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Sample records for peripheral lymphoid system

  1. Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs.

    Science.gov (United States)

    Yuan, Jin; Zhu, Mengjiao; Deng, Shaofeng; Fan, Shuangqi; Xu, Hailuan; Liao, Jiedan; Li, Peng; Zheng, Jingfang; Zhao, Mingqiu; Chen, Jinding

    2018-05-02

    Classical swine fever virus (CSFV) causes a highly lethal disease in pigs, which is characterized by immunosuppression. Leukopenia is known to be a possible mechanism of immunosuppression during CSFV infection. As a new and specialized form of cell death, pyroptosis is the key response of the innate immune system to pathogens, and is widely involved in the occurrence and development of infectious diseases. However, the relationship between CSFV and pyroptosis has not been explored. In this study, we investigated the occurrence of pyroptosis in pigs following CSFV infection. According to qRT-PCR assay results, the prevalence of this virus in peripheral lymphoid organs (tonsils, lymph nodes, and spleen) was much higher than that in other organs. Severe bleeding, necrosis, and a significant reduction in lymphocytes were found in the peripheral lymphoid organs of CSFV-infected pigs based on histological examination. In-depth studies showed that an increased ratio of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were present in the peripheral lymphoid organs of the CSFV-infected group according to immunohistochemistry. Meanwhile, the p10 subunit and activity of caspase-1, which is a regulator of pyroptosis, the N-terminal domain of gasdermin D, which is an executor of pyroptosis, and the cleavage and secretion of IL-1b, which is a product of pyroptosis were increased in the peripheral lymphoid organs of the CSFV-infected group. Together, these results demonstrated that pyroptosis is involved in CSFV-induced cell death in vivo, which provides a new understanding of the mechanism associated with lymphocyte depletion and immunosuppression in pigs infected with this virus. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.

    Science.gov (United States)

    Zhang, Zongde; Li, Jianjian; Zheng, Wencheng; Zhao, Guang; Zhang, Hong; Wang, Xiaofei; Guo, Yaqian; Qin, Chuan; Shi, Yan

    2016-02-16

    Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Peripheral tissue homing receptor control of naïve, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues.

    Science.gov (United States)

    Brinkman, C Colin; Peske, J David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues.

  4. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

    International Nuclear Information System (INIS)

    Skidmore, B.J.; Miller, L.S.

    1978-01-01

    A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 10 5 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

  5. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras

  6. Total lymphoid irradiation in refractory systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-01-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental

  7. Alterations of morphology of lymphoid organs and peripheral blood indicators under the influence of gold nanoparticles in rats

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    Alla B. Bucharskaya

    2016-01-01

    Full Text Available At present, gold nanoparticles (GNPs are widely used in biomedical applications such as cancer diagnostics and therapy. Accordingly, the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant attention. Here, we report the effects of prolonged peroral administration of GNPs with different sizes (2, 15 and 50nm on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals. The experiment was conducted on 24 white mongrel male rats weighing 180–220g, gold nanospheres sizes 2, 15 and 50nm were administered orally for 15 days at a dosage of 190μg/kg of animal body weight. The GNPs were conjugated with polyethylene glycol to increase their biocompatibility and bioavailability. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of GNPs with size of 50nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

  8. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  9. Stroma cell priming in enteric lymphoid organ morphogenesis

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    Manuela eFerreira

    2012-07-01

    Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

  10. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  11. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

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    David R. Withers

    2017-10-01

    Full Text Available The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3 are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  12. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

  13. Immunohistochemical evidences showing the presence of thymulin containing cells located in involuted thymus and in peripheral lymphoid organs

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    Hugo Folch

    2010-01-01

    Full Text Available Thymulin is a well-characterized thymic hormone that exists as a nonapeptide coupled to equimolar amounts of Zn2+. Thymulin is known to have multiple biological roles, including T cell differentiation, immune regulation, and analgesic functions. It has been shown that thymulin is produced by the reticulo-epithelial cells of the thymus, and it circulates in the blood from the moment of birth, maintain its serum level until puberty diminishing thereafter in life. To study the localization of this hormone, we prepared polyclonal and monoclonal antibodies against the commercial peptide and utilized immunocytochemical techniques for visualization. The results indicate that thymulin stains the thymic reticular cells, the outer layers of Hassall's corpuscles and a large round cellular type, which is keratin-negative and does not show affinity for the common leukocyte antigen (CD-45. In mice, this thymulin-positive cell remains in the thymus throughout life and even appears in relatively increased numbers in old involuted thymi. It also appears in thymus-dependent areas of the spleen and lymph nodes, demonstrating that at least one of the thymus cells containing this peptide can be found in peripheral lymphoid tissue.

  14. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest

  15. Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

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    Meike Mitsdoerffer

    2016-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS, which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease, however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function and clinical significance. Mechanistic studies in patiens are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.

  16. 'Managing' the immune system with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.

    1981-01-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis

  17. Determination of the effects of extremely low frequency electromagnetic fields on the percentages of peripheral blood leukocytes and histology of lymphoid organs of the mouse

    International Nuclear Information System (INIS)

    Cicekcibasi, Aynur E.; Salbacak, A.; Buyukmumcu, M.; Okudan, N.; Celik, I.; Ozkan, Y.

    2008-01-01

    Objective was to determine the effects of very weak, extremely low frequency (50Hz) electromagnetic field (ELF-EMF) on the relative spleen weight, lymphoid organ histology, peripheral blood leukocyte and alpha-naphthyl acetate esterase positive (ANAE-positive) lymphocyte percentages of mouse. The study was carried out in the Scientific Research and Application Center of Selcuk University, Konya, Turkey in 2005. A total of 120 Swiss albino mice were divided into 6 groups (20 in each group). The experimental animals were exposed to 1, 2, 3, 4 and 5 uT flux intensities (rms) of EMF at 50 Hz for 40 days. In the exposure groups with 20 animals, the body weight (BW) increased gradually in higher field intensities and reached at peak level in the 4 uT and then slightly decreased. The relative spleen weight (% of BW) was not affected. The ELF-EMF treatment did not cause any significant change in lymphocyte, monocyte and ANA-positive lymphocyte ratios, whereas percentages of neutropholis and basophiles changed non-linearly. Any change in the lymphoid organ histology which attributable to the field effect, was not observed in the exposure groups. Extremely frequency-EMF exposure with the flux intensities between 1-5 uT for 40 days did not cause any effect on the relative spleen weight, lymphoid organ histology, leukocyte and ANAE-positive lymphocyte percentages of the mouse. (author)

  18. Genotypic and phenotypic aspects of primary immunodeficiency diseases of the lymphoid system

    NARCIS (Netherlands)

    J.G. Noordzij

    2002-01-01

    textabstractThis thesis focuses on the immunological phenotype, the mutation analysis, and the residual activity of mutated proteins in patients with PID of the lymphoid system. During this project, we have investigated possible genotype-(immuno)phenotype relationships in patients with antibody

  19. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

    Science.gov (United States)

    Knop, E; Knop, N

    2001-03-01

    Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

  20. Activation of human B lymphocytes. 8. Differential radiosensitivity of subpopulations of lymphoid cells involved in the polyclonally-induced PFC responses of peripheral blood B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Fauci, A S; Pratt, K R; Whalen, G [National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA)

    1978-11-01

    The differential effect of various doses of irradiation on subpopulations of human peripheral blood lymphoid cells involved in the pokeweed mitogen induced PFC response against sheep red blood cells was studied. The plaque forming B cells were quite sensitive to low doses of irradiation with complete suppression of responses at 300 to 500 rad. On the contrary, helper T-cell function was resistant to 2000 rad. Co-culture of irradiated T cells with autologous or allogeneic B cells resulted in marked enhancement of PFC responses consistent with the suppression of naturally occurring suppressor cells with a resulting pure helper effect. Irradiated T-cell-depleted suspensions failed to produce this effect as did heat killed T cells, whereas mitomycin C treated T cells gave effects similar to irradiated T cells. These findings are consistent with a lack of requirement of cell division for a T-cell helper effect and a requirement of mitosis or another irradiation sensitive, mitomycin C sensitive process for a T-suppressor cell effect. These studies have potential relevance in the evaluation of subpopulations of human lymphoid cells involved in antibody production in normal individuals and in disease states.

  1. Imaging of the peripheral vascular system

    International Nuclear Information System (INIS)

    Gould, S.A.; Pond, G.D.; Pinsky, S.; Moss, G.S.; Srikantaswamy, S.; Ryo, U.Y.

    1984-01-01

    This book is limited neither to the peripheral vascular system nor to diagnostic imaging techniques. Its 18 chapters cover nonimaging blood-flow techniques (Doppler ultrasound, plethysmography) as well as noninvasive and invasive imaging techniques (ultrasound, computed tomography, radionuclide digital-subtraction angiography, and contrast angiography). These are applied not only to the peripheral vascular system but also to the aorta and vena cava

  2. Dynamics of Lymphocyte Populations during Trypanosoma cruzi Infection: From Thymocyte Depletion to Differential Cell Expansion/Contraction in Peripheral Lymphoid Organs

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    Alexandre Morrot

    2012-01-01

    Full Text Available The comprehension of the immune responses in infectious diseases is crucial for developing novel therapeutic strategies. Here, we review current findings on the dynamics of lymphocyte subpopulations following experimental acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. In the thymus, although the negative selection process of the T-cell repertoire remains operational, there is a massive thymocyte depletion and abnormal release of immature CD4+CD8+ cells to peripheral lymphoid organs, where they acquire an activated phenotype similar to activated effector or memory T cells. These cells apparently bypassed the negative selection process, and some of them are potentially autoimmune. In infected animals, an atrophy of mesenteric lymph nodes is also observed, in contrast with the lymphocyte expansion in spleen and subcutaneous lymph nodes, illustrating a complex and organ specific dynamics of lymphocyte subpopulations. Accordingly, T- and B-cell activation is seen in subcutaneous lymph nodes and spleen, but not in mesenteric lymph nodes. Lastly, although the function of peripheral CD4+CD8+ T-cell population remains to be defined in vivo, their presence may contribute to the immunopathological events found in both murine and human Chagas disease.

  3. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

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    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.

  4. Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue.

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    Amita Joshi

    Full Text Available Treatment of invasive adenovirus (Ad disease in hematopoietic stem cell transplant (SCT recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977 and late protein hexon (H-892 were compared in peripheral blood (PB and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16-24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients.

  5. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

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    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  6. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  7. Peripheral Nervous System Manifestations in Systemic Autoimmune Diseases

    OpenAIRE

    COJOCARU, Inimioara Mihaela; COJOCARU, Manole; SILOSI, Isabela; VRABIE, Camelia Doina

    2014-01-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement ...

  8. Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide

    OpenAIRE

    Salem, Mohamed L.; Al-Khami, Amir A.; El-Nagaar, Sabry A.; Zidan, Abdel-Aziz A.; Al-Sharkawi, Ismail M.; Díaz-Montero, C. Marcela; Cole, David J.

    2012-01-01

    Recently, we showed that post cyclophosphamide (CTX) microenvironment benefits the function of transferred T cells. Analysis of the kinetics of cellular recovery after CTX treatment showed that a single 4 mg/mouse CTX treatment decreased the absolute number of leukocytes in the peripheral blood (PBL) at days 3-15, and in the spleen and bone marrow (BM) at days 3-6. The absolute numbers of CD11c+CD11b− and CD11c+CD11b+ dendritic cells (DCs), CD11b+ and Ly6G+ myeloid cells, T and B cells, CD4+C...

  9. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: Similar outcomes with umbilical cord blood and unrelated donor peripheral blood

    NARCIS (Netherlands)

    C.A. Rodrigues (Celso Arrais); V. Rocha (Vanderson); P. Dreger (Peter); C.G. Brunstein (Claudio); H. Sengeloev (Henrik); J. Finke (Jürgen); M. Mohty (Mohamad); B. Rio (Bernard); E. Petersen (Eefke); F. Guilhot (François); D. Niederwieser (Dietger); J.J. Cornelissen (Jan); P. Jindra (Pavel); A. Nagler (Arnon); N. Fegueux (Nathalie); H. Schoemans (Hélène); A. Ruggeri (Annelisa); S.P. Robinson (Stephen); E. Gluckman (Eliane); C. Canals (Carmen); A. Sureda (Anna)

    2014-01-01

    textabstractWe have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who

  10. Establishment of an In Vitro System Representing the Chicken Gut-Associated Lymphoid Tissue

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a+, a majority of those emigrating onto the supporting membrane were Bu-1a− and IgM+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined. PMID:23185307

  11. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Noorjahan Banu Alitheen

    Full Text Available The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+, a majority of those emigrating onto the supporting membrane were Bu-1a(- and IgM(+. Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240 was examined.

  12. Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.

    Science.gov (United States)

    Symowski, Cornelia; Voehringer, David

    2017-01-01

    Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell-cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system.

  13. Peripheral pin alignment system for fuel assemblies

    International Nuclear Information System (INIS)

    Anthony, A.J.

    1981-01-01

    An alignment system is provided for nuclear fuel assemblies in a nuclear core. The core support structure of the nuclear reactor includes upwardly pointing alignment pins arranged in a square grid and engage peripheral depressions formed in the lateral periphery of the lower ends of each of the fuel assemblies of the core. In a preferred embodiment, the depressions are located at the corners of the fuel assemblies so that each depression includes one-quarter of a cylindrical void. Accordingly, each fuel assembly is positioned and aligned by one-quarter of four separate alignment pins which engage the fuel assemblies at their lower exterior corners. (author)

  14. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Science.gov (United States)

    Lim, Chee Han; Voedisch, Sabrina; Wahl, Benjamin; Rouf, Syed Fazle; Geffers, Robert; Rhen, Mikael; Pabst, Oliver

    2014-07-01

    Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  15. Independent bottlenecks characterize colonization of systemic compartments and gut lymphoid tissue by salmonella.

    Directory of Open Access Journals (Sweden)

    Chee Han Lim

    2014-07-01

    Full Text Available Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics.

  16. Prion pathogenesis and secondary lymphoid organs (SLO)

    Science.gov (United States)

    Mabbott, Neil A.

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases. PMID:22895090

  17. Peripheral Vestibular System Disease in Vestibular Schwannomas

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

    2015-01-01

    density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas...... are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which...

  18. Artificial engineering of secondary lymphoid organs.

    Science.gov (United States)

    Tan, Jonathan K H; Watanabe, Takeshi

    2010-01-01

    Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or blood. The overall organization of lymphoid tissue is vital for effective antigen screening and recognition, and is a feature which artificially constructed lymphoid organoids endeavor to replicate. Synthesis of artificial lymphoid tissues is an emerging field that aims to provide therapeutic application for the treatment of severe infection, cancer, and age-related involution of secondary lymphoid tissues. The development of murine artificial lymphoid tissues has benefited greatly from an understanding of organogenesis of lymphoid organs, which has delineated cellular and molecular elements essential for the recruitment and organization of lymphocytes into lymphoid structures. Here, the field of artificial lymphoid tissue engineering is considered including elements of lymphoid structure and development relevant to organoid synthesis. (c) 2010 Elsevier Inc. All rights reserved.

  19. [Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

    Science.gov (United States)

    Knop, E; Knop, N

    2003-11-01

    Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

  20. Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing.

    Science.gov (United States)

    Nikolich-Žugich, J; Davies, J S

    2017-03-01

    Ageing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs. © 2017 British Society for Immunology.

  1. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  2. The Multifactorial role of Peripheral Nervous System in Bone Growth

    Science.gov (United States)

    Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

    2017-09-01

    Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

  3. Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

    Science.gov (United States)

    Douglas, Darlene S.; Popko, Brian

    2009-01-01

    Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

  4. The peripheral GABAergic system as a target in endocrine disorders

    NARCIS (Netherlands)

    Gladkevich, A; Korf, J; Hakobyan, VP; Melkonyan, KV

    2006-01-01

    In addition to its well-recognized function as a cerebral inhibitory transmitter, less well established is the role of GABA in peripheral nervous and endocrine systems. We Summarize current evidence that GABA serves as a neurotransmitter or neuromodulator in the autonomic nervous system and as a

  5. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    Science.gov (United States)

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  6. Why Innate Lymphoid Cells?

    Science.gov (United States)

    Kotas, Maya E; Locksley, Richard M

    2018-06-19

    Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 + T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Prions and lymphoid organs

    Science.gov (United States)

    O’Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1−/− lymph nodes and rates of neuroinvasion in TNFR1−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article. PMID:23357827

  8. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    An outline review notes recent work on total lymphoid irradiation (TLI) as a means of preparing patients for grafts and particularly for bone-marrow transplantation. T.L.I. has proved immunosuppressive in rats, mice, dogs, monkeys and baboons; when given before bone-marrow transplantation, engraftment took place without, or with delayed rejection or graft-versus-host disease. Work with mice has indicated that the thymus needs to be included within the irradiation field, since screening of the thymus reduced skin-graft survival from 50 to 18 days, though irradiation of the thymus alone has proved ineffective. A more lasting tolerance has been observed when T.L.I. is followed by an injection of donor bone marrow. 50% of mice treated in this way accepted allogenic skin grafts for more than 100 days, the animals proving to be stable chimeras with 50% of their peripheral blood lymphocytes being of donor origin. Experiments of a similar nature with dogs and baboons were not so successful. (U.K.)

  9. Optical cuff for optogenetic control of the peripheral nervous system

    Science.gov (United States)

    Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

    2018-02-01

    Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

  10. Food allergens and mucosal immune systems with special reference to recognition of food allergens by gut-associated lymphoid tissue

    Directory of Open Access Journals (Sweden)

    Shuichi Kaminogawa

    1999-01-01

    Full Text Available Food allergy, triggered by an aberrant immune response elicited by orally ingested food allergens, is generated through a complicated mechanism because the allergen interacts with the mucosal immune system (the gut- associated lymphoid tissue, GALT and the resulting immune response affects the generation of allergy. This review will describe the process by which antigens or allergens are recognized by the GALT and the characteristic immune responses induced thereafter. Orally administered antigens induce distinct immune responses in the Peyer's patches, lamina propria and the intestinal epithelium. In addition to these local immune responses in the gut, ingested antigens are known to affect systemic immunity. These may induce a suppressed state of systemic immune responsiveness, which is called oral tolerance, or in some cases they may elicit a systemic IgE antibody response which may lead to allergic reactions. Information on the regions on food allergens recognized by T cells and IgE antibodies is important in understanding the fates of food allergens after being recognized by the GALT. The structure of T and B cell epitopes on food allergens and the possibility of modulation of allergic reactions by amino-acid substituted analogs of allergen- derived peptides will also be discussed.

  11. Innate lymphoid cells in secondary lymphoid organs.

    Science.gov (United States)

    Bar-Ephraïm, Yotam E; Mebius, Reina E

    2016-05-01

    The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT).

    Science.gov (United States)

    Walker, D K; Bowers, S J; Mitchell, R J; Potchoiba, M J; Schroeder, C M; Small, H F

    2008-10-01

    1. Growing knowledge of the pathogenesis of human immunodeficiency virus (HIV)-1 infection has led to the identification of potential virus sanctuary sites within the central nervous system and gut-associated lymphoid tissue. 2. Maraviroc is a novel CCR5 antagonist for the treatment of HIV-1 infection. Disposition studies have been performed within the preclinical testing of maraviroc to determine its distribution to these anatomical sites. 3. Maraviroc, which is a substrate of the efflux transporter P-glycoprotein, shows limited distribution to the central nervous system as evidenced by cerebrospinal fluid concentrations that were 10% of the free plasma concentration following intravenous infusion to rats. Tissue distribution studies also indicated limited distribution of radioactivity into brain tissue of rats. 4. Radioactivity in gut-associated lymphoid tissue lymph nodes exceeded the concentrations in blood and concentrations in the contents of thoracic ducts of the lymphatic system were similar to blood levels following intravenous administration to rats.

  13. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  14. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  15. Incidences and range of spontaneous findings in the lymphoid and haemopoietic system of control Charles River CD-1 mice (Crl: CD-1(ICR) BR) used in chronic toxicity studies.

    Science.gov (United States)

    Bradley, Alys; Mukaratirwa, Sydney; Petersen-Jones, Morven

    2012-01-01

    The authors performed a retrospective study to determine the incidences and range of spontaneous pathology findings in the lymphoid and haemopoietic systems of control Charles River CD-1 mice (Crl: CD-1(ICR) BR). Data was collected from 2,560 mice from control dose groups (104-week and 80-week carcinogenicity studies; 13-week studies), from regulatory studies evaluated at the authors' laboratory between 2005 and 2010. Lesions of the lymphoid and hematopoietic systems were uncommon in 13-week studies but were of high incidence in the carcinogenicity studies (80- or 104-week duration). The most common finding overall was lymphoid hyperplasia within the spleen, thymus, and lymph nodes. The finding of benign lymphoid hyperplasia of the thymus is unusual in other mouse strains. The most common cause of death in the carcinogenicity studies was lymphoma. It is hoped that the results presented here will provide a useful database of incidental pathology findings in CD-1 mice on carcinogenicity studies.

  16. alpha-MSH in systemic inflammation. Central and peripheral actions.

    Science.gov (United States)

    Catania, A; Delgado, R; Airaghi, L; Cutuli, M; Garofalo, L; Carlin, A; Demitri, M T; Lipton, J M

    1999-10-20

    Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.

  17. Liposomal α-galactosylceramide is taken up by gut-associated lymphoid tissue and stimulates local and systemic immune responses.

    Science.gov (United States)

    Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

    2017-12-01

    α-Galactosylceramide (α-GalCer), a synthetic glycosphingolipid that exhibits potent immunostimulatory effects through activation of natural killer T (NKT) cells, can be used to treat conditions such as atopy, cancer, infection and autoimmunity. Administration of therapeutics through the oral route has advantages such as patient convenience, safety and reduced cost; however, there has been little research to investigate whether oral delivery of α-GalCer is possible. The aim of this study was therefore to determine whether α-GalCer formulated in either DMSO/Tween 80 or in liposomes, could access lymphoid tissue and stimulate immune activation following oral administration. Fluorescently labelled cationic liposomes incorporating α-GalCer were prepared, characterized and administered by oral gavage to fasted mice. Liposomes were detected inside the Peyer's patches (PPs), in the subepithelial dome just under the follicle-associated epithelium. CD11b + cells and CD11c + were shown to have taken up the formulation in a higher proportion compared to the total cell proportion in the PPs, suggesting that cells with these markers may be the prominent antigen-presenting cells involved in selective uptake. Finally, the liposomal formulation demonstrated a higher degree of immune stimulation compared to the DMSO/Tween 80 solubilized α-GalCer in the PPs, mesenteric lymph nodes and spleen as shown by the increased expression of IL-4 mRNA expression and increased proportion of NKT cells at 6 h and 3 days after administration. These results show that oral delivery of a liposomal α-GalCer can stimulate local and systemic immune responses to a different degree compared to the non-liposomal form. © 2017 Royal Pharmaceutical Society.

  18. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-01-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen

  19. Peripheral nervous system involvement in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    P. R. Kamchatnov

    2016-01-01

    Full Text Available Diabetes mellitus is a widespread disease often affecting peripheral nervous system. This include diabetic autonomous neuropathy that can endanger the patient's life. Timely detection of complications of diabetes mellitus as well as its adequate therapy can improve prognosis of the disease. The possibilities of Milgamma and Tiogamma for pathogenic therapy in patients with diabetic polyneuropathy are considered in this paper. Gabagamma can be effectively relieve neuropathic pain and used together with other drugs that normalize nerve tissue metabolism.

  20. Peripheral nervous system involvement in chronic spinal cord injury

    DEFF Research Database (Denmark)

    Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius

    2015-01-01

    Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included......), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. Conclusion: The presence...

  1. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    Science.gov (United States)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  2. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  3. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    acceptable gene coverage to serve as a comprehensive standard for gene expression profiling of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen, tonsil, and cell lines representing immature B cells, plasma cells, and natural killer (NK) cells, thus covering the entire spectrum...... of lymphoid cells and most stromal elements present in specialized lymphoid tissues. The two standards were co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both had fluorescence intensities above background for approximately 85% of the genes. Despite the limited representation...... of lymphoid cells in the Stratagene standard, only 4.2% genes exhibited expression differences greater than 2-fold including only 0.35% with differences greater than 4-fold. Although the lymphoid standard reflected a more comprehensive representation of immune system-associated genes, the Stratagene standard...

