12-dimethyl benzanthracence (DMBA)/Croton oil- induced two-step skin carcinogenic mouse model. Skin tumor incidence and tumor volume were recorded during the experimental period of 16 weeks. ANP (1 μg/kg body weight/alternate days for 4 weeks) was injected subcutaneously from the 13th week of DMBA/Croton oil induction. ANP treatment markedly inhibited the skin tumor growth (P<0.001). A significant reduction in the level of NF-κB activation (P<0.001), infiltrating mast cell count (P<0.01) and MMP-2/-9 (P<0.001, respectively) were noticed in the ANP treated mice skin tissue. Further, ANP treatment revert back the altered levels of serum LDH-4, C-reactive protein (CRP), and enzymatic antioxidants (SOD and CAT activities) to near normal level. Taken together, the results of this study suggest that ANP opposes the skin carcinogenesis by suppressing the inflammatory response and MMPs.

  11. Radiological and epidemiological aspects of central giant cell granuloma

    Energy Technology Data Exchange (ETDEWEB)

    Noleto, Jose Wilson [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia]. E-mail: wilsonnoleto@ig.com.br; Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Sampaio, Renato Kobler [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina; Irion, Klaus L. [Liverpool NHS Trust, Liverpool (United Kingdom). Cardiothoracic Centre; Collares, Felipe Birchal [Harvard Medical School, Boston, MA (United States). Beth Israel Deaconess Medical Center (BIDMC)

    2007-05-15

    Objective: The present study was aimed at evaluating main radiological and epidemiological aspects of giant cell lesions (central giant cell granuloma and brown tumors of hyperparathyroidism). Materials and methods: The sample consisted of 26 giant cell lesions diagnosed in 22 patients divided into two groups, one of them including 17 patients who were not affected by hyperparathyroidism (group A) and another including five patients with such a disorder (group B). Results: Prevalence was higher in female patients (72.7%). Most frequently, lesions occurred more in the second decade of life (mean age, 27 years). The mandible arc was most frequently involved (61.5%). Radiographically, 57.7% of lesions were multilocular and 42.3% were unilocular with defined limits. All of the 26 lesions caused expansion of bone, 15.4% radicular resorption, 50% dental displacement, and 11.5% produced pain. In the mandible 18.7% of the lesions crossed the midline. Group A showed 66.7% of lesions in the mandible and group B showed an even distribution of lesions between arches. In group A 66.7% of lesions were multilocular, and 33.3% unilocular; in group B 62.5% were unilocular, and 37.5% multilocular. Conclusion: Giant cells lesions may present themselves with a wide spectrum, from small, slow-growing unilocular lesions to extensive multilocular lesions. They present features of benignity, though some lesions may demonstrate a locally aggressive behavior. (author)

  12. High Performance Cathodes for Solid Oxide Fuel Cells Prepared by Infiltration of La0.6Sr0.4CoO32d into Gd-Doped Ceria

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Knibbe, Ruth;

    2011-01-01

    and the number of infiltrations. The cathode polarization resistance was measured using electrochemical impedance spectroscopy on symmetrical cells in ambient air, while the resulting structures were characterized by scanning electron microscopy (SEM) and high temperature X-ray diffraction (HT-XRD). The firing...... temperature of 600C for the LSC40 infiltrate was found to provide a balance between LSC40 material formation and high surface area micro=nanostructure. The lowest polarization resistances measured at 600 and 400C were 0.044 and 2.3 X cm2 in air, respectively. During degradation tests at 600C, the cathode...

  13. Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic plate of placentas from uncomplicated egg cell donation.

    Science.gov (United States)

    Schonkeren, Dorrith; Swings, Godelieve; Roberts, Drucilla; Claas, Frans; de Heer, Emile; Scherjon, Sicco

    2012-01-01

    In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child.In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.

  14. Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic plate of placentas from uncomplicated egg cell donation.

    Directory of Open Access Journals (Sweden)

    Dorrith Schonkeren

    Full Text Available In pregnancies achieved after egg donation (ED tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child.In ten out of twenty-six (38.5% placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2 marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.

  15. Performance Factors and Sulfur Tolerance of Metal Supported Solid Oxide Fuel Cells with Nanostructured Ni:GDC Infiltrated Anodes

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Persson, Åsa Helen; Sudireddy, Bhaskar Reddy;

    2015-01-01

    In recent years, there has been a growing interest in developing metal supported solid oxide fuel cells (MS-SOFCs). MS-SOFCs are interesting as they potentially offer some advantages compared to conventional electrode and electrolyte supported SOFCs, such as low materials cost, better thermal...... conductivity and ductility of the support. The two later aspects improve the shock resistance and lower internal gradients within the stacks. This enables fast start-up and provides higher tolerance towards operation under transient conditions that are particularly desirable for APU applications. Today...

  16. Infiltration and extravasation.

    Science.gov (United States)

    Hadaway, Lynn

    2007-08-01

    The Infusion Nurses Society's national standards of practice require that a nurse who administers IV medication or fluid know its adverse effects and appropriate interventions to take before starting the infusion. A serious complication is the inadvertent administration of a solution or medication into the tissue surrounding the IV catheter--when it is a nonvesicant solution or medication, it is called infiltration; when it is a vesicant medication, it is called extravasation. Both infiltration and extravasation can have serious consequences: the patient may need surgical intervention resulting in large scars, experience limitation of function, or even require amputation. Another long-term effect is complex regional pain syndrome, a neurologic syndrome that requires long-term pain management. These outcomes can be prevented by using appropriate nursing interventions during IV catheter insertion and early recognition and intervention upon the first signs and symptoms of infiltration and extravasation. Nursing interventions include early recognition, prevention, and treatment (including the controversial use of antidotes, and heat and cold therapy). Steps to manage infiltration and extravasation are presented.

  17. Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

    Directory of Open Access Journals (Sweden)

    Koemeter-Cox Andrew I

    2011-05-01

    Full Text Available Abstract Background Exposure to the nerve agent soman (GD causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE. Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model. Methods Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells. Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines. Results We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain. Conclusions A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.

  18. IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.

    Directory of Open Access Journals (Sweden)

    Deanna A Hagge

    2014-09-01

    Full Text Available Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-, as well as mice deficient in both inducible nitric oxide synthase (NOS2-/- and IL-10 (10NOS2-/-. Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP, inflammation increased from C57Bl/6 (B6cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B were significantly increased in the evolved granuloma in NOS2-/- FP compared to B6 and IL-10-/- during early and peak phases. In 10NOS2-/- FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES, ML2038 (bacterioferritin, and ML1877 (EF-Tu. Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2-/- FP.The 10NOS2-/- strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement.

  19. Characterization and comparison of "Standard" and "Young" tumor infiltrating lymphocytes for adoptive cell therapy at a Danish Translational Research Institution

    DEFF Research Database (Denmark)

    Donia, Marco; Junker, Niels; Ellebaek, Eva;

    2012-01-01

    transferred cells. The aim of this study was to establish and validate the novel "Young TIL" method at our institution and perform a head-to-head comparison of clinical grade products generated with this protocol opposed to the conventional "Standard TIL", that we are currently using in a pilot ACT trial......, either slow expansion with high-dose IL-2 only or large numerical expansion with a rapid expansion protocol (REP), that is required for current therapeutic protocols, significantly modified TIL phenotype by reducing the frequency of less differentiated cancer-specific TILs. These studies further support...... the adoption of the Young TIL method in our current ACT trial and highlight the importance of continuous quality control of expansion protocols....

  20. Are astrocytes executive cells within the central nervous system?

    Science.gov (United States)

    Sica, Roberto E; Caccuri, Roberto; Quarracino, Cecilia; Capani, Francisco

    2016-08-01

    Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson's disease, Alzheimer's dementia, Huntington's dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

  1. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes

    Science.gov (United States)

    Laperchia, Claudia; Palomba, Maria; Seke Etet, Paul F.; Rodgers, Jean; Bradley, Barbara; Montague, Paul; Grassi-Zucconi, Gigliola; Bentivoglio, Marina

    2016-01-01

    Background The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications. Methodology Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM) periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses. Principal findings Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion. Conclusion These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging. PMID:28002454

  2. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  3. Grid cells used for Surface-Water Network for the Central Valley Hydrologic Model

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This digital dataset contains the segment and reaches for the surface-water network by model cell for the Central Valley Hydrologic Model (CVHM). The Central Valley...

  4. Stem cell therapy for central nerve system injuries:glial cells hold the key

    Institute of Scientific and Technical Information of China (English)

    Li Xiao; Chikako Saiki; Ryoji Ide

    2014-01-01

    Mammalian adult central nerve system (CNS) injuries are devastating because of the intrinsic dififculties for effective neuronal regeneration. The greatest problem to be overcome for CNS recovery is the poor regeneration of neurons and myelin-forming cells, oligodendrocytes. En-dogenous neural progenitors and transplanted exogenous neuronal stem cells can be the source for neuronal regeneration. However, because of the harsh local microenvironment, they usually have very low efifcacy for functional neural regeneration which cannot compensate for the loss of neurons and oligodendrocytes. Glial cells (including astrocytes, microglia, oligodendrocytes and NG2 glia) are the majority of cells in CNS that provide support and protection for neurons. Inside the local microenvironment, glial cells largely inlfuence local and transplanted neural stem cells survival and fates. This review critically analyzes current ifnding of the roles of glial cells in CNS regeneration, and highlights strategies for regulating glial cells’ behavior to create a permis-sive microenvironment for neuronal stem cells.

  5. Certain types of iron oxide nanoparticles are not suited to passively target inflammatory cells that infiltrate the brain in response to stroke

    Science.gov (United States)

    Harms, Christoph; Datwyler, Anna Lena; Wiekhorst, Frank; Trahms, Lutz; Lindquist, Randall; Schellenberger, Eyk; Mueller, Susanne; Schütz, Gunnar; Roohi, Farnoosh; Ide, Andreas; Füchtemeier, Martina; Gertz, Karen; Kronenberg, Golo; Harms, Ulrike; Endres, Matthias; Dirnagl, Ulrich; Farr, Tracy D

    2013-01-01

    Intravenous administration of iron oxide nanoparticles during the acute stage of experimental stroke can produce signal intensity changes in the ischemic region. This has been attributed, albeit controversially, to the infiltration of iron-laden blood-borne macrophages. The properties of nanoparticles that render them most suitable for phagocytosis is a matter of debate, as is the most relevant timepoint for administration. Both of these questions are examined in the present study. Imaging experiments were performed in mice with 30 minutes of middle cerebral artery occlusion (MCAO). Iron oxide nanoparticles with different charges and sizes were used, and mice received 300 μmol Fe/kg intravenously: either superparamagnetic iron oxide nanoparticles (SPIOs), ultrasmall SPIOs, or very small SPIOs. The particles were administered 7 days before MCAO, at the time of reperfusion, or 72 hours after MCAO. Interestingly, there was no observable signal change in the ischemic brains that could be attributed to iron. Furthermore, no Prussian blue-positive cells were found in the brains or blood leukocytes, despite intense staining in the livers and spleens. This implies that the nanoparticles selected for this study are not phagocytosed by blood-borne leukocytes and do not enter the ischemic mouse brain. PMID:23443176

  6. Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints.

    Science.gov (United States)

    Rodgers, David T; Pineda, Miguel A; McGrath, Mairi A; Al-Riyami, Lamyaa; Harnett, William; Harnett, Margaret M

    2014-03-01

    We have previously reported that ES-62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen-induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises the possibility that ES-62 may have therapeutic potential in rheumatoid arthritis and hence, it is important to fully understand its mechanism of action. To this end, we have established to date that ES-62 protection in CIA is associated with suppressed T helper type 1 (Th1)/Th17 responses, reduced collagen-specific IgG2a antibodies and increased interleukin-10 (IL-10) production by splenocytes. IL-10-producing regulatory B cells have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, although the levels of IL-10-producing B cells were decreased in the spleens of mice with CIA, ES-62 was found to restore these to the levels found in naive mice. In addition, exposure to ES-62 decreased effector B-cell, particularly plasma cell, infiltration of the joints, and such infiltrating B cells showed dramatically reduced levels of Toll-like receptor 4 and the activation markers, CD80 and CD86. Collectively, this induction of hyporesponsiveness of effector B-cell responses, in the context of the resetting of the levels of IL-10-producing B cells, is suggestive of a modulation of the balance between effector and regulatory B-cell responses that may contribute to ES-62-mediated suppression of CIA-associated inflammation and inhibition of production of pathogenic collagen-specific IgG2a antibodies.

  7. Treatment with a hybrid between the synapsin ABC domains and the B subunit of E. coli heat-labile toxin reduces frequency of proinflammatory cells and cytokines in the central nervous system of rats with EAE.

    Science.gov (United States)

    Bibolini, M J; Scerbo, M J; Roth, G A; Monferran, C G

    2014-09-26

    Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are crucially dependent on the invasion of activated autoreactive lymphocytes and blood macrophages into the central nervous system (CNS). Proinflammatory mononuclear cells and activated local microglia mediate inflammation, demyelination and axonal damage at the target organ. Previously, we observed that the administration of a hybrid between the synapsin ABC domains and the B subunit of Escherichia coli heat labile-enterotoxin (LTBABC) to rats with EAE ameliorated disease by modulating the peripheral Th1 response to myelin basic protein (MBP). In the present study, we investigated the effect of LTBABC administration on proinflammatory cell frequency in the CNS of rats with EAE. Treatment with the hybrid in the inductive phase of EAE attenuated disease severity and diminished histological inflammatory infiltrates and demyelination in the spinal cord of rats with acute EAE. Lower frequencies of infiltrating and local macrophages as well as CD4+ T cells that produce the proinflammatory cytokines interferon-gamma (IFN-γ) and interleukin (IL)-17 were found at the target organ. Concomitantly, low levels of INF-γ and IL-17 and increased levels of IL-10 were measured in cultures of CNS infiltrating cells and spinal cord tissue. An increased frequency of CD4+CD25+Foxp3 cells was observed at the disease peak and at the beginning of the recovery stage. These results provide further evidence for the immunomodulatory properties of the fusion protein LTBABC in autoimmune demyelinating disease affecting the central nervous system.

  8. Sm0.5Sr0.5CoO3-δ-infiltrated cathodes for solid oxide fuel cells with improved oxygen reduction activity and stability

    Science.gov (United States)

    Wang, Fucun; Chen, Dengjie; Shao, Zongping

    2012-10-01

    Sm0.5Sr0.5CoO3-δ (SSC)-impregnated cathodes are fabricated by the solution infiltration of metal nitrates. The effects of complexing agents on the phase structure and the effects of pore formers on the porosity of the scaffold are examined and optimized. The thermal expansion behavior, electrical conductivities and electrochemical performance of the cathodes are characterized and optimized. A pure perovskite phase is formed after heating at 800 °C by adding a relatively small quantity of glycine as the complexing agent. Polyvinyl butyral is selected as the pore former for the preparation of porous Sm0.2Ce0.8O1.9 (SDC) scaffolds. The thermal expansion coefficient increases slightly from 12.74 × 10-6 K-1 to 13.28 × 10-6 K-1 after infiltrating 20 wt% SSC into the SDC scaffold. The infiltrated cathode with 20 wt% SSC + 80 wt% SDC shows the electrical conductivity of 15 S cm-1 at 700 °C. A well-connected SSC network is formed in the cathode after infiltrating 20 wt% SSC into the SDC scaffold. Cathode polarization resistance values as low as 0.05 Ω cm2, peak power density values as high as 936 mW cm-2 and stable performance throughout 325 h of operation at 700 °C suggest that the cathodes with the 20 wt% SSC-infiltrated SDC are suitable for practical application. However, for the SSC infiltrated into the 8 mol% yttria-stabilized zirconia scaffold, the interfacial reaction continues to occur during the stability test at 700 °C. SDC is preferred as a scaffold for the infiltration of SSC to ensure long-term operational stability.

  9. Bone marrow granulomas in infiltrating lobular breast cancer.

    OpenAIRE

    Kettle, P.; Allen, D C

    1997-01-01

    A 50 year old woman with a history of infiltrating lobular breast carcinoma presented with back pain. Bone scan and magnetic resonance imaging were not conclusive. A bone marrow aspirate appeared normal. A routine trephine biopsy specimen showed granulomas but no obvious infiltration by carcinoma. Immunohistochemical staining with epithelial markers demonstrated carcinoma cells in the trephine specimen. This case illustrates the difficulty of detecting infiltrating lobular carcinoma in bone m...

  10. Manejo quirúrgico conservador del epitelioma basocelular infiltrante del canto interno Conservative surgical management of the basal cell carcinoma infiltrating inner canthus

    Directory of Open Access Journals (Sweden)

    A.J. Abulafia

    2011-03-01

    Full Text Available El epitelioma basocelular es el tumor maligno más frecuente de la piel. Su histogénesis se relaciona con la exposición actínica, por lo que su mayor incidencia se da a nivel de la cara. Normalmente la dermis actúa como factor de resistencia a la invasión tisular del tumor, situación que no se da en ciertas zonas en las que se observa un crecimiento con mayor invasión en profundidad. De estas zonas reviste importancia por su cercanía a órganos vitales el canto interno ocular, sobre todo en lesiones con extensa invasión local, por la disyuntiva del compromiso ocular y la decisión de su conservación o no. Comentamos nuestra experiencia en el tratamiento de lesiones infiltrativas de canto interno, así como la secuencia de estudio y las opciones terapéuticas.Basal cell epithelioma is the most common malignant tumor affecting the skin. It is mainly located in sun-exposed areas of the body surface due to solar actinic radiation. The facial skin is the most exposed, and the one with the highest incidence of these tumors. The dermis normally acts as a barrier against deepening, a fact which does not occur in certain areas. Among these critical sites the inner canthus region has a critical interest due to its proximity to vital organs with doubts about eye involvement and its preservation. We comment our experience in the management of infiltrative tumors of the inner canthus, diagnostic steps and therapeutical alternatives.

  11. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    Science.gov (United States)

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.

  12. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

    Directory of Open Access Journals (Sweden)

    Noah Saederup

    Full Text Available BACKGROUND: Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents. METHODOLOGY/PRINCIPAL FINDINGS: We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia. CONCLUSION/SIGNIFICANCE: These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

  13. Primary anaplastic large T cell lymphoma of central nervous system

    Directory of Open Access Journals (Sweden)

    ZHANG Yan

    2013-01-01

    Full Text Available Background Primary anaplastic large T cell lymphoma (ALCL of central nervous system (CNS can occur in people of all ages, and is usually unrelated with immunodeficiency. It is often misdiagnosed as meningitis, especially tuberculous meningitis, on clinical practice and imaging examination. In pathological diagnosis, the morphological changes of primary ALCL of CNS are similar to the systemic ALCL and the anaplastic lymphoma kinase-1 (ALK-1 can be positive or negative. Being misdiagnosed as meningitis, hormone therapy with glucocorticoid before biopsy is always used, and massive necrosis and a lot of histocyte proliferation and phagocytosis can be found under histological findings. Therefore, when the material is not enough, primary ALCL of CNS is often misdiagnosed as cerebral infarction or malignant histocytosis and so on. This paper reports a case of primary ALCL of CNS and makes a review of relevant literature, so as to summarize the clinical manifestations and elevate the recognition of clinicians and pathologists on this disease. Methods and Results A 12-year-old boy was admitted because of fever, worsening headache, numbness and weakness of right limbs. MRI showed local gyri swelling and abnormal enhancement of pia mater in the right parietal lobe, expanding to the right temporal lobe, and pia mater enhancement in the left parietal lobe. The right temporo-parietal lobe lesion biopsy revealed irregularly shaped tumor cells of large size, rich and eosinophilic cytoplasm and horseshoe-shaped or kidney-shaped nuclei. Immunohistochemical examination showed tumor cells positive for CD3, CD45RO, CD30, ALK-1 and epithelial membrane antigen (EMA, and negative for CD20 and CD79a. Conclusion Primary ALCL of CNS is an extremely rare tumor which is usually misdiagnosed as meningitis according to clinical and imaging examinations. Therefore, for those patients who are considered as meningitis but with poor treatment effect and replase of illness, brain

  14. Yes is a central mediator of cell growth in malignant mesothelioma cells.

    Science.gov (United States)

    Sato, Ayami; Sekine, Miki; Virgona, Nantiga; Ota, Masako; Yano, Tomohiro

    2012-11-01

    The constitutive activation of the Src family kinases (SFKs) has been established as a poor prognostic factor in malignant mesothelioma (MM), however, the family member(s) which contribute to the malignancy have not been defined. This study aimed to identify the SFK member(s) contributing to cell growth using RNA interference in various MM cell lines. Silencing of Yes but not of c-Src or Fyn in MM cells leads to cell growth suppression. This suppressive effect caused by Yes silencing mainly depends on G1 cell cycle arrest and partly the induction of apoptosis. Also, the knockout of Yes induces the inactivation of β-catenin signaling and subsequently decreases the levels of cyclin D necessary for G1-S transition in the cell cycle. In addition, Yes knockout has less effect on cell growth suppression in β-catenin-deficient H28 MM cells compared to other MM cells which express the catenin. Overall, we conclude that Yes is a central mediator for MM cell growth that is not shared with other SFKs such as c-Src.