  4. Serotonin induces peripheral antinociception via the opioidergic system.

    Science.gov (United States)

    Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda E; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

    2018-01-01

    Studies conducted since 1969 have shown that the release of serotonin (5-HT) in the dorsal horn of the spinal cord contributes to opioid analgesia. In the present study, the participation of the opioidergic system in antinociceptive effect serotonin at the peripheral level was examined. The paw pressure test was used with mice (Swiss, males from 35 g) which had increased pain sensitivity by intraplantar injection of PGE 2 (2 μg). Serotonin (250 ng), administered locally to the right paw of animals, produces antinociception in this model. The selective antagonists for mu, delta and kappa opioid receptors, clocinnamox clocinnamox (40 μg), naltrindole (60 μg) and nor-binaltorfimina (200 μg), respectively, inhibited the antinociceptive effect induced by serotonin. Additionally, bestatin (400 μg), an inhibitor of enkephalinases that degrade peptides opioids, enhanced the antinociceptive effect induced by serotonin (low dose of 62.5 ng). These results suggest that serotonin possibly induce peripheral antinociception through the release of endogenous opioid peptides, possible from immune cells or keratinocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Injectable systems and implantable conduits for peripheral nerve repair

    International Nuclear Information System (INIS)

    Lin, Yen-Chih; Marra, Kacey G

    2012-01-01

    Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

  6. Peripheral Endocannabinoid System Activity in Patients Treated With Sibutramine

    Science.gov (United States)

    Engeli, Stefan; Heusser, Karsten; Janke, Jürgen; Gorzelniak, Kerstin; Bátkai, Sándor; Pacher, Pál; Harvey-White, Judith; Luft, Friedrich C.; Jordan, Jens

    2008-01-01

    Objective The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS. Methods and Procedures Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies. Results Body weight was stable during the acute treatment period and decreased by 6.0 ± 0.8 kg in those patients completing 3 months of sibutramine treatment (P sibutramine treatment. Discussion The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity. PMID:18356837

  7. The Prognostic Value of International Prognostic Index and MIB-l Immunostaining of Peripheral Lymphoid Tissues and Bone Marrow in Patients with High-Grade Non-Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    Assem, M.M.

    2001-01-01

    Cell kinetic data are important indicator of the aggressiveness of tumour and clinical response. The Ki-67 antigen plays a pivotal role in maintaining cell proliferation and the expression of this antigen was found to be a valuable indicator for aggressive disease in a variety of neoplastic disorders. Aim of the study: This study aimed to assess the prognostic significance of the expression of Ki-67 antigen in peripheral lymphoid tissues and bone marrow, using the monoclonal antibody MIB-l that is applicable in formaline-fixed paraffin embedded samples in cases with high-grade non-Hodgkin's lymphomas. Material and methods: The MIB-I immunostaining was performed on 96 samples from 48 patients with high-grade non-Hodgkin's lymphomas. The study was performed on tissue sections, nodal or extra nodal, as well as on BM smears or BM paraffin embedded sections of same patients. Ki-67 index was determined using image analyzer. Results: Forty-five out of the studied 48 cases (93.8%) were positive with a median labelling index of 20.425% (Range, 0-58%). We were able to detect bone marrow involvement by detecting MIB-l positive cells in BM samples of 29 patients who were not morphologically diagnosed to have BM infiltration. There was a strong correlation between BM positivity for Ki-67 and Ki-67 labelling index (p < 0.001). Twenty-eight (58.3%) out of the studied 48 cases achieved complete remission (CR). The median duration of CR was 35 months (range, 8-42 months) and the overall survival at 48 months was 35.4% (median 22 months, 95% CI, 13-31 months). The median Ki-67 index (20.425%) was chosen as a cut-off level for statistical analysis of the variables that influence clinical outcome. The probability of inducing CR was associated with low and low intermediate International Prognostic Index (IPI) whereas a low growth fraction was associated, although not significant, with a trend toward a higher probability of inducing a CR. In univariate analysis, high MIB1 labelling

  8. Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8+ T Cell Peripheral Tolerance in Irradiated Mice.

    Directory of Open Access Journals (Sweden)

    Gabriel Espinosa-Carrasco

    Full Text Available Lymphodepletion is currently used to enhance the efficacy of cytotoxic T lymphocyte adoptive transfer immunotherapy against cancer. This beneficial effect of conditioning regimens is due, at least in part, to promoting the breakdown of peripheral CD8+ T cell tolerance. Lymphodepletion by total body irradiation induces systemic translocation of commensal bacteria LPS from the gastrointestinal tract. Since LPS is a potent activator of the innate immune system, including antigen presenting dendritic cells, we hypothesized that LPS translocation could be required for the breakdown of peripheral tolerance observed in irradiated mice. To address this issue, we have treated irradiated mice with antibiotics in order to prevent LPS translocation and utilized them in T cell adoptive transfer experiments. Surprisingly, we found that despite of completely blocking LPS translocation into the bloodstream, antibiotic treatment did not prevent the breakdown of peripheral tolerance. Although irradiation induced the activation of cross-presenting CD8+ dendritic cells in the lymphoid tissue, LPS could not solely account for this effect. Activation of dendritic cells by mechanisms other than LPS translocation is sufficient to promote the differentiation of potentially autoreactive CD8+ T cells into effectors in irradiated mice. Our data indicate that LPS translocation is dispensable for the breakdown of CD8+ T cell tolerance in irradiated mice.

  9. Computer-based route-definition system for peripheral bronchoscopy.

    Science.gov (United States)

    Graham, Michael W; Gibbs, Jason D; Higgins, William E

    2012-04-01

    Multi-detector computed tomography (MDCT) scanners produce high-resolution images of the chest. Given a patient's MDCT scan, a physician can use an image-guided intervention system to first plan and later perform bronchoscopy to diagnostic sites situated deep in the lung periphery. An accurate definition of complete routes through the airway tree leading to the diagnostic sites, however, is vital for avoiding navigation errors during image-guided bronchoscopy. We present a system for the robust definition of complete airway routes suitable for image-guided bronchoscopy. The system incorporates both automatic and semiautomatic MDCT analysis methods for this purpose. Using an intuitive graphical user interface, the user invokes automatic analysis on a patient's MDCT scan to produce a series of preliminary routes. Next, the user visually inspects each route and quickly corrects the observed route defects using the built-in semiautomatic methods. Application of the system to a human study for the planning and guidance of peripheral bronchoscopy demonstrates the efficacy of the system.

  10. Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Tanay, A.; Schiffman, G.; Strober, S.

    1986-01-01

    The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA

  11. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  13. [Kinesitherapy in patients with the peripheral vestibular system disorders].

    Science.gov (United States)

    Szczepanik, Marcin; Walak, Jarosław; Woszczak, Marek; Józefowicz-Korczyńska, Magdalena

    2013-01-01

    Kinesitherapy is widely accepted management in patients with vertigo and imbalance, but there has been inadequate evidence that one form of therapy is superior to another. of the study was to compare effectiveness of two kinesitherapy protocols in patients with the peripheral vestibular system disorders. Fifty patients (mean age 46.0±13.1 year) with vertigo and balance instability lasting over 3 months with unilateral vestibular disorder, confirmed in Videnystagmography, were included in the study. Thirty patients underwent supervised and 20 patients home-based exercise programs. All of them were assessed three times at the baseline, after 4 weeks and 3 months, on vertigo intensity and frequency with the Vertigo Syndrome Scale (VSS), Vertigo Visual Analog Scale (VAS) and clinical unsteadiness with tests (Romberg, Amended Motor Club Assesment (AMCA), Eurofit test - standing on one leg. In both groups the clinical tasks and the intensity of vertigo in VAS significantly decreased. The mean value of VSS (part physical and emotional)score significantly decreased only in supervised group at the end of 4 weeks and 3 months (p=ns). Recovery was more dynamic in supervised group than home-based exercises group, in AMCA test (3.9 vs. 1.3 s, p<0.05) in Eurofit tests eye open (14.1 vs. 0.9 s, p<0.05) and eye closed (3.5 vs. 1 s, p<0.05). In patients with unilateral peripheral vestibular dysfunction supervised and home-based group kinesitherapy is an effective treatment method. In supervised group patients recovery has been faster. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

  14. 75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-12-06

    ...] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...) and/or abnormal vascularity (abnormal blood supply and circulation) of the central nervous system. The...

  15. Gross anatomy and development of the peripheral nervous system.

    Science.gov (United States)

    Catala, Martin; Kubis, Nathalie

    2013-01-01

    The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Investigation of the effects of experimental autolysis on the detection of abnormal prion protein in lymphoid and central nervous system tissues from elk and sheep using the Western blotting method.

    Science.gov (United States)

    Huang, Hongsheng; Soutyrine, Andrei; Rendulich, Jasmine; O'Rourke, Katherine; Balachandran, Aru

    2011-01-01

    Tissues unsuitable for standard immunohistochemical and histopathological examinations for chronic wasting disease (CWD) in cervids and for scrapie in sheep are frequently submitted for testing. This study investigated the effects of experimental autolysis on the detection of abnormal prion protein (PrPsc) in lymphoid and central nervous system (CNS) tissues from elk and sheep. The PrPsc was detected using a Western blotting (WB) test following PrPsc enrichment using sodium phosphotungstic acid (PTA) precipitation (PTA-WB). A commercial enzyme-linked immunosorbent assay (ELISA) was used as a reference test for quantitative measurement. This study showed that the amount of PrPsc in lymphoid and CNS tssues from elk and sheep decreased gradually as a result of autolysis, but PrPsc was still detectable after 5 and 15 d incubation at 37°C by PTA-WB for all lymphoid and CNS samples. The results of the ELISA supported those of PTA-WB, particularly for CNS tissues. In conclusion, autolysis at 37°C for 15 d would not significantly affect the detection of PrPsc in lymphoid and CNS tissues by WB and ELISA and, particularly, PTA-WB is a valuable and alternative confirmatory test to detect PrPsc in autolyzed lymphoid and CNS samples.

  17. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    International Nuclear Information System (INIS)

    Park, Charn Il; Han, Man Chung

    1981-01-01

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

  18. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1981-06-15

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

  19. Prion pathogenesis and secondary lymphoid organs (SLO): tracking the SLO spread of prions to the brain.

    Science.gov (United States)

    Mabbott, Neil A

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrP (Sc), an abnormally folded isoform of the cellular prion protein (PrP (C)), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases.

  20. 75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-03-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  1. 76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-07-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...

  2. 78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-04-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  3. 78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  4. 75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-06-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  5. 77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-04-03

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  6. 76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  7. 75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-04-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  8. 78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-10-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

  9. Peripheral nervous system insulin resistance in ob/ob mice

    Science.gov (United States)

    2013-01-01

    Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

  10. Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion

    International Nuclear Information System (INIS)

    Thomas, Elaine R.; Dunfee, Rebecca L.; Stanton, Jennifer; Bogdan, Derek; Taylor, Joann; Kunstman, Kevin; Bell, Jeanne E.; Wolinsky, Steven M.; Gabuzda, Dana

    2007-01-01

    HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion

  11. Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

    Science.gov (United States)

    Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico; Ganio, Edward A; Gaudilliere, Dyani K; Tingle, Martha; Lancero, Hope L; McNeil, Leslie S; Spitzer, Matthew H; Wong, Ronald J; Shaw, Gary M; Darmstadt, Gary L; Sylvester, Karl G; Winn, Virginia D; Carvalho, Brendan; Lewis, David B; Stevenson, David K; Nolan, Garry P; Aghaeepour, Nima; Angst, Martin S; Gaudilliere, Brice L

    2016-12-01

    Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 + and CD8 + T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet + CD4 + T cells, CD8 + T cells, B cells, and CD56 lo CD16 + NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Bioengineering of artificial lymphoid organs

    OpenAIRE

    NOSENKO M.A.; DRUTSKAYA M.S.; MOISENOVICH M.M.; NEDOSPASOV S.A.

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cy...

  14. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    Science.gov (United States)

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system.

  15. Bioengineering of Artificial Lymphoid Organs.

    Science.gov (United States)

    Nosenko, M A; Drutskaya, M S; Moisenovich, M M; Nedospasov, S A

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed.

  16. Innate lymphoid cells, precursors and plasticity.

    Science.gov (United States)

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  17. Fundamental studies on ADCC (antibody-dependent cell-mediated cytotoxicity) of human peripheral blood leukocytes using sheep red blood cells as target cells, and the effect of erythrophagocytosis

    International Nuclear Information System (INIS)

    Ichikawa, Yukinobu; Takaya, Masatoshi; Arimori, Shigeru

    1979-01-01

    We investigated antibody-dependent cell-mediated cytotoxicity (ADCC) of human peripheral blood leukocytes by using 51 Cr-labelled sheep red blood cells (SRBC) as target cells and anti-SRBC rabbit antibody. Lysis of SRBC was mediated by either human peripheral lymphoid cells or phagocytes (Monocytes and granulocytes). SRBC were useful as target cells in ADCC assay against human lymphoid cells, since decreased cytotoxic activity of phagocyte-contaminated crude lymphocyte fraction was recovered by elimination of contaminating phagocytes. The monocytes inhibited ADCC of lymphoid cells through phagocytosis of SRBC. This assay system may be useful for estimating not only Fc receptor-mediated cytotoxicity but also Fc receptor-mediated phagocytic activity of human peripheral blood leukocytes. (author)

  18. Radiotherapy of lymphoid diseases of the orbit

    International Nuclear Information System (INIS)

    Austin-Seymour, M.M.; Donaldson, S.S.; Egbert, P.R.; McDougall, I.R.; Kriss, J.P.

    1985-01-01

    Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. Two patients developed cataracts. Carefullly planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma

  19. Stimulation of the peripheral nervous system for pain control.

    Science.gov (United States)

    Long, D M

    1983-01-01

    Transcutaneous stimulation is a proven effective way to relieve pain. Its optimal use requires an accurate patient diagnosis. Treatment of pain as a symptom only is likely to fail. There must be a careful psychosocial evaluation, for the majority of patients who come to the doctor complaining of pain have major psychological, social, or behavioral factors that are most important in the genesis of the complaint. Drug abuse must be corrected. Related symptoms, such as anxiety and depression, must be treated. Then, a thorough trail of transcutaneous stimulation is mandatory. A desultory use will undoubtedly lead to failure. This trial must begin with patient education by experienced personnel. Then the electrodes must be properly applied, and there must be a regular follow-up of stimulation to be certain the patient is utilizing it correctly. The patient must be supported through an adequate trial which should extend over 2-4 weeks before purchase of the device is contemplated. Furthermore, all related nursing and physician personnel must be educated in the proper use of the technique. The uninformed professional who denigrates the therapy is a very effective deterrent to appropriate use. In this situation, transcutaneous electrical stimulation will be of great value in the treatment of acute musculoskeletal injury and acute postoperative pain. It will be effective in the treatment of peripheral nerve injury pain, chronic musculoskeletal abnormalities, chronic pain in the patient who has undergone multiple operations upon the low back and neck, visceral pain, some of the reflex sympathetic dystrophies, and postherpetic neuralgia. Stimulation will not help a complaint which is psychosomatic in origin. It will not influence drug addiction. It is not likely to be useful in any situation where secondary gain is important. The metabolic neuropathies, pain of spinal cord injury, and pain from cerebrovascular accident will not respond frequently enough to warrant more than

  20. The Innate Lymphoid Cell Precursor.

    Science.gov (United States)

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  1. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

    Science.gov (United States)

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-01-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment. PMID:26628041

  2. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  3. [RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

    Science.gov (United States)

    Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

    2016-02-01

    To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

  4. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  5. Morphology of mucosa-associated lymphoid tissue in odontocetes.

    Science.gov (United States)

    Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

    2016-09-01

    This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. © 2016 Wiley Periodicals, Inc.

  6. The effect of ionizing radiation on lipid metabolism in lymphoid cells

    International Nuclear Information System (INIS)

    Kolomiytseva, I.K.; Novoselova, E.G.; Kulagina, T.P.; Kuzin, A.M.

    1987-01-01

    Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14 C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose. (author)

  7. Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

    Science.gov (United States)

    Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

    2016-06-15

    Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

  8. Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Course of development and effects of insulin treatment

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Cristino, N.A.; Rutten, G.J.; Hamers, F.P.; Erkelens, D.W.

    1999-01-01

    Diabetes mellitus can affect both the peripheral and the central nervous system. However, central deficits are documented less well than peripheral deficits. We therefore compared the course of development of neurophysiological changes in the central and peripheral nervous systems in

  9. Peripheral nervous system neuroimmunology seen by a neuro-pathologist.

    Science.gov (United States)

    Vallat, J-M

    2014-10-01

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

  10. Lymphoid Tissue Grafts in Man

    Energy Technology Data Exchange (ETDEWEB)

    Kay, H. E.M. [Royal Marsden Hospital, Institute of Cancer Research, London (United Kingdom)

    1969-07-15

    Grafts of lymphoid tissue or of lymphoid stem cells may be appropriate in the treatment of some congenital immune deficiency disorders. The reasons for preferring tissues of foetal origin are discussed and the evidence for foetal immunocompetence is briefly summarized. Methods of storing foetal liver cells and cells or fragments of thymus are mentioned, and the organization of the Foetal Tissue Bank of the Royal Marsden Hospital is described. Clinical data from transplantation of lymphoid cells in various immune deficiency disorders are briefly presented. (author)

  11. Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs.

    Science.gov (United States)

    Wang, Chao; Sun, Wujin; Ye, Yanqi; Bomba, Hunter N; Gu, Zhen

    2017-01-01

    The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

  12. 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.

  13. Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

    2003-01-01

    Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

  14. RESTOP: Retaining External Peripheral State in Intermittently-Powered Sensor Systems.

    Science.gov (United States)

    Rodriguez Arreola, Alberto; Balsamo, Domenico; Merrett, Geoff V; Weddell, Alex S

    2018-01-10

    Energy harvesting sensor systems typically incorporate energy buffers (e.g., rechargeable batteries and supercapacitors) to accommodate fluctuations in supply. However, the presence of these elements limits the miniaturization of devices. In recent years, researchers have proposed a new paradigm, transient computing, where systems operate directly from the energy harvesting source and allow computation to span across power cycles, without adding energy buffers. Various transient computing approaches have addressed the challenge of power intermittency by retaining the processor's state using non-volatile memory. However, no generic approach has yet been proposed to retain the state of peripherals external to the processing element. This paper proposes RESTOP, flexible middleware which retains the state of multiple external peripherals that are connected to a computing element (i.e., a microcontroller) through protocols such as SPI or I 2 C. RESTOP acts as an interface between the main application and the peripheral, which keeps a record, at run-time, of the transmitted data in order to restore peripheral configuration after a power interruption. RESTOP is practically implemented and validated using three digitally interfaced peripherals, successfully restoring their configuration after power interruptions, imposing a maximum time overhead of 15% when configuring a peripheral. However, this represents an overhead of only 0.82% during complete execution of our typical sensing application, which is substantially lower than existing approaches.

  15. Relationship of the Van Herick Grading System with Peripheral Iris Configuration and Level of Iris Insertion.

    Science.gov (United States)

    Khan, Faisal Aziz; Niazi, Shafaq Pervez Khan; Khan, Assad Zaman

    2017-09-01

    To determine the relationship of the van Herick angle grading system with the level of iris insertion and peripheral iris configuration. Observational study. Eye department, Combined Military Hospital, Malir Cantt., Karachi, from May to October 2015. Sixty-five eyes of 65 patients were recruited. Anterior chamber depth at the temporal limbus was measured as a fraction of corneal section thickness using van Herick technique and graded on the standard 4-point scale of the van Herick grading system. Gonioscopy of the temporal quadrant was performed with a Posner 4 mirror goniolens and both the true level of iris insertion and peripheral iris configuration were recorded on a 4-point scale so as to equate with the van Herick 4-point grading system. Spearman's rho test was applied to determine the relationship of the van Herick grading system with level of iris root insertion and peripheral iris configuration. Amoderate positive correlation between van Herick grade and peripheral iris configuration was found which was statistically significant (rs=0.42, p < 0.001). Astatistically significant and moderate positive correlation was also detected between van Herick grade and the level of iris insertion (rs=0.45, p < 0.001). The van Herick grade has a moderately positive relationship with the peripheral iris configuration and true level of iris insertion.

  16. CAMAC - an introduction into a system of standardized highways between computers and their peripherals

    International Nuclear Information System (INIS)

    Stuckenberg, H.J.

    1975-10-01

    CAMAC, which is a synonym for 'Computer Automated Measurement and Control', is a set of rules widely used in many countries for connecting processors and computers to the on-line peripherals. There are rules for an interface transferring the information via a common highway as well as for modular mechanical units in which the peripheral devices are housed together with the multipole connectors combining the computer with the controlled process. All peripherals in a system are sending the data and control information to the computer through parallel or serial highways which are defined also by the CAMAC rules. The use of CAMAC assures the possibility to combine compatible hardware of various suppliers in any system without mechanical or electrical difficulties making the hardware and software implementation much more easier. Also the reconfiguration of a system needed for new and other activities is done relatively fast and simple. Compatible devices are offered by about 60 suppliers in all five continents. (orig.) [de

  17. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  18. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

    Science.gov (United States)

    Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

    2010-08-24

    The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

  19. Central and peripheral nervous systems: master controllers in cancer metastasis.

    Science.gov (United States)

    Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

    2013-12-01

    Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

  20. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    International Nuclear Information System (INIS)

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%

  1. Alzheimer-associated Aβ oligomers impact the central nervous system to induce peripheral metabolic deregulation

    Science.gov (United States)

    Clarke, Julia R; Lyra e Silva, Natalia M; Figueiredo, Claudia P; Frozza, Rudimar L; Ledo, Jose H; Beckman, Danielle; Katashima, Carlos K; Razolli, Daniela; Carvalho, Bruno M; Frazão, Renata; Silveira, Marina A; Ribeiro, Felipe C; Bomfim, Theresa R; Neves, Fernanda S; Klein, William L; Medeiros, Rodrigo; LaFerla, Frank M; Carvalheira, Jose B; Saad, Mario J; Munoz, Douglas P; Velloso, Licio A; Ferreira, Sergio T; De Felice, Fernanda G

    2015-01-01

    Alzheimer's disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion of AD-associated Aβ oligomers (AβOs) in mice triggered peripheral glucose intolerance, a phenomenon further verified in two transgenic mouse models of AD. Systemically injected AβOs failed to induce glucose intolerance, suggesting AβOs target brain regions involved in peripheral metabolic control. Accordingly, we show that AβOs affected hypothalamic neurons in culture, inducing eukaryotic translation initiation factor 2α phosphorylation (eIF2α-P). AβOs further induced eIF2α-P and activated pro-inflammatory IKKβ/NF-κB signaling in the hypothalamus of mice and macaques. AβOs failed to trigger peripheral glucose intolerance in tumor necrosis factor-α (TNF-α) receptor 1 knockout mice. Pharmacological inhibition of brain inflammation and endoplasmic reticulum stress prevented glucose intolerance in mice, indicating that AβOs act via a central route to affect peripheral glucose homeostasis. While the hypothalamus has been largely ignored in the AD field, our findings indicate that AβOs affect this brain region and reveal novel shared molecular mechanisms between hypothalamic dysfunction in metabolic disorders and AD. PMID:25617315

  2. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367?1371, 2010, Nat Rev Immunol 13: 145?149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  3. Florid reactive lymphoid hyperplasia of terminal ileum

    OpenAIRE

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may b...

  4. [Neurophysiology of the development and maturation of the peripheral nervous system].

    Science.gov (United States)

    García-García, A; Calleja-Fernández, J

    Peripheral nerve maturation accounts during fetal life and infancy and varies with age. Nerve conduction studies are an objective procedure to investigate the development of the motor and sensory nerves. We present a review of peripheral nervous system maturation studies in infancy, including our normal control group of infants from 1 week to 6 years of age. Motor and sensory nerve conduction velocity at birth is about one-half that of the normal adults, increases very quickly during the first year of life and reaches adult values between 3 and 5 years of age. All these electrophysiologic changes parallel the increase in numbers of large myelinated fibres throughout infancy. Nerve conduction studies are an accurate and non-invasive method of evaluating the peripheral nerve maturation in paediatric population when motor and sensory functions are particularly difficult to assess clinically.

  5. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    International Nuclear Information System (INIS)

    Sakaguchi, N.; Sakaguchi, S.; Miyai, K.

    1992-01-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4 + T cells mediated the autoimmune prevention but CD8 + T cells did not. CD4 + T cells also appeared to mediate the TLI-induced autoimmune disease because CD4 + T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs

  6. Interactions between the intestinal microbiota and innate lymphoid cells

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741

  7. Changes in the Peripheral Endocannabinoid System as a Risk Factor for the Development of Eating Disorders.

    Science.gov (United States)

    Capasso, Anna; Milano, Walter; Cauli, Omar

    2018-02-12

    Eating Disorder (ED) is characterized by persistently and severely disturbed eating behaviours. They arise from a combination of long-standing behavioural, emotional, psychological, interpersonal, and social factors and result in insufficient nutrient ingestion and/or adsorption. The three main EDs are: anorexia nervosa, bulimia nervosa, and binge eating disorder. We review the role of peripheral endocannabinoids in eating behaviour. The neuronal pathways involved in feeding behaviours are closely related to catecholaminergic, serotoninergic and peptidergic systems. Accordingly, feeding is promoted by serotonin, dopamine, and prostaglandin and inhibited by neuropeptide Y, norepinephrine, GABA, and opioid peptides. The endocannabinoid system plays a role in EDs, and multiple lines of evidence indicate that the cannabinoid signalling system is a key modulatory factor of the activity in the brain areas involved in EDs as well as in reward processes. Besides their central role in controlling food behaviours, peripheral cannabinoids are also involved in regulating adipose tissue and insulin signalling as well as cell metabolism in peripheral tissues such as liver, pancreas, fatty tissue, and skeletal muscle. Altogether, these data indicate that peripheral cannabinoids can provide new therapeutic targets not only for EDs but also for metabolic disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

    Science.gov (United States)

    Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

    2017-01-01

    Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

  9. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  10. Peripheral Insertion of a Central Venous Access Device Under Fluoroscopic Guidance Using a Peripherally Accessed System (PAS) Port in the Forearm

    International Nuclear Information System (INIS)

    Hata, Yasuhiro; Morita, Sojiro; Morita, Yoshitaka; Awatani, Toshihide; Takasaki, Motohiro; Horimi, Tadashi; Ozawa, Zen

    1998-01-01

    Purpose: We describe the technique, efficacy, and complications of fluoroscopy-guided implantation of a central venous access device using a peripherally accessed system (PAS) port via the forearm. Methods: Beginning in July 1994, 105 central venous access devices were implanted in 104 patients for the long-term infusion of antibiotics or antineoplasmic agents, blood products, or parenteral nutrition. The devices was inserted under fluoroscopic guidance with real-time venography from a peripheral route. Results: All ports were successfully implanted. There were no procedure-related complications. No thrombosis or local infection was observed; however, in six patients catheter-related phlebitis occurred. Conclusion: Fluoroscopy-guided implantation of a central venous access device using a PAS port via the forearm is safe and efficacious, and injection of contrast medium through a peripheral IV catheter before introduction of the catheter helps to avoid catheter-related phlebitis

  11. ChR2 transgenic animals in peripheral sensory system: Sensing light as various sensations.

    Science.gov (United States)

    Ji, Zhi-Gang; Wang, Hongxia

    2016-04-01

    Since the introduction of Channelrhodopsin-2 (ChR2) to neuroscience, optogenetics technology was developed, making it possible to activate specific neurons or circuits with spatial and temporal precision. Various ChR2 transgenic animal models have been generated and are playing important roles in revealing the mechanisms of neural activities, mapping neural circuits, controlling the behaviors of animals as well as exploring new strategy for treating the neurological diseases in both central and peripheral nervous system. An animal including humans senses environments through Aristotle's five senses (sight, hearing, smell, taste and touch). Usually, each sense is associated with a kind of sensory organ (eyes, ears, nose, tongue and skin). Is it possible that one could hear light, smell light, taste light and touch light? When ChR2 is targeted to different peripheral sensory neurons by viral vectors or generating ChR2 transgenic animals, the animals can sense the light as various sensations such as hearing, touch, pain, smell and taste. In this review, we focus on ChR2 transgenic animals in the peripheral nervous system. Firstly the working principle of ChR2 as an optogenetic actuator is simply described. Then the current transgenic animal lines where ChR2 was expressed in peripheral sensory neurons are presented and the findings obtained by these animal models are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Competitor localization and innovation activity of peripheral industrial systems in Poland

    OpenAIRE

    Arkadiusz Swiadek

    2013-01-01

    Spatial proximity to competitors is an important factor in the acceleration of technological change in industrial systems in most developed countries, but is it also in Poland? The main objective of the study was to identify and evaluation the impact of distance from the nearest competitor on the innovative activity of selected peripheral regional industrial systems in Poland. Surveys conducted in the years 2007-11, including a group of 1 860 industrial companies in the five diverse and locat...

  13. Experimental alkylmercurial poisoning in swine. Lesions in the peripheral and central nervous systems

    Energy Technology Data Exchange (ETDEWEB)

    Charlton, K M

    1974-01-01

    The effects of alkylmercurial poisoning were studied in 16 pigs poisoned with daily oral doses of a fungicide containing methylmercury 2, 3-dihydroxy propyl mercaptide and methylmercury acetate. Clinical signs included weakness, wobbling gait, blindness, recumbency and death. Microscopic studies of the peripheral nervous system revealed Wallerian degeneration in sensory fibers and neuronal degeneration in dorsal root ganglia. In the central nervous system, there were neuronal degeneration of ischemic type, glial degeneration, gliosis and necrosis of the media of meningeal arterioles. The last mentioned lesion was not extensive. The sequential development of lesions and the absence of segmental demyelination suggest that the primary lesion in the peripheral nervous system was neuronal-axonal degeneration rather than degeneration of the Schwann cell and myelin sheath. 25 references.

  14. Acute injury in the peripheral nervous system triggers an alternative macrophage response

    Directory of Open Access Journals (Sweden)

    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  15. Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism.

    Science.gov (United States)

    Rossmeisl, J H

    2010-01-01

    Hypothyroidism has been implicated in the development of multiple peripheral mono- and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. Eighteen purpose-bred, female dogs. Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic-tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic-tibial and ulnar F-wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (Pmuscle action potentials over time, which were attributed to the concurrent myopathy. No significant differences between control and hypothyroid dogs were detected in electrophysiologic tests of motor (P>or=.1) or sensory nerve conduction velocity (P>or=.24) or nerve roots (P>or=.16) throughout the study period, with values remaining within reference ranges in all dogs. Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.

  16. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  17. IL-17 producing innate lymphoid cells 3 (ILC3) but not Th17 cells might be the potential danger factor for preeclampsia and other pregnancy associated diseases.

    Science.gov (United States)

    Barnie, Prince A; Lin, Xin; Liu, Yueqin; Xu, Huaxi; Su, Zhaoliang

    2015-01-01

    In pregnancy, the immunologic system plays an important role that ensures normal pregnancy development and can as well promote the development of complications. Pregnancy success appears to rely on a discrete balance between the Th cytokines, which are involved in fetal growth and development. Preeclampsia and gestational diabetes are known complications associated with pregnancy. However, the source of the increased IL-17 cytokine in preeclampsia and other pregnancy associated diseases still remains unclear amidst numerous inconsistencies. The recent identification of innate lymphoid cells (ILC) has raised more doubts about the sources of most of the Th associated cytokines. We investigated the source of peripheral IL-17 levels in preeclamptic, gestational diabetics and chronic diabetics compared to healthy pregnancy subjects. To evaluate the source of the increased IL-17 cytokine among preeclampsia, chronic diabetic and gestational diabetic patients we investigated the proportion of Th17 cell populations in peripheral blood mononuclear cells using flow cytometry as well as analyzing levels of IFN-γ, IL-17, IL-1β and HMGB1. This study found that the Th17 cell populations in peripheral blood of preeclamptic, gestational nor chronic diabetes during pregnancy did not correlate with the increased IL-17. We report that the increased IL-17 levels observed in patients with preeclampsia, gestational diabetes and chronic diabetes are associated with innate lymphoid cells 3 (ILC3) and may pose threats to the fetus if disregulated.

  18. Innate lymphoid cells and asthma.

    Science.gov (United States)

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  20. DNA apoptosis and stability in B-cell chronic lymphoid leukaemia: implication of the DNA double-strand breaks repair system by non homologous recombination

    International Nuclear Information System (INIS)

    Deriano, L.

    2005-01-01

    After an introduction presenting the diagnosis and treatment of chronic lymphoid leukaemia, its molecular and genetic characteristics, and its cellular origin and clonal evolution, this research thesis describes the apoptosis (definition and characteristics, cancer and chemotherapy, apoptotic ways induced by gamma irradiation), the genotoxic stresses, the different repair mechanisms for different damages, and the DNA repair processes. It reports how human chronic lymphocytic leukaemia B cells can escape DNA damage-induced apoptosis through the non-homologous end-joining DNA repair pathway, and presents non-homologous end-joining DNA repair as a potent mutagenic process in human chronic lymphocytic leukaemia B cells

  1. Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

    Science.gov (United States)

    Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

    2015-07-15

    Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. Copyright © 2015 the authors 0270-6474/15/3510135-11$15.00/0.

  2. Genetic pathways for differentiation of the peripheral nervous system in ascidians

    Science.gov (United States)

    Waki, Kana; Imai, Kaoru S.; Satou, Yutaka

    2015-01-01

    Ascidians belong to tunicates, the sister group of vertebrates. Peripheral nervous systems (PNSs) including epidermal sensory neurons (ESNs) in the trunk and dorsal tail regions of ascidian larvae are derived from cells adjacent to the neural plate, as in vertebrates. On the other hand, peripheral ESNs in the ventral tail region are derived from the ventral ectoderm under the control of BMP signalling, reminiscent of sensory neurons of amphioxus and protostomes. In this study, we show that two distinct mechanisms activate a common gene circuit consisting of Msx, Ascl.b, Tox, Delta.b and Pou4 in the dorsal and ventral regions to differentiate ESNs. Our results suggest that ventral ESNs of the ascidian larva are not directly homologous to vertebrate PNSs. The dorsal ESNs might have arisen via co-option of the original PNS gene circuit to the neural plate border in an ancestral chordate. PMID:26515371

  3. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    Science.gov (United States)

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  4. Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

    Science.gov (United States)

    Krajnak, Kristine; Miller, G R; Waugh, Stacey

    2018-01-01

    Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

  5. Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease

    Science.gov (United States)

    McLane, Laura M.; Steblyanko, Maria; Anikeeva, Nadia; Ablanedo-Terrazas, Yuria; Demers, Korey; Eller, Michael A.; Streeck, Hendrik; Jansson, Marianne; Sönnerborg, Anders; Canaday, David H.; Naji, Ali; Wherry, E. John; Robb, Merlin L.; Reyes-Teran, Gustavo; Sykulev, Yuri; Betts, Michael R.

    2018-01-01

    CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues. PMID:29652923

  6. Skin-associated lymphoid tissues (SALT): origins and functions

    International Nuclear Information System (INIS)

    Streilein, J.W.

    1983-01-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT

  7. ID’ing Innate and Innate-like Lymphoid Cells

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  8. ID'ing innate and innate-like lymphoid cells.

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

    2014-09-01

    The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils.

    Science.gov (United States)

    Ayers, Jacob I; Brooks, Mieu M; Rutherford, Nicola J; Howard, Jasie K; Sorrentino, Zachary A; Riffe, Cara J; Giasson, Benoit I

    2017-01-15

    Misfolded α-synuclein (αS) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 αS transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of αS fibrils by comparing various peripheral sites of inoculations with different αS protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83 +/+ ) mice, robust αS pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of αS fibrils in hemizygous M83 transgenic (M83 +/- ) mice resulted in CNS αS pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated αS resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 αS, human βS, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of αS fibrils also induced CNS αS pathology in another αS transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of αS fibrils was more efficient in inducing CNS αS pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated αS in M83 +/- mice also induced paralysis and CNS αS pathology, although less efficiently. These results further demonstrate the prion-like characteristics of αS and reveal its efficiency to invade the CNS via multiple routes of peripheral administration. The misfolding and accumulation of α-synuclein (αS) inclusions are found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson

  10. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

  11. Shaping Innate Lymphoid Cell Diversity

    Directory of Open Access Journals (Sweden)

    Qiutong Huang

    2017-11-01

    Full Text Available Innate lymphoid cells (ILCs are a key cell type that are enriched at mucosal surfaces and within tissues. Our understanding of these cells is growing rapidly. Paradoxically, these cells play a role in maintaining tissue integrity but they also function as key drivers of allergy and inflammation. We present here the most recent understanding of how genomics has provided significant insight into how ILCs are generated and the enormous heterogeneity present within the canonical subsets. This has allowed the generation of a detailed blueprint for ILCs to become highly sensitive and adaptive sensors of environmental changes and therefore exquisitely equipped to protect immune surfaces.

  12. A SYSTEM AND A DEVICE FOR ISOLATING CIRCULATING TUMOR CELLS FROM THE PERIPHERAL BLOOD IN VIVO

    Directory of Open Access Journals (Sweden)

    Michal Mego

    2015-08-01

    Full Text Available Circulating tumor cells (CTC play a crucial role in disseminating tumors and in the metastatic cascade. CTCs are found only in small numbers, and the limited amount of isolated CTCs makes it impossible to characterize them closely. This paper presents a proposal for a new system for isolating CTCs from the peripheral blood in vivo. The system enables CTCs to be isolated from the whole blood volume for further research and applications. The proposed system consists of magnetic nanoparticles covered by monoclonal antibodies against a common epithelial antigen, large supermagnets, which are used to control the position of the nanoparticles within the human body, and a special wire made of a magnetic core wrapped in a non-magnetic shell. The system could be used not only for isolating CTCs, but also for in vivo isolation of other rare cells from the peripheral blood, including hematopoietic and/or mesenchymal stem cells, with applications in regenerative medicine and/or in stem cell transplantation.

  13. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

    Science.gov (United States)

    Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

    2014-11-11

    Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

  14. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  15. Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide

    Energy Technology Data Exchange (ETDEWEB)

    Carratu, M.R. (Inst. of Pharmacology, Bari Univ. (Italy)); Renna, G. (Inst. of Pharmacology, Bari Univ. (Italy)); Giustino, A. (Inst. of Pharmacology, Bari Univ. (Italy)); De Salvia, M.A. (Inst. of Pharmacology, Bari Univ. (Italy)); Cuomo, V. (Inst. of Pharmacology, Bari Univ. (Italy))

    1993-06-01

    The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h[sub [infinity

  16. Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections.

    Science.gov (United States)

    Adzemovic, Milena Z; Zeitelhofer, Manuel; Leisser, Marianne; Köck, Ulricke; Kury, Angela; Olsson, Tomas

    2016-11-14

    Immunohistochemistry (IHC) provides highly specific, reliable and attractive protein visualization. Correct performance and interpretation of an IHC-based multicolor labeling is challenging, especially when utilized for assessing interrelations between target proteins in the tissue with a high fat content such as the central nervous system (CNS). Our protocol represents a refinement of the standard immunolabeling technique particularly adjusted for detection of both structural and soluble proteins in the rat CNS and peripheral lymph nodes (LN) affected by neuroinflammation. Nonetheless, with or without further modifications, our protocol could likely be used for detection of other related protein targets, even in other organs and species than here presented.

  17. Effect of insulin-induced hypoglycaemia on the peripheral nervous system

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Mølck, A.-M.; Bøgh, I. B.

    2014-01-01

    Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly...... state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more...

  18. CRITICAL ANALYSIS OF REFERRALS TO ELECTRODIAGNOSTIC EXAMINATION OF THE PERIPHERAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    Simon Podnar

    2003-04-01

    Full Text Available Background. Clinical neurophysiologists observe a large number of examinees referred to a electromyographic (EMG laboratory without clinical symptoms or signs of the peripheral nervous system lesion. Such referrals do not improve management of patients, but only unnecessarily burden examinees and laboratory personnel. The aim of the present study was to check appropriateness of referrals to electrodiagnostic examination, look for reasons for problems and suggest possible improvements.Methods. From the database of the Institute of Clinical Neurophysiology in Ljubljana all examinees evaluated by the author in a »general« EMG laboratory in the first 4 months of 2002 were included. From data about examinees, referral doctors, referral diagnoses, clinical symptoms and signs and electrophysiological findings, predictive values for neurological referral diagnoses and electrodiagnostic abnormalities were calculated using descriptive and multivariate statistical analyses.Results. Three hundred examinees (42% men were included. Neurological diagnosis was provided in 55% of referrals. Electrodiagnostic abnormalities were found in 45% of examinees (carpal tunnel syndrome 50%, radiculopathy 25%, other mononeuropathies 15%, polineuropathy 9%. In 9% of examinees only clinical, and in 47% neither clinical nor electrodiagnostic abnormalities were demonstrated. Using a multivariate analysis positive effect of referral with neurological diagnosis, of paraesthesiae and findings of weakness and sensory loss, and negative effect of pain and referral diagnosis cervicobrachialgia or lumboischialgia on pathological electrodiagnostic findings were found. Isolated pain and paraesthesiae (with carpal tunnel syndrome excluded were particularly poor predictors of abnormal electrodiagnostic findings (9% and 16%, respectively. With exception of 20 patients with carpal tunnel syndrome, none with normal clinical neurological examination had abnormal electrodiagnostic findings

  19. Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

    Science.gov (United States)

    Mortha, Arthur; Burrows, Kyle

    2018-01-01

    Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.

  20. Innate lymphoid cells: the new kids on the block.

    Science.gov (United States)

    Withers, David R; Mackley, Emma C; Jones, Nick D

    2015-08-01

    The purpose of this article is to review recent advances in our understanding of innate lymphoid cell function and to speculate on how these cells may become activated and influence the immune response to allogeneic tissues and cells following transplantation. Innate lymphoid cells encompass several novel cell types whose wide-ranging roles in the immune system are only now being uncovered. Through cytokine production, cross-talk with both haematopoietic and nonhaematopoietic populations and antigen presentation to T cells, these cells have been shown to be key regulators in maintaining tissue integrity, as well as initiating and then sustaining immune responses. It is now clear that innate lymphoid cells markedly contribute to immune responses and tissue repair in a number of disease contexts. Although experimental and clinical data on the behaviour of these cells following transplantation are scant, it is highly likely that innate lymphoid cells will perform similar functions in the alloimmune response following transplantation and therefore may be potential therapeutic targets for manipulation to prevent allograft rejection.

  1. Innate lymphoid cells in inflammation and immunity

    NARCIS (Netherlands)

    McKenzie, Andrew N. J.; Spits, Hergen; Eberl, Gerard

    2014-01-01

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles

  2. Transcriptional control of innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Bernink, Jochem; Peters, Charlotte; Spits, Hergen

    2012-01-01

    Cells that belong to the family of innate lymphoid cells (ILCs) not only form a first line of defense against invading microbes, but also play essential roles in tissue remodeling and immune pathology. Ror?t+ ILCs, producing the cytokines IL-22 and IL-17, include lymphoid tissue inducer (LTi) cells

  3. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  4. Microcomputer-based system for registration of oxygen tension in peripheral muscle.

    Science.gov (United States)

    Odman, S; Bratt, H; Erlandsson, I; Sjögren, L

    1986-01-01

    For registration of oxygen tension fields in peripheral muscle a microcomputer based system was designed on the M6800 microprocessor. The system was designed to record the signals from a multiwire oxygen electrode, MDO, which is a multiwire electrode for measuring oxygen on the surface of an organ. The system contained patient safety isolation unit built on optocopplers and the upper frequency limit was 0.64 Hz. Collected data were corrected for drift and temperature changes during the measurement by using pre- and after calibrations and a linear compensation technique. Measure drift of the electrodes were proved to be linear and thus the drift could be compensated for. The system was tested in an experiment on pig. To study the distribution of oxygen statistically mean, standard deviation, skewness and curtosis were calculated. To see changes or differences between histograms a Kolmogorv-Smirnov test was used.

  5. Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system

    Directory of Open Access Journals (Sweden)

    Swift-Gallant Ashlyn

    2012-05-01

    Full Text Available Abstract Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.

  6. Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

    International Nuclear Information System (INIS)

    Fonseca, Fernando LA; Sant Ana, Aleksandra VL; Bendit, Israel; Arias, Vitor; Costa, Luciano J; Pinhal, Aparecida A; Giglio, Auro del

    2005-01-01

    Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

  7. Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

    Science.gov (United States)

    Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai

    2016-01-01

    Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed. © 2016 Elsevier Inc. All rights reserved.

  8. Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

    Science.gov (United States)

    Puhakka, A; Forssell, H; Soinila, S; Virtanen, A; Röyttä, M; Laine, M; Tenovuo, O; Teerijoki-Oksa, T; Jääskeläinen, S K

    2016-05-01

    The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  10. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-04-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

  11. A hybrid image fusion system for endovascular interventions of peripheral artery disease.

    Science.gov (United States)

    Lalys, Florent; Favre, Ketty; Villena, Alexandre; Durrmann, Vincent; Colleaux, Mathieu; Lucas, Antoine; Kaladji, Adrien

    2018-03-16

    Interventional endovascular treatment has become the first line of management in the treatment of peripheral artery disease (PAD). However, contrast and radiation exposure continue to limit the feasibility of these procedures. This paper presents a novel hybrid image fusion system for endovascular intervention of PAD. We present two different roadmapping methods from intra- and pre-interventional imaging that can be used either simultaneously or independently, constituting the navigation system. The navigation system is decomposed into several steps that can be entirely integrated within the procedure workflow without modifying it to benefit from the roadmapping. First, a 2D panorama of the entire peripheral artery system is automatically created based on a sequence of stepping fluoroscopic images acquired during the intra-interventional diagnosis phase. During the interventional phase, the live image can be synchronized on the panorama to form the basis of the image fusion system. Two types of augmented information are then integrated. First, an angiography panorama is proposed to avoid contrast media re-injection. Information exploiting the pre-interventional computed tomography angiography (CTA) is also brought to the surgeon by means of semiautomatic 3D/2D registration on the 2D panorama. Each step of the workflow was independently validated. Experiments for both the 2D panorama creation and the synchronization processes showed very accurate results (errors of 1.24 and [Formula: see text] mm, respectively), similarly to the registration on the 3D CTA (errors of [Formula: see text] mm), with minimal user interaction and very low computation time. First results of an on-going clinical study highlighted its major clinical added value on intraoperative parameters. No image fusion system has been proposed yet for endovascular procedures of PAD in lower extremities. More globally, such a navigation system, combining image fusion from different 2D and 3D image

  12. Lactococcus lactis, an alternative system for functional expression of peripheral and intrinsic Arabidopsis membrane proteins.

    Directory of Open Access Journals (Sweden)

    Annie Frelet-Barrand

    Full Text Available BACKGROUND: Despite their functional and biotechnological importance, the study of membrane proteins remains difficult due to their hydrophobicity and their low natural abundance in cells. Furthermore, into established heterologous systems, these proteins are frequently only produced at very low levels, toxic and mis- or unfolded. Lactococcus lactis, a gram-positive lactic bacterium, has been traditionally used in food fermentations. This expression system is also widely used in biotechnology for large-scale production of heterologous proteins. Various expression vectors, based either on constitutive or inducible promoters, are available for this system. While previously used to produce bacterial and eukaryotic membrane proteins, the ability of this system to produce plant membrane proteins was until now not tested. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to test the expression, in Lactococcus lactis, of either peripheral or intrinsic Arabidopsis membrane proteins that could not be produced, or in too low amount, using more classical heterologous expression systems. In an effort to easily transfer genes from Gateway-based Arabidopsis cDNA libraries to the L. lactis expression vector pNZ8148, we first established a cloning strategy compatible with Gateway entry vectors. Interestingly, the six tested Arabidopsis membrane proteins could be produced, in Lactococcus lactis, at levels compatible with further biochemical analyses. We then successfully developed solubilization and purification processes for three of these proteins. Finally, we questioned the functionality of a peripheral and an intrinsic membrane protein, and demonstrated that both proteins were active when produced in this system. CONCLUSIONS/SIGNIFICANCE: Altogether, these data suggest that Lactococcus lactis might be an attractive system for the efficient and functional production of difficult plant membrane proteins.