  15. HIV-1 Tat-induced microgliosis and synaptic damage via interactions between peripheral and central myeloid cells.

    Directory of Open Access Journals (Sweden)

    Shao-Ming Lu

    Full Text Available Despite the ability of combination antiretroviral treatment (cART to reduce viral burden to nearly undetectable levels in cerebrospinal fluid and serum, HIV-1 associated neurocognitive disorders (HAND continue to persist in as many as half the patients living with this disease. There is growing consensus that the actual substrate for HAND is destruction of normal synaptic architecture but the sequence of cellular events that leads to this outcome has never been resolved. To address whether central vs. peripheral myeloid lineage cells contribute to synaptic damage during acute neuroinflammation we injected a single dose of the HIV-1 transactivator of transcription protein (Tat or control vehicle into hippocampus of wild-type or chimeric C57Bl/6 mice genetically marked to distinguish infiltrating and resident immune cells. Between 8-24 hr after injection of Tat, invading CD11b(+ and/or myeloperoxidase-positive leukocytes with granulocyte characteristics were found to engulf both microglia and synaptic structures, and microglia reciprocally engulfed invading leukocytes. By 24 hr, microglial processes were also seen ensheathing dendrites, followed by inclusion of synaptic elements in microglia 7 d after Tat injection, with a durable microgliosis lasting at least 28 d. Thus, central nervous system (CNS exposure to Tat induces early activation of peripheral myeloid lineage cells with phagocytosis of synaptic elements and reciprocal microglial engulfment of peripheral leukocytes, and enduring microgliosis. Our data suggest that a single exposure to a foreign antigen such as HIV-1 Tat can lead to long-lasting disruption of normal neuroimmune homeostasis with deleterious consequences for synaptic architecture, and further suggest a possible mechanism for enduring neuroinflammation in the absence of productive viral replication in the CNS.

  16. Herpes simplex virus-specific T cells infiltrate the cornea of patients with herpetic stromal keratitis: no evidence for autoreactive T cells

    NARCIS (Netherlands)

    L. Remeijer (Lies); C.M. Mooy (Cornelia); A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George)

    2000-01-01

    textabstractPURPOSE: Herpetic stromal keratitis (HSK) is a T-cell-mediated inflammatory disease initiated by a herpes simplex virus (HSV) infection of the cornea. Recently, studies in the HSK mouse model have shown that the immunopathogenic T cells are directed against the HSV prot

  17. Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+ T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Wanshuai Li

    2013-01-01

    Full Text Available Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC cells. Methods. LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days. Results. Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8+ T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon-γ (ifn-γ, perforin-1 (prf-1, and granzyme B (gzmb in CD8+ T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn-γ, prf-1, and gzmb in CD8+ T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8+ T cells. Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8+ T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China.

  18. Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8(+) T Lymphocytes.

    Science.gov (United States)

    Li, Wanshuai; Yang, Yang; Ouyang, Zijun; Zhang, Qi; Wang, Lu; Tao, Feifei; Shu, Yongqian; Gu, Yanhong; Xu, Qiang; Sun, Yang

    2013-01-01

    Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC) cells. Methods. LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days. Results. Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8(+) T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon- γ (ifn- γ ), perforin-1 (prf-1), and granzyme B (gzmb) in CD8(+) T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn- γ , prf-1, and gzmb in CD8(+) T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8(+) T cells. Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8(+) T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China.

  19. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.

    Science.gov (United States)

    Matsumoto, Hirofumi; Thike, Aye Aye; Li, Huihua; Yeong, Joe; Koo, Si-Lin; Dent, Rebecca Alexandra; Tan, Puay Hoon; Iqbal, Jabed

    2016-04-01

    Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.

  20. Structural relationships among central cell and egg apparatus cells of barley as related to transmission of male gametes

    Directory of Open Access Journals (Sweden)

    David D. Cass

    2014-01-01

    Full Text Available Barley embryo sacs were examined using light and electron microscopy before and during fertilization. One synergid degenerates after pollination with loss of nuclear and cytoplasmic organization and cell wall material between synergid and central cell. Some wall between egg and central cell is also lost. After pollen tube discharge into the degenerate synergid, the male gametes leave the synergid entering a pocket of central cell cytoplasm separated from the synergid only by membranes. This could provide for efficient gamete transmission and possible recognition through specific membrane contacts.

  1. LaNi1-xCoxO3-δ (x=0.4 to 0.7) cathodes for solid oxide fuel cells by infiltration

    DEFF Research Database (Denmark)

    Chrzan, Aleksander; Ovtar, Simona; Chen, Ming

    2015-01-01

    Performance of LaNi1-xCoxO3-δ (LNC) (x=0.4 to 0.7) as a cathode in solid oxide fuel cell (SOFC) is evaluated. Symmetrical cathode/electrolyte/cathode cells for electrochemical testing are prepared by infiltration of yttria stabilized zirconia (YSZ) backbone with LNC solutions. It is showed that t...... of the materials is single-phased after heat treatment at 800 °C as they contain residues of La2O3 and La2NiO4-δ....

  2. Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

    Directory of Open Access Journals (Sweden)

    Yu Ri Kim

    2013-01-01

    Full Text Available High doses of acetaminophen (APAP; N-acetyl-p-aminophenol cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg. Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity.

  3. IL-17-producing double-negative T cells are expanded in the peripheral blood, infiltrate the salivary gland and are partially resistant to corticosteroid therapy in patients with Sjögren’s syndrome

    Directory of Open Access Journals (Sweden)

    A. Alunno

    2013-10-01

    Full Text Available A small CD3+ T-cell population, that lacks both CD4 and CD8 molecules, defined as double negative (DN, is expanded in the peripheral blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during lupus nephritis. Since IL-17 production is enhanced in salivary gland infiltrates of patients with primary Sjögren’s syndrome (pSS, we aimed to investigate whether DN T cells may be involved in the pathogenesis of salivary gland damage. Fifteen patients with SS and 15 normal controls (NC were enrolled. Peripheral blood mononuclear cells were stimulated with anti-CD3 antibody and cultured in presence or absence of dexamethasone (Dex. Phenotypic characterization was performed by flow cytometry in freshly isolated cells and after culture. Minor salivary glands (MSG from pSS were processed for immunofluorescence staining. Total circulating DN T cells were increased in pSS compared to NC (4.7±0.4% vs 2.6±0.4%. NC and pSS freshly isolated DN T cells produce consistent amounts of IL-17 (67.7±5.6 in NC vs 69.2±3.3 in pSS. Notably, DN T cells were found in the pSS-MSG infiltrate. Dex was able to down-regulate IL-17 in vitro production in NC (29±2.6% vs 15.2±1.9% vs 13±1.6% and pSS (49±4.8% vs 16±3.8% vs 10.2±0.8% conventional Th17 cells and in DN T cells of NC (80±2.8% vs 3.8±2.1% vs 4.2±1.8%, but not of pSS (81±1.5% vs 85.4±0.8% vs 86.2±1.7%. DN T cells are expanded in pSS PB, produce IL-17 and infiltrate pSS MSG. In pSS, conventional Th17 cells are inhibited by Dex, but DN T cells appear to be resistant to this effect. Taken together, these data suggest a key role of this T-cell subset in the perpetuation of chronic sialoadenitis and eventually in pSS prognosis.

  4. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD.

  5. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  6. [Lung infiltrations in Hodgkin lymphoma].

    Science.gov (United States)

    Ciurea-Löchel, A; Ciurea, A; Stey, C; Pestalozzi, B

    2001-08-02

    We report the case of a young patient presenting with cervical lymphadenopathy and interstitial pulmonary infiltrates due to Hodgkin's Disease. Although lung involvement regressed under chemotherapy, we observed new alveolar infiltrates during treatment. Steroid administration after exclusion of an infectious cause was followed by rapid clinical and radiological improvement, indicating the probable presence of pulmonary bleomycine toxicity.

  7. Proliferative cell types in embryonic lineages of the central complex of the grasshopper Schistocerca gregaria.

    Science.gov (United States)

    Boyan, George; Williams, Leslie; Legl, Andrea; Herbert, Zsofia

    2010-08-01

    The central complex of the grasshopper Schistocerca gregaria develops to completion during embryogenesis. A major cellular contribution to the central complex is from the w, x, y, z lineages of the pars intercerebralis, each of which comprises over 100 cells, making them by far the largest in the embryonic protocerebrum. Our focus has been to find a cellular mechanism that allows such a large number of cell progeny to be generated within a restricted period of time. Immunohistochemical visualization of the chromosomes of mitotically active cells has revealed an almost identical linear array of proliferative cells present simultaneously in each w, x, y, z lineage at 50% of embryogenesis. This array is maintained relatively unchanged until almost 70% of embryogenesis, after which mitotic activity declines and then ceases. The array is absent from smaller lineages of the protocerebrum not associated with the central complex. The proliferative cells are located apically to the zone of ganglion mother cells and amongst the progeny of the neuroblast. Comparisons of cell morphology, immunoreactivity (horseradish peroxidase, repo, Prospero), location in lineages and spindle orientation have allowed us to distinguish the proliferative cells in an array from neuroblasts, ganglion mother cells, neuronal progeny and glia. Our data are consistent with the proliferative cells being secondary (amplifying) progenitors and originating from a specific subtype of ganglion mother cell. We propose a model of the way that neuroblasts, ganglion mother cells and secondary progenitors together produce the large cell numbers found in central complex lineages.

  8. Acute myoinjury induce the intramuscular infiltration of CD8+CTL cells%损伤骨骼肌组织内CD8+T细胞的功能特性

    Institute of Scientific and Technical Information of China (English)

    冯利强; 曾慧君; 刘幸卉; 陈荣; 黄维一; 廖华

    2012-01-01

    目的 分析骨骼肌损伤后CD8+T细胞的渗出及其功能特性.方法 机械挤压法制备小鼠胫骨前肌(TA)损伤模型.免疫组化、免疫荧光检测损伤肌组织内CD8+T细胞的渗出及其可能的CTL功能.结果 HE染色证实机械挤压引发显著的TA肌纤维坏死、退变和再生.损伤肌组织内出现广泛的炎性渗出,损伤后7d(再生初期)可见较多的CD8+T细胞,少量CD8+T细胞共表达Perforin以及IFN-γ.结论 与慢性肌炎的免疫反应相似,急性损伤同样会引发CD8a+T细胞的渗出、活化并具备CTL功能.但这种活化的CD8+ CTL细胞仅短暂出现于肌组织的再生初期.%Objective To investigate the intramuscular infiltration of CD8+ cytotoxic T-cells (CTL cells) after crush myoinjury. Methods Tibialis antierior muscle(TA) crush was performed in C57BIV6 mice. HE staining was used to identify inflammatory reaction,degeneration and regeneration of crushed TA muscle. Immunofluorecence was used to detect pro- and anti- inflammatory cytokines, and the intramuscular infiltration of CTLs in injuried muscle. Results Crush induced significant myofiber necrosis, degeneration and regeneration. Conspicuous mononuclear cell infiltrates were detected at both d4 and d7 after crush injury. At d7 post-injury CTLs expressing perform or IFN-γ were conspicuously detected in crushed muscle where CD8+ T-cells were found in close contact with regenerating myofibers. Conclusions After crush injury, CD8+ T cells infiltrate the injured muscle at regenerating period, and are transiently activated as CTL cells.

  9. Limbal stem cells: Central concepts of corneal epithelial homeostasis

    Institute of Scientific and Technical Information of China (English)

    Jinny; J; Yoon; Salim; Ismail; Trevor; Sherwin

    2014-01-01

    A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent stud-ies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface

  10. Circulating and Tumor-Infiltrating Foxp3+ Regulatory T Cell Subset in Chinese Patients with Extranodal NK/T Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Rou-Jun Peng, Zhou-Feng Huang, Yi-Lan Zhang, Zhong-Yu Yuan, Yi Xia, Wen-Qi Jiang, Yi-Xin Zeng, Jiang Li

    2011-01-01

    Full Text Available Foxp3+ regulatory T lymphocytes (Tregs usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3+ subset in peripheral blood mononuclear cells (PBMCs and tumor tissues from extranodal NK/T cell lymphoma (ENKTL. Our study showed the percentage of Foxp3+ subset from PBMC was significantly higher than that of healthy individuals (P<0.001. The Foxp3+ subset from PBMCs expressed CD45RO, CTLA4, GITR, CCR7, and had an IL-10highIFNγ+TGFβ+IL-2lowIL-17low cytokine secreting phenotype. Interestingly, the existence of EBV antigen-specific CD8+Foxp3+ Tregs was discovered in ENKTL. Furthermore, the high density of Foxp3+ TILs was associated with improved progression-free survival (PFS in ENKTL patients (P<0.05. Collectively, our study implicates that EBV antigens could induce antigen-specific CD8+Foxp3+ Tregs in ENKTL, and Foxp3+ TILs is an independent factor for PFS in ENKTL.

  11. Central nervous system mast cells in peripheral inflammatory nociception

    Directory of Open Access Journals (Sweden)

    Ellmeier Wilfried

    2011-06-01

    Full Text Available Abstract Background Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. Results Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. Conclusion The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

  12. Central giant cell granuloma of the mandibular condyle: Case-report

    OpenAIRE

    Munzenmayer,J; Tapia, P.; Zeballos,J; Martínez, A.; Compan,Á; Urra, A.; Spencer,ML

    2013-01-01

    This case report describes a 19-year-old female patient with a central giant cell granuloma in the left mandibular condyle, treated with en bloc resection and reconstruction with fibula graft. This occurrence is considered very unusual.

  13. 18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan findings in Rosai-Dorfman disease with IgG4-positive plasma cell infiltration mimicking breast malignancy: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Fu Liping

    2012-11-01

    Full Text Available Abstract Introduction Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare benign disorder characterized histologically by lymphatic sinus dilatation due to histiocyte proliferation. Rosai-Dorfman disease accompanied by IgG4+ plasma cell infiltration is an even rarer situation. To the best of our knowledge, no imaging report of fluoro-deoxyglucose positron emission tomography/computed tomography findings of Rosai-Dorfman disease with IgG4+ plasma cell infiltration has been published, although a series of pathological research has focused on this phenomenon. Case presentation We reviewed the 18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan of a 78-year-old Chinese woman with a solid mass that was found in her right breast during a health checkup. 18F-fluoro-deoxyglucose positron emission tomography/computed tomography showed a hypermetabolic nodule in her right breast and slightly heterogeneous increased fluoro-deoxyglucose uptake of the pulmonary nodules, which were histologically proven to be mammary Rosai-Dorfman disease with IgG4+ plasma cell infiltration and pulmonary amyloidosis, respectively. A literature review was performed to gather information on this rare disease process. Conclusions Although distinguishing benign lymphoplasmacytic proliferation from malignancy may be difficult with 18F-fluoro-deoxyglucose positron emission tomography/computed tomography in light of the pattern and intensity of fluoro-deoxyglucose uptake, our case highlights that whole-body positron emission tomography/computed tomography imaging not only can display the extent of the disease to help complete staging but also can provide functional information about disease activity to guide biopsy.

  14. The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells.

    Directory of Open Access Journals (Sweden)

    Conrad von Schubert

    Full Text Available The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

  15. Langerhans cell histiocytosis in monozygotic twins with central diabetes insipidus and hypophyseal masses

    Science.gov (United States)

    Wei, Sung-Tai; Chen, Der-Cherng; Cho, Der-Yang; Lin, Hung-Lin

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a systemic disease mainly affecting children and young adults. It can manifest as single system disorder or multi-system involvement. When the central nervous system is involved, the hypothalamic–pituitary axis is the most common location affected. Herein we report a rare case of Langerhans cell histiocytosis in monozygotic twins both with central diabetes and hypophyseal masses. This is the first report about LCH in monozygotic twins with hypophyseal lesions. PMID:25972939

  16. Differentiation: A Central Topic in Developmental and Cell Biology

    Science.gov (United States)

    Müller, W. A.

    The concept of "differentiation" encompasses all processes leading to differently specialized cell types, beginning with the progressive divergence of developmental pathways and ending with the successive programming and final elaboration of each particular cell type. Guidance and positional information are provided by external cues, by differentially allotted cytoplasmic determinants such as mRNA for transcription factors, and by cascades of intercellular signals. Eventually cell type specific selector genes, such as the muscle cell determining MyoD/myogenin genes and neural key genes (e.g., achaete scute-C, neurogenin), are switched on which control entire sets of subordinate effector genes. In multiplying cells "cell heredity" based on an epigenetic cellular memory enables transmission of the cell type determining program from parental to daughter cells. This memory can be based on autocatalytic self-activation of cell type specific selector genes and on the enduring action of gene groups such as the Polycomb and thrithorax complexes that code for proteins which bind to DNA sequences called cellular memory modules. These modules confer permanent accessibility (potentiation) or inaccessibility (silencing) upon many different gene loci on the chromosomes.

  17. Innate immune responses in central nervous system inflammation

    DEFF Research Database (Denmark)

    Finsen, Bente; Owens, Trevor

    2011-01-01

    In autoimmune diseases of the central nervous system (CNS), innate glial cell responses play a key role in determining the outcome of leukocyte infiltration. Access of leukocytes is controlled via complex interactions with glial components of the blood-brain barrier that include angiotensin II...

  18. Fertilization in Torenia fournieri: actin organization and nuclear behavior in the central cell and primary endosperm

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Studies of the living embryo sacs of Torenia fournieri reveal that the actin cytoskeleton undergoes dramatic changes that correlate with nuclear migration within the central cell and the primary endosperm. Before pollination, actin filaments appear as short bundles randomly distributed in the cortex of the central cell. Two days after anthesis, they become organized into a distinct actin network. At this stage the secondary nucleus, which is located in the central region of the central cell, possesses an associated array of short actin filaments. Soon after pollination, the actin filaments become fragmented in the micropylar end and the secondary nucleus is located next to the egg apparatus. After fertilization, the primary endosperm nucleus moves away from the egg cell and actin filaments reorganize into a prominent network in the cytoplasm of the primary endosperm. Disruption of the actin cytoskeleton with latrunculin A and cytochalasin B indicates that actin is involved in the migration of the nucleus in the central cell. Our data also suggest that the dynamics of actin cytoskeleton may be responsible for the reorganization of the central cell and primary endosperm cytoplasm during fertilization.

  19. Pollution from Urban Stormwater Infiltration

    DEFF Research Database (Denmark)

    Mikkelsen, Peter Steen; Weyer, G.; Berry, C.

    1994-01-01

    , and it is therefore difficult to assess the overall environmental impact. This paper gives a state of the art assessment of the water quality aspects of stormwater infiltration and proposes ways of managing the inherent problems. The major stormwater pollution sources are highlighted and the different processes......Stormwater infiltration in urban areas gives cause for concern with regard to the risk of soil and groundwater pollution. Compared with conventional storm drainage, infiltration introduces different and widely unknown conditions governing the impacts and the fate of the pollutants...

  20. MEAN INFILTRATION SPEED IN A VERTISOL UNDER DIFFERENT TILLAGE SYSTEMS

    Directory of Open Access Journals (Sweden)

    Juan José Martínez Villanueva

    2015-03-01

    Full Text Available Soil compaction is regarded as the most serious environmental problem caused by conventional agriculture. Few studies are concerned with the assessment of soil compaction using infiltration speed, specifically in the Vertisol soil characteristic of the main maize producing area of the Toluca-Atlacomulco Valley in central Mexico. The aim of this research was to examine the effect on infiltration speed and penetration resistance of a Vertisol soil when compacted by wheeled agricultural traffic in three different types of tillage systems: zero, minimal and conventional. Penetration resistance was measured on the wheel track with a portable digital penetrometer, and the mean infiltration speed was determined according to the double cylinder infiltrometer method. The pressure exerted by the number of wheeled traffic passes increased Vertisol soil compaction at 30 cm depth. Even though the benefits of zero tillage were similar to those showed by minimum tillage during the experimental period, minimum tillage reported the highest infiltration speed.

  1. Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance.