  13. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

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    Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  14. Peripheral circadian misalignment: contributor to systemic insulin resistance and potential intervention to improve bariatric surgical outcomes

    Science.gov (United States)

    Kunze, Kyle N.; Hanlon, Erin C.; Prachand, Vivek N.

    2016-01-01

    Thirteen percent of the world's population suffers from obesity and 39% from being overweight, which correlates with an increase in numerous secondary metabolic complications, such as Type 2 diabetes mellitus. Bariatric surgery is the most effective treatment for severe obesity and results in significant weight loss and the amelioration of obesity-related comorbidities through changes in enteroendocrine activity, caloric intake, and alterations in gut microbiota composition. The circadian system has recently been found to be a critical regulatory component in the control of metabolism and, thus, may potentially play an important role in inappropriate weight gain. Indeed, some behaviors and lifestyle factors associated with an increased risk of obesity are also risk factors for misalignment in the circadian clock system and for the metabolic syndrome. It is thus possible that alterations in peripheral circadian clocks in metabolically relevant tissues are a contributor to the current obesity epidemic. As such, it is plausible that postsurgical alterations in central circadian alignment, as well as peripheral gene expression in metabolic tissues may represent another mechanism for the beneficial effects of bariatric surgery. Bariatric surgery may represent an opportunity to identify changes in the circadian expression of clock genes that have been altered by environmental factors, allowing for a better understanding of the mechanism of action of surgery. These studies could also reveal an overlooked target for behavioral intervention to improve metabolic outcomes following bariatric surgery. PMID:27465735

  15. Paradigms for restoration of somatosensory feedback via stimulation of the peripheral nervous system.

    Science.gov (United States)

    Pasluosta, Cristian; Kiele, Patrick; Stieglitz, Thomas

    2018-04-01

    The somatosensory system contributes substantially to the integration of multiple sensor modalities into perception. Tactile sensations, proprioception and even temperature perception are integrated to perceive embodiment of our limbs. Damage of somatosensory networks can severely affect the execution of daily life activities. Peripheral injuries are optimally corrected via direct interfacing of the peripheral nerves. Recent advances in implantable devices, stimulation paradigms, and biomimetic sensors enabled the restoration of natural sensations after amputation of the limb. The refinement of stimulation patterns to deliver natural feedback that can be interpreted intuitively such to prescind from long-learning sessions is crucial to function restoration. For this review, we collected state-of-the-art knowledge on the evolution of stimulation paradigms from single fiber stimulation to the eliciting of multisensory sensations. Data from the literature are structured into six sections: (a) physiology of the somatosensory system; (b) stimulation of single fibers; (c) restoral of multisensory percepts; (d) closure of the control loop in hand prostheses; (e) sensory restoration and the sense of embodiment, and (f) methodologies to assess stimulation outcomes. Full functional recovery demands further research on multisensory integration and brain plasticity, which will bring new paradigms for intuitive sensory feedback in the next generation of limb prostheses. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. Peripheral nervous system assessment in acromegaly patients under somatostatin analogue therapy.

    Science.gov (United States)

    Alibas, H; Gogas Yavuz, D; Kahraman Koytak, P; Uygur, M; Tanridag, T; Uluc, K

    2017-01-01

    Acromegaly is known to affect peripheral nervous system (PNS) causing carpal tunnel syndrome (CTS) and polyneuropathy. The frequency of these disorders and the evaluation methods vary among studies. In the present study, we aimed to examine PNS of acromegaly patients under somatostatin analogue (SSA) therapy. Forty-eight acromegaly patients (26 F/22 M, 45.58 ± 11.6 years) under SSA treatment and 44 healthy controls (25 F/19 M, 47.46 ± 8.7 years) were assessed by symptom questionnaires, neurologic examination and electrophysiological studies. 87.5 % of the acromegaly patients had at least one abnormal finding regarding PNS. With the incorporation of palm-wrist median nerve conduction velocity method, we detected CTS in 50 % of patients. Polyneuropathy was less frequent (29.2 %). Both conditions were independent from the coexisting diabetes mellitus (p = 0.22 for CTS, p = 0.71 for polyneuropathy). Polyneuropathy but not CTS was more common among biochemically uncontrolled acromegaly patients rather than those under control (p = 0.03; p = 0.68, respectively). Our findings emphasize the high prevalence of peripheral nervous system involvement in acromegaly patients under SSA therapy and importance of neurological evaluation of these patients. Early diagnosis and treatment of the disease may reduce the PNS involvement.

  17. Effects of alpha-glucosylhesperidin on the peripheral body temperature and autonomic nervous system.

    Science.gov (United States)

    Takumi, Hiroko; Fujishima, Noboru; Shiraishi, Koso; Mori, Yuka; Ariyama, Ai; Kometani, Takashi; Hashimoto, Shinichi; Nadamoto, Tomonori

    2010-01-01

    We studied the effects of alpha-glucosylhesperidin (G-Hsp) on the peripheral body temperature and autonomic nervous system in humans. We first conducted a survey of 97 female university students about excessive sensitivity to the cold; 74% of them replied that they were susceptible or somewhat susceptible to the cold. We subsequently conducted a three-step experiment. In the first experiment, G-Hsp (500 mg) was proven to prevent a decrease in the peripheral body temperature under an ambient temperature of 24 degrees C. In the second experiment, a warm beverage containing G-Hsp promoted blood circulation and kept the finger temperature higher for a longer time. We finally used a heart-rate variability analysis to study whether G-Hsp changed the autonomic nervous activity. The high-frequency (HF) component tended to be higher, while the ratio of the low-frequency (LF)/HF components tended to be lower after the G-Hsp administration. These results suggest that the mechanism for temperature control by G-Hsp might involve an effect on the autonomic nervous system.

  18. Most B cells in non-lymphoid tissues are naïve.

    Science.gov (United States)

    Inman, Charlotte F; Murray, Tamsin Zangerle; Bailey, Mick; Cose, Stephen

    2012-02-01

    The current view of lymphocyte migration states that naïve lymphocytes re-circulate between the blood and the lymph via the lymph nodes, but are not able to access non-lymphoid tissues. We examined B lymphocytes in peripheral tissues and found that the majority were phenotypically similar to naïve B cells in lymphoid tissues and were located within the parenchyma, not associated with blood vessels. The mutation rate within the Vh region of these cells was substantially less than the rate attributed to somatic hypermutation and was identical to that observed in naïve B cells isolated from the lymph nodes, showing the presence of naïve B cells in the non-lymphoid organs. Further, using FTY720-treated mice, we showed that naïve B cells migrate through the peripheral tissues and, using pertussis toxin, that the entry of B cells was not controlled by chemokine-mediated signalling events. Overall, these results show that naïve B lymphocytes constitute the majority of the total B-cell population in non-lymphoid tissues and suggest that these cells may re-circulate through the periphery as part of their normal migration pathway. This has implications for the current view of the role of naïve B cells in priming and tolerance.

  19. Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors

    Science.gov (United States)

    Hu, Desheng; Mohanta, Sarajo K.; Yin, Changjun; Peng, Li; Ma, Zhe; Srikakulapu, Prasad; Grassia, Gianluca; MacRitchie, Neil; Dever, Gary; Gordon, Peter; Burton, Francis L.; Ialenti, Armando; Sabir, Suleman R.; McInnes, Iain B.; Brewer, James M.; Garside, Paul; Weber, Christian; Lehmann, Thomas; Teupser, Daniel; Habenicht, Livia; Beer, Michael; Grabner, Rolf; Maffia, Pasquale; Weih, Falk; Habenicht, Andreas J.R.

    2015-01-01

    Summary Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs. PMID:26084025

  20. Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon

    Directory of Open Access Journals (Sweden)

    Manuela Buettner

    2016-09-01

    Full Text Available The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP in the small intestine and their colonic counterparts that develop in a programmed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT. In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP to large, mature isolated lymphoid follicles (ILF. Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi cells and the requirement for lymphotoxin beta (LTβ receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO. While so far it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  1. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  2. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon.

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer's patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  3. Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

    Science.gov (United States)

    Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

    2017-06-01

    Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

  4. [The brothers of Jumiege--the peripheral nervous system in early French mythology].

    Science.gov (United States)

    Brean, Are

    2002-03-20

    This article reviews the process of discovery of the nervous system from Pythagoras (570-500 BC) to Galen (130-201 AD). After Galen, no anatomical studies were performed before the renaissance. According to a legend, probably produced for political reasons, two brothers, sons of the French king Clovis II, revolted against their father and were sentenced to loose their physical powers by having the nerves of their arms and legs cut. They were then set adrift on the river Seine, stranding at the Jumiège monastery. The earliest written version of this legend stems from the fourteenth century; it was probably a part of the local French mythology. This indicates that the existence of the peripheral nervous system, and therefore also in part the knowledge contained in the early anatomical works, quite early may have been more or less known outside academic circles.

  5. Effect of Diet and Exercise on the Peripheral Immune System in Young Balb/c Mice

    Science.gov (United States)

    Martínez-Carrillo, B. E.; Jarillo-Luna, R. A.; Campos-Rodríguez, R.; Valdés-Ramos, R.; Rivera-Aguilar, V.

    2015-01-01

    Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise. PMID:26634209

  6. Role of the peripheral innate immune system in the development of Alzheimer's disease.

    Science.gov (United States)

    Le Page, Aurélie; Dupuis, Gilles; Frost, Eric H; Larbi, Anis; Pawelec, Graham; Witkowski, Jacek M; Fulop, Tamas

    2017-12-21

    Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography.

    Science.gov (United States)

    Kimura, Kaoru; Yokoyama, Kazuhito; Sato, Hajime; Nordin, Rusli Bin; Naing, Lin; Kimura, Satoshi; Okabe, Shingo; Maeno, Takashi; Kobayashi, Yasuki; Kitamura, Fumihiko; Araki, Shunichi

    2005-04-01

    We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.

  8. Innate Lymphoid Cells in Tumor Immunity.

    Science.gov (United States)

    van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

    2016-02-25

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

  9. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

    Science.gov (United States)

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  10. Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2016-01-01

    Full Text Available It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage.

  11. 75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

    Science.gov (United States)

    2010-09-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

  12. Clinical and electrodiagnostic findings in a cohort of 61 dogs with peripheral nervous system diseases - a retrospective study

    Directory of Open Access Journals (Sweden)

    EG Giza, JE Nicpon and MA Wrzosek

    2014-04-01

    Full Text Available The electrodiagnostic examination provides the basis for a diagnostic workup in diseases involving nerve roots, peripheral nerves, neuromuscular junctions and muscles in humans and animals. It is a functional test that enables identification, localization and characterization of the disease within the peripheral nervous system. The study was carried out retrospectively on a group of 61 dogs of different breeds referred for an electrodiagnostic examination because of local or generalized peripheral nervous system impairment. The electrodiagnostic examination consisted of electromyography, electroneurography, F-wave and repetitive nerve stimulation testing. The results of electrodiagnostic studies and their impact on the diagnosis of neuromuscular diseases of different etiology is presented in the study. The lesion was localized to peripheral nerves in 38%, nerve roots in 34%, skeletal muscles in 18% and the neuromuscular junction in 10% of cases. Electrodiagnostics enabled an objective assessment of the extent, distribution and nature of the disease in the study group. However, only when it is used in conjunction with a complete physical and neurological examination and appropriate laboratory or imaging studies, it may be helpful in determining the etiological diagnosis in patients with peripheral nervous system disease.

  13. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Field, E.H.; Strober, S.; Hoppe, R.T.

    1983-01-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values

  14. The Role of TOX in the Development of Innate Lymphoid Cells.

    Science.gov (United States)

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  15. The Role of TOX in the Development of Innate Lymphoid Cells

    Directory of Open Access Journals (Sweden)

    Corey R. Seehus

    2015-01-01

    Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  16. Innate lymphoid cells and their stromal microenvironments.

    Science.gov (United States)

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  17. A cost-effective peripheral venous port system placed at the bedside.

    Science.gov (United States)

    Finney, R; Albrink, M H; Hart, M B; Rosemurgy, A S

    1992-07-01

    High costs and a paucity of available operating time have led us to seek alternatives to operatively placed vascular access systems. This prospective study is the initial report of a peripheral port system (P.A.S. PORT System, Pharmacia Deltec, Inc.) placed at the bedside. Seventy-nine patients (52 male, 27 female), ages 3-92 years, had ports implanted by surgical residents with attending supervision. Sixty-eight (86%) received the P.A.S. PORT for long-term antibiotics, antifungal, or antiviral therapy; four (5%) for TPN infusion; three (4%) for blood products; two (3%) for chemotherapy; and two (3%) for iv narcotics. Ports were placed in 10 (13%) HIV(+) patients, three (4%) who were fully anticoagulated, and one who was a hemophiliac with a platelet count of zero. Eight patients (10%) developed superficial phlebitis, all of which resolved with nonsteroidal anti-inflammatory agents within 48 hr without port removal. Seven patients (9%) had their port removed due to infection. The average hospital charge to place the P.A.S. PORT System was $1488.00 vs $2811.00 for a tunneled external chest catheter and $3729.00 for the placement of a chest port. Bedside insertion of vascular access devices can be safely performed with acceptable infection rates allowing more efficient use of hospital operating rooms and with substantial cost savings.

  18. Participation of the peripheral taste system in aging-dependent changes in taste sensitivity.

    Science.gov (United States)

    Narukawa, Masataka; Kurokawa, Azusa; Kohta, Rie; Misaka, Takumi

    2017-09-01

    Previous studies have shown that aging modifies taste sensitivity. However, the factors affecting the changes in taste sensitivity remain unclear. To investigate the cause of the age-related changes in taste sensitivity, we compared the peripheral taste detection systems in young and old mice. First, we examined whether taste sensitivity varied according to age using behavioral assays. We confirmed that the taste sensitivities to salty and bitter tastes decreased with aging. In other assays, the gustatory nerve responses to salty and sweet tastes increased significantly with aging, while those to bitter taste did not change. Thus, the profile of the gustatory nerve responses was inconsistent with the profile of the behavioral responses. Next, we evaluated the expressions of taste-related molecules in the taste buds. Although no apparent differences in the expressions of representative taste receptors were observed between the two age groups, the mRNA expressions of signaling effectors were slightly, but significantly, decreased in old mice. No significant differences in the turnover rates of taste bud cells were observed between the two age groups. Thus, we did not observe any large decreases in the expressions of taste-related molecules and turnover rates of taste bud cells with aging. Based on these findings, we conclude that changes in taste sensitivity with aging were not caused by aging-related degradation of peripheral taste organs. Meanwhile, the concentrations of several serum components that modify taste responses changed with age. Thus, taste signal-modifying factors such as serum components may have a contributing role in aging-related changes in taste sensitivity. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  19. Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

    Full Text Available Group 1 innate lymphoid cells (ILC comprise the natural killer (NK cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs, that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILC and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells.

  20. Migration and Tissue Tropism of Innate Lymphoid Cells

    Science.gov (United States)

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  1. HCV Virus and Lymphoid Neoplasms

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  2. Metabolic and physiologic studies of nonimmune lymphoid cells cytotoxic for fibroblastic cells in vitro

    International Nuclear Information System (INIS)

    Mayhew, E.; Bennett, M.

    1974-01-01

    An in vitro reaction between mouse lymphoid cells and target fibroblastic cells in wells of microtest plates, which appears to simulate the in vivo rejection of hemopoietic allografts, has been analyzed for metabolic and physiologic requirements. Protein synthesis was required for only the first few hours of culture. Inhibition of RNA synthesis and alteration of cell surface charge with various agents were without obvious effects. Metabolic slowing at 4 0 C or deviation of the pH of the culture medium suppressed the reaction. Thymus cells, which are not cytotoxic in this system, significantly but not completely inhibited the cytotoxicity of lymph node cells. Antiserum directed against target cells specifically protected them from the cytotoxic lymphoid cells in the absence of complement. Precursors of cytotoxic lymphoid cells were radiosensitive, unlike the cytotoxic cells themselves. BALB/c anti-C57BL/6 spleen cell serum and 89 Sr both are able to prevent rejection of marrow allografts in vivo. Lymphoid cells incubated with this antiserum plus complement lost much of their cytotoxicity but were still effective at high ratios of aggressor to target cells. Lymphoid cells of mice treated with 89 Sr were effectively cytotoxic but lost practically all of their cytotoxicity after incubation with the antiserum plus complement. Thus, it appears that this reaction detects two different cytotoxic lymphoid cells, either of which can function in vitro. Both cell types may need to cooperate in vivo during marrow allograft rejections

  3. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  4. Immunophenotype of cells within cervine rectoanal mucosa-associated lymphoid tissue and mesenteric lymph nodes.

    Science.gov (United States)

    Dagleish, M P; Finlayson, J; Steele, P J; Pang, Y; Hamilton, S; Eaton, S L; Sales, J; González, L; Chianini, F

    2012-05-01

    Rectoanal mucosa-associated lymphoid tissue (RAMALT) is a part of the lymphoid system that can be sampled easily in live animals, especially ruminants. RAMALT biopsy is useful for the diagnosis of transmissible spongiform encephalopathies, including scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. Diagnosis is reliant on detection of abnormal prion protein (PrP(d)), which is associated with lymphoid follicles. For enzyme linked immunosorbent assays (ELISAs) detecting PrP(d) it is necessary to ensure that lymphoid follicles are present in biopsy samples to avoid false-negative results. Monoclonal antibodies known to recognize specific immune cell subsets present in lymphoid tissues of sheep were tested for cross-reactivity with cervine RAMALT and mesenteric lymph nodes (MLNs) preserved in zinc salts fixative. The distribution of cells expressing CD3, CD4, CD79, CD21 and class II molecules of the major histocompatibility complex was determined in these tissues. Cells of each immunophenotype had similar distributions in RAMALT and MLNs and these distributions were similar to those reported previously for sheep and cattle. The identification and validation of cervine lymphoid follicle cell markers (CD79 and CD21) may allow reduction in false-negative results during diagnosis of CWD by ELISA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  6. Location and function of serotonin in the central and peripheral nervous system of the Colorado potato beetle

    NARCIS (Netherlands)

    Haeften, van T.

    1993-01-01

    In this thesis we have localized serotoninergic neurons in the central and peripheral nervous system of the Colorado potato beetle, Leptinotarsa decemlineata by means of immunohistochemistry with a specific antiserurn to serotonin and assessed the possible role of these

  7. Transcription factor Fos-Related Antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis

    OpenAIRE

    Maurer, B; Busch, N; Jüngel, A; Pileckyte, M; Gay, R E; Michel, B A; Schett, G; Gay, S; Distler, J; Distler, O

    2009-01-01

    BACKGROUND: -Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Methods and Results-Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endo...

  8. Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

    Science.gov (United States)

    Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

    2017-10-05

    Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

  9. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

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

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  10. Implications of Schwann Cells Biomechanics and Mechanosensitivity for Peripheral Nervous System Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-10-01

    Full Text Available The presence of bones around the central nervous system (CNS provides it with highly effective physiologically crucial mechanical protection. The peripheral nervous system (PNS, in contrast, lacks this barrier. Consequently, the long held belief is that the PNS is mechanically vulnerable. On the other hand, the PNS is exposed to a variety of physiological mechanical stresses during regular daily activities. This fact prompts us to question the dogma of PNS mechanical vulnerability. As a matter of fact, impaired mechanics of PNS nerves is associated with neuropathies with the liability to mechanical stresses paralleled by significant impairment of PNS physiological functions. Our recent biomechanical integrity investigations on nerve fibers from wild-type and neuropathic mice lend strong support in favor of natural mechanical protection of the PNS and demonstrate a key role of Schwann cells (SCs therein. Moreover, recent works point out that SCs can sense mechanical properties of their microenvironment and the evidence is growing that SCs mechanosensitivity is important for PNS development and myelination. Hence, SCs exhibit mechanical strength necessary for PNS mechanoprotection as well as mechanosensitivity necessary for PNS development and myelination. This mini review reflects on the intriguing dual ability of SCs and implications for PNS physiology and pathophysiology.

  11. Development of a microculture system for stimulation of chicken peripheral blood lymphocytes with concanavalin A.

    Science.gov (United States)

    Maheswaran, S K; Thies, E S

    1975-07-01

    A microculture system in conjunction with a semiautomatic multiple sample harvester (SAMSH) was used to study the in vitro properties of chicken peripheral lymphocytes. This new procedure enabled doing rapid multiple tests, using relatively few cells, and was highly reproducible. Data were presented to show many variables that are involved in studying the concanavalin A (Con A) response of chicken lymphocytes in a microculture system. Analysis indicated that the conditions for optimal Con A stimulation as measured by incorporation of 3H-TdR include: (a) use of 2 x 10(6) cells per culture in RPMI 1640 culture medium in the absence of any serum, (b) use of 0.4 mug of Con A per culture, (c) incubation at 37 degrees C for 72 hours, and (d) addition of 1 muCi of 3H-TdR to each culture 12 to 24 hours prior to termination. This technique could be used to monitor immunocompetence of the chicken.

  12. Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.

    Science.gov (United States)

    Ding, Tao; Yao, Yeumang; Praticò, Domenico

    2005-05-01

    In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.

  13. Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment

    Directory of Open Access Journals (Sweden)

    R.A. Orujov

    2017-12-01

    Full Text Available Benzene is a widely spread chemical health risk factor. Our research goal was to examine the nervous system state and the blood system state under benzene intoxication during an experiment. An acute experiment was performed on 45 white mice with 5-fold poisoning with benzene; a chronic one was performed on 72 rabbits being under inhalation exposure to benzene during 4 months, its concentrations increasing and fluctuating. We determined the following blood parameters: number of reticulocytes, eosinophils, basocytes, and erythrocytes; erythrocytes sedimentation rate; blood clotting period; blood clot retraction; plasma re-calcification period; plasma tolerance to heparin; prothrombin time; prothrombin index; fibrinogen concentration; blood fibrinolytic activity; acetylcholine and choline esterase contents. We also determined adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine contents in urine. Acute experiments results revealed that one-time exposure to benzene exerted a narcotic effect on the central nervous system which had an excitation phase and inhibition phase. Under a repeat exposure to benzene animals' drug intoxication was shorter. And here neutrophils / leucocytes gradient first increased to 139.5 % from its standards value and then when down under consequent intoxications. We detected relevant changes in morphological picture of animals' peripheral blood and their central and vegetative nervous system under chronic exposure to intermittent and increasing benzene concentrations. So, our research revealed that effects exerted by benzene in small concentrations led to apparent shifts in white blood and catecholamines (adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine. We also detected certain signs that cate-cholamines endogenous reserves (dihydroxyphenylalanine were depleted and, and also signs of eosinophils-basocytes disso-ciation; such prognostic signs were considered to be unfavorable as it was exactly at that

  14. Immunosuppressive effect of total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bendel, V.; Medizinische Hochschule Hannover

    1981-01-01

    Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

  15. Insulin in Central Nervous System: More than Just a Peripheral Hormone

    Directory of Open Access Journals (Sweden)

    Ana I. Duarte

    2012-01-01

    Full Text Available Insulin signaling in central nervous system (CNS has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

  16. PARANEOPLASTIC DAMAGE TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM IN BREAST CANCER: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    E. S. Koroleva

    2017-01-01

    Full Text Available Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed.

  17. Neutron emission in peripheral heavy ion collisions in the system Ho + Ne

    International Nuclear Information System (INIS)

    Orf, H.