    Science.gov (United States)

    Cantaert, Tineke; Schickel, Jean-Nicolas; Bannock, Jason M; Ng, Yen-Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Lavoie, Aubert; Walter, Jolan E; Notarangelo, Luigi D; Al-Herz, Waleed; Kilic, Sara Sebnem; Ochs, Hans D; Nonoyama, Shigeaki; Durandy, Anne; Meffre, Eric

    2015-11-17

    Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells.

  2. Childhood Central Nervous System Germ Cell Tumors Treatment

    Science.gov (United States)

    ... germ cell tumors to form is near the pineal gland and in an area of the brain ... of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal ...

  3. Direct and indirect effects of immune and central nervous system-resident cells on human oligodendrocyte progenitor cell differentiation.

    Science.gov (United States)

    Moore, Craig S; Cui, Qiao-Ling; Warsi, Nebras M; Durafourt, Bryce A; Zorko, Nika; Owen, David R; Antel, Jack P; Bar-Or, Amit

    2015-01-15

    In multiple sclerosis, successful remyelination within the injured CNS is largely dependent on the survival and differentiation of oligodendrocyte progenitor cells. During inflammatory injury, oligodendrocytes and oligodendrocyte progenitor cells within lesion sites are exposed to secreted products derived from both infiltrating immune cell subsets and CNS-resident cells. Such products may be considered either proinflammatory or anti-inflammatory and have the potential to contribute to both injury and repair processes. Within the CNS, astrocytes also contribute significantly to oligodendrocyte biology during development and following inflammatory injury. The overall objective of the current study was to determine how functionally distinct proinflammatory and anti-inflammatory human immune cell subsets, implicated in multiple sclerosis, can directly and/or indirectly (via astrocytes) impact human oligodendrocyte progenitor cell survival and differentiation. Proinflammatory T cell (Th1/Th17) and M1-polarized myeloid cell supernatants had a direct cytotoxic effect on human A2B5(+) neural progenitors, resulting in decreased O4(+) and GalC(+) oligodendrocyte lineage cells. Astrocyte-conditioned media collected from astrocytes pre-exposed to the same proinflammatory supernatants also resulted in decreased oligodendrocyte progenitor cell differentiation without an apparent increase in cell death and was mediated through astrocyte-derived CXCL10, yet this decrease in differentiation was not observed in the more differentiated oligodendrocytes. Th2 and M2 macrophage or microglia supernatants had neither a direct nor an indirect impact on oligodendrocyte progenitor cell differentiation. We conclude that proinflammatory immune cell responses can directly and indirectly (through astrocytes) impact the fate of immature oligodendrocyte-lineage cells, with oligodendrocyte progenitor cells more vulnerable to injury compared with mature oligodendrocytes.

  4. Phosphoinositide 3-kinase/Akt Pathway Mediates Fip1-like1-platelet-derived Growth Factor Receptor α-induced Cell Infiltration and Activation: Possible Molecular Mechanism for the Malignant Phenotype of Chronic Eosinophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-01-01

    Full Text Available The fip1-like1/platelet-derived growth factor receptor-α fusion gene (F/P is responsible for 14-60% cases of hypereosinophilia syndrome (HES, also known as F/P-positive chronic eosinophilic leukemia (F/P(+ CEL. The major pathogenesis of F/P(+ CEL is known to involve migration and activation of mast cells and eosinophils, leading to severe multi-organ dysfunction, but the mechanism was still unclear. Phosphoinositide 3-kinase (PI3K and serine-threonine protein kinase Akt have been reported to be targets of F/P in the F/P-promoted cell proliferation. They are extensively involved in the migration and adhesion of hematopoietic stem/progenitor cells, and also control cell invasion in some leukemias. The PI3K/Akt pathway is involved in eosinophil/neutrophil activation and infiltration; its possible role in regulating F/P induced cytotoxicity and upregulation of A4-integrin in eosinophils, and inducing eosinophil activation through controlling F/P-induced Nuclear factor-kB activity. Akt was recently shown to be stimulated by F/P, synergistically with stem cell factor, resulting in the induction of MCs migration and excessive activation. PI3K/Akt pathway is also a principal mediator of interleukin-5 (IL-5-induced signal transduction promoting eosinophil trafficking and degranulation, whereas IL-5 is a necessary cytokine for F/P-mediated CEL development. We, therefore, propose the hypothesis that the PI3K/Akt pathway might be vital downstream of F/P to induce target cell activation and tissue infiltration, resulting in the malignant phenotype seen in F/P(+ CEL.

  5. Nestin Reporter Transgene Labels Multiple Central Nervous System Precursor Cells

    Directory of Open Access Journals (Sweden)

    Avery S. Walker

    2010-01-01

    Full Text Available Embryonic neuroepithelia and adult subventricular zone (SVZ stem and progenitor cells express nestin. We characterized a transgenic line that expresses enhanced green fluorescent protein (eGFP specified to neural tissue by the second intronic enhancer of the nestin promoter that had several novel features. During embryogenesis, the dorsal telencephalon contained many and the ventral telencephalon few eGFP+ cells. eGFP+ cells were found in postnatal and adult neurogenic regions. eGFP+ cells in the SVZ expressed multiple phenotype markers, glial fibrillary acidic protein, Dlx, and neuroblast-specific molecules suggesting the transgene is expressed through the lineage. eGFP+ cell numbers increased in the SVZ after cortical injury, suggesting this line will be useful in probing postinjury neurogenesis. In non-neurogenic regions, eGFP was strongly expressed in oligodendrocyte progenitors, but not in astrocytes, even when they were reactive. This eGFP+ mouse will facilitate studies of proliferative neuroepithelia and adult neurogenesis, as well as of parenchymal oligodendrocytes.

  6. Upregulation of endothelial cell adhesion molecules characterizes veins close to granulomatous infiltrates in the renal cortex of cats with feline infectious peritonitis and is indirectly triggered by feline infectious peritonitis virus-infected monocytes in vitro.

    Science.gov (United States)

    Acar, Delphine D; Olyslaegers, Dominique A J; Dedeurwaerder, Annelike; Roukaerts, Inge D M; Baetens, Wendy; Van Bockstael, Sebastiaan; De Gryse, Gaëtan M A; Desmarets, Lowiese M B; Nauwynck, Hans J

    2016-10-01

    One of the most characteristic pathological changes in cats that have succumbed to feline infectious peritonitis (FIP) is a multifocal granulomatous phlebitis. Although it is now well established that leukocyte extravasation elicits the inflammation typically associated with FIP lesions, relatively few studies have aimed at elucidating this key pathogenic event. The upregulation of adhesion molecules on the endothelium is a prerequisite for stable leukocyte-endothelial cell (EC) adhesion that necessarily precedes leukocyte diapedesis. Therefore, the present work focused on the expression of the EC adhesion molecules and possible triggers of EC activation during the development of FIP. Immunofluorescence analysis revealed that the endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was elevated in veins close to granulomatous infiltrates in the renal cortex of FIP patients compared to non-infiltrated regions and specimens from healthy cats. Next, we showed that feline venous ECs become activated when exposed to supernatant from feline infectious peritonitis virus (FIPV)-infected monocytes, as indicated by increased adhesion molecule expression. Active viral replication seemed to be required to induce the EC-stimulating activity in monocytes. Finally, adhesion assays revealed an increased adhesion of naive monocytes to ECs treated with supernatant from FIPV-infected monocytes. Taken together, our results strongly indicate that FIPV activates ECs to increase monocyte adhesion by an indirect route, in which proinflammatory factors released from virus-infected monocytes act as key intermediates.

  7. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

    Science.gov (United States)

    Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

    2014-10-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive.

  8. Role of metallothionein-III following central nervous system damage

    DEFF Research Database (Denmark)

    Carrasco, Javier; Penkowa, Milena; Giralt, Mercedes

    2003-01-01

    We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area...... the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process....

  9. Enhanced methane steam reforming activity and electrochemical performance of Ni0.9Fe0.1-supported solid oxide fuel cells with infiltrated Ni-TiO2 particles

    Science.gov (United States)

    Li, Kai; Jia, Lichao; Wang, Xin; Pu, Jian; Chi, Bo; Li, Jian

    2016-01-01

    Ni0.9Fe0.1 alloy-supported solid oxide fuel cells with NiTiO3 (NTO) infiltrated into the cell support from 0 to 4 wt.% are prepared and investigated for CH4 steam reforming activity and electrochemical performance. The infiltrated NiTiO3 is reduced to TiO2-supported Ni particles in H2 at 650 °C. The reforming activity of the Ni0.9Fe0.1-support is increased by the presence of the TiO2-supported Ni particles; 3 wt.% is the optimal value of the added NTO, corresponding to the highest reforming activity, resistance to carbon deposition and electrochemical performance of the cell. Fueled wet CH4 at 100 mL min−1, the cell with 3 wt.% of NTO demonstrates a peak power density of 1.20 W cm−2 and a high limiting current density of 2.83 A cm−2 at 650 °C. It performs steadily for 96 h at 0.4 A cm−2 without the presence of deposited carbon in the Ni0.9Fe0.1-support and functional anode. Five polarization processes are identified by deconvoluting and data-fitting the electrochemical impedance spectra of the cells under the testing conditions; and the addition of TiO2-supported Ni particles into the Ni0.9Fe0.1-support reduces the polarization resistance of the processes ascribed to CH4 steam reforming and gas diffusion in the Ni0.9Fe0.1-support and functional anode. PMID:27775092

  10. [Calcium distribution in the central cell of lettuce (Lactuca sativa L.) before and after pollination].

    Science.gov (United States)

    Qiu, Yi Lan; Liu, Ru Shi; Ye, Lv; Tian, Hui

    2008-02-01

    Potassium antimonite precipitation was used to locate calcium in the central cell of lettuce (Lactuca sativa L.) before and after pollination. At 3d before anthesis, two polar nuclei of central cell separately located at two polarity of the cell, and few calcium precipitates (ppts) appeared in the polar nuclei and cytoplasm, but some ppts in its small vacuoles. At 2d before anthesis, two polar nuclei moved toward the middle of the cell and fused to form a secondary nucleus, and the ppts evidently increased in the nucleus and cytoplasm. At 1d before anthesis, secondary nucleus again moved toward micropylar end and located near the egg to prepare for fertilization. Calcium precipitates were mainly accumulated in the secondary nucleus. After pollination and before fertilization, the distribution of calcium ppts was similar to that before pollination. At 4h after pollination, the central cell was fertilized, and calcium ppts evidently increased in the cell and numerous were accumulated in its nucleus and cytoplasm. At 6h after pollination, the primary endosperm nucleus completed its first division and formed two dissociate endosperm nuclei, and still many calcium precipitates appeared in the nucleus and cytoplasm. With endosperm development, calcium ppts decreased in the endosperm cell. At 1d after emasculated and without pollination, the secondary nucleus of the cell still bordered on the egg and some calcium ppts appeared in the secondary nucleus. The results indicated that the temporal and spatial changes of calcium in the central cell may play an important physiological role during the development of the central cell and endosperm.

  11. Langerhans cell histiocytosis involving central nervous system: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Park, Dong Woo; Lee, Seung Ro; Hahm, Chang Kok; Ju, Kyung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Tae [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1997-01-01

    Langerhans cell histiocytosis(LCH) is a systemic disorder characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system; CNS involvement outside the hypothalamus or pituitary gland is uncommon. We present a case of LCH involving the brainstem, cerebellum, and temporal lobes, and also showing hypothalamic involvement. The lesions were isointense or hypointense on T1WI and hyperintense on T2WI, and showed multifocal enhancing nodules on post-contrast CT and Gd-enhanced MRI.

  12. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Zhenwen Zhang

    2016-01-01

    Full Text Available Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats.

  13. Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

    2016-11-10

    Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

  14. CCR7 deficient inflammatory Dendritic Cells are retained in the Central Nervous System

    Science.gov (United States)

    Clarkson, Benjamin D.; Walker, Alec; Harris, Melissa G.; Rayasam, Aditya; Hsu, Martin; Sandor, Matyas; Fabry, Zsuzsanna

    2017-01-01

    Dendritic cells (DC) accumulate in the CNS during neuroinflammation, yet, how these cells contribute to CNS antigen drainage is still unknown. We have previously shown that after intracerebral injection, antigen-loaded bone marrow DC migrate to deep cervical lymph nodes where they prime antigen-specific T cells and exacerbate experimental autoimmune encephalomyelitis (EAE) in mice. Here, we report that DC migration from brain parenchyma is dependent upon the chemokine receptor CCR7. During EAE, both wild type and CCR7−/− CD11c-eYFP cells infiltrated into the CNS but cells that lacked CCR7 were retained in brain and spinal cord while wild type DC migrated to cervical lymph nodes. Retention of CCR7-deficient CD11c-eYFP cells in the CNS exacerbated EAE. These data are the first to show that CD11chigh DC use CCR7 for migration out of the CNS, and in the absence of this receptor they remain in the CNS in situ and exacerbate EAE. PMID:28216674

  15. Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension.

    Science.gov (United States)

    Pollow, Dennis P; Uhrlaub, Jennifer; Romero-Aleshire, Melissa J; Sandberg, Kathryn; Nikolich-Zugich, Janko; Brooks, Heddwen L; Hay, Meredith

    2014-08-01

    There is extensive evidence that activation of the immune system is both necessary and required for the development of angiotensin II (Ang II)-induced hypertension in males. The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T-cell infiltration during Ang II-induced hypertension is sex dependent. Recombinant activating gene-1 (Rag-1)(-/-) mice, lacking both T and B cells, were used. Male and female Rag-1(-/-) mice received adoptive transfer of male CD3(+) T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mm : Hg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mm : Hg; Phypertension when compared with their male counterparts, and this protection may involve sex differences in the magnitude of T-cell infiltration of the kidney and brain.

  16. Tumor necrosis factor-α-mediated threonine 435 phosphorylation of p65 nuclear factor-κB subunit in endothelial cells induces vasogenic edema and neutrophil infiltration in the rat piriform cortex following status epilepticus

    Directory of Open Access Journals (Sweden)

    Kim Ji-Eun

    2012-01-01

    Full Text Available Abstract Background Status epilepticus (SE induces severe vasogenic edema in the piriform cortex (PC accompanied by neuronal and astroglial damages. To elucidate the mechanism of SE-induced vasogenic edema, we investigated the roles of tumor necrosis factor (TNF-α in blood-brain barrier (BBB disruption during vasogenic edema and its related events in rat epilepsy models provoked by pilocarpine-induced SE. Methods SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, and soluble TNF p55 receptor (sTNFp55R prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunits. Results Following SE, most activated microglia showed strong TNF-α immunoreactivity. In addition, TNF p75 receptor expression was detected in endothelial cells as well as astrocytes. In addition, only p65-Thr435 phosphorylation was increased in endothelial cells accompanied by SMI-71 expression (an endothelial barrier antigen. Neutralization of TNF-α by soluble TNF p55 receptor (sTNFp55R infusion attenuated SE-induced vasogenic edema and neuronal damages via inhibition of p65-Thr435 phosphorylation in endothelial cells. Furthermore, sTNFp55R infusion reduced SE-induced neutrophil infiltration in the PC. Conclusion These findings suggest that impairments of endothelial cell functions via TNF-α-mediated p65-Thr 485 NF-κB phosphorylation may be involved in SE-induced vasogenic edema. Subsequently, vasogenic edema results in extensive neutrophil infiltration and neuronal-astroglial loss.

  17. Shadowing on Apollo 12 Solar Cells and Possible Movement of the ALSEP Central Station

    Science.gov (United States)

    Berman, Paul A.; Williams, David R.

    2014-01-01

    A fortuitous arrangement of a west-facing solar cell and a bracket on the Apollo 12 ALSEP (Apollo Lunar Surface Experiments Package) has allowed us to precisely determine the relative position of the Sun near sunset relative to the Apollo 12 central station over a period of nearly 8 years. The small bracket, mounted on the central station due west of the cell, casts a shadow on the cell near sunset, decreasing the output of the cell proportional to the area of shadow covering the cell. The pattern of shadowing by the bracket gives good agreement with the known change of solar azimuth on a yearly timescale, but the pattern gradually but constantly changed from year-to-year, in a manner inconsistent with the known and changing position of the Sun.

  18. Effects of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell counts.

    Science.gov (United States)

    Gao, Feng; Lin, Tao; Pan, Yingzhe

    2016-09-01

    Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: 10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.

  19. Application of a novel (Pr0.9La0.1)2(Ni0.74Cu0.21Nb0.05)O4+δ-infiltrated BaZr0.1Ce0.7Y0.2O3-δ cathode for high performance protonic ceramic fuel cells

    Science.gov (United States)

    Li, Geng; Jin, Hongyun; Cui, Yuexiao; Gui, Liangqi; He, Beibei; Zhao, Ling

    2017-02-01

    A Ruddlesden-Popper oxide (Pr0.9La0.1)2(Ni0.74Cu0.21Nb0.05)O4+δ (PLNCN)-infiltrated BaZr0.1Ce0.7Y0.2O3-δ (BZCY) is developed as an electrode for protonic ceramic fuel cells (PCFCs). PLNCN nanoparticles are evenly dispersed on the surface of BZCY skeleton by using the infiltration technology. The electrochemical behavior of the PLNCN-infiltrated BZCY electrodes are evaluated in terms of infiltration loading and temperature. The impedance results of symmetric cells suggest that the optimized loading of PLNCN is approximately 46.1 wt%. Power density of the single cell as high as 0.77 W cm-2 is achieved at 700 °C by using the 43.6 wt% PLNCN-infiltrated BZCY cathode, and the cell could be operated without degradation at 600 °C for 200 h; this finding indicates a promising alternative cathode for PCFCs.

  20. Fss/Tbx6 is required for central dermomyotome cell fate in zebrafish

    Directory of Open Access Journals (Sweden)

    Stefanie Elisabeth Windner

    2012-06-01

    The dermomyotome is a pool of progenitor cells on the surface of the myotome. In zebrafish, dermomyotome precursors (anterior border cells, ABCs can be first identified in the anterior portion of recently formed somites. They must be prevented from undergoing terminal differentiation during segmentation, even while mesodermal cells around them respond to signaling cues and differentiate. T-box containing transcription factors regulate many aspects of mesoderm fate including segmentation and somite patterning. The fused somites (fss gene is the zebrafish ortholog of tbx6. We demonstrate that in addition to its requirement for segmentation, fss/tbx6 is also required for the specification of ABCs and subsequently the central dermomyotome. The absence of Tbx6-dependent central dermomyotome cells in fss/tbx6 mutants is spatially coincident with a patterning defect in the myotome. Using transgenic fish with a heat-shock inducible tbx6 gene in the fss/tbx6 mutant background, we further demonstrate that ubiquitous fss/tbx6 expression has spatially distinct effects on recovery of the dermomyotome and segment boundaries, suggesting that the mechanism of Fss/Tbx6 action is distinct with respect to dermomyotome development and segmentation. We propose that Fss/Tbx6 is required for preventing myogenic differentiation of central dermomyotome precursors before and after segmentation and that central dermomyotome cells represent a genetically and functionally distinct subpopulation within the zebrafish dermomyotome.

  1. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  2. Effects of intra-mammary bacterial infection with coagulase negative staphylococci and stage of lactation on shedding of epithelial cells and infiltration of leukocytes into milk: comparison among cows, goats and sheep.

    Science.gov (United States)

    Leitner, Gabriel; Merin, Uzi; Krifucks, Oleg; Blum, Shlomo; Rivas, Ariel L; Silanikove, Nissim

    2012-06-30

    The effects of mammary gland bacterial infection and stage of lactation on leukocyte infiltration into the mammary gland were compared among cows, goats and sheep. Animals were at two stages of lactation: mid or late. In mid-lactation animals, bacterial-free glands and coagulase negative Staphylococcus (CNS)-infected glands were compared. In late lactation only uninfected glands were studied. Of mid-lactation bacteria-free animals, goats had the highest number of leukocytes and % polymorphonuclears (PMNs), whereas sheep had the lowest and leukocytes number in cows were intermediate between sheep and goats. Based on %PMN, two cell clusters were found in sheep, which overlapped with the parallel cell clusters of cows and goats, but with a slightly higher number of leukocytes in each cell cluster. At late lactation, goats had higher values for %PMN and leukocyte numbers in comparison to cows, which had a similar cellular profile to sheep. The cellular immune response to CNS infection was similar for the three animal species, although the number of cells was different, while the basal cell level at mid-lactation and especially at the end of lactation was species specific.

  3. Central nervous system myeloid cells as drug targets: current status and translational challenges.

    Science.gov (United States)

    Biber, Knut; Möller, Thomas; Boddeke, Erik; Prinz, Marco

    2016-02-01

    Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.