    1983-01-01

    In the present thesis peripheral collision processes in the system 165 Ho + 20 Ne were studied. The measurement of the neutrons in coincidence with projectile-like fragments should answer the central question whether at incident energies of approx.=15 respectively 20 MeV/nucleon a thermal equilibrium is reached yet during the interaction time. The analysis of the neutron spectra resulted that the largest part of the neutrons was evaporated just after reaching the thermal equilibrium from the fragments fully accelerated in the Coulomb field. About 10% of the neutrons however were emitted during the interaction time and showed the same spectral shape as the pre-equilibrium neutrons in central collisions. A further hint for pre-equilibrium effects yielded the result that the temperatures of the projectile-like fragments were larger than those of the target-like. This could be explained for quasi-elastic processes by assuming a fluctuation in the partition of the excitation energy. For deep inelastic processes such explanation wasn't possible. At neon fragment with low energy loss furthermore direct processes could be observed in which the projectile has picked up a neutron from the target nucleus without excitation of it. From the known width of the observed state in 21 Ne the reaction time could be fixed to values lower than 6x10 -21 s. (HSI) [de

  18. Systemic inflammation is higher in peripheral artery disease than in stable coronary artery disease.

    Science.gov (United States)

    Rein, Philipp; Saely, Christoph H; Silbernagel, Günther; Vonbank, Alexander; Mathies, Rainer; Drexel, Heinz; Baumgartner, Iris

    2015-04-01

    The knowledge on the level of systemic inflammation in peripheral artery disease (PAD) is less well established than that in coronary artery disease (CAD). Systemic inflammation frequently coincides with atherosclerosis, but also with various traits of the metabolic syndrome (MetS). The individual contribution of CAD, PAD, and the MetS to inflammation is not known. We enrolled a total of 1396 patients, 460 patients with PAD Fontaine stages IIa-IV verified by duplex ultrasound (PAD group) and 936 patients free of limb claudication undergoing coronary angiography, of whom 507 had significant CAD with coronary stenoses ≥50% (CAD group), and 429 did not have significant CAD at angiography (control group). C-reactive protein (CRP) was significantly higher in the PAD than in the CAD or in the control group (0.86 ± 1.85 mg/dl versus 0.44 ± 0.87 mg/dl and 0.39 ± 0.52 mg/dl, respectively, p < 0.001 for both comparisons). These significant differences were confirmed when patients with and subjects without the MetS were analyzed separately. In particular, within the PAD group, CRP was significantly higher in patients with the MetS than in subjects without the MetS (1.04 ± 2.01 vs. 0.67 ± 1.64 mg/dl; p = 0.001) and both, the presence of PAD and the MetS proved to be independently associated with CRP in analysis of covariance (F = 31.84; p < 0.001 and F = 10.52; p = 0.001, respectively). Inflammatory activity in PAD patients is higher than in CAD patients and is particularly high in PAD patients affected by the MetS. Low grade systemic inflammation is independently associated with both the MetS and PAD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Mustafa, M; Ljungdahl, A

    1995-01-01

    , the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal...... to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4...... cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act...

  20. Anatomical and histological profile of bronchus-associated lymphoid tissue and localization of melatonin receptor types (Mel 1a and Mel 1b) in the lung-associated immune system of a tropical bird, Perdicula asiatica.

    Science.gov (United States)

    Kumar Kharwar, Rajesh; Haldar, Chandana

    2011-05-01

    The histological distribution of the lung-associated immune system (LAIS) and the expressional pattern of melatonin receptors are still unknown in birds. The aim of the present study was to determine the localization of the bronchus-associated lymphoid tissue (BALT nodule) in a tropical bird, the Indian jungle bush quail, Perdicula asiatica. We also demonstrate the expression of melatonin receptor types (Mel(1a) and Mel(1b)) in order to propose an immunomodulatory role of melatonin in LAIS. Localization of melatonin receptors in the lung of the Indian jungle bush quail, P. asiatica was supported immunohistochemically and by Western blot analysis using specific antibodies for those receptors. Immunolocalization for Mel(1b) receptor was noted in the bronchial region of the lungs, in finger-like projections of mucosal foldings, in lymphocytes in the BALT nodule as well as in free form. In contrast, immunolocalization for Mel(1a) receptor was noted in various areas of the lung instead of in the bronchial region. Western blot analysis showed a single band at 37 and 39kDa for Mel(1a) and Mel(1b) receptors, respectively, with the latter showing higher expression. The results demonstrate a well-developed LAIS and region-specific distribution of melatonin receptors in the lung and provide evidence for a possible functional role for melatonin in the LAIS of birds. Copyright © 2010 Elsevier GmbH. All rights reserved.

  1. A High Density Electrophysiological Data Analysis System for a Peripheral Nerve Interface Communicating with Individual Neurons in the Brain

    Science.gov (United States)

    2016-11-14

    of-the-art instrumentation to communicate with individual neurons in the brain and the peripheral nervous system. The major theme of the research is...Nerve Interface Communicating with Individual Neurons in the Brain The views, opinions and/or findings contained in this report are those of the author... Communicating with Individual Neurons in the Brain Report Title The high density electrophysiological data acquisition system obtained through this

  2. Consistent analysis of peripheral reaction channels and fusion for the 16,18O+58Ni systems

    International Nuclear Information System (INIS)

    Alves, J.J.S.; Gomes, P.R.S.; Lubian, J.; Chamon, L.C.; Pereira, D.; Anjos, R.M.; Rossi, E.S.; Silva, C.P.; Alvarez, M.A.G.; Nobre, G.P.A.; Gasques, L.R.

    2005-01-01

    We have measured elastic scattering and peripheral reaction channel cross sections for the 16,18 O+ 58 Ni systems at ELab=46 MeV. The data were analyzed through extensive coupled-channel calculations. It was investigated the consistency of the present analysis with a previous one at sub-barrier energies. Experimental fusion cross sections for these systems are also compared with the corresponding predictions of the coupled-channel calculations

  3. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  4. TOX sets the stage for innate lymphoid cells

    NARCIS (Netherlands)

    Spits, Hergen

    2015-01-01

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

  5. Deficits of anticipatory grip force control after damage to peripheral and central sensorimotor systems.

    Science.gov (United States)

    Hermsdörfer, Joachim; Hagl, Elke; Nowak, Dennis A

    2004-11-01

    Healthy subjects adjust their grip force economically to the weight of a hand-held object. In addition, inertial loads, which arise from arm movements with the grasped object, are anticipated by parallel grip force modulations. Internal forward models have been proposed to predict the consequences of voluntary movements. Anesthesia of the fingers impairs grip force economy but the feedforward character of the grip force/load coupling is preserved. To further analyze the role of sensory input for internal forward models and to characterize the consequences of central nervous system damage for anticipatory grip force control, we measured grip force behavior in neurological patients. We tested a group of stroke patients with varying degrees of impaired fine motor control and sensory loss, a single patient with complete and permanent differentation from all tactile and proprioceptive input, and a group of patients with amyotrophic lateral sclerosis (ALS) that exclusively impairs the motor system without affecting sensory modalities. Increased grip forces were a common finding in all patients. Sensory deficits were a strong but not the only predictor of impaired grip force economy. The feedforward mode of grip force control was typically preserved in the stroke patients despite their central sensory deficits, but was severely disturbed in the patient with peripheral sensory deafferentation and in a minority of stroke patients. Moderate deficits of feedforward control were also obvious in ALS patients. Thus, the function of the internal forward model and the precision of grip force production may depend on a complex anatomical and functional network of sensory and motor structures and their interaction in time and space.

  6. Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    Sadhu Rejina

    2007-12-01

    Full Text Available Abstract Background During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS and the central nervous system (CNS. Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS. Results Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point. Conclusion Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

  7. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    OpenAIRE

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of ly...

  8. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  9. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-01-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21

  10. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

    DEFF Research Database (Denmark)

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received...... an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97......%, respectively; Pblood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28...

  11. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves.

    Science.gov (United States)

    Anholt, R R; Murphy, K M; Mack, G E; Snyder, S H

    1984-02-01

    Binding levels of [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, are substantially higher in homogenates of the olfactory bulb than in the rest of the brain. Among peripheral tissues evaluated, high levels of [3H]Ro5-4864 binding are found in the nasal epithelium. Drug displacement studies show that these binding sites are pharmacologically of the peripheral type. Their presence in the nasal epithelium and in the olfactory bulb can be demonstrated in several different mammalian species. Autoradiographic studies of murine nose reveal a bipolar staining pattern around the cell bodies of the olfactory receptor cells, suggesting the presence of peripheral-type benzodiazepine receptors on both processes of these bipolar neurons. In the brain a high density of [3H]Ro5-4864 binding sites occurs in the nerve fiber and glomerular layers of the olfactory bulb. Throughout the rest of the brain [3H]Ro5-4864-associated silver grains are diffusely distributed with intense staining over the choroid plexus and along the ependymal linings of the ventricles. Both the distribution and the ontogenic development of the peripheral-type benzodiazepine receptors differ from the central-type receptors. Intranasal irrigation with 5% ZnSO4 results in a 50% reduction of peripheral-type benzodiazepine receptors in the olfactory bulb without affecting the density of central-type benzodiazepine receptors. Thus, [3H]Ro5-4864 binding sites in the olfactory bulb appear in large part to be localized to olfactory nerves which originate in the nasal epithelium.

  12. Unconsciously perceived fear in peripheral vision alerts the limbic system: a MEG study.

    Directory of Open Access Journals (Sweden)

    Dimitri J Bayle

    Full Text Available BACKGROUND: In ecological situations, threatening stimuli often come out from the peripheral vision. Such aggressive messages must trigger rapid attention to the periphery to allow a fast and adapted motor reaction. Several clues converge to hypothesize that peripheral danger presentation can trigger off a fast arousal network potentially independent of the consciousness spot. METHODOLOGY/PRINCIPAL FINDINGS: In the present MEG study, spatio-temporal dynamics of the neural processing of danger related stimuli were explored as a function of the stimuli position in the visual field. Fearful and neutral faces were briefly presented in the central or peripheral visual field, and were followed by target faces stimuli. An event-related beamformer source analysis model was applied in three time windows following the first face presentations: 80 to 130 ms, 140 to 190 ms, and 210 to 260 ms. The frontal lobe and the right internal temporal lobe part, including the amygdala, reacted as soon as 80 ms of latency to fear occurring in the peripheral vision. For central presentation, fearful faces evoked the classical neuronal activity along the occipito-temporal visual pathway between 140 and 190 ms. CONCLUSIONS: Thus, the high spatio-temporal resolution of MEG allowed disclosing a fast response of a network involving medial temporal and frontal structures in the processing of fear related stimuli occurring unconsciously in the peripheral visual field. Whereas centrally presented stimuli are precisely processed by the ventral occipito-temporal cortex, the related-to-danger stimuli appearing in the peripheral visual field are more efficient to produce a fast automatic alert response possibly conveyed by subcortical structures.

  13. Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

    Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

  14. Peripheral nervous system maturation in preterm infants: longitudinal motor and sensory nerve conduction studies.

    Science.gov (United States)

    Lori, S; Bertini, Giovanna; Bastianelli, M; Gabbanini, S; Gualandi, D; Molesti, E; Dani, C

    2018-04-10

    To study the evolution of sensory-motor nerves in the upper and lower limbs in neurologically healthy preterm infants and to use sensory-motor studies to compare the rate of maturation in preterm infants at term age and full-term healthy neonates. The study comprised 26 neurologically normal preterm infants born at 23-33 weeks of gestational age, who underwent sensory nerve conduction and motor nerve conduction studies from plantar medial and median nerves and from tibial and ulnar nerves, respectively. We repeated the same neurophysiological studies in 19 of the preterm infants every 2 weeks until postnatal term age. The data from the preterm infants at term was matched with a group of ten full-term babies a few days after birth. The motor nerve conduction velocity of the tibial and ulnar nerves showed progressive increases in values in relation to gestational age, but there was a decrease of values in distal latencies and F wave latencies. Similarly, there was a gradual increase of sensory nerve conduction velocity values of the medial plantar and median nerves and decreases in latencies in relation to gestational age. At term age, the preterm infants showed significantly lower values of conduction velocities and distal latencies than the full-term neonates. These results were probably because the preterm infants had significantly lower weights, total length and, in particular, distal segments of the limbs at term age. The sensory-motor conduction parameters were clearly related to gestational age, but extrauterine life did not affect the maturation of the peripheral nervous system in the very preterm babies who were neurologically healthy.

  15. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  16. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    International Nuclear Information System (INIS)

    Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji

    2012-01-01

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

  17. Professional risk of developing diseases of the peripheral nervous system in tractor drivers – machine operators of agricultural production

    Directory of Open Access Journals (Sweden)

    G.A. Bezrukova

    2015-09-01

    Full Text Available Based on the results of the hygienic assessment of working conditions in the domestic agricultural machinery of old and new models when performing the main types of seasonal agricultural work during the annual production cycle and analysis of accumulated occupational diseases’ nosology structure in agricultural workers of the Saratov region over the period from 2004 to 2014, the estimation of professional risk diseases of the peripheral nervous system in tractor drivers – machine operators of agricultural production is given. Professional risk assessment carried out under the procedure set forth in P2.2.1766-03 has shown that the category of a priori risk to their health during an annual production cycle ranged from high to very high (unbearable. It was revealed that the most important factors shaping the harmful working conditions when working on agricultural machinery that can act as a trigger in the formation of vertebral diseases of the peripheral nervous system, are general and local vibration, adverse micro-climatic conditions, long uncomfortable static working posture and physical stress. The risk of diseases in the peripheral uneven system in machine operators of agriculture was attributed to the high risk category with an index of professional diseases (IPD equal to 0,5 %.

  18. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  19. Total lymphoid irradiation of intractable rheumatoid arthritis

    International Nuclear Information System (INIS)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored. (author)

  20. Total lymphoid irradiation of intractable rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-12-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored.

  1. The new WHO nomenclature: lymphoid neoplasms.

    Science.gov (United States)

    Leclair, Susan J; Rodak, Bernadette F

    2002-01-01

    The development of the WHO classification of lymphoid neoplasms is a remarkable example of cooperation and communication between pathologists and oncologists from around the world. Joint classification committees of the major hematopathology societies will periodically review and update this classification, facilitating further progress in the understanding and treatment of hematologic malignancies.

  2. Conjunctival lymphoma arising from reactive lymphoid hyperplasia

    Directory of Open Access Journals (Sweden)

    Fukuhara Junichi

    2012-09-01

    Full Text Available Abstract Extra nodal marginal zone B-cell lymphoma (EMZL of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU. Specimens from conjunctival tumors in the right eye, oculus dexter (OD, revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS, and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

  3. Perfusion imaging in the peripheral vasculature using interventional C-arm systems

    NARCIS (Netherlands)

    Giordano, M.G.

    2013-01-01

    In peripheral revascularization procedures, an obstructed vessel is unblocked to restore the blood flow to the tissue. Currently, treatment assessment is carried out by angiography which allows only for a qualitative inspection of the blood flow in arteries. Periprocedural assessment of tissue

  4. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

    Directory of Open Access Journals (Sweden)

    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  5. Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

    Science.gov (United States)

    Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric

    2012-01-01

    Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORγt+ ILCs with a lineage−CD94−CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. PMID:23181063

  6. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

    Science.gov (United States)

    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  7. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  8. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Directory of Open Access Journals (Sweden)

    Melissa D Clouse

    Full Text Available The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc comes into contact with native prion protein (PrPC and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  9. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Science.gov (United States)

    Clouse, Melissa D; Shikiya, Ronald A; Bartz, Jason C; Kincaid, Anthony E

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  10. The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates

    Directory of Open Access Journals (Sweden)

    Kludka-Sternik M

    2010-04-01

    Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendriticcells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty ninehealthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. Theexpression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performedusing a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentageof BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood ofhealthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatorymolecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 moleculesenable appropriate development of immune response.

  11. The expression of B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in cord blood of healthy neonates.

    Directory of Open Access Journals (Sweden)

    S Radej

    2011-04-01

    Full Text Available The aim of our study was to estimate both B7-H1 and B7-H4 molecules on immature myeloid and lymphoid dendritic cells in umbilical cord blood of healthy neonates in comparison with peripheral blood of healthy adults. Thirty nine healthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. The expression of B7-H1 and B7-H4 was revealed using the immunofluorescence method. Statistical analysis was performed using a non-parametric test (Mann-Whitney U-Test. The percentages of BDCA-1+ dendritic cells with B7-H1 and B7-H4 expressions were significantly higher in peripheral blood of healthy adults (p<0.00003. It was either observed that the percentage of BDCA-2+ dendritic cells with the expression of B7-H4 molecules was significantly higher in peripheral blood of healthy adults in comparison with umbilical cord blood (p<0.02. Decreased percentages of dendritic cells and co-stimulatory molecules indicate that neonates have immature immune system. Depletion of co-stimulatory B7-H1 and B7-H4 molecules enable appropriate development of immune response.

  12. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system.

    Science.gov (United States)

    Godbout, Jonathan P; Moreau, Maïté; Lestage, Jacques; Chen, Jing; Sparkman, Nathan L; O'Connor, Jason; Castanon, Nathalie; Kelley, Keith W; Dantzer, Robert; Johnson, Rodney W

    2008-09-01

    Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.

  13. Transfer of vesicles from Schwann cell to axon: a novel mechanism of communication in the peripheral nervous system

    Directory of Open Access Journals (Sweden)

    María Alejandra eLopez-Verrilli

    2012-06-01

    Full Text Available Schwann cells (SCs are the glial component of the peripheral nervous system, with essential roles during development and maintenance of axons, as well as during regenerative processes after nerve injury. SCs increase conduction velocities by myelinating axons, regulate synaptic activity at presynaptic nerve terminals and are a source of trophic factors to neurons. Thus, development and maintenance of peripheral nerves are crucially dependent on local signalling between SCs and axons. In addition to the classic mechanisms of intercellular signalling, the possibility of communication through secreted vesicles has been poorly explored to date. Interesting recent findings suggest the occurrence of lateral transfer mediated by vesicles from glial cells to axons that could have important roles in axonal growth and axonal regeneration. Here, we review the role of vesicular transfer from SCs to axons and propose the benefits of this means in supporting neuronal and axonal maintenance and regeneration after nerve damage.

  14. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    Science.gov (United States)

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  15. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib.

    Science.gov (United States)

    Messina, Julia A; Maziarz, Eileen K; Spec, Andrej; Kontoyiannis, Dimitrios P; Perfect, John R

    2017-01-01

    We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  16. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib

    OpenAIRE

    Messina, Julia A.; Maziarz, Eileen K.; Spec, Andrej; Kontoyiannis, Dimitrios P.; Perfect, John R.

    2017-01-01

    Abstract We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  17. Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration

    Directory of Open Access Journals (Sweden)

    Reilly Petrina

    2010-03-01

    Full Text Available Abstract Background Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. Results A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P P P P P P P Conclusion Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.

  18. Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration.

    Science.gov (United States)

    Lejeune, Alexandre; Monahan, Frank J; Moloney, Aidan P; Earley, Bernadette; Black, Alistair D; Campion, Deirdre P; Englishby, Tanya; Reilly, Petrina; O'Doherty, John; Sweeney, Torres

    2010-03-31

    Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P outdoor animals (P outdoor animals with elevated levels of serum pepsinogen (P outdoor animals in comparison to the indoor animals. Lower levels of copper and iodine were measured in the outdoor animals in comparison to indoor animals (P < 0.001). Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.

  19. Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system

    NARCIS (Netherlands)

    Blits, B; Dijkhuizen, Paul A; Carlstedt, Thomas P; Poldervaart, H A; Schiemanck, S; Boer, G J; Verhaagen, J

    1999-01-01

    Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the

  20. Cerebellum tunes the excitability of the motor system: evidence from peripheral motor axons.

    Science.gov (United States)

    Nodera, Hiroyuki; Manto, Mario

    2014-12-01

    Cerebellum is highly connected with the contralateral cerebral cortex. So far, the motor deficits observed in acute focal cerebellar lesions in human have been mainly explained on the basis of a disruption of the cerebello-thalamo-cortical projections. Cerebellar circuits have also numerous anatomical and functional interactions with brainstem nuclei and projects also directly to the spinal cord. Cerebellar lesions alter the excitability of peripheral motor axons as demonstrated by peripheral motor threshold-tracking techniques in cerebellar stroke. The biophysical changes are correlated with the functional scores. Nerve excitability measurements represent an attractive tool to extract the rules underlying the tuning of excitability of the motor pathways by the cerebellum and to discover the contributions of each cerebellar nucleus in this key function, contributing to early plasticity and sensorimotor learning.

  1. [Age-related changes of sensory peripheral nerve system in healthy subjects.

    Science.gov (United States)

    Voitenkov, V B; Ekusheva, E V; Komancev, V N; Skripchenko, N V; Grigoryev, S G; Klimkin, A V; Aksenova, A I

    2017-01-01

    Our aim was to present and evaluate age-related changes of peripheral nerves of limbs on a huge population of healthy subjects of different ages. In 2009-2016 subjects aged from 1months to 90 years were studied by nerve conduction velocity studies (NCV). Data of those confirmed healthy was included in our study. In total there were 372 healthy subjects. NCV for nn. Medianus et Ulnaris was registered, with NCV and amplitude of compound sensory action potential (CSAP) being analyzed. There were significant differences on both these parameters between different age groups. Since the childhood the improvement of conduction (which was reflected in rising of CSAP amplitudes and NCV quickening) was registered; from 40-50 years steady decline of both these parameters were observed in both nerves. Conduction studies of peripheral nerves may be implemented in gerontology for early detection of neurophysiology patterns reflecting physiological aging. Also our results may be implemented for accelerated aging detection.

  2. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.

    Science.gov (United States)

    Tommola, Päivi; Bützow, Ralf; Unkila-Kallio, Leila; Paavonen, Jorma; Meri, Seppo

    2015-04-01

    Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cells were found in patients than in controls (P associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Lymphoid follicles in children with Helicobacter pylori-negative gastritis

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, pgastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835

  4. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

    International Nuclear Information System (INIS)

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

    2009-01-01

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45 high CD11b + ) and CD8 + T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8 + T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

  5. Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

    Science.gov (United States)

    Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

    2014-02-01

    Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The role of innate lymphoid cells in healthy and inflamed skin

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte M.; Geisler, Carsten

    2016-01-01

    system. During the last years, it has become clear that innate lymphoid cells play a role in homeostasis and inflammation of the skin in humans and mice. In this review, we will discuss the role of innate lymphoid cells in healthy and inflamed skin with special focus on their role in atopic dermatitis.......The skin constitutes the interface between the organism and the environment, and it protects the body from harmful substances in the environment via physical, chemical and immunological barriers. The immunological barrier of the skin comprises both cells from the innate and the adaptive immune...

  7. A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

    Science.gov (United States)

    Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

    2018-01-19

    OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

  8. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

    DEFF Research Database (Denmark)

    Benninger, Yves; Thurnherr, Tina; Pereira, Jorge A

    2007-01-01

    During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific......During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue...

  9. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

    Science.gov (United States)

    Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

    2009-12-08

    Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

  10. Tertiary lymphoid structures in cancer and beyond.

    Science.gov (United States)

    Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    Science.gov (United States)

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  12. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

    International Nuclear Information System (INIS)

    Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

  13. Tertiary lymphoid organs in Takayasu Arteritis

    OpenAIRE

    Marc eClement; Marc eClement; Adrien eGaly; Patrick eBruneval; Marion eMorvan; Fabien eHyafil; Fabien eHyafil; Khadija eBenali; Nicoletta ePasi; Lydia eDeschamps; Quentin ePellenc; Quentin ePellenc; Thomas ePapo; Antonino eNicoletti; Antonino eNicoletti

    2016-01-01

    Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from t...

  14. Tertiary Lymphoid Organs in Takayasu Arteritis

    OpenAIRE

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    Objective The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Methods Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune ce...

  15. An artificial arm/hand system with a haptic sensory function using electric stimulation of peripheral sensory nerve fibers.

    Science.gov (United States)

    Mabuchi, Kunihiko

    2013-01-01

    We are currently developing an artificial arm/hand system which is capable of sensing stimuli and then transferring these stimuli to users as somatic sensations. Presently, we are evoking the virtual somatic sensations by electrically stimulating a sensory nerve fiber which innervates a single mechanoreceptor unit at the target area; this is done using a tungsten microelectrode that was percutaneously inserted into the use's peripheral nerve (a microstimulation method). The artificial arm/hand system is composed of a robot hand equipped with a pressure sensor system on its fingers. The sensor system detects mechanical stimuli, which are transferred to the user by means of the microstimulation method so that the user experiences the stimuli as the corresponding somatic sensations. In trials, the system worked satisfactorily and there was a good correlation between the pressure applied to the pressure sensors on the robot fingers and the subjective intensities of the evoked pressure sensations.