  4. IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis

    Science.gov (United States)

    Phares, Timothy W.; DiSano, Krista D.; Hinton, David R.; Hwang, Mihyun; Zajac, Allan J.; Stohlman, Stephen A.; Bergmann, Cornelia C.

    2013-01-01

    Acute coronavirus encephalomyelitis is controlled by T cells while humoral responses suppress virus persistence. This study defines the contribution of interleukin (IL)-21, a regulator of T and B cell function, to central nervous system (CNS) immunity. IL-21 receptor deficiency did not affect peripheral T cell activation or trafficking, but dampened granzyme B, gamma interferon and IL-10 expression by CNS T cells and reduced serum and intrathecal humoral responses. Viral control was already lost prior to humoral CNS responses, but demyelination remained comparable. These data demonstrate a critical role of IL-21 in regulating CNS immunity, sustaining viral persistence and preventing mortality. PMID:23992866

  5. DNA damage-induced cell death: lessons from the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Helena Lobo Borges; Rafael Linden; Jean YJ Wang

    2008-01-01

    DNA damage can, but does not always, induce cell death. While several pathways linking DNA damage signals to mitochondria-dependent and -independent death machineries have been elucidated, the connectivity of these pathways is subject to regulation by multiple other factors that are not well understood. We have proposed two conceptual models to explain the delayed and variable cell death response to DNA damage: integrative surveillance versus autonomous pathways. In this review, we discuss how these two models may explain the in vivo regulation of cell death induced by ionizing radiation (IR) in the developing central nervous system, where the death response is regulated by radiation dose, cell cycle status and neuronal development.

  6. Culturing and expansion of "clinical grade" precursors cells from the fetal human central nervous system.

    Science.gov (United States)

    Gelati, Maurizio; Profico, Daniela; Projetti-Pensi, Massimo; Muzi, Gianmarco; Sgaravizzi, Giada; Vescovi, Angelo Luigi

    2013-01-01

    NSCs have been demonstrated to be very useful in grafts into the mammalian central nervous system to investigate the exploitation of NSC for the therapy of neurodegenerative disorders in animal models of neurodegenerative diseases. To push cell therapy in CNS on stage of clinical application, it is necessary to establish a continuous and standardized, clinical grade (i.e., produced following the good manufacturing practice guidelines) human neural stem cell lines. In this chapter, we illustrate some of the protocols routinely used into our GMP cell bank for the production of "clinical grade" human neural stem cell lines.

  7. Study of molecular mechanism on PESV in inhibiting acute leukemic cell extramedullary infiltration and transmutation%蝎毒多肽干预急性白血病髓外浸润传变的机制

    Institute of Scientific and Technical Information of China (English)

    郝征; 杨文华

    2012-01-01

    Objective: To investigate the peptide extracts from scorpion venom (PESVs) interfering in urokinase-type PA(uPA) and its receptor, the matrix metalloproteinase2(MMP2), matrix metalloproteinase9(MMP9) expression in leukemia-NOD/SCID Mice, and to research the mechanism of PESV inhibiting the multiplication and infiltration of leukemic cells. Methods: To begin with, bone marrow mononuclear cells of leukemia patients were injected into NOD/SCID mice, irradiated 270 cGy on body by 137Cs beforehand, in order to establish the animal model of outer marrow infiltration of human leukemia in NOD/SCID mice. What's more, randomly to divide the mice of model establishment into four groups. Group Ⅰ-Ⅲ were respectively cured by the peptide extract from scorpion venom (PESV) with different concentrations and Group Ⅳ was the model group injected by the physiological saline water. Group Ⅴ was taken as control. Finally, To kill these mice after four weeks and to use Real-time PCR method to examine MMP2, MMP9 mRNA expression in mice, simultaneously to use western blot method to examine MMP2, MMP9 protein expression. Furthermore, to use ELISA method to examine uPA and uPAR expression in mice's blood serum. Results: The PESV, anticancer peptide in east asian pliers scorpion poisonous, has good inhibitory role in leukemic cell multiplication and infiltration, which effectively suppress the MMP2, MMP9 mRNA and protein expression and inhibit the uPA and its receptor in leukemia-NOD/SCID mice. The effect of inhibiting them was related to PESV concentration. Conclusion: The PESV has good role in inhibiting acute leukemic cell extramedullary infiltration and transmutation by influencing ECM degradation system.%目的:观察蝎毒多肽(PESV)对人白血病NOD/SCID小鼠髓外浸润模型体内uPA、uPAR、MMP2、MMP9表达的影响,探讨PESV干预急性白血病髓外浸润传变的机制.方法:首先选取急性白血病患者骨髓单个核细胞注入经过铯-137源照射的NOD

  8. The neurosteroid allopregnanolone modulates specific functions in central and peripheral glial cells

    Directory of Open Access Journals (Sweden)

    Alessandro eFaroni

    2011-12-01

    Full Text Available Since the first observations on the existence of neurosteroids in the 1980’s, our understanding of the importance of these endogenous steroids in the control of the central and peripheral nervous system has increased progressively. Although most of the observations were made in neuronal cells, equally important are the effects that neurosteroids exert on glial cells. Among the different classes of neurosteroids acting on glial cells, the progesterone 5α-3α metabolite, allopregnanolone, displays a particular mechanism of action involving primarily the modulation of classic GABA receptors. In this review, we focus our attention on allopregnanolone because its effects on the physiology of glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues.

  9. Production of Lentiviral Vectors for Transducing Cells from the Central Nervous System

    OpenAIRE

    Li, Mingjie; Husic, Nada; Lin, Ying; Snider, B. Joy

    2012-01-01

    Efficient gene delivery in the central nervous system (CNS) is important in studying gene functions, modeling neurological diseases and developing therapeutic approaches. Lentiviral vectors are attractive tools in transduction of neurons and other cell types in CNS as they transduce both dividing and non-dividing cells, support sustained expression of transgenes, and have relatively large packaging capacity and low toxicity 1-3. Lentiviral vectors have been successfully used in transducing ma...

  10. A Central Composite Face-Centered Design for Parameters Estimation of PEM Fuel Cell Electrochemical Model

    OpenAIRE

    Khaled MAMMAR; CHAKER, Abdelkader

    2013-01-01

    In this paper, a new approach based on Experimental of design methodology (DoE) is used to estimate the optimal of unknown model parameters proton exchange membrane fuel cell (PEMFC). This proposed approach combines the central composite face-centered (CCF) and numerical PEMFC electrochemical. Simulation results obtained using electrochemical model help to predict the cell voltage in terms of inlet partial pressures of hydrogen and oxygen, stack temperature, and operating current. The value o...

  11. Central diabetes insipidus: Is it Langerhans cell histiocytosis of the pituitary stalk? A diagnostic pitfall.

    NARCIS (Netherlands)

    Prosch, H.; Grois, N.; Bökkerink, J.P.M.; Prayer, D.; Leuschner, I.; Minkov, M.; Gadner, H.

    2006-01-01

    Central diabetes insipidus (CDI) is a rare disorder that may be caused by a variety of diseases. In pediatric and adolescent patients the most common causes for CDI are Langerhans cell histiocytosis (LCH) and germinoma. To avoid a potentially hazardous biopsy of the hypothalamic pituitary region it

  12. Dilemma in the management of central giant cell granuloma of maxilla

    Directory of Open Access Journals (Sweden)

    Rajendra B Metgudmath

    2013-01-01

    Full Text Available Central giant cell granuloma is a rare benign lesion occasionally causing severe local destruction. Surgical excision is the main stay of treatment. As this lesion is unusual in clinical practice and is associated with dilemma in the treatment, we present here a case report with review of the literature concerning management.

  13. High Performance Infiltrated Backbones for Cathode-Supported SOFC's

    DEFF Research Database (Denmark)

    Gil, Vanesa; Kammer Hansen, Kent

    2014-01-01

    The concept of using highly ionic conducting backbones with subsequent infiltration of electronically conducting particles has widely been used to develop alternative anode-supported SOFC's. In this work, the idea was to develop infiltrated backbones as an alternative design based on cathode......-supported SOFC. The cathodes are obtained by infiltrating LSM into a sintered either thick (300 μm) yttria stabilized zirconia (YSZ) backbone or a thin YSZ backbone (10-15 μm) integrated onto a thick (300 μm) porous strontium substituted lanthanum manganite (LSM) and YSZ composite. Fabrication challenges...... printed symmetrical cells. Samples with LSM/YSZ composite and YSZ backbones made with graphite+PMMA as pore formers exhibited comparable Rp values to the screen printed LSM/YSZ cathode. This route was chosen as the best to fabricate the cathode supported cells. SEM micrograph of a cathode supported cell...

  14. Intracerebroventricular infusions of TNF-alpha preferentially recruit blood lymphocytes and induce a perivascular leukocyte infiltrate.

    Science.gov (United States)

    Seabrook, T J; Hay, J B

    2001-02-01

    Tumour necrosis factor (TNF)-alpha is important in several central nervous system (CNS) inflammatory diseases, however, its role in the recruitment of leukocytes into the cerebral spinal fluid (CSF) and CNS is incompletely understood. Therefore, we examined the effect of intracerebroventricular (icv) and parenchymal infusions of TNF-alpha on the type of leukocyte, the pool and subset of lymphocytes recruited into CSF and brain parenchyma. Parenchymal injections of 500 ng of recombinant human TNF-alpha did not induce inflammation, whereas an icv infusion of TNF-alpha caused CSF leuckocytosis and a perivascular infiltrate. Twenty-four hours after the icv infusion neutrophils predominated, with CD4+ T cells being the major lymphocyte subset in CSF. By 48 h lymphocytes were the dominant cell type with CD8+ cells surpassing CD4+ cells in both the CSF and the perivascular infiltrate. The labeled recirculating lymphocyte pool prevailed in normal CSF, but after the infusion of TNF-alpha, the blood pool of lymphocytes was preferentially recruited. These results have implications for the immune surveillance of the CNS.

  15. T-cell receptor v-alpha and v-Beta gene usage in interleukin-2-cultured tumor-infiltrating lymphocytes from patients with breast-cancer

    DEFF Research Database (Denmark)

    Andersen, E; Scholler, J; Straten, P;

    1994-01-01

    surface through the T cell receptor (TCR) complex. We have studied the phenotype, cytotoxicity, and expression of TCR variable (V) alpha and beta chain on in vitro IL-2-cultured TIL isolated from primary malignant breast tumors from 11 patients. 10/11 cultures were dominated by CD4(+) (T-helper) cells....... The different TIL cultures exhibited varying levels of cytotoxicity against the natural killer (NK)-sensitive cell line K562 and breast cancer cell line T47D. The level of clonality, as measured by PCR-based analyses of usage of the different V segments was low, as only a few tumors showed patterns...... of restricted V gene expression. The mean number of V alpha segments per TIL culture was higher than the number of V beta segments per culture. A significant negative correlation was observed between the number of CD4+ cells and the number of V beta segments per culture, and no other correlations between...

  16. Primary central nervous system peripheral T-cell lymphoma in a child.

    Science.gov (United States)

    Gualco, Gabriela; Wludarski, Sheila; Hayashi-Silva, Luciana; Medeiros Filho, Plinio; Veras, Geni; Bacchi, Carlos Eduardo

    2010-01-01

    A 10-year-old Caucasian boy was admitted to the hospital with a 3-month history of headache, vomiting, ataxia, and right amaurosis. A magnetic resonance imaging (MRI) showed a solid, expansive, parasagittal mass in the right parietal hemisphere that extended sagitally to include the optical chiasm. The lesion was considered unresectable. Histology and immunophenotyping of biopsy tissue revealed characteristics of peripheral T-cell lymphoma. No other anatomical region, including bone marrow, was compromised. Primary T-cell lymphomas of the central nervous system are rare, especially in childhood. Here, we describe the rapidly deteriorating and fatal clinical course of a boy with a primary T-cell lymphoma in the central nervous system.

  17. Modelling the spatial organization of cell proliferation in the developing central nervous system

    CERN Document Server

    Clairambault, Jean; Perthame, Benoit; Rapacioli, Melina; Rofman, Edmundo; Verdes, Rafael

    2010-01-01

    How far is neuroepithelial cell proliferation in the developing central nervous system a deterministic process? Or, to put it in a more precise way, how accurately can it be described by a deterministic mathematical model? To provide tracks to answer this question, a deterministic system of transport and diffusion partial differential equations, both physiologically and spatially structured, is introduced as a model to describe the spatially organized process of cell proliferation during the development of the central nervous system. As an initial step towards dealing with the three-dimensional case, a unidimensional version of the model is presented. Numerical analysis and numerical tests are performed. In this work we also achieve a first experimental validation of the proposed model, by using cell proliferation data recorded from histological sections obtained during the development of the optic tectum in the chick embryo.

  18. Myeloid and T Cell-Derived TNF Protects against Central Nervous System Tuberculosis

    Science.gov (United States)

    Hsu, Nai-Jen; Francisco, Ngiambudulu M.; Keeton, Roanne; Allie, Nasiema; Quesniaux, Valérie F. J.; Ryffel, Bernhard; Jacobs, Muazzam

    2017-01-01

    Tuberculosis of the central nervous system (CNS-TB) is a devastating complication of tuberculosis, and tumor necrosis factor (TNF) is crucial for innate immunity and controlling the infection. TNF is produced by many cell types upon activation, in particularly the myeloid and T cells during neuroinflammation. Here we used mice with TNF ablation targeted to myeloid and T cell (MT-TNF−/−) to assess the contribution of myeloid and T cell-derived TNF in immune responses during CNS-TB. These mice exhibited impaired innate immunity and high susceptibility to cerebral Mycobacterium tuberculosis infection, a similar phenotype to complete TNF-deficient mice. Further, MT-TNF−/− mice were not able to control T cell responses and cytokine/chemokine production. Thus, our data suggested that collective TNF production by both myeloid and T cells are required to provide overall protective immunity against CNS-TB infection. PMID:28280495

  19. Infectious complications associated with the use of central venous catheters in patients undergoing hematopoietic stem cell transplantation.

    Science.gov (United States)

    Martinho, Gláucia Helena; Romanelli, Roberta M C; Teixeira, Gustavo Machado; Macedo, Antonio V; Chaia, Juliana M C; Nobre, Vandack

    2013-07-01

    In this prospective, observational study, we sought to investigate the incidence, risk factors, and outcomes of central venous catheter-associated infection in 56 patients admitted for hematopoietic stem cell transplantation. In multivariate analysis, we found a 7-fold higher risk of central line-associated bloodstream infection with central venous catheter insertion in the internal jugular vein as compared with the subclavian access. Patients with central line-associated bloodstream infection had a higher incidence of acute renal failure.

  20. Study on Compressive Behavior of Open-cell Aluminum Foam by Gypsum Mould Infiltrating Casting%石膏型渗流法制备的开孔泡沫铝的压缩行为研究

    Institute of Scientific and Technical Information of China (English)

    吴进; 程和法; 黄笑梅; 张燕瑰; 胡志君

    2011-01-01

    本文采用可溶石膏型预制块,通过加压渗流的方法制备了泡沫纯铝、泡沫ZL101合金和泡沫ZL102合金,并通过准静态压缩实验研究了3种不同基体材料的泡沫铝的压缩行为及吸能性能.结果表明:通过石膏型渗流法制备的开孔泡沫铝合金的孔隙率可以达到85%~93.5%;泡沫铝基体材料的力学性能对泡沫铝压缩力学性能有重要影响;泡沫ZL101合金能够吸收最多的能量,且在较大的应力、应变范围内对材料起到缓冲保护作用.%The polymeric reticular sponge was choosen as the mother plate to make the soluble gypsum mould,and after that, through infiltrating casting to fabricate three kinds of open-cell aluminum foam, which are pure aluminum foam, ZL101 aluminum alloy foam and ZL102 aluminum alloy foam. The compressive behaviors and energy-absorption capacities of those different kinds of foams were investigated by the quasi-static compression test. The experimental results indicate that the porosity of the aluminum foams made by the gypsum mould infiltrating casting are 85%~93. 5%;The matrix properties have notable effects on the mechanical behaviors of foams;The ZL101 aluminum alloy foam can absorb the most energy and also can protect the materials in the larger ranges of stress and strain.

  1. BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance.

    Science.gov (United States)

    Kuraoka, Masayuki; Snowden, Pilar B; Nojima, Takuya; Verkoczy, Laurent; Haynes, Barton F; Kitamura, Daisuke; Kelsoe, Garnett

    2017-02-14

    Activation-induced cytidine deaminase (AID) is required to purge autoreactive immature and transitional-1 (immature/T1) B cells at the first tolerance checkpoint, but how AID selectively removes self-reactive B cells is unclear. We now show that B cell antigen receptor (BCR) and endosomal Toll-like receptor (TLR) signals synergize to elicit high levels of AID expression in immature/T1 B cells. This synergy is restricted to ligands for endocytic TLR and requires phospholipase-D activation, endosomal acidification, and MyD88. The first checkpoint is significantly impaired in AID- or MyD88-deficient mice and in mice doubly heterozygous for AID and MyD88, suggesting interaction of these factors in central B cell tolerance. Moreover, administration of chloroquine, an inhibitor of endosomal acidification, results in a failure to remove autoreactive immature/T1 B cells in mice. We propose that a BCR/TLR pathway coordinately establishes central tolerance by hyper-activating AID in immature/T1 B cells that bind ligands for endosomal TLRs.

  2. Diffuse pulmonary infiltrates in immunocompromised patients

    NARCIS (Netherlands)

    Fijen, JW; van der Werf, TS; Ligtenberg, JJM; Tulleken, JE; Zijlstra, JG

    1999-01-01

    The differential diagnosis of bilateral interstitial pulmonary infiltrates in immunocompromised patients is very extensive. We describe two immunocompromised patients with diffuse pulmonary infiltrative changes. Bronchoscopic bronchoalveolar lavage after orotracheal intubation using topical anaesthe

  3. GROUND WATER CONTAMINATION POTENTIAL FROM STORMWATER INFILTRATION

    Science.gov (United States)

    Prior to urbanization, ground water recharge resulted from infiltration of precipitation through pervious surfaces, including grasslands and woods. This infiltration water was relatively uncontaminated. With urbanization, the permeable soil surface area through which recharge by...

  4. Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

    Institute of Scientific and Technical Information of China (English)

    Sen Yang; Yi-Ping Li; Wei Chen; Liang Hao; Matthew McConnell; Xuedong Zhou; Min Wang; Yan Zhang; John D. Mountz; Michael Reddy; Paul D. Eleazer

    2013-01-01

    Regulator of G-protein Signaling 10 (Rgs10) plays an important function in osteoclast differentiation. However, the role of Rgs10 in immune cells and inflammatory responses, which activate osteoclasts in inflam-matory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus (AAV-) mediated RNAi (AAV-shRNA-Rgs10) knockdown approach to study Rgs10’s function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgs10 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and acti-vation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.

  5. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

    Science.gov (United States)

    Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

    2014-09-28

    Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted.

  6. MelanA-negative spindle-cell associated melanoma, a distinct inflammatory phenotype correlated with dense infiltration of CD163 macrophages and loss of E-cadherin

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Steiniche, Torben; Damsgaard, Tine E

    2015-01-01

    MelanA is a known melanocyte marker and is important in melanoma diagnostics. Some tumours, however, show loss of MelanA expression and may therefore be difficult to distinguish from tumours of mesenchymal origin. Pure spindle-cell melanoma is a rare event, and little is known about its biological...

  7. Intratumoral Interleukin-21 Increases Antitumor Immunity, Tumor-infiltrating CD8(+) T-cell Density and Activity, and Enlarges Draining Lymph Nodes

    DEFF Research Database (Denmark)

    Sondergaard, H.; Galsgaard, E.D.; Bartholomaeussen, M.

    2010-01-01

    Interleukin (IL)-21 is a novel cytokine in clinical development for the treatment of cancer. In this study, we have compared the efficacy of subcutaneous and intratumoral (IT) administration of IL-21 protein in two syngeneic mouse tumor models, RenCa renal cell carcinoma and B16 melanoma, and inv...

  8. Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy

    DEFF Research Database (Denmark)

    Thygesen, P; Hougen, H P; Christensen, H B;

    1990-01-01

    Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an ...

  9. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment

    NARCIS (Netherlands)

    A.W.R. van Kuijk; P. Reinders-Blankert; T.J.M. Smeets; B.A.C. Dijkmans; P.P. Tak

    2006-01-01

    Background: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis ( PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. Objective: To investigate extensively the features of cell i

  10. 多西环素对碱烧伤大鼠角膜炎症细胞浸润的抑制作用%Doxycycline inhibits the infiltration of inflammatory cells in rat alkali burn corneas

    Institute of Scientific and Technical Information of China (English)

    赵静博; 邹文进; 付馨余

    2013-01-01

    AIM: To investigate the inhibited effect of Doxycycline on the infiltration of inflammatory cells in rat alkali burn corneas.METHODS: Corneas of 32 SD rats were injured with 1 mol/L NaOH, then divided into two groups: control and doxycycline - treated. All agents were administered topically 4 times daily. Slit - lamp microscope was performed and inflammatory index was calculated at 3, 7, 14 and 21 days after injury. Then 4 rats were randomly sacrificed and each cornea was divided into two parts, one for histopathology, the other for ICAM - 1 ELISA assay.RESULTS:ln control group, the inflammatory index and the number of inflammatory cell was higher than the doxycycline-treated dramatically at all time points ( P< 0.05). Compared with control group, corneal ICAM - 1 expression decreased significantly in doxycycline-treated group at all time points( P < 0.05).CONCLUSION: Doxycycline may inhibit inflammatory cell infiltration by down-regulating ICAM-1 expression.%目的:观察多西环素对碱烧伤大鼠角膜炎症细胞浸润的抑制作用.方法:健康SD大鼠32只,随机分为对照组、多西环素组,每组16只大鼠.建立角膜碱烧伤模型后,多西环素组予3g/L多西环素眼液点眼,对照组予眼液溶媒点眼.分别于碱烧伤后第3,7,14,21d观察计算炎症指数,角膜取材后进行病理切片及炎症细胞计数,行ICAM-1的ELISA检测.结果:多西环素组各时间点结膜充血、角膜水肿较对照组轻,炎症指数均明显低于对照组,差异有统计学意义(P< 0.05).多西环素组各时间点炎症细胞计数少于对照组(P< 0.05).多西环素组各时间点大鼠角膜的ICAM-1表达低于对照组(P<0.05).结论:多西环素可以抑制碱烧伤大鼠角膜的炎症细胞浸润,其机制可能是抑制ICAM-1的表达.

  11. Infiltration of local immune cells in the sow reproductive tracts after intra-uterine and deep intra-uterine insemination with a reduced number of spermatozoa is less than conventional artificial insemination.

    Science.gov (United States)

    Tummaruk, Padet; Tienthai, Paisan

    2011-05-01

    The present study investigated the infiltration of leukocyte subpopulations in the utero-tubal junction (UTJ) and each part of the oviducts at about 24 hr after intra-uterine insemination (IUI) and deep intra-uterine insemination (DIUI) compared to conventional artificial insemination (CAI) in sows. Fifteen crossbred Landrace x Yorkshire multiparous sows were used (CAI, n=5; IUI, n=5; DIUI, n=5). The sperm dose contained 3,000 × 10(6) (100 ml), 1,000 × 10(6) (50 ml) and 150 × 10(6) (5 ml) motile spermatozoa for CAI, IUI and DIUI, respectively. The sows were inseminated with extended fresh semen at 6 to 8 hr prior to the expected time of ovulation. At 25.2 ± 1.6 hr after insemination, the oviducts and the UTJ were collected. The tissue samples of UTJ, caudal isthmus, cranial isthmus and ampulla were transversely cut to a thickness of 5 µm and stained with H&E. The total numbers of lymphocytes, neutrophils, macrophages, eosinophils and plasma cells were determined under light microscope. It was found that the numbers of lymphocytes, eosinophils and macrophages after CAI, IUI and DIUI were not significantly different (P>0.1) in both epithelial and sub-epithelial connective tissue layer of the UTJ, caudal isthmus, cranial isthmus and ampulla. Intra-epithelial neutrophils in the UTJ were higher than cranial isthmus (P<0.05) and ampulla (P<0.05). In the UTJ, the intra-epithelial neutrophil in the CAI group was higher than DIUI group (P<0.01). Plasma cells in sub-epithelial layer of the endosalpinx in the CAI group were higher than DIUI group (P<0.05) and tended to be higher than the IUI group (P=0.08). In conclusion, compared to CAI, IUI and DIUI do not influence the infiltration of lymphocytes, macrophages and eosinophils in the UTJ and the oviduct prior to fertilization. But a lower number of neutrophils in the intra-epithelial layer of the UTJ and plasma cells in the sub-epithelial layers of the oviduct was observed in the DIUI group compared to CAI.

  12. Suppression of Brain Mast Cells Degranulation Inhibits Microglial Activation and Central Nervous System Inflammation.

    Science.gov (United States)

    Dong, Hongquan; Zhang, Xiang; Wang, Yiming; Zhou, Xiqiao; Qian, Yanning; Zhang, Shu

    2017-03-01

    Brain inflammation has a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells are the "first responder" in the injury rather than microglia. Functional aspects of mast cell-microglia interactions remain poorly understood. Our results demonstrated that site-directed injection of the "mast cell degranulator" compound 48/80 (C48/80) in the hypothalamus induced mast cell degranulation, microglial activation, and inflammatory factor production, which initiated the acute brain inflammatory response. "Mast cell stabilizer" disodium cromoglycate (cromolyn) inhibited this effect, including decrease of inflammatory cytokines, reduced microglial activation, inhibition of MAPK and AKT pathways, and repression of protein expression of histamine receptor 1 (H1R), histamine receptor 4 (H4R), protease-activated receptor 2 (PAR2), and toll-like receptor 4 (TLR4) in microglia. We also demonstrated that C48/80 had no effect on microglial activation in mast cell-deficient Kit(W-sh/W-sh) mice. These results implicate that activated brain mast cells trigger microglial activation and stabilization of mast cell inhibits microglial activation-induced central nervous system (CNS) inflammation. Interactions between mast cells and microglia could constitute a new and unique therapeutic target for CNS immune inflammation-related diseases.

  13. Study on development and localization of CTGF-immunoreactive cells in central nervous system of rats

    Institute of Scientific and Technical Information of China (English)

    SU Bing-yin; CAI Wen-qin; ZHANNG Cheng-gang; B.Perbal

    2001-01-01

    Objective: To study the development of connective tissue growth factor(CTGF) immunoreactive cells in the central nervous system (CNS) of E8-P300 rats. Methods: Immunocytochemistry was employed in our study. Results: No CTGF-immunoreactive cells were detected in the CNS of rats during prenatal stages. A few of CTGF-positive cells were detected in the early postnatal stage. However, the positive cells increased gradually in later stages. CTGF-immunoreactive cells widely distributed in the CNS of rats in the first 30 to 60 days postnatally, and the density of immunoreactive products was the highest in these days. The number and staining intensity of CTGF-positive cells decreased and their area of distribution diminished gradually with age. The positive cells included neurons mainly located in the cingulate cortex,striatum, hippocampus, hypothalamus and cerebellum, and astrocytes in white matter of the spinal cord and ependymal cells of the brain. Most of CTGF-immunoreactive cells were quite big in size with a long process. Conclusion: CTGF-immunoreactive cells were found in the CNS of rats, and their numbers and positive signal decreased with the age.

  14. Dental pulp stem cells and their potential roles in central nervous system regeneration and repair.

    Science.gov (United States)

    Young, Fraser; Sloan, Alastair; Song, Bing

    2013-11-01

    Functional recovery from injuries to the brain or spinal cord represents a major clinical challenge. The transplantation of stem cells, traditionally isolated from embryonic tissue, may help to reduce damage following such events and promote regeneration and repair through both direct cell replacement and neurotrophic mechanisms. However, the therapeutic potential of using embryonic stem/progenitor cells is significantly restricted by the availability of embryonic tissues and associated ethical issues. Populations of stem cells reside within the dental pulp, representing an alternative source of cells that can be isolated with minimal invasiveness, and thus should illicit fewer moral objections, as a replacement for embryonic/fetal-derived stem cells. Here we discuss the similarities between dental pulp stem cells (DPSCs) and the endogenous stem cells of the central nervous system (CNS) and their ability to differentiate into neuronal cell types. We also consider in vitro and in vivo studies demonstrating the ability of DPSCs to help protect against and repair neuronal damage, suggesting that dental pulp may provide a viable alternative source of stem cells for replacement therapy following CNS damage.

  15. Experimental study on central nervous toxicity of 'misonidazole' a hypoxic cell radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, I. (Gunma Univ., Maebashi (Japan). School of Medicine)

    1981-11-01

    'Misonidazole', a radiosensitizer for hypoxic cells is expected to be applied to the treatment of malignant tumors, but its side effect becomes a subject of study, because its effective dose is close to its lethal dose. The author performed experiments with mice on the central nervous toxicity, which is the most lethal of the side effects of Misonidazole, with the following results; 1. The abrupt death seen after the administration of a large dose of Misonidazole was attributable to the central nervous toxicity. LD/sub 50/ for d.d. strain mouse was 1.55 mg per body weight g. 2. The used mice always developed convulsion before death. But the administration of anticonvulsant failed to free them from death. 3. Autopsy findings were such abnormal ones as the degeneration and exfoliation of nerve cells and diapedetic focus. After sacrifice, however, no findings indicative of disturbance of central nerve could be detected. 4. Misonidazole, even in a small divided dose, left intracerebral retention, though slightly, indicating that its accumulation in the brain would be increased with increase in the dose. 5. The disturbance of central nerve was not exacerbated by the whole brain irradiation with Misonidazole.

  16. Opposing roles for CD34 in B16 melanoma tumor growth alter early stage vasculature and late stage immune cell infiltration.

    Directory of Open Access Journals (Sweden)

    Steven Maltby

    Full Text Available Tumor growth and metastasis are determined by the complex interplay of factors, including those intrinsic to tumor cells and extrinsic factors associated with the tumor microenvironment. Our previous work demonstrated key roles for CD34 in the maintenance of vascular integrity and eosinophil and mast cell homing. Since both of these functions affect tumor development, we characterized the effect of CD34 ablation on tumor growth using the B16F1 melanoma model. Intriguingly, we found that CD34 plays a biphasic role in tumor progression. In early growth, both subcutaneous-injected tumors and intravenous-injected lung metastases grew more slowly in Cd34(-/- mice. This correlated with abnormal vessel morphology and increased vascular permeability in these mice. Bone marrow transplantation experiments confirmed that this reflects a non-hematopoietic function of CD34. At later stages, subcutaneous tumor growth was accelerated in Cd34(-/- mice and surpassed growth in wildtype mice. Bone marrow chimera experiments demonstrated this difference was due to a hematopoietic function for CD34 and, correspondingly we found reduced intra-tumor mast cell numbers in Cd34(-/- mice. In aggregate, our analysis reveals a novel role for CD34 in both early and late tumor growth and provides novel insights into the role of the tumor microenvironment in tumor progression.

  17. Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Li-min Xu

    Full Text Available All-trans retinoic acid (ATRA is a revolutionary agent for acute promyelocytic leukemia (APL treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1 expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1β secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.

  18. Neural stem cells and strategies for the regeneration of the central nervous system

    OpenAIRE

    Okano, Hideyuki

    2010-01-01

    The adult mammalian central nervous system (CNS), especially that of adult humans, is a representative example of organs that do not regenerate. However, increasing interest has focused on the development of innovative therapeutic methods that aim to regenerate damaged CNS tissue by taking advantage of recent advances in stem cell and neuroscience research. In fact, the recapitulation of normal neural development has become a vital strategy for CNS regeneration. Normal CNS development is init...

  19. Herpesvirus-Associated Central Nervous System Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    2013-01-01

    Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesv...

  20. SURGICAL TREATMENT AND RECONSTRUCTION FOR CENTRAL GIANT CELL GRANULOMA OF MANDIBLE - case report and literature review.

    Directory of Open Access Journals (Sweden)

    Elitsa G. Deliverska

    2013-11-01

    Full Text Available Introduction: Central giant cell granuloma (CGCG is a benign aggressive destructive osteolytic lesion of osteoclastic origin. The central giant cell granuloma is often found in the mandible, anterior to the first molars. It most commonly occurs in patients under the age of 30, with a clear female prevalencePurpose: To present a case of CGCG of the lower jaw in Department of Oral and maxillofacial surgery, University Hospital "St. Anna". Although en bloc resection provides the lowest recurrence rate, only a few single case reports describe the use of this technique followed by reconstruction with autogenous bone grafts.Material and methods: The medical history of a 28 years patient with a large central giant cell granuloma in the mandible. Biopsy specimen taken from the lesion showed CGCG followed by curettage with peripheral ostectomy with preservation of the continuity of the mandible.Result: At the 1-year clinical and radiological follow up there was no sign of recurrence. Conclusion: After complete healing of the graft, prosthetic rehabilitation with implants will be perfomed. This allows the best functional and aesthetic results.

  1. Anatomy of the Hesse photoreceptor cell axonal system in the central nervous system of amphioxus.

    Science.gov (United States)

    Castro, Antonio; Becerra, Manuela; Manso, María Jesús; Sherwood, Nancy M; Anadón, Ramón

    2006-01-01

    The present study reports the organization of the Hesse cell axonal system in the central nervous system of the amphioxus, with the use of a polyclonal antiserum raised against lamprey gonadotropin-releasing hormone-I (GnRH-I). In the spinal cord, the rhabdomeric photoreceptor cells of the bicellular organs were well labeled with this antibody. These cells sent smooth, straight, lateral processes that bent and became beaded as they passed ventrally and crossed to the contralateral side of the cord. There, the processes of several cells aggregated to give rise to a longitudinal fiber bundle. Beaded collaterals of these processes were directed to ventral neuropil and did not appear to contact giant Rohde cell axons. The crossed projections of the Hesse photoreceptors are compared with those of vertebrate retinal ganglion cells. Other antisera raised against GnRH weakly labeled rhabdomeric photoreceptors located dorsally in the brain, the Joseph cells. The finding that GnRH antibodies label amphioxus photoreceptor cells and axons is not definitive proof that the photoreceptors contain GnRH. Regardless of whether the antibody recognizes amphioxus GnRH, which has not yet been identified by structure, the antibody has revealed the processes of the Hesse photoreceptor cells.

  2. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    Science.gov (United States)

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd

    2015-09-01

    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer.

  3. Unusual location of central nervous system langerhans cell histiocytosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, E. Yup; Lee, Jae Kyu; Kim, Chan Kyo; Lee, Chang Hyun; Kang, Chang Ho; Chung, Phil Wook [Armed Forces Capital Hospital, Seongnam (Korea, Republic of)

    2003-03-01

    Langerhans cell histiocytosis of the central nervous system (CNS) usually involves the hypothalamic-pituitary axis, and T1-weighted MR images normally demonstrate infundibular thickening and/or a mass lesion in the hypothalamus and the absence of a posterior pituitary 'bright spot'. We recently encountered a case of CNS langerhans cell histiocytosis with no posterior pituitary 'bright spot' and with lesions involving the cerebellum and basal ganglia but not the hypothalamic-pituitary axis.

  4. The spinal cord ependymal region: a stem cell niche in the caudal central nervous system.

    Science.gov (United States)

    Hugnot, Jean Philippe; Franzen, Rachelle

    2011-01-01

    In the brain, specific signalling pathways localized in highly organized regions called niches, allow the persistence of a pool of stem and progenitor cells that generate new neurons and glial cells in adulthood. Much less is known on the spinal cord central canal niche where a sustained adult neurogenesis is not observed. Here we review our current knowledge of this caudal niche in normal and pathological situations. Far from being a simple layer of homogenous cells, this region is composed of several cell types localized at specific locations, expressing characteristic markers and with different morphologies and functions. We further report on a screen of online gene-expression databases to better define this spinal cord niche. Several genes were found to be preferentially expressed within or around the central canal region (Bmp6, CXCR4, Gdf10, Fzd3, Mdk, Nrtn, Rbp1, Shh, Sox4, Wnt7a) some of which by specific cellular subtypes. In depth characterization of the spinal cord niche constitutes a framework to make the most out of this endogenous cell pool in spinal cord disorders.

  5. Organization of the cytoplasmic reticulum in the central vacuole of parenchyma cells in Allium cepa L.

    Directory of Open Access Journals (Sweden)

    Tomasz J. Wodzicki

    2015-01-01

    Full Text Available An elaborate and complex cytoplasmic reticulum composed of fine filaments and lamellae ranging from 0.1 to 4 microns in size is revealed by viewing the central vacuole of onion bulb parenchyma cells with the scanning election microscope. The larger cytoplasmic strands, visible with the light microscope, are composed of numerous smaller filaments (some tubular which might explain the observed bidirectional movement of particles in these larger strands. The finely divided cytoplasmic network of filaments is continuous with the parietal cytoplasm inclosing the vacuolar sap. In these highly vacuolated cells the mass of the protoplast is in the form of an intravacuolar reticulum immersed in the cell sap. The probable significance of the vacuolar sap in relation to physiological processes of the cell is discussed.

  6. Effects of over-expression of TLR2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells

    Directory of Open Access Journals (Sweden)

    Deng Shoulong

    2012-10-01

    Full Text Available Abstract Background Toll-like receptor 2 (TLR2 is important to host recognition of invading gram-positive microbes. In goats, these microbes can cause serious mastitis, anthrax, tetanus, and other problems. Transgenic goats constitutively over-expressing TLR2 in many tissues serve as a suitable model for the study of the role of TLR2 over-expression in bacterial clearance. Results Capra hircus TLR2 over-expression vector (p3S-LoxP-TLR2 was used to generate transgenic goats by egg microinjection. The integration efficiency was 8.57%. Real-time PCR and immunohistochemical results confirmed that the goats over-expressing the TLR2 gene (Tg expressed more TLR2 than wild-type goats (WT. Monocyte-macrophages from the bloodstreams of transgenic goats were stimulated with synthetic bacterial lipoprotein (Pam3CSK4 and by the promotion of interleukin-6 (IL-6 and IL-10 expression in vitro. The oxidative damage was significantly reduced, and lysozyme (LZM secretion was found to be up-regulated. Ear tissue samples from transgenic goats that had been stimulated with Pam3CSK4 via hypodermic injection showed that transgenic individuals can undergo the inflammation response very quickly. Conclusions Over-expression of TLR2 was found to decrease radical damage to host cells through low-level production of NO and MDA and to promote the clearance of invasive bacteria by up-regulating lysozyme secretion and filtration of inflammatory cells to the infected site.

  7. A METHOD AND AN ELECTRODE PRODUCED BY INFILTRATION

    DEFF Research Database (Denmark)

    2014-01-01

    firing. The high temperature firing allows the Pr ions to diffuse into the CGO backbone. The resulting backbone would then have a co-doped subsurface exhibiting electronic conductivity having improved performance when used as electrode in, e.g. a fuel cell. Remaining particles of praseodymium oxide......The present invention relates to electrodes having Gd and Pr -doped cerium oxide (CGPO)backbones infiltrated with Sr -doped LaCoO3 (LSC) and a method to manufacture them. Pr ions have been introduced into a prefabricated CGO backbone by infiltrating Pr nitrate solution followed by high temperature...

  8. Metabolic peculiarity of 134Cs and its radioimmunotoxicological effect on central and peripheral immune cells

    Institute of Scientific and Technical Information of China (English)

    朱寿彭; 夏芬

    1996-01-01

    A fitted equation with least square method to describe the retention of 134Cs in whole body is obtained by a whole body counter.That is R(t)=18.04exp(-9.3175t)+ 45.13exp(-0.0423t),where R(t) is in %,and t in d.The equationn consists of two half-life components,the fast component is T1/2=0.07d,and the slow is T1/2=16.14d,Study on the localization of 134Cs at cellular level was carried out by freezing microautoradiography.The results indicate of 134Cs at cellular level was carried out by freezing microautoradiography.The results indicate that 134Cs was chiefly in ionizing form accumulated in red as well as white blood cells.In bone marrow cells 134Cs predominantly deposited in young cells and less in mature cells.Distribution of 134Cs penetrated quickly into the tissue cells.The observation of investigating radioimmunotoxicological effect induced by 134Cs shows that the inhibition of thymocytes is higher than bone marrow cells,the spleen T lynmphocytes are more sensitive to 134Cs than B lymphocytes and lymphocytes of peripheral immune cells are more sensitive to radiation than central immune cells.

  9. Regenerative medicine for central nervous system disorders: Role of therapeutic molecules in stem cell therapy

    Directory of Open Access Journals (Sweden)

    Paola Suárez-Meade

    2015-01-01

    Full Text Available The efficacy of stem cell therapy is greatly influenced by their secretory properties. Evidence suggests that there is a high concentration of growth factors such as brain-derived neurotrophic factor (BDNF, vascular endothelial growth factor (VEGF, and glial cell line-derived neurotrophic factor (GDNF after stem cell transplantation. Also, the presence of therapeutic molecules and cytokines such as stem cell factor (SCF, stromal cell-derived factor-1α (SDF-1α, RNAs, nuclear enriched abundant transcript 1 (NEAT1, and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1 is consistent throughout several studies. Apart from modulating the homeostasis of the surrounding tissues, these factors have pleiotropic properties over the host tissue, among which are angiogenic, anti-inflammatory, antiapoptotic, and neurogenic effects. In the present manuscript, we discuss the different secretion factors and their beneficial activity after stem cell transplantation. Recent developments in emerging technologies for coadjunctive therapies that may aid in stem cell transplantation into the central nervous system, such as cell encapsulation, molecular Trojan horses, and viral vectors, are also presented in this article.