  16. Ex vivo and in vivo coherent Raman imaging of the peripheral and central nervous system

    Science.gov (United States)

    Huff, Terry Brandon

    A hallmark of nervous system disorders is damage or degradation of the myelin sheath. Unraveling the mechanisms underlying myelin degeneration and repair represent one of the great challenges in medicine. This thesis work details the development and utilization of advanced optical imaging methods to gain insight into the structure and function of myelin in both healthy and diseased states in the in vivo environment. This first part of this thesis discusses ex vivo studies of the effects of high-frequency stimulation of spinal tissues on the structure of the node of Ranvier as investigated by coherent anti-Stokes Raman scattering (CARS) imaging (manuscript submitted to Journal of Neurosciece). Reversible paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation, beginning minutes after the onset and continuing for up to 10 min after stimulation was ceased. A mechanistic study revealed a Ca2+ dependent pathway: high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down. Also, the construction of dual-scanning CARS microscope for large area mapping of CNS tissues is detailed (Optics Express, 2008, 16:19396-193409). A confocal scanning head equipped with a rotating polygon mirror provides high speed, high resolution imaging and is coupled with a motorized sample stage to generate high-resolution large-area images of mouse brain coronal section and guinea pig spinal cord cross section. The polygon mirror decreases the mosaic acquisition time significantly without reducing the resolution of individual images. The ex vivo studies are then extended to in vivo imaging of mouse sciatic nerve tissue by CARS and second harmonic generation (SHG) imaging (Journal of Microscopy, 2007, 225: 175-182). Following a minimally invasive surgery to open the skin, CARS imaging of myelinated axons and SHG imaging of the

  17. Characteristic of innate lymphoid cells (ILC

    Directory of Open Access Journals (Sweden)

    Mateusz Adamiak

    2014-12-01

    Full Text Available Innate lymphoid cells (ILC is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer and lymphoid tissue inducer T cells (LTi, which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell - TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22 - which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22 cells or NK receptor-positive (LTi NKR+ LTi cells. Fourth population of ILC cells are ILC17 - producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2, nuocyte, innate type 2 helper cells (IH2 and multi-potent progenitor type 2 cells (MPPtype2. Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T.

  18. [Vertigo and peripheral ischemic cochleovestibular syndrome caused by circulatory insufficiency in the vertebrobasilar system].

    Science.gov (United States)

    Alekseeva, N S; Kirichenko, I M

    2006-01-01

    We studied characteristics of vestibular and acoustic disorders in patients with arterial hypertension, atherosclerosis and vascular dystonia; correlation between peripheral cochleovestibular syndromes (PCVS) and circulation in the major and intracranial arteries, central hemodynamics, organic changes in the brain. We discovered that anomalies and asymmetry in vertebral arteries diameters, stenoses, reduced stroke and minute blood volumes play an essential role in development of PCVS. The latter are rarely accompanied with ischemic foci in the brain. Medication of vascular vertigo consists in administration of an adequate drug. We believe that betaserk is most effective.

  19. Three-dimensional Acoustic Localisation via Directed Movements of a Two-dimensional Model of the Lizard Peripheral Auditory System

    DEFF Research Database (Denmark)

    Shaikh, Danish; Kjær Schmidt, Michael

    2017-01-01

    of the acoustic target with respect to one plane of rotation. A multi-layer perceptron neural network is trained via supervised learning to translate the combination of the two measurements into an estimate of the relative location of the acoustic target in terms of its azimuth and elevation. The acoustic...... localisation performance of the system is evaluated in simulation for noiseless as well as noisy sinusoidal auditory signals with a 20 dB signal-to-noise ratio for four different sound frequencies of 1450 Hz, 1650 Hz, 1850 Hz and 2050 Hz that span the response frequency range of the peripheral auditory model...

  20. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NARCIS (Netherlands)

    van de Pavert, Serge A; Ferreira, Manuela; Domingues, Rita G; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R; Habani, Yasmin; Haak, Esther; Santori, Fabio R; Littman, Dan R; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J Pedro; Mebius, Reina E; Veiga-Fernandes, Henrique

    2014-01-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally

  1. Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

    Science.gov (United States)

    Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

    2018-01-25

    The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

  2. Stromal cell regulation of homeostatic and inflammatory lymphoid organogenesis

    Science.gov (United States)

    Kain, Matthew J W; Owens, Benjamin M J

    2013-01-01

    Summary Secondary lymphoid organs function to increase the efficiency of interactions between rare, antigen-specific lymphocytes and antigen presenting cells, concentrating antigen and lymphocytes in a supportive environment that facilitates the initiation of an adaptive immune response. Homeostatic lymphoid tissue organogenesis proceeds via exquisitely controlled spatiotemporal interactions between haematopoietic lymphoid tissue inducer populations and multiple subsets of non-haematopoietic stromal cells. However, it is becoming clear that in a range of inflammatory contexts, ectopic or tertiary lymphoid tissues can develop inappropriately under pathological stress. Here we summarize the role of stromal cells in the development of homeostatic lymphoid tissue, and assess emerging evidence that suggests a critical role for stromal involvement in the tertiary lymphoid tissue development associated with chronic infections and inflammation. PMID:23621403

  3. Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.

    Science.gov (United States)

    Shakhbazau, Antos; Martinez, Jose A; Xu, Qing-Gui; Kawasoe, Jean; van Minnen, Jan; Midha, Rajiv

    2012-08-01

    Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats. We have found that unilateral sciatic nerve transection results in the elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the contralateral side, commonly considered as a control. Bilateral transection further increased NGF but not other neurotrophins in the nerve segment distal to the transection site, as compared to the unilateral injury. To further investigate the distinct role of NGF in regeneration and its potential for peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding lentivirus and transplanted the over-expressing cells into the distal segment of a transected nerve. Axonal regeneration was studied at 2 weeks time-point using pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the regenerating nerve. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  4. The Role of the Peripheral and Central Nervous Systems in Rotator Cuff Disease

    Science.gov (United States)

    Bachasson, Damien; Singh, Anshuman; Shah, Sameer; Lane, John G.; Ward, Samuel R.

    2015-01-01

    Rotator cuff (RC) disease is an extremely common condition associated with shoulder pain, reduced functional capacities and impaired quality of life. It primarily involves alterations in tendon health and mechanical properties that can ultimately lead to tendon failure. RC tendon tears induce progressive muscular changes that negatively impact surgical reparability of the RC tendons and clinical outcomes. At the same time, a significant base of clinical data suggests a relatively weak relationship between RC integrity and clinical presentation, emphasizing the multifactorial aspects of RC disease. This review aims to summarize the potential contribution of peripheral, spinal and supraspinal neural factors that may: (i) exacerbate structural and functional muscle changes induced by tendon tear, (ii) compromise the reversal of these changes during surgery and rehabilitation, (iii) contribute to pain generation and persistence of pain, iv) impair shoulder function through reduced proprioception, kinematics and muscle recruitment, and iv) help to explain interindividual differences and response to treatment. Given the current clinical and scientific interest in peripheral nerve injury in the context of RC disease and surgery, we carefully reviewed this body of literature with a particular emphasis for suprascapular neuropathy that has generated a large number of studies in the past decade. Within this process, we highlight the gaps in current knowledge and suggest research avenues for scientists and clinicians. PMID:26189809

  5. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  6. Innate lymphoid cells in tissue homeostasis and diseases.

    Science.gov (United States)

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  7. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  8. Trafficking of α-L-fucosidase in lymphoid cells

    International Nuclear Information System (INIS)

    DiCioccio, R.A.; Brown, K.S.

    1987-01-01

    The quantity of α-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high α-L-fucosidase in serum were established. Steady state levels of extracellular α-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of α-L-fucosidase are not adequately expressed in this system. α-L-Fucosidase was also metabolically labelled with 35 S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of α-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between α-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells

  9. Kidney allograft survival in dogs treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  10. Spatial distribution of cannabinoid receptor type 1 (CB1 in normal canine central and peripheral nervous system.

    Directory of Open Access Journals (Sweden)

    Jessica Freundt-Revilla

    Full Text Available The endocannabinoid system is a regulatory pathway consisting of two main types of cannabinoid receptors (CB1 and CB2 and their endogenous ligands, the endocannabinoids. The CB1 receptor is highly expressed in the central and peripheral nervous systems (PNS in mammalians and is involved in neuromodulatory functions. Since endocannabinoids were shown to be elevated in cerebrospinal fluid of epileptic dogs, knowledge about the species specific CB receptor expression in the nervous system is required. Therefore, we assessed the spatial distribution of CB1 receptors in the normal canine CNS and PNS. Immunohistochemistry of several regions of the brain, spinal cord and peripheral nerves from a healthy four-week-old puppy, three six-month-old dogs, and one ten-year-old dog revealed strong dot-like immunoreactivity in the neuropil of the cerebral cortex, Cornu Ammonis (CA and dentate gyrus of the hippocampus, midbrain, cerebellum, medulla oblongata and grey matter of the spinal cord. Dense CB1 expression was found in fibres of the globus pallidus and substantia nigra surrounding immunonegative neurons. Astrocytes were constantly positive in all examined regions. CB1 labelled neurons and satellite cells of the dorsal root ganglia, and myelinating Schwann cells in the PNS. These results demonstrate for the first time the spatial distribution of CB1 receptors in the healthy canine CNS and PNS. These results can be used as a basis for further studies aiming to elucidate the physiological consequences of this particular anatomical and cellular distribution.

  11. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.

    Science.gov (United States)

    Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

    2016-04-01

    Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ(+)RORγt(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Mechanism of lumen gain with a novel rotational aspiration atherectomy system for peripheral arterial disease: examination by intravascular ultrasound.

    Science.gov (United States)

    Hassan, Ali H M; Ako, Junya; Waseda, Katsuhisa; Honda, Yasuhiro; Zeller, Thomas; Leon, Martin B; Fitzgerald, Peter J

    2010-01-01

    The purpose of this study was to evaluate the mechanism of luminal gain with a novel atheroablation system (Pathway PV) for the treatment of peripheral artery disease using intravascular ultrasound (IVUS). The atherectomy system is a rotational atherectomy device, which employs expandable rotating blades with ports that allow flushing and aspiration of the plaque material or thrombus. In this first-in-man clinical study, IVUS analysis was available in 6 patients with lower limb ischemia treated with this device. The treatment results were assessed using IVUS at pre and post atherectomy. Lumen beyond burr size (LBB) was defined as lumen gain divided by the estimated burr area determined by the burr-size. IVUS analysis was available in six patients (superficial femoral artery n=3, popliteal artery n=2, posterior tibial artery n=1). Atheroablation achieved a significant increase in lumen area (LA) (preintervention 3.9+/-0.4, postatheroablation 8.0+/-1.7 mm(2), Patherectomy device achieved significant luminal gain by debulking in the absence of vessel stretching. The LA was greater than burr-sized lumen expectancy at cross-sections along the treated segments, suggesting a complimentary role of aspiration in luminal gain in atherosclerotic peripheral artery lesions.

  13. Sextant localization of prostate cancer in peripheral zone by MRI: correlation with systemic biopsy pathology

    International Nuclear Information System (INIS)

    Huang Rong; Wang Xiaoying; Li Feiyu; Xu Yufeng; Jiang Xuexiang; He Yunfeng; Liu Pengcheng

    2006-01-01

    Objective: To determine the efficacy of sextant localization of prostate cancer (PCa) in PZ (peripheral zone) by MR Imaging. Methods: Fifty-one cases of PCa and 29 cases of benign prostate diseases were enrolled in the study. Each peripheral zone was divided into 6 sections (left/right bottom, middle and tip ) in the same fashion for biopsy and the characteristics of each sextant was evaluated separately. Being blinded to clinical data, 2 radiologists with different subspeciahy experience analyzed MR images of the 480 sections of these 80 cases retrospectively. Each sextant region impression of likelihood for cancer was estimated by the rank of a five-point rating scale (1=definite PCa, 2=probable PCa, 3=possible PCa, 4=probably not PCa, 5=definitely not PCa). If definite PCa was considered, then it was staged furthermore. Each diagnosis of sextant region was compared with the pathological result of corresponding biopsy site. Result: (1) Four hundred and seventy sections (205 cancerous and 265 benign) were proved by biopsy. The diagnosis efficacy was best when cutoff point was 2. There was moderate consistency between the results of MRI and pathology with the kappa value of 0.549-0.560. The total accuracy was 78.1%-78.3% with the sensitivity of 69.3%-76.1% and the specificity of 84.9%-80.0%. The positive predictive value was 78.0%-74.6% and the negative predictive value was 78.1%-81.2%. (2) The ROC analysis demonstrated that Az with total impression recorded by two readers had not significant difference(0.829±0.020 vs. 0.840±0.019, U=-0.3988, P>0.05). Conclusion: MRI may be an elementary way to localize PCa in PZ, but the diagnosis efficacy need to be improved furthermore. (authors)

  14. Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

    Science.gov (United States)

    Klein, S; Kretz, C C; Ruland, V; Stumpf, C; Haust, M; Hartschuh, W; Hartmann, M; Enk, A; Suri-Payer, E; Oberle, N; Krammer, P H; Kuhn, A

    2011-08-01

    To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

  15. Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

    Science.gov (United States)

    Xiong, Tingting; Turner, Jan-Eric

    2018-03-22

    Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

  16. The Development of Adult Innate Lymphoid Cells

    Science.gov (United States)

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  17. Total lymphoid irradiation in rhesus monkeys

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Maat, B.; Hogeweg, B.

    Total lymphoid irradiation (TLI) consists of three contiguous fields, a mantle, an inverted Y and a spleen field. TLI induces a state of immunosuppression in patients with Hodgkin disease or in small rodents. Infusion of allogeneic bone marrow cells into mice after TLI led to the development split haemopoietic chimerism and indefinite survival of skin grafts from the bone marrow donor. A protocol for TLI was developed for rhesus monkeys to attempt to verify these interesting observations in a pre-clinical animal model. (Auth.)

  18. Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    Emily K. Calton

    2017-08-01

    Full Text Available Background: Vitamin D status [25(OHD] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs. No study has tracked the seasonal variation of 25(OHD and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Material and methods: Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test was performed using the Seahorse XFe96 flux analyser. 25(OHD was assessed using the Architect immunoassay method. Results: 25(OHD increased by a median (IQR of 14.40 (20.13 nmol/L (p75 nmol/L. The absolute change in 25(OHD was not associated with altered bioenergetics. Conclusion: Seasonal improvements in 25(OHD was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OHD in winter. The data warrants confirmation through cause and effect study designs. Keywords: Peripheral blood mononuclear cells, Bioenergetics, Vitamin D, Season, Inflammation, Insulin sensitivity

  19. Reorganization of neural systems mediating peripheral visual selective attention in the deaf: An optical imaging study.

    Science.gov (United States)

    Seymour, Jenessa L; Low, Kathy A; Maclin, Edward L; Chiarelli, Antonio M; Mathewson, Kyle E; Fabiani, Monica; Gratton, Gabriele; Dye, Matthew W G

    2017-01-01

    Theories of brain plasticity propose that, in the absence of input from the preferred sensory modality, some specialized brain areas may be recruited when processing information from other modalities, which may result in improved performance. The Useful Field of View task has previously been used to demonstrate that early deafness positively impacts peripheral visual attention. The current study sought to determine the neural changes associated with those deafness-related enhancements in visual performance. Based on previous findings, we hypothesized that recruitment of posterior portions of Brodmann area 22, a brain region most commonly associated with auditory processing, would be correlated with peripheral selective attention as measured using the Useful Field of View task. We report data from severe to profoundly deaf adults and normal-hearing controls who performed the Useful Field of View task while cortical activity was recorded using the event-related optical signal. Behavioral performance, obtained in a separate session, showed that deaf subjects had lower thresholds (i.e., better performance) on the Useful Field of View task. The event-related optical data indicated greater activity for the deaf adults than for the normal-hearing controls during the task in the posterior portion of Brodmann area 22 in the right hemisphere. Furthermore, the behavioral thresholds correlated significantly with this neural activity. This work provides further support for the hypothesis that cross-modal plasticity in deaf individuals appears in higher-order auditory cortices, whereas no similar evidence was obtained for primary auditory areas. It is also the only neuroimaging study to date that has linked deaf-related changes in the right temporal lobe to visual task performance outside of the imaging environment. The event-related optical signal is a valuable technique for studying cross-modal plasticity in deaf humans. The non-invasive and relatively quiet characteristics of

  20. Suppression of pokeweed mitogen-stimulated immunoglobulin production in patients with rheumatoid arthritis after treatment with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Kotzin, B.L.; Strober, S.; Kansas, G.S.; Terrell, C.P.; Engleman, E.G.

    1984-01-01

    Patients with intractable rheumatoid arthritis (RA) were treated with total lymphoid irradiation (TLI, 200 rad). The authors previously reported long-lasting clinical improvement in this group associated with a persistent decrease in circulating Leu-3 (helper subset) T cells and marked impairment of in vitro lymphocyte function. In the present experiments, they studied the mechanisms underlying the decrease in pokeweed mitogen stimulated immunoglobulin (Ig) secretion observed after TLI. Peripheral blood mononuclear cells (PBL) from TLI-treated patients produced 10-fold less Ig (both IgM and IgG) in response to pokeweed mitogen than before radiotherapy. This decrease in Ig production was associated with the presence of suppressor cells in co-culture studies. By using responder cells obtained from normal individuals (allogeneic system), PBL from eight of 12 patients after TLI suppressed Ig synthesis by more than 50%. In contrast, PBL from the same patients before TLI failed to suppress Ig synthesis. PBL with suppressive activity contained suppressor T cells, and the latter cells bore the Leu-2 surface antigen. In 50% of the patients studied suppressor cells were also found in the non-T fraction and were adherent to plastic. Interestingly, the Leu-2 + cells from TLI-treated patients were no more potent on a cell per cell basis than purified Leu-2 + cells obtained before TLI. Additional experiments suggested that the suppression mediated by T cells after TLI is related to the increased ratio of Leu-2 to Leu-3 cells observed after radiotherapy

  1. Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination.

    Science.gov (United States)

    Shimada, Masaru; Yoshizaki, Shinji; Ichino, Motohide; Klinman, Dennis M; Okuda, Kenji

    2014-09-08

    The gut-associated lymphoid tissue (GALT) represents a major reservoir of HIV in infected individuals. Vaccines can induce strong systemic immune responses but these have less impact on CD4 T cells activity and numbers in GALT. In this study, we vaccinated mice with an adenovirus vector that expressed the envelope gene from HIV and observed immune responses in the peripheral blood, spleen, liver, mesenteric lymph nodes, and Peyer's patches. We found that (1) the number of HIV-specific CD8 T cells was dramatically lower in GALT than in other tissues; (2) the programmed cell death protein-1 (PD-1) was expressed at high levels in HIV-specific CD8 T cells including memory T cells in GALT; and (3) high levels of HIV-specific CD8 T cell apoptosis were occurring in GALT. These results suggest that contributing to GALT becoming an HIV reservoir during infection is a combination of exhaustion and/or dysfunction of HIV-specific CTLs at that site. These results emphasize the importance of developing of an effective mucosal vaccine against HIV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

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    Fernanda Menezes de Oliveira e Silva

    2013-10-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2013v26n4p233 Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  3. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Fernanda Menezes de Oliveira e Silva

    2013-11-01

    Full Text Available Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  4. Peripheral blood RNA gene expression profiling in illicit methcathinone users reveals effect on immune system

    Directory of Open Access Journals (Sweden)

    Katrin eSikk

    2011-08-01

    Full Text Available Methcathinone (ephedrone is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese, or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We analyzed whole genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data was analyzed by Bayesian modelling and functional annotation. In order to verify the genechip results we performed quantitative real-time (RT PCR in selected genes. 326 out of analyzed 28,869 genes showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative RT-PCR confirmed differential expression for the most of selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation immunological disease, cellular movement and cardiovascular disease gene network (enrichment score 42. As HIV and HCV infections were confounding factors, we performed additional stratification of patients. A similar functional activation of the immunological disease pathway was evident when we compared patients according to the injection status (past versus current users, balanced for HIV and HCV infection. However, this difference was not large therefore the major effect was related to the HIV status of the patients. Mn-methcathinone abusers have blood transcriptional patterns mostly caused by their HIV and HCV infections.

  5. Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system.

    Science.gov (United States)

    Gordon, Tessa; Udina, Esther; Verge, Valerie M K; de Chaves, Elena I Posse

    2009-10-01

    Injured peripheral but not central nerves regenerate their axons but functional recovery is often poor. We demonstrate that prolonged periods of axon separation from targets and Schwann cell denervation eliminate regenerative capacity in the peripheral nervous system (PNS). A substantial delay of 4 weeks for all regenerating axons to cross a site of repair of sectioned nerve contributes to the long period of separation. Findings that 1h 20Hz bipolar electrical stimulation accelerates axon outgrowth across the repair site and the downstream reinnervation of denervated muscles in rats and human patients, provides a new and exciting method to improve functional recovery after nerve injuries. Drugs that elevate neuronal cAMP and activate PKA promote axon outgrowth in vivo and in vitro, mimicking the electrical stimulation effect. Rapid expression of neurotrophic factors and their receptors and then of growth associated proteins thereafter via cAMP, is the likely mechanism by which electrical stimulation accelerates axon outgrowth from the site of injury in both peripheral and central nervous systems.

  6. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  7. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  8. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    International Nuclear Information System (INIS)

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

  9. Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

    Science.gov (United States)

    Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing

    2016-09-02

    Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.

  10. Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues.

    Science.gov (United States)

    Flaminio, M Julia B F; Tallmadge, Rebecca L; Salles-Gomes, Cristina O M; Matychak, Mary Beth

    2009-01-01

    Common variable immunodeficiency (CVID) in horse patients is characterized by late-onset B cell lymphopenia or depletion, hypo- or agammaglobulinemia, impaired humoral response to tetanus toxoid vaccination, and recurrent fevers and bacterial infections. This study describes the clinical and immunologic findings of 14 affected horses (average age 10.7 +/- 4.4 years) of both genders (six females, eight males) and different breeds (eight Thoroughbreds, four Quarter Horses, one Warmblood, one Pony). Serial immunological testing in peripheral blood revealed persistent, severe B cell lymphopenia (mean 1.3 +/- 2.3% positive cells) in all patients. Serum IgG (range horses. Serum IgA concentrations declined with time. Histopathology and immunohistochemistry revealed absence of lymphoid follicles and B cells in primary and secondary lymphoid tissues. CVID is a cause of recurrent pneumonia, septicemia, and meningitis in adult horses and has a grave prognosis for clinical management and survival.

  11. Speech processing: from peripheral to hemispheric asymmetry of the auditory system.

    Science.gov (United States)

    Lazard, Diane S; Collette, Jean-Louis; Perrot, Xavier

    2012-01-01

    Language processing from the cochlea to auditory association cortices shows side-dependent specificities with an apparent left hemispheric dominance. The aim of this article was to propose to nonspeech specialists a didactic review of two complementary theories about hemispheric asymmetry in speech processing. Starting from anatomico-physiological and clinical observations of auditory asymmetry and interhemispheric connections, this review then exposes behavioral (dichotic listening paradigm) as well as functional (functional magnetic resonance imaging and positron emission tomography) experiments that assessed hemispheric specialization for speech processing. Even though speech at an early phonological level is regarded as being processed bilaterally, a left-hemispheric dominance exists for higher-level processing. This asymmetry may arise from a segregation of the speech signal, broken apart within nonprimary auditory areas in two distinct temporal integration windows--a fast one on the left and a slower one on the right--modeled through the asymmetric sampling in time theory or a spectro-temporal trade-off, with a higher temporal resolution in the left hemisphere and a higher spectral resolution in the right hemisphere, modeled through the spectral/temporal resolution trade-off theory. Both theories deal with the concept that lower-order tuning principles for acoustic signal might drive higher-order organization for speech processing. However, the precise nature, mechanisms, and origin of speech processing asymmetry are still being debated. Finally, an example of hemispheric asymmetry alteration, which has direct clinical implications, is given through the case of auditory aging that mixes peripheral disorder and modifications of central processing. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  12. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  13. [Baroreflexes originated in vertebral artery zones upon peripheral vein tonus, systemic arterial blood pressure, and external respiration].

    Science.gov (United States)

    Agadzhanian, N A; Kupriianov, S V

    2008-06-01

    The investigation was intended to study the role ofbaroreceptors ofhemodynamically isolated zone of vertebral arteries in regulation of peripheral veins tonus, arterial pressure and external respiration. Pressure decrease in this vascular reflexogenic zone led to reflex responses of increase in femoral vein tonus, elevation of blood pressure level and stimulation of external respiration. The opposite reflex responses of cardio-respiratory functional system to initial pressure activation of vertebral arteries baroreceptors are observed. Basing on generalization of our own findings and similar physiological and morphological researches of other authors, it is established that afferentation from the vertebral artery zone is a reflexogenic factor of somatic muscles' veins tonus regulation. These reflexes of capacity vessels tonic activity changes are part of cardio-respiratory responses of maintaining the tissue gaseous exchange.