  10. How Does Transcranial Magnetic Stimulation Influence Glial Cells in the Central Nervous System?

    Science.gov (United States)

    Cullen, Carlie L; Young, Kaylene M

    2016-01-01

    Transcranial magnetic stimulation (TMS) is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signaling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell (NSPC) proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the central nervous system (CNS), the influence that TMS has on glial cells is certainly an area that warrants careful examination.

  11. Durability and Performance of High Performance Infiltration Cathodes

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Hjalmarsson, Per

    2013-01-01

    The performance and durability of solid oxide fuel cell (SOFC) cathodes consisting of a porous Ce0.9Gd0.1O1.95 (CGO) infiltrated with nitrates corresponding to the nominal compositions La0.6Sr0.4Co1.05O3-δ (LSC), LaCoO3-δ (LC), and Co3O4 are discussed. At 600°C, the polarization resistance, Rp......, varied as: LSC (0.062Ωcm2)cathode was found to depend on the infiltrate firing temperature and is suggested to originate...... of the infiltrate but also from a better surface exchange property. A 450h test of an LSC-infiltrated CGO cathode showed an Rp with final degradation rate of only 11mΩcm2kh-1. An SOFC with an LSC-infiltrated CGO cathode tested for 1,500h at 700°C and 0.5Acm-2 (60% fuel, 20% air utilization) revealed no measurable...

  12. Improved performance of dye-sensitized solar cells using TiO2 nanotubes infiltrated by TiO2 nanoparticles using a dipping-rinsing-hydrolysis process

    Science.gov (United States)

    Lin, Lu-Yin; Chen, Chia-Yuan; Yeh, Min-Hsin; Tsai, Keng-Wei; Lee, Chuan-Pei; Vittal, R.; Wu, Chun-Guey; Ho, Kuo-Chuan

    2013-12-01

    An efficient back-illuminated dye-sensitized solar cell (DSSC) is made with a flexible Ti-foil based photoanode composed of a composite TiO2 film with TiO2 nanotubes (TNT) and TiO2 nanoparticles (TNP). The composite TiO2 film is fabricated through a novel dipping-rinsing-hydrolysis (DRH) process by inserting TiO2 into TNT and sintering the product to form TNP inside TNT. By directly placing TiO2 nanoparticles into TNT, the former grow internally from the base of TNT to occupy it completely. This solves previous problems of incomplete filling of TNP into TNT, which used partial penetration of TiCl4 reactant from the top of the TNT. In the present case, the TNP are grown from the base of TNT. A DSSC containing TNT and TNP prepared in this way shows a photoelectric efficiency of 6.45%, which is much higher than that (4.21%) of a DSSC with untreated TNT. The films are characterized by using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. The improvement in the photoelectric efficiency is explained by using electrochemical impedance spectroscopy (EIS), incident photon-to-current conversion efficiency (IPCE) analysis, and UV-absorption spectra analysis.

  13. Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

    Science.gov (United States)

    Guo, Chenglin; Pu, Qiang; Ma, Lin; Liu, Chengwu; Lin, Feng; Liao, Hu; You, Zongbing; Liu, Lunxu

    2016-01-01

    Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients. However, the pooled HR of 4 studies showed that high density of CD68+ TAMs in the tumor islet predicted better OS, while the pooled HR of 6 studies showed that high density of CD68+ TAMs in the tumor stroma was associated with poor OS. A high islet/stroma ratio of CD68+ TAMs was associated with better OS. A high density of M1 TAMs in the tumor islet was associated with better OS, while a high density of M2 TAMs in the tumor stroma predicted poor OS. These findings suggest that, although the density of total CD68+ TAMs is not associated with OS, the localization and M1/M2 polarization of TAMs are potential prognostic predictors of NSCLC. PMID:27144518

  14. Performance Improvement of an Inhomogeneous Cathode by Infiltration

    DEFF Research Database (Denmark)

    Seyed-Vakili, S. V.; Graves, Christopher R.; Babaei, A.

    2017-01-01

    The performance of solid oxide fuel cells (SOFCs) is considerably influenced by the microstructure and chemical composition of cathode materials. Porous La0.85Sr0.15FeO3– Ce0.9Gd0.1O2 composite electrodes were infiltrated by La0.6Sr0.4CoO3 and La0.6Sr0.4FeO3. The effects of infiltration loading...... performance of the electrodes. The electrochemical results revealed that the polarization resistance of the cathodes significantly was decreased by infiltration from 2.59 to 0.034 Ω cm2 measured at 670 °C. The best electrode performance was achieved at a calcination temperature of 770 °C. It was also found...

  15. Increased specific T cell cytokine responses in patients with active pulmonary tuberculosis from Central Africa.

    Science.gov (United States)

    Winkler, Stefan; Necek, Magdalena; Winkler, Heidi; Adegnika, Ayola A; Perkmann, Thomas; Ramharter, Michael; Kremsner, Peter G

    2005-07-01

    An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3) cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n=30) as well as in healthy individuals (controls, n=21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-gamma, and TNF-alpha in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-alpha expression seen in controls towards an increased frequency of IFN-gamma/IL-2 or IFN-gamma/TNF-alpha co-expression in TB. Higher levels of PPD-induced IFN-gamma in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRgammadelta+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-gamma in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-alpha was not different. Non-specific cytokine responses of TCRgammadelta+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.

  16. Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation--an International Primary Central Nervous System Lymphoma Study Group project.

    Science.gov (United States)

    Bromberg, Jacoline E; Doorduijn, Jeanette K; Illerhaus, Gerald; Jahnke, Kristoph; Korfel, Agniezka; Fischer, Lars; Fritsch, Kristina; Kuittinen, Outti; Issa, Samar; van Montfort, Cees; van den Bent, Martin J

    2013-05-01

    Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival

  17. IL-4 induces the formation of multinucleated giant cells and expression of β5 integrin in central giant cell lesion

    Science.gov (United States)

    Aghbali, Amirala; Rafieyan, Sona; Mohamed-Khosroshahi, Leila; Baradaran, Behzad; Shanehbandi, Dariush

    2017-01-01

    Background It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells. Key words:β5 integrin, giant cell, Il-4, monocyte, rank. PMID:27918730

  18. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.

    Science.gov (United States)

    Ding, Xiaoli; Cao, Fang; Cui, Langjun; Ciric, Bogoljub; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-12-01

    Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.

  19. Neural stem cells and strategies for the regeneration of the central nervous system.

    Science.gov (United States)

    Okano, Hideyuki

    2010-01-01

    The adult mammalian central nervous system (CNS), especially that of adult humans, is a representative example of organs that do not regenerate. However, increasing interest has focused on the development of innovative therapeutic methods that aim to regenerate damaged CNS tissue by taking advantage of recent advances in stem cell and neuroscience research. In fact, the recapitulation of normal neural development has become a vital strategy for CNS regeneration. Normal CNS development is initiated by the induction of stem cells in the CNS, i.e., neural stem cells (NSCs). Thus, the introduction or mobilization of NSCs could be expected to lead to CNS regeneration by recapitulating normal CNS development, in terms of the activation of the endogenous regenerative capacity and cell transplantation therapy. Here, the recent progress in basic stem cell biology, including the author's own studies, on the prospective identification of NSCs, the elucidation of the mechanisms of ontogenic changes in the differentiation potential of NSCs, the induction of neural fate and NSCs from pluripotent stem cells, and their therapeutic applications are summarized. These lines of research will, hopefully, contribute to a basic understanding of the nature of NSCs, which should in turn lead to feasible strategies for the development of ideal "stem cell therapies" for the treatment of damaged brain and spinal cord tissue.

  20. A moonlighting enzyme links Escherichia coli cell size with central metabolism.

    Directory of Open Access Journals (Sweden)

    Norbert S Hill

    Full Text Available Growth rate and nutrient availability are the primary determinants of size in single-celled organisms: rapidly growing Escherichia coli cells are more than twice as large as their slow growing counterparts. Here we report the identification of the glucosyltransferase OpgH as a nutrient-dependent regulator of E. coli cell size. During growth under nutrient-rich conditions, OpgH localizes to the nascent septal site, where it antagonizes assembly of the tubulin-like cell division protein FtsZ, delaying division and increasing cell size. Biochemical analysis is consistent with OpgH sequestering FtsZ from growing polymers. OpgH is functionally analogous to UgtP, a Bacillus subtilis glucosyltransferase that inhibits cell division in a growth rate-dependent fashion. In a striking example of convergent evolution, OpgH and UgtP share no homology, have distinct enzymatic activities, and appear to inhibit FtsZ assembly through different mechanisms. Comparative analysis of E. coli and B. subtilis reveals conserved aspects of growth rate regulation and cell size control that are likely to be broadly applicable. These include the conservation of uridine diphosphate glucose as a proxy for nutrient status and the use of moonlighting enzymes to couple growth rate-dependent phenomena to central metabolism.

  1. Infiltration kinetics of pressureless infiltration in SiCp/Al composites

    Institute of Scientific and Technical Information of China (English)

    QIN Zhen-kai; YU Jia-kang; ZHANG Xiao-yu

    2005-01-01

    The pressureless infiltration kinetics was investigated by plotting the infiltration distance as function of the infiltration time. The effects of key process parameters such as time, temperature, Mg content on the pressureless infiltration of silicon carbide particle compacts were studied and quantified. The preform with high volume fraction SiC was obtained by mixing SiC particles with bimodal size distribution, whose diameters are 5 and 50 μm, respectively. The results show that an incubation period exists before infiltration, the influence of temperature on the incubation time exceeds that of Mg content, infiltration rate increases with the increasing temperature and Mg content, infiltration rate decreases as Mg consumes. A model of macroscopical infiltration and microscopical infiltration of liquid alloy in porous SiC preform was proposed.

  2. Tumor infiltrating lymphocytes in ovarian cancer.

    Science.gov (United States)

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  3. Deciphering Human Cell-Autonomous Anti-HSV-1 Immunity in the Central Nervous System.

    Science.gov (United States)

    Lafaille, Fabien G; Ciancanelli, Michael J; Studer, Lorenz; Smith, Gregory; Notarangelo, Luigi; Casanova, Jean-Laurent; Zhang, Shen-Ying

    2015-01-01

    Herpes simplex virus 1 (HSV-1) is a common virus that can rarely invade the human central nervous system (CNS), causing devastating encephalitis. The permissiveness to HSV-1 of the various relevant cell types of the CNS, neurons, astrocytes, oligodendrocytes, and microglia cells, as well as their response to viral infection, has been extensively studied in humans and other animals. Nevertheless, human CNS cell-based models of anti-HSV-1 immunity are of particular importance, as responses to any given neurotropic virus may differ between humans and other animals. Human CNS neuron cell lines as well as primary human CNS neurons, astrocytes, and microglia cells cultured/isolated from embryos or cadavers, have enabled the study of cell-autonomous anti-HSV-1 immunity in vitro. However, the paucity of biological samples and their lack of purity have hindered progress in the field, which furthermore suffers from the absence of testable primary human oligodendrocytes. Recently, the authors have established a human induced pluripotent stem cells (hiPSCs)-based model of anti-HSV-1 immunity in neurons, oligodendrocyte precursor cells, astrocytes, and neural stem cells, which has widened the scope of possible in vitro studies while permitting in-depth explorations. This mini-review summarizes the available data on human primary and iPSC-derived CNS cells for anti-HSV-1 immunity. The hiPSC-mediated study of anti-viral immunity in both healthy individuals and patients with viral encephalitis will be a powerful tool in dissecting the disease pathogenesis of CNS infections with HSV-1 and other neurotropic viruses.

  4. BM-12CEREBRAL INFARCTION SECONDARY TO PULMONARY VEIN COMPRESSION AND LEFT ATRIAL APPENDAGE TUMOR INFILTRATION AS THE PRESENTING SIGN OF METASTATIC SQUAMOUS CELL CARCINOMA OF THE BASE OF THE TONGUE

    Science.gov (United States)

    Dredla, Brynn; Siegel, Jason; Jaeckle, Kurt

    2014-01-01

    BACKGROUND: Squamous cell carcinoma of the tongue has been documented to metastasize to the lungs and rarely involve the heart. The majority of documented cases of cardiac metastases are from postmortem analysis. Cases of sudden death, syncope, and dyspnea have been reported. However, stroke and tumor embolization to the brain as the initial clinical presentation has not been documented in the English literature. METHODS: Case Report. RESULTS: This case addresses a 61-year-old male with Stage IVA squamous cell carcinoma of the left tongue base, believed to be in remission after systemic chemotherapy and local radiation, who presented with acute cerebral infarctions involving multiple vascular territories. Cardiac CT obtained during stroke etiology evaluation displayed metastatic disease compressing the pulmonary vein resulting in virtual pulmonary vein thrombus. Transthoracic echocardiogram was negative for cardiac valvular pathology. Anticoagulation was initiated. Twelve days later he returned with recurrent strokes and suspected tumor embolization to the brain. Imaging displayed left atrial appendage structural abnormality highly suggestive of tumor infiltration. CONCLUSION: Cardiac metastases are rare and non-myxomatous tumor embolization to the brain even rarer especially in the setting of cerebral infarction due to pulmonary vein thrombus. Here we describe a case of multiple acute cerebral infarctions appearing from a proximal source refractory to anticoagulation. Thromboembolism from the pulmonary vein and tumor embolization from cardiac metastases are the likely mechanisms for his clinical presentation and radiographic findings. This case demonstrates the complexity of multiple stroke etiologies in one patient and the importance of cardiac imaging in stroke evaluation, particularly in the setting of a patient with a history of cancer.

  5. Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome.

    Directory of Open Access Journals (Sweden)

    Cecile Dessapt-Baradez

    Full Text Available OBJECTIVE: Subjects with Polycystic ovarian syndrome (PCOS are at increased risk of Type 2 diabetes mellitus (T2DM. The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness predict cardio-metabolic disease in at-risk populations. DESIGN: We studied VPC and arterial stiffness measures in non-obese PCOS subjects as compared to age and body mass index (BMI matched healthy controls in a cross-sectional study. METHODS: Fourteen subjects with PCOS and 12 controls of similar age, BMI (all <30 kg/m(2 and metabolic profile were studied. VPC number and in vitro function were studied by flow cytometry and tube formation assays respectively. Augmentation index (AIx, a measure of central arterial stiffness, and central (aortic blood pressures (BP were measured by applanation tonometry. RESULTS: Subjects with PCOS had a reduced number, mean±SEM, of circulating CD34(+133(+ VPCs (317.5±51.0 vs. 558.3±101.2, p = 0.03 and impaired in vitro tube formation (completed tube area 1.0±0.06 vs. 1.2±0.05×10(6 µm(2 p = 0.02. PCOS subjects had significantly higher AIx (18.4±1.9% vs. 4.9±2.0% and this difference remained significant even after adjustments for age, BMI and smoking (p = 0.003 in multivariate analyses. Central systolic and pulse pressure were higher in PCOS subjects but these differences were not statistically significant after adjustment for age. Brachial systolic and pulse pressures were similar. VPC number/function and arterial stiffness or BP measures were not correlated. CONCLUSIONS: Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness. These changes in novel vascular risk markers may explain the enhanced risk of T2DM and CVD in PCOS.

  6. Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the forebrain and midbrain

    Directory of Open Access Journals (Sweden)

    Schmitt Charlotte

    2012-08-01

    Full Text Available Abstract Background Cerebrospinal fluid (CSF has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis, we performed a time-course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease. Methods Guinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified. Results Freund’s adjuvant-induced peripheral inflammation in the absence of brain antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within forebrain/midbrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from rats included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments. Conclusion These results identified distinctive velae and cisterns of the forebrain and midbrain as preferential sites of immune cell homing following

  7. Infiltration of SOFC Stacks: Evaluation of the Electrochemical Performance Enhancement and the Underlying Changes in the Microstructure

    DEFF Research Database (Denmark)

    Kiebach, Wolff-Ragnar; Zielke, Philipp; Høgh, Jens Valdemar Thorvald;

    2016-01-01

    Experimental SOFC stacks with 10 SOFCs (LSM-YSZ/YSZ/Ni-YSZ) were infiltrated with CGO and Ni-CGO on the air and fuel side, respectively in an attempt to counter degradation and improve the output. The electrochemical performance of each cell was characterized (i) before infiltration, (ii) after...... infiltration on the cathode side, and (iii) after the infiltration of the anode side. A significant performance enhancement was observed after the infiltration with CGO on the cathode, while the infiltration of the anode side with Ni-CGO had no significant effect on the electrochemical performance. After...... testing the cells were characterized by SEM and TEM/EELS. A thin layer of CGO nanoparticles around the LSM-YSZ back bone structure was found after infiltration. On the anode side nano sized Ni particles were found embedded in a CGO layer formed around the Ni-YSZ structure. EELS analysis showed...

  8. Diffuse large B-cell lymphoma involving the central nervous system.

    Science.gov (United States)

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.

  9. Storm-water management through Infiltration trenches

    OpenAIRE

    Chahar, Bhagu Ram; Graillot, Didier; Gaur, Shishir

    2012-01-01

    International audience; With urbanization, the permeable soil surface area through which recharge by infiltration can occur is reducing. This is resulting in much less ground-water recharge and greatly increased surface run-off. Infiltration devices, which redirect run-off waters from the surface to the sub-surface environments, are commonly adopted to mitigate the negative hydrologic effects associated with urbanization. An infiltration trench alone or in combination with other storm water m...

  10. T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62L(highCD44(low Sca-1(+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells.

  11. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord ☆

    OpenAIRE

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-01-01

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is ...

  12. Application of spreadsheet to estimate infiltration parameters

    Directory of Open Access Journals (Sweden)

    Mohammad Zakwan

    2016-09-01

    Full Text Available Infiltration is the process of flow of water into the ground through the soil surface. Soil water although contributes a negligible fraction of total water present on earth surface, but is of utmost importance for plant life. Estimation of infiltration rates is of paramount importance for estimation of effective rainfall, groundwater recharge, and designing of irrigation systems. Numerous infiltration models are in use for estimation of infiltration rates. The conventional graphical approach for estimation of infiltration parameters often fails to estimate the infiltration parameters precisely. The generalised reduced gradient (GRG solver is reported to be a powerful tool for estimating parameters of nonlinear equations and it has, therefore, been implemented to estimate the infiltration parameters in the present paper. Field data of infiltration rate available in literature for sandy loam soils of Umuahia, Nigeria were used to evaluate the performance of GRG solver. A comparative study of graphical method and GRG solver shows that the performance of GRG solver is better than that of conventional graphical method for estimation of infiltration rates. Further, the performance of Kostiakov model has been found to be better than the Horton and Philip's model in most of the cases based on both the approaches of parameter estimation.

  13. Monostotic Langerhans' cell histiocytosis in a child with central diabetes insipidus.

    Science.gov (United States)

    Soares, Eduardo Costa Studart; Quidute, Ana Rosa Pinto; Costa, Fábio Wildson Gurgel; Gurgel, Maria Helane Costa; Alves, Ana Paula Negreiros Nunes; Fonteles, Cristiane Sá Roriz

    2012-01-01

    Langerhans'cell histiocytosis (LCH) comprises a rare group of reticuloendothelial system disorders that can produce focal or systemic manifestations. Diabetes insipidus is considered to be an important indicator of serious underlying diseases in children, including LCH. We report the case of a young patient with monostotic LCH confined to the mandibular ramus, who was diagnosed with the disease after presenting symptoms of central diabetes insipidus and was satisfactorily treated with multi-agent chemotherapy. Additionally, we discuss the clinical, radiographic, histological and immunohistochemical findings, as well as the multidisciplinary approach of this important disease, which should receive attention by dental practitioners, especially when it occurs in children.

  14. Central Granular Cell Odontogenic Tumor: Report of a Case with CBCT Features.

    Directory of Open Access Journals (Sweden)

    Najmeh Anbiaee

    2014-06-01

    Full Text Available Central granular cell odontogenic tumor CGCOT of the jaw is an exceedingly rare benign odontogenic neoplasm with 35 reported cases in the literature. Among these, very few studies have focused on the cone-beam CT features of CGCOT. Here, we report a case of an asymptomatic CGCOT in a 16-year-old girl and focus on the cone-beam CT features. Only 36 cases of this lesion, including this one, have been reported so far. The case presented is of special importance due to the young age of the patient, the posterior location of the lesion and the multilocular pattern in the cone beam CT images.