  14. Cross-Tissue Transcriptomic Analysis of Human Secondary Lymphoid Organ-Residing ILC3s Reveals a Quiescent State in the Absence of Inflammation

    Directory of Open Access Journals (Sweden)

    Yotam E. Bar-Ephraim

    2017-10-01

    Full Text Available A substantial number of human and mouse group 3 innate lymphoid cells (ILC3s reside in secondary lymphoid organs, yet the phenotype and function of these ILC3s is incompletely understood. Here, we employed an unbiased cross-tissue transcriptomic approach to compare human ILC3s from non-inflamed lymph nodes and spleen to their phenotypic counterparts in inflamed tonsils and from circulation. These analyses revealed that, in the absence of inflammation, lymphoid organ-residing ILC3s lack transcription of cytokines associated with classical ILC3 functions. This was independent of expression of the natural cytotoxicity receptor NKp44. However, and in contrast to ILC3s from peripheral blood, lymphoid organ-residing ILC3s express activating cytokine receptors and have acquired the ability to be recruited into immune responses by inflammatory cytokines. This comprehensive cross-tissue dataset will allow for identification of functional changes in human lymphoid organ ILC3s associated with human disease.

  15. Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

    Science.gov (United States)

    Kusaka, M; Okamoto, M; Takenaka, M; Sasaki, H; Fukami, N; Kataoka, K; Ito, T; Kenmochi, T; Hoshinaga, K; Shiroki, R

    2017-06-01

    Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

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    Ribeiro-Resende Victor

    2012-07-01

    Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

  17. Argon laser peripheral iridoplasty versus systemic intraocular pressure-lowering medications as immediate management for acute phacomorphic angle closure

    Directory of Open Access Journals (Sweden)

    Lee JW

    2013-01-01

    Full Text Available Jacky WY Lee,1 Jimmy SM Lai,1 Doris WF Yick,2 Can YF Yuen21Department of Ophthalmology, University of Hong Kong, 2Department of Ophthalmology, The Caritas Medical Centre, Kowloon West Cluster, Hong Kong, People’s Republic of ChinaBackground: The purpose of this study was to compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI and systemic intraocular pressure (IOP-lowering medications in the immediate management of acute phacomorphic angle closure.Methods: Consecutive cases of acute phacomorphic angle closure were randomized to receive ALPI and an intravenous or oral carbonic anhydrase inhibitor as initial treatment. Intravenous mannitol was administered for presenting IOP > 60 mmHg or IOP > 40 mmHg 2 hours posttreatment in both arms.Results: Of 10 consecutive cases, six received medical therapy and four received ALPI. Fifty percent in the medical group and none in the ALPI group required intravenous mannitol. The ALPI group took less time to achieve IOP < 25 mmHg (18.8 ± 7.5 minutes versus 115.0 ± 97.0 minutes, P = 0.001, F test; had a greater IOP reduction within 30 minutes (69.8% ± 7.7% versus 40.9 ± 23.9%, P = 0.03, t-test; and had a consistently smaller post-attack cup to disc ratio (0.50 ± 0.02 versus 0.60 ± 0.20, P = 0.002, F test.Conclusion: ALPI offers greater safety, consistency, and efficacy than systemic IOP-lowering medications as initial treatment for phacomorphic angle closure.Keywords: phacomorphic, glaucoma, argon laser peripheral iridoplasty, medical, intraocular pressure

  18. Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

    Science.gov (United States)

    Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

    2017-05-01

    Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. [Comparative study of lymphoid follicles in mucosa of pharynx and mucosal associated lymphoid tissues in paranasal sinuses].

    Science.gov (United States)

    Zhai, Weigang; Yao, Min; Chen, Jue

    2013-08-01

    To study the relationship between the lymphoid follicles in mucous membrane of pharynx and mucosal associated lymphoid tissues (MALT). Ten folliculi obtained from 10 patients of follicular pharyngitis and mucosa taken form 10 patients of paranasal sinusitis were fixed in neutral formalin and embedded in paraffin. Sections were prepared, stained by H. E and by immunohistochemical method staining with S-100,and observe by light microscopy. We observed the morphology of lymphoid follicles in mucous membrane of pharynx with MALT in mucosa of paranasal sinusitis as the contrast. Lymphoid follicles in mucosa of pharynx compared with MALT in the mucosa of paranasal sinuses, there was no mantle zone, no typical germinal center and no mucosal epithelium, immunological staining with S-100 was week. The lymphoid follicles in mucosa of pharynx does not belong to the MALT.

  20. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    Directory of Open Access Journals (Sweden)

    B. Cam-Etoz

    2012-03-01

    Full Text Available Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g female rats (N = 7 in each group the effects of intracerebroventricularly (icv injected adrenomedullin (ADM on blood pressure and heart rate (HR, and to determine if ADM and calcitonin gene-related peptide (CGRP receptors, peripheral V1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1 icv ADM (750 ng/10 µL caused an increase in both blood pressure and HR (DMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm. 2 Pretreatment with a CGRP receptor antagonist (CGRP8-37 and ADM receptor antagonist (ADM22-52 blocked the effect of central ADM on blood pressure and HR. 3 The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv. 4 The V1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl¹, O-me-Tyr²,Arg8]-vasopressin (V2255; 10 µg/kg, that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V1 receptors in the increasing effects of icv ADM on blood pressure and HR.

  1. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    Energy Technology Data Exchange (ETDEWEB)

    Cam-Etoz, B.; Isbil-Buyukcoskun, N.; Ozluk, K. [Department of Physiology, Uludag University Medical Faculty, Gorukle/Bursa (Turkey)

    2012-03-02

    Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V{sub 1} receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP{sub 8-37}) and ADM receptor antagonist (ADM{sub 22-52}) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V{sub 1} receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl{sup 1}, O-me-Tyr{sup 2},Arg{sup 8}]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V{sub 1} receptors in the increasing effects of icv ADM on blood pressure and HR.

  2. Cardiovascular effects of the intracerebroventricular injection of adrenomedullin: roles of the peripheral vasopressin and central cholinergic systems

    International Nuclear Information System (INIS)

    Cam-Etoz, B.; Isbil-Buyukcoskun, N.; Ozluk, K.

    2012-01-01

    Our objective was to investigate in conscious Sprague-Dawley (6-8 weeks, 250-300 g) female rats (N = 7 in each group) the effects of intracerebroventricularly (icv) injected adrenomedullin (ADM) on blood pressure and heart rate (HR), and to determine if ADM and calcitonin gene-related peptide (CGRP) receptors, peripheral V 1 receptors or the central cholinergic system play roles in these cardiovascular effects. Blood pressure and HR were observed before and for 30 min following drug injections. The following results were obtained: 1) icv ADM (750 ng/10 µL) caused an increase in both blood pressure and HR (ΔMAP = 11.8 ± 2.3 mmHg and ΔHR = 39.7 ± 4.8 bpm). 2) Pretreatment with a CGRP receptor antagonist (CGRP 8-37 ) and ADM receptor antagonist (ADM 22-52 ) blocked the effect of central ADM on blood pressure and HR. 3) The nicotinic receptor antagonist mecamylamine (25 µg/10 µL, icv) and the muscarinic receptor antagonist atropine (5 µg/10 µL, icv) prevented the stimulating effect of ADM on blood pressure. The effect of ADM on HR was blocked only by atropine (5 µg/10 µL, icv). 4) The V 1 receptor antagonist [β-mercapto-β-β-cyclopentamethylenepropionyl 1 , O-me-Tyr 2 ,Arg 8 ]-vasopressin (V2255; 10 µg/kg), that was applied intravenously, prevented the effect of ADM on blood pressure and HR. This is the first study reporting the role of specific ADM and CGRP receptors, especially the role of nicotinic and muscarinic central cholinergic receptors and the role of peripheral V 1 receptors in the increasing effects of icv ADM on blood pressure and HR

  3. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  4. Innate lymphoid cells and the MHC.

    Science.gov (United States)

    Robinette, M L; Colonna, M

    2016-01-01

    Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Deciphering the Innate Lymphoid Cell Transcriptional Program

    Directory of Open Access Journals (Sweden)

    Cyril Seillet

    2016-10-01

    Full Text Available Innate lymphoid cells (ILCs are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development.

  6. Clinical epidemiological aspects of chronic lymphoid leukaemia

    International Nuclear Information System (INIS)

    Rodriguez Brunet, Marisol; Hernandez Galano, Geldris P; Suarez Beyries, Lidia C; Duverger Magdaleon, Ernesto

    2011-01-01

    A descriptive and retrospective study of 71 patients with chronic lymphoid leukemia, attended at the Hematology Service from 'Dr Juan Bruno Zayas Alfonso' Teaching General Hospital in Santiago de Cuba was carried out from January, 2001 to November, 2006, in order to identify some clinical epidemiological variables on them, to show the therapeutical variables more used, as well as to assess survival, mortality, and the main causes of the clinical entity. Elderly, male sex, and high risk category related to advanced stage were predominant in the series. The therapeutical schedule of chlorambucil and prednisone was the most used, achieving good results in the majority of the case material. The survival of patients, in general, ranged among 1-5 years, whereas deaths occurred due to disease progression, infectious respiratory processes, pro-lymphocytic transformation, second neoplasias, and strokes. (author)

  7. Tertiary lymphoid organs in Takayasu Arteritis

    Directory of Open Access Journals (Sweden)

    Marc eClement

    2016-04-01

    Full Text Available Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20, follicular dendritic cells (FDCs, CD21, and high endothelial venules (HEVs, PNAd was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment and follow up data were extracted from medical records.Results: Aorta specimens from Bentall procedures were available from 7 patients (five female, aged 22 to 57 years with TA. Surgical treatment was performed at TA diagnosis (n=4 or at a median of 108 months [84-156] after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient.. Of note, ectopic follicles containing CD21+ FDCs were found in all patients (4/4 with increased aortic FDG uptake before surgery but were absent in all but one patients (2/3 with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center–like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells.Conclusion: Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  8. Tertiary Lymphoid Organs in Takayasu Arteritis.

    Science.gov (United States)

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  9. Design And Implementation Of Smart Parking System Using Peripheral Interface Controllers And Infrared Sensors

    Directory of Open Access Journals (Sweden)

    May Thaw Htet

    2015-08-01

    Full Text Available With the increase in world population and vehicle production parking spaces and facilities are required. As the numbers of vehicles on the road are increasing day by day parking problems which are increasing at an alarming rate in every major city cause drivers frustration traffic congestion and time wasting especially during the peak business hours. Lot of researches was being done all over the world to implement better parking management system which reduces parking problems. SPARK Smart Parking is parking garage system that utilizes various technologies to implement best parking system. The proposed system is aimed to inform drivers about the number of available parking spaces without any parking difficulties. This system is designed for two- level parking slots with twenty six parking spaces and one aisle on each floor. The condition of parking slots is detected by IR sensors and is reported periodically to main controller via floor controllers and self controllers. PIC 18F4550 is chosen to be used as controllers because it is suitable for the proposed system. Each floor contains LCD display which will show available parking spaces of that floor. LCD display at the entrance gate will show overall available parking slots of two floors. In this paper a new parking system called Smart Parking system is proposed to help drivers getting the real-time parking information and to find vacant spaces in a car park in a shorter time. This kind of system minimizes not only traffic congestion problems but also staff requirements to control the traffic in the car park.

  10. Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2012-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1 to estimate LC activity in rats with estradiol valerate (EV-induced PCO; (2 to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1 LC and yohimbine and 2 control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001, while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats.

  11. Investigation of Peripheral Effects of Citrus Limon Essential Oil on Somatic Pain in Male Wistar Rats: Role of Histaminergic System

    Directory of Open Access Journals (Sweden)

    Ali Mojtahedin

    2016-12-01

    Full Text Available Background & Objective: One of the plants used in traditional medicine is lemon which has analgesic effect. However, little research has been performed on the analgesic effect of lemon and mechanisms of action with an emphasis on neurotransmitters systems. Therefore, the present study set to investigate the peripheral effects of lemon essential oil on somatic pain using formalin test with an emphasis on histaminergic system in male Wistar rats. Materiala & Methods: Sixty male rats weighing approximately 200-250g and aged 14-16 wk were divided into 10 groups: sham (Salin + Formalin 1% intraplantar, three treatment groups with lemon essential oil (EO (12.5, 25 and 50 mg/kg, three treatment groups with Chlorpheniramine (5, 10 and 20 mg/kg, 1 treatment group with Histamine (10 mg/kg, 1 pretreatment group with Chlorpheniramine (20 mg/kg + EO (50mg/kg, and 1 pretreatment group with Histamine (10 mg/kg + EO (50 mg/kg. Formalin test was used to assess somatic pain. Data analysis was performed using one-way ANOVA. Results:  Intraperitoneal injection of lemon essential oil reduced the pain response induced by formalin in both phases (P<0.05. Pretreatment with chlorpheniramine and lemon essential oil enhanced the analgesic response in both phases (P<0.05. Conclusion: Lemon essential oil had analgesic effects, probably caused by the histaminergic system.

  12. High-resolution CT of lymphoid interstitial pneumonia

    International Nuclear Information System (INIS)

    Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

    1989-01-01

    Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

  13. System for keeping atmospheric pressure in nuclear facility and its peripheral equipments

    International Nuclear Information System (INIS)

    Matsumoto, Hatsuo

    1993-02-01

    The design to keep radioactive materials in the facility and not to make them spread inside the facility and into the environments is an essential issue in the construction of nuclear facilities. One reason of the contamination is due to the diffusion with air flow, therefore, negative pressure for the ambients has been utilized to keep gaseous radioactivities inside the facility of interest. The pressure difference is not so large, though, the atmospheric pressure level of the contaminated and possibly contaminated areas are always kept to be lower than those of the ambient one to prevent the dissemination of radioactivity from the defined area. The technique using negative pressure, at present, is employed widely in nuclear facilities, and the basic system is the same as that of JRR-1 built as the first nuclear facility in Japan. In the present work, the conventional system with negative pressure was reexamined on the sate-of-art of the regulations for the nuclear facilities, and consequently some shortages of the system has been found. Thus, an advanced system with an excellent performance keeping the negative pressure has been developed to cover the shortage. In this report, the new system is introduced with a couple of comments, acquired from the author's experience, to the design and the maintenance of the composite equipments of the system. (author)

  14. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Expression and distributeion of 'high affinity' glutamate transporters GLT1, GLAST, EAAC and of GCPII in the rat peripheral nervous system

    Czech Academy of Sciences Publication Activity Database

    Carozzi, V. A.; Canta, A.; Oggioni, N.; Ceresa, C.; Marmiroli, P.; Konvalinka, Jan; Zoia, Ch.; Bossi, M.; Ferrarese, C.; Tredici, G.; Cavaletti, G.

    2008-01-01

    Roč. 213, č. 4 (2008), s. 539-546 ISSN 0021-8782 Institutional research plan: CEZ:AV0Z40550506 Keywords : glutamate * glutamate transporters * immunoblotting * immunohistochemistry * peripheral nervous system Subject RIV: CE - Biochemistry Impact factor: 2.063, year: 2008

  16. The effect of γ-linolenic acid-α-lipoic acid on functional deficits in the peripheral and central nervous system of streptozotocin- diabetic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Smale, S.; Duis, S.E.; Kamal, A.

    2001-01-01

    Diabetes mellitus can lead to functional and structural deficits in both the peripheral and central nervous system. The pathogenesis of these deficits is multifactorial, probably involving, among others, microvascular dysfunction and oxidative stress. The present study examined the effects of 12

  17. THE ROLE OF ANDROGENS AND ESTROGENS IN THE DEVELOPMENT OF BRAIN AND PERIPHERAL NERVOUS SYSTEM: APPROACHES TO DEVELOPING ANIMAL MODELS FOR SEXUALLY DIMORPHIC BEHAVIORS

    Science.gov (United States)

    This presentation provides an overview of research on the effects of hormonally active chemicals on sexual differentiation of the brain including (a) research on the role of androgens and estrogens in the development of the brain and peripheral nervous system, (b) approaches to d...

  18. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H

    1991-01-01

    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  19. Experimental study of peripheral reactions in the 16O +63,65 Cu systems

    International Nuclear Information System (INIS)

    Razeto, G.R.

    1987-01-01

    In this work elastic scattering and ( 16 O,N) ( 16 O,C) transfer reaction data are presented for the 16 O + 63,65 Cu systems at the incident energy range of 40 to 64MeV. The data was analized with the Optical Model, and the total reaction cross section was compared with the fusion cross section data available from a previus work. Furthermore correlation was made between transfer processes with the different optical potential parameters for these systems. The Frahnand Venter fenomelogical modelo and DWBA calculations were employed for analysis of the transfer reaction data. For the 16 O + 63 Cu system beside the threshold anomaly, an atypical angles (θ cm > 140 0 ). The Regge poles ressonances formalism was used to explain it. (author) [pt

  20. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  1. Mucosal immunity in HIV infection: what can be done to restore gastrointestinal-associated lymphoid tissue function?

    Science.gov (United States)

    George, Michael D; Asmuth, David M

    2014-06-01

    This review describes the impact of HIV infection on gut-associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid tissue dysfunction despite effective antiretroviral therapy, and potential strategies to restore gut-associated lymphoid tissue function and promote immune reconstitution. Recent studies indicate that unresolved microbial translocation and intestinal dysbiosis may continue to promote enteropathy as well as HIV-associated and non-HIV-associated conditions in many HIV patients who otherwise maintain therapeutic control of systemic viral replication. Several novel therapeutic approaches to reduce intestinal inflammation and mitigate microbial translocation may hold promise for restoring gastrointestinal health and thereby increasing the efficacy of immune reconstitution in HIV-infected patients undergoing antiretroviral therapy.

  2. Peripheral aneurysm rupture in a patient with inactive systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Engelke, Christoph; Sabharwal, Tarun; Reidy, John F. [Department of Radiology, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom); Mohan, Aarthi R. [Department of Chest Medicine, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom)

    2002-12-01

    We describe a patient with inactive systemic lupus erythematosus (SLE) presenting with sudden haemothorax, due to a ruptured internal mammary artery (IMA) aneurysm 7 years after the corticosteroid treatment was terminated. The unusual imaging findings and the treatment with embolization are discussed with a view to the role of a regular vascular screening in this patient group. (orig.)

  3. Systemic control of brown fat thermogenesis: integration of peripheral and central signals.

    Science.gov (United States)

    Schulz, Tim J; Tseng, Yu-Hua

    2013-10-01

    Brown adipose tissue (BAT) is of great scientific interest as a potential target to treat obesity. The development of novel strategies to quantify brown fat thermogenesis in adult humans now enables minimally invasive assessment of novel pharmacotherapeutics. Input from the central nervous system via sympathetic efferents is widely regarded as the key controller of BAT-mediated thermogenesis in response to changes in body temperature or nutrient availability. More recently, however, it has become clear that locally secreted signals and endocrine factors originating from multiple organs can control the recruitment of brown adipocytes and, more importantly, induce thermogenesis in brown fat. Thus, they provide an attractive strategy to fine-tune brown fat thermogenesis independent of classical temperature sensing. Here, we summarize recent findings on bone morphogenetic protein signaling as an example of secreted factors in the regulation of brown adipocyte formation and systemic control of energy metabolism. We further highlight endocrine communication routes between the different types of brown adipocytes and other organs that contribute to regulation of thermogenesis. Thus, emerging evidence suggests that the classical mechanisms of central temperature sensing and sympathetic nervous system-driven thermogenesis are complemented by local and endocrine signals to determine systemic energy homeostasis. © 2013 New York Academy of Sciences.

  4. The Higher Education System in Malaysia: Metropolitan, Cross-National, Peripheral or National?

    Science.gov (United States)

    Selvaratnam, V.

    1985-01-01

    Burton Clark's theory of higher education institutions as academic organization governed by unique elements and disciplinary logic is outlined and applied to Malaysia. The theory's weakness in underplaying the role of national policies and environmental factors in determining a national higher education system is noted. (MSE)

  5. PERIPHERAL IMMUNE SYSTEM SUPPRESSION IN EARLY ABSTINENT ALCOHOL DEPENDENT INDIVIDUALS: LINKS TO STRESS AND CUE-RELATED CRAVING

    Science.gov (United States)

    Fox, Helen C; Milivojevic, Verica; Angarita, Gustavo A; Stowe, Raymond; Sinha, Rajita

    2017-01-01

    Background Peripheral immune system cytokines may play an integral role in underlying sensitized stress response and alcohol craving during early withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods Thirty-nine early abstinent, treatment-seeking alcohol dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. Conclusions Findings demonstrate that broad immuno-suppression is still observed in alcohol dependent individuals after three weeks of abstinence and may be linked to motivation for alcohol. PMID:28675117

  6. Towards a closed-loop cochlear implant system: application of embedded monitoring of peripheral and central neural activity.

    Science.gov (United States)

    Mc Laughlin, Myles; Lu, Thomas; Dimitrijevic, Andrew; Zeng, Fan-Gang

    2012-07-01

    Although the cochlear implant (CI) is widely considered the most successful neural prosthesis, it is essentially an open-loop system that requires extensive initial fitting and frequent tuning to maintain a high, but not necessarily optimal, level of performance. Two developments in neuroscience and neuroengineering now make it feasible to design a closed-loop CI. One development is the recording and interpretation of evoked potentials (EPs) from the peripheral to the central nervous system. The other is the embedded hardware and software of a modern CI that allows recording of EPs. We review EPs that are pertinent to behavioral functions from simple signal detection and loudness growth to speech discrimination and recognition. We also describe signal processing algorithms used for electric artifact reduction and cancellation, critical to the recording of electric EPs. We then present a conceptual design for a closed-loop CI that utilizes in an innovative way the embedded implant receiver and stimulators to record short latency compound action potentials ( ~1 ms), auditory brainstem responses (1-10 ms) and mid-to-late cortical potentials (20-300 ms). We compare EPs recorded using the CI to EPs obtained using standard scalp electrodes recording techniques. Future applications and capabilities are discussed in terms of the development of a new generation of closed-loop CIs and other neural prostheses.

  7. Contribution of glycogen in supporting axon conduction in the peripheral and central nervous systems: the role of lactate

    Directory of Open Access Journals (Sweden)

    Angus M Brown

    2014-11-01

    Full Text Available The role of glycogen in the central nervous system is intimately linked with the glycolytic pathway. Glycogen is synthesized from glucose, the primary substrate for glycolysis, and degraded to glucose-6-phosphate. The metabolic cost of shunting glucose via glycogen exceeds that of simple phosphorylation of glucose to glucose-6-phosphate by hexokinase; thus, there must be a metabolic advantage in utilizing this shunt pathway. The dogmatic view of glycogen as a storage depot persists, based on initial descriptions of glycogen supporting neural function in the face of aglycemia. The variable latency to conduction failure, dependent upon tissue glycogen levels, provided convincing evidence of the role played by glycogen in supporting neural function. Glycogen is located predominantly in astrocytes in the central nervous system, thus for glycogen to benefit neural elements, intercellular metabolic communication must exist in the form of astrocyte to neuron substrate transfer. Experimental evidence supports a model where glycogen is metabolized to lactate in astrocytes, with cellular expression of monocarboxylate transporters and enzymes appropriately located for lactate shuttling between astrocytes and neural elements, where lactate acts as a substrate for oxidative metabolism. Biosensor recordings have demonstrated a significant steady concentration of lactate present on the periphery of both central white matter and peripheral nerve under unstimulated baseline conditions, indicating continuous cellular efflux of lactate to the interstitium. The existence of this lactate pool argues we must reexamine the ‘on demand’ shuttling of lactate between cellular elements, and suggests continuous lactate efflux surplus to immediate neural requirements.

  8. Treatment strategy based on targeting P-glycoprotein on peripheral lymphocytes in patients with systemic autoimmune disease.