  15. Corneal endothelial cell density and morphology and central corneal thickness in Guangxi Maonan and Han adolescent students of China

    Institute of Scientific and Technical Information of China (English)

    Hao; Liang; Hui-Yi; Zuo; Jin-Mao; Chen; Jie; Cai; Yu-Zhua; Qin; Yu-Ping; Huang; Ying-Ying; Chen; Dong-Yong; Tang; Shao-Jian; Tan

    2015-01-01

    AIM: To investigate the corneal endothelial cell density and morphology and central corneal thickness in the Guangxi Maonan and Han adolescent students of China.METHODS: Noncontact specular microscope(Topcon SP3000 P, Tokyo, Japan) was performed in 133 adolescent students of Maonan nationality(M:F 54:79)and 105 adolescent students of Han nationality(M:F 50:55),5 to 20 y of age, who were randomly selected from 3schools in Huanjiang Maonan Autonomous County of Guangxi Zhuang Autonomous Region of China.Parameters studied included endothelial cell density,mean cell area, coefficient of variation in cell size,percentage hexagonality and central corneal thickness. RESULTS: Endothelial cell density, mean cell area,coefficient of variation in cell size, percentage hexagonality and central corneal thickness in the study population were(2969.50 ±253.93) cells/mm2,(339.23 ±29.44) μm2,(29.96 ±4.07) %,(64.58 ±9.41) % and(523.71 ±32.82) μm in Maonan and(2998.26 ±262.65) cells/mm2,(336.11±30.07) μm2,(29.89±5.03) %,(64.91±11.64) % and(524.39 ±33.15) μm in Han, respectively. No significant differences were observed in endothelial cell density,mean cell area, coefficient of variation in cell size,percentage hexagonality and central corneal thickness between Maonan and Han(P =0.615, 0.659, 0.528, 0.551,0.999). In Maonan and Han, we found age was negatively correlated with endothelial cell density and percentagehexagonality and positively correlated with mean cell area and coefficient of variation in cell size. Negative correlation was also found between central corneal thickness and age in Han, whereas no correlation was found in Maonan. CONCLUSION: There were no differences between Maonan and Han in corneal endothelial cell density and morphology and central corneal thickness. In these two nationalities, there were statistically significant decrease in endothelial cell density and percentage hexagonality with increasing age and statistically significant increase in

  16. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells.

    Science.gov (United States)

    Lefrançais, Emma; Duval, Anais; Mirey, Emilie; Roga, Stéphane; Espinosa, Eric; Cayrol, Corinne; Girard, Jean-Philippe

    2014-10-28

    Interleukin-33 (IL-33) is an alarmin cytokine from the IL-1 family. IL-33 activates many immune cell types expressing the interleukin 1 receptor-like 1 (IL1RL1) receptor ST2, including group-2 innate lymphoid cells (ILC2s, natural helper cells, nuocytes), the major producers of IL-5 and IL-13 during type-2 innate immune responses and allergic airway inflammation. IL-33 is likely to play a critical role in asthma because the IL33 and ST2/IL1RL1 genes have been reproducibly identified as major susceptibility loci in large-scale genome-wide association studies. A better understanding of the mechanisms regulating IL-33 activity is thus urgently needed. Here, we investigated the role of mast cells, critical effector cells in allergic disorders, known to interact with ILC2s in vivo. We found that serine proteases secreted by activated mast cells (chymase and tryptase) generate mature forms of IL-33 with potent activity on ILC2s. The major forms produced by mast cell proteases, IL-33(95-270), IL-33(107-270), and IL-33(109-270), were 30-fold more potent than full-length human IL-33(1-270) for activation of ILC2s ex vivo. They induced a strong expansion of ILC2s and eosinophils in vivo, associated with elevated concentrations of IL-5 and IL-13. Murine IL-33 is also cleaved by mast cell tryptase, and a tryptase inhibitor reduced IL-33-dependent allergic airway inflammation in vivo. Our study identifies the central cleavage/activation domain of IL-33 (amino acids 66-111) as an important functional domain of the protein and suggests that interference with IL-33 cleavage and activation by mast cell and other inflammatory proteases could be useful to reduce IL-33-mediated responses in allergic asthma and other inflammatory diseases.

  17. Current understanding of circulating tumor cells – potential value in malignancies of the central nervous system

    Directory of Open Access Journals (Sweden)

    Lukasz A. Adamczyk

    2015-08-01

    Full Text Available Detection of circulating tumor cells (CTCs in the blood via so-called 'liquid biopsies' carries enormous clinical potential in malignancies of the central nervous system (CNS because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems such as the widely used Cell Search system are reliant on markers such as the epithelial cell adhesion molecule (EpCAM which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors.

  18. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  19. Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant?

    Directory of Open Access Journals (Sweden)

    Gesa eWeise

    2012-12-01

    Full Text Available Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain (BBB or blood nerve barrier (BNB preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd-DTPA-enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO and perfluorocarbons (PFC enable assessment of leukocyte (mainly macrophage infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis (MS, cerebral ischemia and traumatic nerve injury and review corresponding findings in patients.

  20. Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant?

    Science.gov (United States)

    Weise, Gesa; Stoll, Guido

    2012-01-01

    Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain barrier (BBB) or blood nerve barrier (BNB) preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI) as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf) allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd)-DTPA enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO) and perfluorocarbons enable assessment of leukocyte (mainly macrophage) infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis, cerebral ischemia, and traumatic nerve injury and review corresponding findings in patients.

  1. A Central Composite Face-Centered Design for Parameters Estimation of PEM Fuel Cell Electrochemical Model

    Directory of Open Access Journals (Sweden)

    Khaled MAMMAR

    2013-11-01

    Full Text Available In this paper, a new approach based on Experimental of design methodology (DoE is used to estimate the optimal of unknown model parameters proton exchange membrane fuel cell (PEMFC. This proposed approach combines the central composite face-centered (CCF and numerical PEMFC electrochemical. Simulation results obtained using electrochemical model help to predict the cell voltage in terms of inlet partial pressures of hydrogen and oxygen, stack temperature, and operating current. The value of the previous model and (CCF design methodology is used for parametric analysis of electrochemical model. Thus it is possible to evaluate the relative importance of each parameter to the simulation accuracy. However this methodology is able to define the exact values of the parameters from the manufacture data. It was tested for the BCS 500-W stack PEM Generator, a stack rated at 500 W, manufactured by American Company BCS Technologies FC.

  2. Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells.

    LENUS (Irish Health Repository)

    Kinsella, J A

    2012-02-01

    Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.(1,2) Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and\\/or leptomeninges, similar to that seen in Takayasu\\'s or giant cell arteritis.(1-3) We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis.

  3. Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Meiqing Wu

    Full Text Available Herpesvirus infections of the central nervous system (CNS are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV-associated diseases (4 encephalitis and 11 lymphoproliferative diseases, 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542 days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+CD20(+ B cells (7/11 and had clonal rearrangement of immunoglobulin genes (3/11 in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

  4. Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

    Directory of Open Access Journals (Sweden)

    Hsu Kenneth

    2009-12-01

    Full Text Available Abstract Background HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD. But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood. Methods To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24, anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation. Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA. Results Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures. Conclusion Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.

  5. Infiltration as Ventilation: Weather-Induced Dilution

    Energy Technology Data Exchange (ETDEWEB)

    Sherman, Max H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Turner, William J.N. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Walker, Iain S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-06-01

    The purpose of outdoor air ventilation is to dilute or remove indoor contaminants to which occupants are exposed. It can be provided by mechanical or natural means. In most homes, especially older homes, weather-driven infiltration provides the dominant fraction of the total ventilation. As we seek to provide good indoor air quality at minimum energy cost, it is important to neither over-ventilate nor under-ventilate. Thus, it becomes critically important to evaluate correctly the contribution infiltration makes to the total outdoor air ventilation rate. Because weather-driven infiltration is dependent on building air leakage and weather-induced pressure differences, a given amount of air leakage will provide different amounts of infiltration. Varying rates of infiltration will provide different levels of contaminant dilution and hence effective ventilation. This paper derives these interactions and then calculates the impact of weather-driven infiltration for different climates. A new “N-factor” is introduced to provide a convenient method for calculating the ventilation contribution of infiltration for over 1,000 locations across North America. The results of this work could be used in indoor air quality standards (specifically ASHRAE 62.2) to account for the contribution of weather-driven infiltration towards the dilution of indoor pollutants.

  6. Infiltration into soils: Conceptual approaches and solutions

    Science.gov (United States)

    Assouline, Shmuel

    2013-04-01

    Infiltration is a key process in aspects of hydrology, agricultural and civil engineering, irrigation design, and soil and water conservation. It is complex, depending on soil and rainfall properties and initial and boundary conditions within the flow domain. During the last century, a great deal of effort has been invested to understand the physics of infiltration and to develop quantitative predictors of infiltration dynamics. Jean-Yves Parlange and Wilfried Brutsaert have made seminal contributions, especially in the area of infiltration theory and related analytical solutions to the flow equations. This review retraces the landmark discoveries and the evolution of the conceptual approaches and the mathematical solutions applied to the problem of infiltration into porous media, highlighting the pivotal contributions of Parlange and Brutsaert. A historical retrospective of physical models of infiltration is followed by the presentation of mathematical methods leading to analytical solutions of the flow equations. This review then addresses the time compression approximation developed to estimate infiltration at the transition between preponding and postponding conditions. Finally, the effects of special conditions, such as the presence of air and heterogeneity in soil properties, on infiltration are considered.

  7. Key bifurcations of bursting polyrhythms in 3-cell central pattern generators.

    Directory of Open Access Journals (Sweden)

    Jeremy Wojcik

    Full Text Available We identify and describe the key qualitative rhythmic states in various 3-cell network motifs of a multifunctional central pattern generator (CPG. Such CPGs are neural microcircuits of cells whose synergetic interactions produce multiple states with distinct phase-locked patterns of bursting activity. To study biologically plausible CPG models, we develop a suite of computational tools that reduce the problem of stability and existence of rhythmic patterns in networks to the bifurcation analysis of fixed points and invariant curves of a Poincaré return maps for phase lags between cells. We explore different functional possibilities for motifs involving symmetry breaking and heterogeneity. This is achieved by varying coupling properties of the synapses between the cells and studying the qualitative changes in the structure of the corresponding return maps. Our findings provide a systematic basis for understanding plausible biophysical mechanisms for the regulation of rhythmic patterns generated by various CPGs in the context of motor control such as gait-switching in locomotion. Our analysis does not require knowledge of the equations modeling the system and provides a powerful qualitative approach to studying detailed models of rhythmic behavior. Thus, our approach is applicable to a wide range of biological phenomena beyond motor control.

  8. Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells

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    Ma Isabel Salazar

    2013-01-01

    Full Text Available An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS, characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa and two less apparent proteins (100 and 130 kDa. Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1 that DENV-2 exhibited a direct tropism for human neurons and (2 that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2.

  9. Net-Infiltration map of the Navajo Sandstone outcrop area in western Washington County, Utah

    Science.gov (United States)

    Heilweil, Victor M.; McKinney, Tim S.

    2007-01-01

    As populations grow in the arid southwestern United States and desert bedrock aquifers are increasingly targeted for future development, understanding and quantifying the spatial variability of net infiltration and recharge becomes critically important for inventorying groundwater resources and mapping contamination vulnerability. A Geographic Information System (GIS)-based model utilizing readily available soils, topographic, precipitation, and outcrop data has been developed for predicting net infiltration to exposed and soil-covered areas of the Navajo Sandstone outcrop of southwestern Utah. The Navajo Sandstone is an important regional bedrock aquifer. The GIS model determines the net-infiltration percentage of precipitation by using an empirical equation. This relation is derived from least squares linear regression between three surficial parameters (soil coarseness, topographic slope, and downgradient distance from outcrop) and the percentage of estimated net infiltration based on environmental tracer data from excavations and boreholes at Sand Hollow Reservoir in the southeastern part of the study area.Processed GIS raster layers are applied as parameters in the empirical equation for determining net infiltration for soil-covered areas as a percentage of precipitation. This net-infiltration percentage is multiplied by average annual Parameter-elevation Regressions on Independent Slopes Model (PRISM) precipitation data to obtain an infiltration rate for each model cell. Additionally, net infiltration on exposed outcrop areas is set to 10 percent of precipitation on the basis of borehole net-infiltration estimates. Soils and outcrop net-infiltration rates are merged to form a final map.Areas of low, medium, and high potential for ground-water recharge have been identified, and estimates of net infiltration range from 0.1 to 66 millimeters per year (mm/yr). Estimated net-infiltration rates of less than 10 mm/yr are considered low, rates of 10 to 50 mm/yr are

  10. Glycosylations in demilunar and central acinar cells of the submandibular salivary gland of ferret investigated by lectin histochemistry.

    Science.gov (United States)

    Triantafyllou, Asterios; Fletcher, David; Scott, John

    2004-09-01

    'Resting' submandibular salivary glands obtained post-mortem from mature ferrets of both sexes were examined here. The binding patterns of labelled lectins applied to paraffin sections of tissue slivers fixed in an aldehyde-HgCl2 mixture and the effects of pretreatment procedures on the results were assessed lightmicroscopically. Lectins with affinity for terminal GalNAc residues (DBA, SBA) bound preferentially to demilunar acinar cells which were also strongly reactive with Fuc-directed UEA I. In contrast, lectins with affinity for neuraminic acid (SNA, WGA) bound to central acinar cells where consistent binding of DBA and SNA occurred only after neuraminidase digestion, and variation in the binding of UEA I was seen. The reactivities corresponded with the distribution of secretory granules, but staining in Golgi-like areas occurred in central acinar cells with PNA lectin. The results suggest that glycosylations are more advanced in central than demilunar acinar cells of the ferret submandibular gland. Possibly demilunar and central acinar cells reflect phenotypic changes of a single secretory cell, the 'central' acinar phenotype being influenced by incorporation of neuraminic acid in glycoprotein side chains and by increased Golgi activity.

  11. Central nervous system involvement in T-cell lymphoma: A single center experience.

    Science.gov (United States)

    Gurion, Ronit; Mehta, Neha; Migliacci, Jocelyn C; Zelenetz, Andrew; Moskowitz, Alison; Lunning, Matthew; Moskowitz, Craig; Hamlin, Paul; Horwitz, Steven

    2016-05-01

    Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

  12. Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte infiltration

    Institute of Scientific and Technical Information of China (English)

    She-Yu Li; Xiang-Yang Huang; Yong-Tao Chen; Yi Liu; Sha Zhao

    2011-01-01

    Autoimmune pancreatitis (AIP) is a rare form of pancreatitis characterized by prominent lymphocyte infiltration and pancreatic fibrosis resulting in organ dysfunction.The pathogenesis and pathology of AIP remain unknown. A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas, elevated IgG levels, and negative autoimmune antibody responses. A pylorus-preserving pancreatoduodenectomy was performed and a pancreatic tumor was suspected. However,periductal lymphoplasmacytic infiltration and fibrosis were found in the head of pancreas and nearby organs instead of tumor cells. Four months after surgery, the patient was readmitted because of reoccurrence of severe jaundice and sustained abdominal distension. Prednisone 30 mg/d was administered orally as an AIP was suspected. One and a half months later, the symptoms of the patient disappeared, and globulin, aminotransferase and bilirubin levels decreased significantly. Over a 9-mo follow-up period, the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition. We further demonstrated dominant CD3+/CD8+ populations, CD20+ cells and a few CD4+ cells in the pancreatic parenchyma, duodenum and gallbladder wall by immunohistochemical assay. This AIP case presented with significant CD8+ T lymphocyte infiltration in the pancreas and extra-pancreatic lesions, indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.

  13. Identification and Charaterization of Genes Encoding Melanoma Antigens Recognized by Tumor-infiltrating Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Rong-FuWang; StevenA.Rosenberg

    1995-01-01

    Adoptive transfer of tumor infiltrating lymphocytes (TILs) into the autologous patient with melanoma resulted in the objective regression of tumor, suggesting that these TILs recognize tumor rejection antigens on the tumor cells.

  14. Genomic signatures characterize leukocyte infiltration in myositis muscles

    Directory of Open Access Journals (Sweden)

    Zhu Wei

    2012-11-01

    Full Text Available Abstract Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity. Currently, there is a lack of: efficacious therapies for myositis; understanding of the molecular features important for disease pathogenesis; and potential molecular biomarkers for characterizing inflammatory myopathies to aid in clinical development. Methods In this study, we developed a simple model and predicted that 1 leukocyte-specific transcripts (including both protein-coding transcripts and microRNAs should be coherently overexpressed in myositis muscle and 2 the level of over-expression of these transcripts should be correlated with leukocyte infiltration. We applied this model to assess immune cell infiltration in myositis by examining mRNA and microRNA (miRNA expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls. Results Several gene signatures, including a leukocyte index, type 1 interferon (IFN, MHC class I, and immunoglobulin signature, were developed to characterize myositis patients at the molecular level. The leukocyte index, consisting of genes predominantly associated with immune function, displayed strong concordance with pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to differentiate transcriptional changes due to leukocyte infiltration from other alterations in myositis muscle. Results from this differentiation revealed biologically relevant differences in the relationship between the type 1 IFN pathway, miR-146a, and leukocyte infiltration within various myositis subtypes. Conclusions Results indicate that a likely interaction between miR-146a expression and the type 1 IFN pathway is confounded by the level of leukocyte infiltration into muscle tissue. Although the role of miR-146a in myositis remains uncertain, our results highlight the potential benefit of deconvoluting the

  15. Gene Rearrangement Analysis of Orbital Lymphoid Infiltrating Disorders

    Institute of Scientific and Technical Information of China (English)

    Jianhua Yan; Zhongyao Wu; Shuqi Huang; Yongping Li

    2000-01-01

    Purpose: To determine whether the use of polymerase chain reaction for B-cell gene rearrangement in patients with orbital lymphoid infiltrate disorders could be useful in the diagnosis of lymphoma, especially, in differentiating benign lesion from malignant one. Methods: In addition to clinical, pathological, and immunohistochemical evaluations,48 cases of orbital lymphoid infiltrate disorders were examined for immunoglobulin heavy (IgH) gene rearrangement by means of PCR to amplify the FR3 region with formalin-fixed and paraffin-embedded tissues. Results: Gene rearrangement in the third frame-work of the IgH region was detected in specimens obtained from 15 cases of malignant lymphoma, 4 of reactive lymphoid hyperplasia and 3 of orbital pseudotumor. All of these patients showed a discrete band (100bp) which reflected monoclonal proliferation of B lymphocytes. 5 cases of malignant lymphoma, 6 of reactive lymphoid hyperplasia and 15 of orbital pseudotumor did not show a discrete band on PCR. Conclusions: The FR3 region gene rearrangement of Ig heavy in patients with orbital lymphoid infiltrate disorders may be an additional diagnostic tool in differentiating benign from malignant lymphoid diseases and in offering a useful adjunct for diagnosis in difficult or unclear cases. It is a reliable and practical method of gene diagnosis in orbital lymphoid infiltrate disorders and helps to identify the molecular mechanism of malignant lymphoma. Eye Science 2000; 16:15 ~ 21.

  16. Landslide triggering by rain infiltration

    Science.gov (United States)

    Iverson, Richard M.

    2000-01-01

    Landsliding in response to rainfall involves physical processes that operate on disparate timescales. Relationships between these timescales guide development of a mathematical model that uses reduced forms of Richards equation to evaluate effects of rainfall infiltration on landslide occurrence, timing, depth, and acceleration in diverse situations. The longest pertinent timescale is A/D0, where D0 is the maximum hydraulic diffusivity of the soil and A is the catchment area that potentially affects groundwater pressures at a prospective landslide slip surface location with areal coordinates x, y and depth H. Times greater than A/D0 are necessary for establishment of steady background water pressures that develop at (x, y, H) in response to rainfall averaged over periods that commonly range from days to many decades. These steady groundwater pressures influence the propensity for landsliding at (x, y, H), but they do not trigger slope failure. Failure results from rainfall over a typically shorter timescale H2/D0 associated with transient pore pressure transmission during and following storms. Commonly, this timescale ranges from minutes to months. The shortest timescale affecting landslide responses to rainfall is √(H/g), where g is the magnitude of gravitational acceleration. Postfailure landslide motion occurs on this timescale, which indicates that the thinnest landslides accelerate most quickly if all other factors are constant. Effects of hydrologic processes on landslide processes across these diverse timescales are encapsulated by a response function, R(t*) = √(t*/π) exp (-1/t*) - erfc (1/√t*), which depends only on normalized time, t*. Use of R(t*) in conjunction with topographic data, rainfall intensity and duration information, an infinite-slope failure criterion, and Newton's second law predicts the timing, depth, and acceleration of rainfall-triggered landslides. Data from contrasting landslides that exhibit rapid, shallow motion and slow, deep

  17. Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

    Directory of Open Access Journals (Sweden)

    Koji Ataka

    Full Text Available BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(lowCCR2(+CXCR4(high, as distinct from CX3CR1(highCCR2(-CXCR4(low resident microglia, and express higher levels of interleukin-1β (IL-1β but lower levels of tumor necrosis factor-α (TNF-α. Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1 in the bone marrow and increases the frequency of CXCR4(+ monocytes in peripheral circulation. And then a chemokine (C-C motif receptor 2 (CCR2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

  18. Alefacept (anti-CD2 causes a selective reduction in circulating effector memory T cells (Tem and relative preservation of central memory T cells (Tcm in psoriasis

    Directory of Open Access Journals (Sweden)

    Novitskaya Inna

    2007-06-01

    Full Text Available Abstract Background Alefacept (anti-CD2 biological therapy selectively targets effector memory T cells (Tem in psoriasis vulgaris, a model Type 1 autoimmune disease. Methods Circulating leukocytes were phenotyped in patients receiving alefacept for moderate to severe psoriasis. Results In all patients, this treatment caused a preferential decrease in effector memory T cells (CCR7- CD45RA- (mean 63% reduction for both CD4+ and CD8+ Tem, while central memory T cells (Tcm (CCR7+CD45RA- were less affected, and naïve T cells (CCR7+CD45RA+ were relatively spared. Circulating CD8+ effector T cells and Type 1 T cells (IFN-γ-producing were also significantly reduced. Conclusion Alefacept causes a selective reduction in circulating effector memory T cells (Tem and relative preservation of central memory T cells (Tcm in psoriasis.

  19. The MADS domain protein DIANA acts together with AGAMOUS-LIKE80 to specify the central cell in Arabidopsis ovules.

    Science.gov (United States)

    Bemer, Marian; Wolters-Arts, Mieke; Grossniklaus, Ueli; Angenent, Gerco C

    2008-08-01

    MADS box genes in plants consist of MIKC-type and type I genes. While MIKC-type genes have been studied extensively, the functions of type I genes are still poorly understood. Evidence suggests that type I MADS box genes are involved in embryo sac and seed development. We investigated two independent T-DNA insertion alleles of the Arabidopsis thaliana type I MADS box gene AGAMOUS-LIKE61 (AGL61) and showed that in agl61 mutant ovules, the polar nuclei do not fuse and central cell morphology is aberrant. Furthermore, the central cell begins to degenerate before fertilization takes place. Although pollen tubes are attracted and perceived by the mutant ovules, neither endosperm development nor zygote formation occurs. AGL61 is expressed in the central cell during the final stages of embryo sac development. An AGL61:green fluorescent protein-beta-glucoronidase fusion protein localizes exclusively to the polar nuclei and the secondary nucleus of the central cell. Yeast two-hybrid analysis showed that AGL61 can form a heterodimer with AGL80 and that the nuclear localization of AGL61 is lost in the agl80 mutant. Thus, AGL61 and AGL80 appear to function together to differentiate the central cell in Arabidopsis. We renamed AGL61 DIANA, after the virginal Roman goddess of the hunt.

  20. Central Nervous System-Peripheral Immune System Dialogue in Neurological Disorders: Possible Application of Neuroimmunology in Urology.

    Science.gov (United States)

    Park, Hyun-Sun; Park, Min-Jung; Kwon, Min-Soo

    2016-05-01

    Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood-brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction.

  1. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    DEFF Research Database (Denmark)

    Hannibal, J; Kankipati, L; Strang, C E

    2014-01-01

    ). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we......-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex...... including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey...

  2. System dynamics modeling of nitrogen removal in a stormwater infiltration basin with biosorption-activated media.

    Science.gov (United States)

    Xuan, Zhemin; Chang, Ni-Bin; Wanielista, Martin P; Williams, Evan Shane

    2013-07-01

    Stormwater infiltration basins, one of the typical stormwater best management practices, are commonly constructed for surface water pollution control, flood mitigation, and groundwater restoration in rural or residential areas. These basins have soils with better infiltration capacity than the native soil; however, the ever-increasing contribution of nutrients to groundwater from stormwater due to urban expansion makes existing infiltration basins unable to meet groundwater quality criteria related to environmental sustainability and public health. This issue requires retrofitting current infiltration basins for flood control as well as nutrient control before the stormwater enters the groundwater. An existing stormwater infiltration basin in north-central Florida was selected, retrofitted, and monitored to identify subsurface physiochemical and biological processes during 2007-2010 to investigate nutrient control processes. This implementation in the nexus of contaminant hydrology and ecological engineering adopted amended soil layers packed with biosorption activated media (BAM; tire crumb, silt, clay, and sand) to perform nutrient removal in a partitioned forebay using a berm. This study presents an infiltration basin-nitrogen removal (IBNR) model, a system dynamics model that simulates nitrogen cycling in this BAM-based stormwater infiltration basin with respect to changing hydrologic conditions and varying dissolved nitrogen concentrations. Modeling outputs of IBNR indicate that denitrification is the biogeochemical indicator in the BAM layer that accounted for a loss of about one third of the total dissolved nitrogen mass input.

  3. Co-occurrence of Calcifying Odontogenic Cyst, Aggressive Central Giant Cell Granuloma and Central Odontogenic Fibroma: Report of a Very Rare Entity and Its Surgical Management

    Directory of Open Access Journals (Sweden)

    Touraj Vaezi

    2016-09-01

    Full Text Available Calcifying odontogenic cyst (COC, Central odontogenic fibroma (COF and aggressive central giant cell granuloma (CGCG are rare pathologic diseases affecting the jaws. While the Co-existence of two of them is reported in the literature, existence of all three conditions in one patient is an extremely rare entity. In the present report, initial biopsy revealed fibrosarcoma, therefore mandibular resection was performed for the subject. Sectional Histopathologic evaluation revealed the co-existence of three conditions through histopathologic evaluation. This report emphasizes the importance of precise microscopical evaluation of jaw lesions and thorough sectional examination of the lesions to reach the precise diagnosis. Treatment modalities and follow-up radiographs are also provided to help clinicians manage these entities.

  4. Relationship between S-100 positive dendritic cell and lymphocyte infiltration in thyroid papillary carcinoma and cervical metastasis in papillary thyroid cancer%甲状腺乳头状癌组织中S-100阳性树突状细胞及淋巴细胞浸润与颈部淋巴结转移关系的研究

    Institute of Scientific and Technical Information of China (English)

    牛少雄; 木拉提·沙特巴尔德; 袁明; 牛建华

    2012-01-01

    目的 探讨甲状腺乳头状癌组织中S-100阳性树突状细胞及淋巴细胞浸润与颈部淋巴结转移的关系.方法 50例甲状腺乳头状癌行颈部淋巴结清扫术患者,采用免疫组织化学方法检测甲状腺癌组织中S-100阳性树突状细胞及淋巴细胞浸润情况,分为S-100阳性树突状细胞及淋巴细胞阳性浸润者(A组)与单独S-100阳性树突状细胞或淋巴细胞浸润者(B组),均行术后颈部淋巴结组织病理检查,比较2组颈部淋巴结转移率.结果 A组颈部淋巴结转移率(27.78%)低于B组(78.12%),2组比较差异有统计学意义(P<0.05).结论 甲状腺乳头癌组织中S-100阳性树突状细胞及淋巴细胞浸润情况与颈部淋巴结转移密切相关.%Objective To study the relationship between S-100 positive dendritic cell and lymphocytes infiltration in thyroid papillary carcinoma and cervical metastasis in patients with papillary thyroid cancer. Methods S-100 positive dendritic cell and lymphocytes infiltration in thyroid papillary carcinoma in fifty patients with neck lymph node dissection were detected with immunohistochemical technique. According to results, the patients were divided into group A with both dendritic cell and lymphocyte infiltration and group B with dendritic cell or lymphocyte infiltration. After lymph node dissection, the two groups were detected pathologically and the rate of metastasis of two groups was compared statistically. Results The metastatic rate of cervical lymphocyte was lower in group A (27. 78%) than that in group B (78. 12%), which showed a significant difference between two groups(P<0. 05). Conclusion S-100 positive dendritic cell and lymphocyte infiltration in thyroid papillary carcinoma are closely correlated with cervical metastasis.

  5. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J

    2012-01-01

    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...

  6. Insulin-like growth factor actions during development of neural stem cells and progenitors in the central nervous system.

    Science.gov (United States)

    Ye, Ping; D'Ercole, A Joseph

    2006-01-01

    Insulin-like growth factor-I (IGF-I) plays a key role in normal development. Recent studies show that IGF-I exerts a wide variety actions in the central nervous system during development as well as in adulthood. This report reviews recent developments on IGF-I actions and its mechanisms in the central nervous system, with a focus on its actions during the development of neural stem cells and progenitors. Available data strongly indicate that IGF-I shortens the length of the cell cycle in neuron progenitors during embryonic life and has an influence on the growth of all neural cell types. The phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase pathways seem to be the predominant mediators of IGF-I-stimulated neural cell proliferation and survival. IGF-I actions, however, likely depend on cell type, developmental stage, and microenvironmental milieu.

  7. INFILTRATION CHARACTERISTICS IN MULTI-FLOOR BUILDINGS

    Directory of Open Access Journals (Sweden)

    Dilek KUMLUTAŞ

    1999-02-01

    Full Text Available Infiltration or in other words the air leakage in buildings has an important role on heat load calculations. The rate of this loss has been estimated as 20 to 30 % of the total load. The indicated important effect of infiltration on the load calculations needs a reliable method for the determination of air leakeage level in buildings. Meantime, the rate of infiltration has an additional importance at the area of thermal comfort studies which deals with the air quality of enclosed volumes. During this research study, first the mechanism of infiltration and the major components of the phenomena (wind pressure, temperature difference was discussed together with the theoretical considerations. Later, several conventional engineering approachs and emprical methods was reviewed and compared among each others. At the last part of the paper, the modified DIN 4701 method which is presently used in Turkey, and some other algorithms was applied to some pilot buildings and the predictions was compared with experimental results.

  8. Tunable Beam Diffraction in Infiltrated Microstructured Fibers

    DEFF Research Database (Denmark)

    Rosberg, Christian Romer; Bennet, Francis H.; Neshev, Dragomir N.;

    We experimentally study beam propagation in two dimensional photonic lattices in microstructured optical fibers infiltrated with high index liquids. We demonstrate strongly tunable beam diffraction by dynamically varying the coupling between individual lattice sites....

  9. Mathematical Analysis and Optimization of Infiltration Processes

    Science.gov (United States)

    Chang, H.-C.; Gottlieb, D.; Marion, M.; Sheldon, B. W.

    1997-01-01

    A variety of infiltration techniques can be used to fabricate solid materials, particularly composites. In general these processes can be described with at least one time dependent partial differential equation describing the evolution of the solid phase, coupled to one or more partial differential equations describing mass transport through a porous structure. This paper presents a detailed mathematical analysis of a relatively simple set of equations which is used to describe chemical vapor infiltration. The results demonstrate that the process is controlled by only two parameters, alpha and beta. The optimization problem associated with minimizing the infiltration time is also considered. Allowing alpha and beta to vary with time leads to significant reductions in the infiltration time, compared with the conventional case where alpha and beta are treated as constants.

  10. 24 CFR 3280.505 - Air infiltration.

    Science.gov (United States)

    2010-04-01

    ... DEVELOPMENT MANUFACTURED HOME CONSTRUCTION AND SAFETY STANDARDS Thermal Protection § 3280.505 Air infiltration...-to-ceiling and wall-to-floor connections shall be caulked or otherwise sealed. When walls...

  11. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    Directory of Open Access Journals (Sweden)

    Theodore S. Johnson

    2012-01-01

    Full Text Available Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

  12. Stormwater infiltration trenches: a conceptual modelling approach.

    Science.gov (United States)

    Freni, Gabriele; Mannina, Giorgio; Viviani, Gaspare

    2009-01-01

    In recent years, limitations linked to traditional urban drainage schemes have been pointed out and new approaches are developing introducing more natural methods for retaining and/or disposing of stormwater. These mitigation measures are generally called Best Management Practices or Sustainable Urban Drainage System and they include practices such as infiltration and storage tanks in order to reduce the peak flow and retain part of the polluting components. The introduction of such practices in urban drainage systems entails an upgrade of existing modelling frameworks in order to evaluate their efficiency in mitigating the impact of urban drainage systems on receiving water bodies. While storage tank modelling approaches are quite well documented in literature, some gaps are still present about infiltration facilities mainly dependent on the complexity of the involved physical processes. In this study, a simplified conceptual modelling approach for the simulation of the infiltration trenches is presented. The model enables to assess the performance of infiltration trenches. The main goal is to develop a model that can be employed for the assessment of the mitigation efficiency of infiltration trenches in an integrated urban drainage context. Particular care was given to the simulation of infiltration structures considering the performance reduction due to clogging phenomena. The proposed model has been compared with other simplified modelling approaches and with a physically based model adopted as benchmark. The model performed better compared to other approaches considering both unclogged facilities and the effect of clogging. On the basis of a long-term simulation of six years of rain data, the performance and the effectiveness of an infiltration trench measure are assessed. The study confirmed the important role played by the clogging phenomenon on such infiltration structures.

  13. Reversible fatty infiltration of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Bostel, F.; Hauger, W.

    1987-11-01

    Case studies show that acute pancreatitis occurring independently or combined with a preceding abuse of alcohol may be the cause of fatty infiltration of the liver. These fat areas can evolve in a very short time and provoke in the case of focal incidence diagnostic problems of differentiation against abscesses of metastases. Due to this fact and because of the rapid reversibility of the fatty infiltration under therapy, the safest method to clarify the situation consists of short-term CT controls.

  14. Small early gastric cancer with special reference to macrophage infiltration.

    Science.gov (United States)

    Caruso, R A; Vitullo, P; Modesti, A; Inferrera, C

    1999-04-01

    The authors investigate the tumor-infiltrating cells in small early gastric cancer (EGC) (ultrastructural features and interactions of macrophages with tumor cells and other inflammatory cells. Sections from 20 small EGCs were stained by immunohistochemical methods for CD20, UCHL1, CD4, CD8, and CD68 (electron microscopic examination was used in 6 of the 20). In all of the tumors, CD68-positive macrophages accounted for most tumor-infiltrating cells, with UCHL1-positive T lymphocytes, eosinophils, and neutrophils being the next most frequent. We found only a few CD20-positive B lymphocytes. Electron microscopic analysis revealed macrophages with many phagocytic vesicles, cellular debris, and apoptotic bodies. These morphologic data show that macrophages are actively phagocytic. The tumor cells in contact with macrophages showed no cytopathic changes. These data do not support a macrophage-mediated cancer lysis like the ones reported in some systems in vitro. Contacts among macrophages and other inflammatory cells formed a recurrent ultrastructural hallmark and suggest a communication among varying inflammatory cell types during the precocious host response to gastric neoplasia.

  15. PROPHYLACTIC ADMINISTRATION OF DOXYCYCLINE REDUCES CENTRAL VENOUS CATHETER INFECTIONS IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Mohamed Kharfan-Dabaja

    2013-02-01

    Full Text Available Hematopoietic stem cells are usually transfused through a central venous catheter (CVC, which also facilitates administration of medications and intravenous fluids. We had observed high rate of catheter-related blood-stream infection (CR-BSI at our Bone Marrow Transplantation (BMT unit despite prescribing fluoroquinolones for anti-bacterial prophylaxis. Accordingly, we implemented prophylactic use of a relatively inexpensive broad spectrum antibiotic, namely doxycycline to address this problem. We wanted to investigate whether doxycycline prophylaxis reduces CR-BSI rate. Data was collected retrospectively on 54 consecutive patients, 26 of whom received doxycycline (doxycycline group, and we compared their outcomes to a previous cohort of 28 patients who did not receive doxycycline (comparison group. The groups were comparable in regards to age, gender, hematopoietic cell transplant type, and primary diagnosis. No CVC infection (0% was observed in the doxycycline group, while 5 infection episodes (18.5% occurred in 4 patients in the comparison group (p<0.001. Episodes of CR-BSI were due to: Escherichia-coli (EC=1, coagulase-negative Staphylococcus-spp (CNSS=2, both EC & CNSS=1. Our results demonstrate that CR-BSI was reduced significantly after introducing doxycycline. This finding suggests a beneficial role for systemic use of doxycycline prophylaxis to prevent CR-BSI in adult BMT patients. Nevertheless, a randomized controlled study is warranted to confirm these findings.

  16. Early central nervous system complications after reduced-intensity stem cell transplantation.

    Science.gov (United States)

    Kishi, Yukiko; Miyakoshi, Shigesaburo; Kami, Masahiro; Ikeda, Masayuki; Katayama, Yuta; Murashige, Naoko; Kusumi, Eiji; Yuji, Koichiro; Kobayashi, Kazuhiko; Kato, Daisuke; Hamaki, Tamae; Matsumura, Tomoko; Kim, Sung-Won; Morinaga, Shinichi; Mori, Shinichiro; Kanemaru, Mineo; Hayashi, Tatsuyuki; Takaue, Yoichi; Taniguchi, Shuichi

    2004-08-01

    To investigate clinical characteristics of early central nervous system (CNS) complications after reduced-intensity stem cell transplantation (RIST), we reviewed the medical records of 232 patients who had undergone RIST for hematologic diseases at our institutions between September 1999 and June 2003. All patients had received purine analog-based preparative regimens. Stem cell sources comprised granulocyte colony-stimulating factor-mobilized blood from HLA-identical or 1 locus-mismatched related donors (n = 151), unrelated bone marrow (n = 44), or unrelated cord blood (n = 37). Graft-versus-host disease prophylaxis incorporated cyclosporine with or without methotrexate. Diagnosis of CNS complications was based on clinical, radiologic, and microbiological findings. CNS complications occurred in 18 patients (7.8%), with a median onset of 22 days, and were infectious (n = 1), metabolic (n = 15), or cerebrovascular (n = 2). Symptoms included seizures (n = 7), visual disturbance (n = 2), headache (n = 8), nausea (n = 8), vomiting (n = 6), impaired consciousness (n = 16), and hemiparesis (n = 3). Complications improved promptly in 10 patients, and 8 patients died without improvement within 30 days. Multivariate analysis with logistic regression identified umbilical cord blood transplantation as a significant risk factor for early CNS complications (odds ratio, 14.5; 95% confidence interval, 3.7-56.9; P <.0001). CNS complications are a significant problem after RIST, particularly with umbilical cord blood. Limbic encephalopathy is an unrecognized subtype of neurotoxicity after umbilical cord blood transplantation.

  17. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord.

    Science.gov (United States)

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-10-11

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is known to affect cells within other postnatal neurogenic niches. This study used whole cell patch clamp electrophysiology and intracellular dye-loading in in vitro Wistar rat spinal cord slices to characterise ependymal cells and their ability to respond to GABA. Ependymal cells were defined by their passive response properties and low input resistances. Extensive dye-coupling was observed between ependymal cells; this was confirmed as gap junction coupling using the gap junction blocker, 18β-glycyrrhetinic acid, which significantly increased the input resistance of ependymal cells. GABA depolarised all ependymal cells tested; the partial antagonism of this response by bicuculline and gabazine indicates that GABA(A) receptors contribute to this response. A lack of effect by baclofen suggests that GABA(B) receptors do not contribute to the GABAergic response. The ability of ependymal cells to respond to GABA suggests that GABA could be capable of influencing the proliferation and differentiation of cells within the neurogenic niche of the postnatal spinal cord.

  18. In vivo imaging in autoimmune diseases in the central nervous system.

    Science.gov (United States)

    Kawakami, Naoto

    2016-07-01

    Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood-brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments.

  19. Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.

    Science.gov (United States)

    Chen, Hsuen-Chin; Lai, Show-Yun; Sung, Jui-Min; Lee, Shu-Hwae; Lin, Yu-Chin; Wang, Wei-Kung; Chen, Yee-Chun; Kao, Chuan-Liang; King, Chwan-Chuen; Wu-Hsieh, Betty A

    2004-07-01

    Activation and expansion of dengue virus-specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8(+) T cell