    Science.gov (United States)

    Tsujimura, Shizuyo; Tanaka, Yoshiya

    2012-02-01

    Although corticosteroids, immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) are widely used in the treatment of various systemic autoimmune diseases such as systemic lupus erythematosus (SLE), we often experience patients with systemic autoimmune diseases who are resistant to these treatments. P-glycoprotein (P-gp) of membrane transporters, a product of the multiple drug resistance (MDR)-1 gene, is known to play a pivotal role in the acquisition of drug resistance to chemotherapy in malignancy. However, the relevance of MDR-1 and P-gp to resting and activated lymphocytes, which are the major target in the treatment of systemic autoimmune diseases, remains unclear. Studies from our laboratories found surface expression of P-gp on peripheral lymphocytes in patients with SLE and a significant correlation between the expression level and disease activity. Such expression is induced not only by genotoxic stresses but also by various stimuli including cytokines, resulting in active efflux of drugs from the cytoplasm of lymphocytes, resulting in drug-resistance and high disease activity. However, the use of both P-gp antagonists (e.g., cyclosporine) and inhibition of P-gp synthesis with intensive immunosuppressive therapy successfully reduces the efflux of corticosteroids from lymphocytes in vitro, suggesting that P-gp antagonists and P-gp synthesis inhibitors could be used to overcome drug-resistance in vivo and improve outcome. In conclusion, lymphocytes activated by various stimuli in patients with highly active disease apparently acquire MDR-1-mediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. The expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable target to combat drug resistance in patients with active systemic autoimmune diseases.

  9. Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells

    Science.gov (United States)

    Vetro, Calogero; Romano, Alessandra; Ancora, Flavia; Coppolino, Francesco; Brundo, Maria V.; Raccuia, Salvatore A.; Puglisi, Fabrizio; Tibullo, Daniele; La Cava, Piera; Giallongo, Cesarina; Parrinello, Nunziatina L.

    2015-01-01

    The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells (MDSCs) have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of MDSCs in the settings of lymphoid malignancies. PMID:26052505

  10. Distribution of Hydroxychloroquine in Lymphoid Tissue in a Rabbit Model for HIV Infection

    Science.gov (United States)

    González-Hernández, Iliana; Aguirre-Cruz, Lucinda; Sotelo, Julio; López-Arellano, Raquel; Morales-Hipólito, Adriana

    2014-01-01

    Hydroxychloroquine has been proposed for HIV treatment; however, little is known about its disposition in the lymphatic system, where replication takes place. Therefore, its distribution in lymphoid tissues (Peyer's patches and popliteal, submandibular, femoral, splenic, and prescapular lymph nodes) was evaluated and compared with that in blood. Results showed a high affinity of hydroxychloroquine for all of these tissues, with higher affinity for the splenic and submandibular lymph nodes, suggesting its potential use as a coadjuvant in HIV therapy. PMID:24145523

  11. Bone marrow transplantation in aplastic anaemia using cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

    1980-01-01

    Six patients with severe aplastic anaemia received a bone-marrow graft after conditioning with cyclophosphamide and total lymphoid irradiation (TLI). No rejections occurred. Acute graft-versus-host disease developed in 3 patients and was fatal in one. Another patient died from systemic aspergillus infection. Chronic GVHD of the skin developed in a patient who was grafted with bone marrow from her HLA-phenotypically identical father. These data suggest that conditioning with cyclophosphamide and TLI is a promising regimen. (orig.) [de

  12. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N.; Kazer, Samuel W.; Mjösberg, Jenny

    2016-01-01

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-on ILCs remains unknown. We found that human blood...... upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential...... mechanistic link between acute HIV-infection, lymphoid tissue breakdown, and persistent immune dysfunction....

  13. Apoptosis of gut-associated lymphoid tissue in rainbow trout Oncorhynchus mykiss after incubation with Candida albicans and bacterial lipopolysaccharide.

    Science.gov (United States)

    Passantino, L; Ostillio, A; Cianciotta, A; Russo, C; Carrassi, M; Patruno, R; Dhaskali, L; Passantino, G F; Passantino, A

    2011-06-01

    Until now a few studies have been carried out on the gut lymphoid system in fish despite its protective role in the host. Here, we have evaluated the effects of Candida albicans (Ca) and lipopolysaccaride (LPS) on the pyloric and terminal segments of gut in the rainbow trout Oncorhynchus mykiss. In particular, data show that both Ca and LPS are able to cause apoptosis of intestinal lymphoid cells as detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) procedure. These findings suggest a further modality of gut response in fish to environmental antigens.

  14. Design And Implementation Of Smart Parking System Using Peripheral Interface Controllers And Infrared Sensors

    OpenAIRE

    May Thaw Htet; Chaw Myat New; Hla Myo Tun

    2015-01-01

    With the increase in world population and vehicle production parking spaces and facilities are required. As the numbers of vehicles on the road are increasing day by day parking problems which are increasing at an alarming rate in every major city cause drivers frustration traffic congestion and time wasting especially during the peak business hours. Lot of researches was being done all over the world to implement better parking management system which reduces parking problems. SPARK Smart Pa...

  15. Nonselective inhibition of the epigenetic transcriptional regulator BET induces marked lymphoid and hematopoietic toxicity in mice

    International Nuclear Information System (INIS)

    Lee, Dong U.; Katavolos, Paula; Palanisamy, Gopinath; Katewa, Arna; Sioson, Charly; Corpuz, Janice; Pang, Jodie; DeMent, Kevin; Choo, Edna; Ghilardi, Nico; Diaz, Dolores; Danilenko, Dimitry M.

    2016-01-01

    Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are epigenetic transcriptional regulators required for efficient expression of growth promoting, cell cycle progression and antiapoptotic genes. Through their bromodomain, these proteins bind to acetylated lysine residues of histones and are recruited to transcriptionally active chromatin. Inhibition of the BET-histone interaction provides a tractable therapeutic strategy to treat diseases that may have epigenetic dysregulation. JQ1 is a small molecule that blocks BET interaction with histones. It has been shown to decrease proliferation of patient-derived multiple myeloma in vitro and to decrease tumor burden in vivo in xenograft mouse models. While targeting BET appears to be a viable and efficacious approach, the nonclinical safety profile of BET inhibition remains to be well-defined. We report that mice dosed with JQ1 at efficacious exposures demonstrate dose-dependent decreases in their lymphoid and immune cell compartments. At higher doses, JQ1 was not tolerated and due to induction of significant body weight loss led to early euthanasia. Flow cytometry analysis of lymphoid tissues showed a decrease in both B- and T-lymphocytes with a concomitant decrease in peripheral white blood cells that was confirmed by hematology. Further investigation with the inactive enantiomer of JQ1 showed that these in vivo effects were on-target mediated and not elicited through secondary pharmacology due to chemical structure.

  16. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

    Science.gov (United States)

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

    2016-01-01

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

  17. Nonselective inhibition of the epigenetic transcriptional regulator BET induces marked lymphoid and hematopoietic toxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong U., E-mail: lee.dong@gene.com [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Katavolos, Paula; Palanisamy, Gopinath [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Katewa, Arna [Department of Research Immunology, Genentech, Inc., South San Francisco, CA 94080 (United States); Sioson, Charly; Corpuz, Janice [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States); Pang, Jodie; DeMent, Kevin; Choo, Edna [Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA 94080 (United States); Ghilardi, Nico [Department of Research Immunology, Genentech, Inc., South San Francisco, CA 94080 (United States); Diaz, Dolores; Danilenko, Dimitry M. [Department of Safety Assessment, Genentech, Inc., South San Francisco, CA 94080 (United States)

    2016-06-01

    Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are epigenetic transcriptional regulators required for efficient expression of growth promoting, cell cycle progression and antiapoptotic genes. Through their bromodomain, these proteins bind to acetylated lysine residues of histones and are recruited to transcriptionally active chromatin. Inhibition of the BET-histone interaction provides a tractable therapeutic strategy to treat diseases that may have epigenetic dysregulation. JQ1 is a small molecule that blocks BET interaction with histones. It has been shown to decrease proliferation of patient-derived multiple myeloma in vitro and to decrease tumor burden in vivo in xenograft mouse models. While targeting BET appears to be a viable and efficacious approach, the nonclinical safety profile of BET inhibition remains to be well-defined. We report that mice dosed with JQ1 at efficacious exposures demonstrate dose-dependent decreases in their lymphoid and immune cell compartments. At higher doses, JQ1 was not tolerated and due to induction of significant body weight loss led to early euthanasia. Flow cytometry analysis of lymphoid tissues showed a decrease in both B- and T-lymphocytes with a concomitant decrease in peripheral white blood cells that was confirmed by hematology. Further investigation with the inactive enantiomer of JQ1 showed that these in vivo effects were on-target mediated and not elicited through secondary pharmacology due to chemical structure.

  18. Pulmonary infiltration with eosinophilia complicated with mucosa-associated lymphoid tissue lymphoma: A case report.

    Science.gov (United States)

    Liu, Yin; Tangsun, Yinyan; Xiao, Yonglong; Zhang, Deping; Cao, Min

    2016-09-01

    Tissue eosinophilia is rarely observed in cases of non-Hodgkin's lymphoma of B cell origin. The present study describes a rare case of mucosa-associated lymphoid tissue (MALT) lymphoma, which was initially misdiagnosed as eosinophilic pneumonia. The initial diagnosis was formed based on the results of chest radiography, peripheral eosinophilia tests and bronchoalveolar lavage, and the clinical course of the patient. Following administration of methylprednisolone (40 mg/day) for 4 days and oral administration of prednisolone (30 mg/day), the clinical course rapidly improved and the eosinophil count immediately decreased a to normal level. However, abnormal shadows observed on computed tomography (CT) scans of the chest did not diminish. At 6 months after the initiation of treatment, CT-guided percutaneous lung biopsy was performed, and a final diagnosis of primary pulmonary mucosa-associated lymphoid tissue lymphoma was made based on immunohistochemical examination. Primary lung MALT lymphoma remains a rare entity, with an indolent course and a reasonably favorable prognosis, whose diagnosis may be challenging.

  19. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

  20. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

    2012-08-17

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

  1. Complex Nonlinear Autonomic Nervous System Modulation Link Cardiac Autonomic Neuropathy and Peripheral Vascular Disease

    Directory of Open Access Journals (Sweden)

    Kinda eKhalaf

    2015-03-01

    Full Text Available Background: Physiological interactions are abundant within, and between, body systems. These interactions may evolve into discrete states during pathophysiological processes resulting from common mechanisms. An association between arterial stenosis, identified by low ankle-brachial pressure index (ABPI and cardiovascular disease (CVD as been reported. Whether an association between vascular calcification - characterized by high ABPI and a different pathophysiology - is similarly associated with CVD, has not been established. The current study aims to investigate the association between ABPI, and cardiac rhythm, as an indicator of cardiovascular health and functionality, utilising heart rate variability (HRV.Methods and Results: Two hundred and thirty six patients underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV measures were determined from 5-minute electrocardiogram. ABPI data were divided into normal (n=101, low (n=67 and high (n=66 and compared to HRV measures.(DFAα1 and SampEn were significantly different between the low ABPI, high ABPI and control groups (p<0.05.Conclusion: A possible coupling between arterial stenosis and vascular calcification with decreased and increased HRV respectively was observed. Our results suggest a model for interpreting the relationship between vascular pathophysiology and cardiac rhythm. The cardiovascular system may be viewed as a complex system comprising a number of interacting subsystems. These cardiac and vascular subsystems/networks may be coupled and undergo transitions in response to internal or external perturbations. From a clinical perspective, the significantly increased sample entropy compared to the normal ABPI group and the decreased and increased complex correlation properties measured by DFA for the low and high ABPI groups respectively, may be useful indicators that a more holistic treatment approach in line with this more complex clinical picture is required.

  2. Development of a fragment detector system for the study of peripheral collisions at high beam energies

    International Nuclear Information System (INIS)

    Spies, H.

    1992-06-01

    In the framework of the experimental program at the accelerator facilities SIS/ESR of the Society for Heavy-Ion research in Darmstadt one of the essential research aims of the LAND collaboration is the study of high-lying collective states after electromagnetic excitation in heavy-ion collisions at nearly relativistic beam energies. By the exchange of virtual photons with high energy giant resonances are excited with high probabilities. The main decay channel of giant resonances in heavy nuclei is the emission of neutrons as well as below the particle threshold the emission of γ radiation. For the study of these states a detector system was developed, which makes the kinematically complete measurement of all reaction partners possible. For the determination of the neutron energy serves the Large Area Neutron Detector LAND, a time-of-flight spectrometer for high-energetic neutrons. For the measurement of the γ radiation emitted by the excited projectile the target is surrounded by an array of 48 BaF 2 crystals. A radiation detector system consisting of 6 single detectors and further 5 help detectors allows together with the magnetic spectrometer ALADIN the identification of the heavy projectile fragments by charge, momentum, and mass. Four position-sensitive plastic scintillators serve for the measurement of the trajectory of the projectile respectively the projectile fragments in front and behind the deviating magnet. Additionally with these detectors the velocity is measured. For the determination of the nuclear charge of the projectile fragments serve a multiple-ionization chamber and a Cherenkov detector. In this thesis the development and taking into operation of the LAND radiation detector system is described. (orig./HSI) [de

  3. Glucagon-like Peptide-1 and the Central/Peripheral Nervous System

    DEFF Research Database (Denmark)

    Muscogiuri, Giovanna; DeFronzo, Ralph A; Gastaldelli, Amalia

    2017-01-01

    Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary trac...... human trials report a neuroprotective effect of GLP-1-RAs in Alzheimer's and Parkinson's disease. In this review, we discuss the role of GLP-1 and GLP-1-RAs in the nervous system with focus on GLP-1 actions on appetite regulation, glucose homeostasis, and neuroprotection....

  4. [Central nervous system vasculitis and of the peripheral nerves in the elderly].

    Science.gov (United States)

    Boddaert, Jacques; Verny, Marc

    2002-11-01

    Vasculitis of the nervous system are rare in the elderly. When present, they may constitute an urgent diagnosis and a therapeutic emergency. Clinical expression is rich and without specificity. Atypical signs (unusual course of dementia, systemic signs) or atypical laboratory results (inflammatory syndrome) may suggest the diagnosis of vasculitis. However, as multiple comorbidity is the rule in elderly subjects, searching for intercurrent factors (e.g. atrial fibrilation due to infectious disease causing embolic stroke) may be more contributive than searching for proof of a rare disease (vasculitis) with invasive procedures in this population. Giant cell (temporal) arteritis is the only vasculitis specifically related with age; the vital prognosis of vision may be compromised. Corticosterid therapy must be instituted without delay. Periartritis nodosa begins in 30% of cases after 60 years of age. The clinical features are the same as in younger subjects. Other vasculidis are rare in the elderly. In absence of specific studies in this population, therapeutic protocols are the same as in younger subjects but may have to be adjusted.

  5. Early lymphoid lesions: conceptual, diagnostic and clinical challenges

    OpenAIRE

    Ganapathi, Karthik A.; Pittaluga, Stefania; Odejide, Oreofe O.; Freedman, Arnold S.; Jaffe, Elaine S.

    2014-01-01

    There are no “benign lymphomas”, a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH transl...

  6. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  7. Network node for peripheral sharing

    International Nuclear Information System (INIS)

    Bobbitt, J.; Johnson, M.

    1977-01-01

    A module which enables several independent computer systems to share the peripherals (graphics display and line printer) of a PDP-11 computer is described. The module requires no software support in the PDP-11

  8. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  9. High-frequency Doppler ultrasound transducer for the peripheral circulatory system

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Youngmin; Yang, Jeongwon; Kang, Uk; Kim, Guanghoon [Korea Electrotechnology Research Institute, Ansan (Korea, Republic of)

    2011-12-15

    A Doppler ultrasound transducer was designed and implemented to measure the blood flow velocity in tiny vessels near the skin of hands or feet. The geometric parameters of the transducer for defining the observation volume were derived and implemented with an acoustic window made of polystyrene. The observation volume designed in this study was located 6.5 mm from the transducer, which was comparable to the value predicted geometrically. The two-way insertion loss of the transducer was -11.3 dB on ultrasound frequency of 20 MHz, and the 3-dB bandwidth was approximately 2 MHz. In addition, the Doppler shift in the frequency measured by using a Doppler device composed of the transducer and a Doppler signal processing unit was proportional to the flow velocity generated by a homemade flowing system. Finally, we concluded that the transducer could be applied to measure the blood flow velocity in hands or feet.

  10. High-frequency Doppler ultrasound transducer for the peripheral circulatory system

    International Nuclear Information System (INIS)

    Bae, Youngmin; Yang, Jeongwon; Kang, Uk; Kim, Guanghoon

    2011-01-01

    A Doppler ultrasound transducer was designed and implemented to measure the blood flow velocity in tiny vessels near the skin of hands or feet. The geometric parameters of the transducer for defining the observation volume were derived and implemented with an acoustic window made of polystyrene. The observation volume designed in this study was located 6.5 mm from the transducer, which was comparable to the value predicted geometrically. The two-way insertion loss of the transducer was -11.3 dB on ultrasound frequency of 20 MHz, and the 3-dB bandwidth was approximately 2 MHz. In addition, the Doppler shift in the frequency measured by using a Doppler device composed of the transducer and a Doppler signal processing unit was proportional to the flow velocity generated by a homemade flowing system. Finally, we concluded that the transducer could be applied to measure the blood flow velocity in hands or feet.

  11. Pluralistic roles for glycogen in the central and peripheral nervous systems.

    Science.gov (United States)

    Fryer, Kirsty L; Brown, Angus M

    2015-02-01

    Glycogen is present in the mammalian nervous system, but at concentrations of up to one hundred times lower than those found in liver and skeletal muscle. This relatively low concentration has resulted in neglect of assigning a role(s) for brain glycogen, but in the last 15 years enormous progress has been made in revealing the multifaceted roles that glycogen plays in the mammalian nervous system. Initial studies highlighted a role for glycogen in supporting neural elements (neurons and axons) during aglycemia, where glycogen supplied supplementary energy substrate in the form of lactate to fuel neural oxidative metabolism. The appropriate enzymes and membrane bound transporters have been localized to cellular locations consistent with astrocyte to neuron energy substrate shuttling. A role for glycogen in supporting the induction of long term potential (LTP) in the hippocampus has recently been described, where glycogen is metabolized to lactate and shuttled to neurons via the extracellular space by monocarboxylate transporters, where it plays an integral role in the induction process of LTP. This is the first time that glycogen has been assigned a role in a distinct, complex physiological brain function, where the lack of glycogen, in the presence of normoglycemia, results in disturbance of the function. The signalling pathway that alerts astrocytes to increased neuronal activity has been recently described, highlighting a pivotal role for increased extracellular potassium ([K(+)]o) that routinely accompanies increased neural activity. An astrocyte membrane bound bicarbonate transporter is activated by the [K(+)]o, the resulting increase in intracellular bicarbonate alkalizing the cell's interior and activating soluble adenyl cyclase (sAC). The sAC promotes glycogenolysis via increases in cyclic AMP, ultimately producing lactate, which is shuttled out of the astrocyte and presumably taken up by neurons from the extracellular space.

  12. Superficially located enlarged lymphoid follicles characterise nodular gastritis.

    Science.gov (United States)

    Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro

    2015-01-01

    Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis.

  13. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    International Nuclear Information System (INIS)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-01-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable

  14. Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y.

    Science.gov (United States)

    Hoffmann, Peter; Bentley, Phil; Sahota, Pritam; Schoenfeld, Heidi; Martin, Lori; Longo, Linda; Spaet, Robert; Moulin, Pierre; Pantano, Serafino; Dubost, Valerie; Lapadula, Dan; Burkey, Bryan; Kaushik, Virendar; Zhou, Wei; Hayes, Michael; Flavahan, Nick; Chibout, Salah-Dine; Busch, Steve

    2014-06-01

    The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity. © 2014 by The Author(s).

  15. Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

    Science.gov (United States)

    Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

    2017-12-01

    We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

  16. Classification of activity engagement in individuals with severe physical disabilities using signals of the peripheral nervous system.

    Directory of Open Access Journals (Sweden)

    Azadeh Kushki

    Full Text Available Communication barriers often result in exclusion of children and youth with disabilities from activities and social settings that are essential to their psychosocial development. In particular, difficulties in describing their experiences of activities and social settings hinder our understanding of the factors that promote inclusion and participation of this group of individuals. To address this specific communication challenge, we examined the feasibility of developing a language-free measure of experience in youth with severe physical disabilities. To do this, we used the activity of the peripheral nervous system to detect patterns of psychological arousal associated with activities requiring different patterns of cognitive/affective and interpersonal involvement (activity engagement. We demonstrated that these signals can differentiate among patterns of arousal associated with these activities with high accuracy (two levels: 81%, three levels: 74%. These results demonstrate the potential for development of a real-time, motor- and language-free measure for describing the experiences of children and youth with disabilities.

  17. The Influence of Hepatitis C Virus Therapy on the DNA Base Excision Repair System of Peripheral Blood Mononuclear Cells.

    Science.gov (United States)

    Czarny, Piotr; Merecz-Sadowska, Anna; Majchrzak, Kinga; Jabłkowski, Maciej; Szemraj, Janusz; Śliwiński, Tomasz; Karwowski, Bolesław

    2017-07-01

    Hepatitis C virus (HCV) can infect extrahepatic tissues, including lymphocytes, creating reservoir of the virus. Moreover, HCV proteins can interact with DNA damage response proteins of infected cells. In this article we investigated the influence of the virus infection and a new ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) anti-HCV therapy on the PBMCs (peripheral blood mononuclear cells, mainly lymphocytes) DNA base excision repair (BER) system. BER protein activity was analyzed in the nuclear and mitochondrial extracts (NE and ME) of PBMC isolated from patients before and after therapy, and from subjects without HCV, using modeled double-strand DNA, with 2'-deoxyuridine substitution as the DNA damage. The NE and ME obtained from patients before therapy demonstrated lower efficacy of 2'-deoxyuridine removal and DNA repair polymerization than those of the control group or patients after therapy. Moreover, the extracts from the patients after therapy had similar activity to those from the control group. However, the efficacy of apurinic/apyrimidinic site excision in NE did not differ between the studied groups. We postulate that infection of lymphocytes by the HCV can lead to a decrease in the activity of BER enzymes. However, the use of novel therapy results in the improvement of glycosylase activity as well as the regeneration of endonuclease and other crucial repair enzymes.

  18. Effects of interactive instructional techniques in a web-based peripheral nervous system component for human anatomy.

    Science.gov (United States)

    Allen, Edwin B; Walls, Richard T; Reilly, Frank D

    2008-02-01

    This study investigated the effects of interactive instructional techniques in a web-based peripheral nervous system (PNS) component of a first year medical school human anatomy course. Existing data from 9 years of instruction involving 856 students were used to determine (1) the effect of web-based interactive instructional techniques on written exam item performance and (2) differences between student opinions of the benefit level of five different types of interactive learning objects used. The interactive learning objects included Patient Case studies, review Games, Simulated Interactive Patients (SIP), Flashcards, and unit Quizzes. Exam item analysis scores were found to be significantly higher (p < 0.05) for students receiving the instructional treatment incorporating the web-based interactive learning objects than for students not receiving this treatment. Questionnaires using a five-point Likert scale were analysed to determine student opinion ratings of the interactive learning objects. Students reported favorably on the benefit level of all learning objects. Students rated the benefit level of the Simulated Interactive Patients (SIP) highest, and this rating was significantly higher (p < 0.05) than all other learning objects. This study suggests that web-based interactive instructional techniques improve student exam performance. Students indicated a strong acceptance of Simulated Interactive Patient learning objects.

  19. Study on GH receptors and PRL receptors on peripheral blood lymphocytes in patients of systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Li Feng; Rao Junchang; Feng Shufang; Lu Yun; Deng Shouzhen

    2002-01-01

    Objective: To study the association of growth hormone (GH) and prolactin (PRL) and their receptors in patients with systemic lupus erythematosus. Methods: The authors measured serum PRL and GH level with radioimmunoassay (RIA) in 25 untreated patients of active SLE, 20 patients of inactive SLE and in 20 gender-age-paired control subjects. The authors also measured peripheral blood lymphocytes (PBMC) GH receptors (GHR) and PRL receptors (PRLR) with radioactive binding ligand assay (RLBA). Results: The specific binding (SB) ratio of PRLR was 6.7 ± 2.3%, the total binding ratio was 10.5 ± 4.6% in active patients of SLE. The SB of PRLR in active patients was higher than that of inactive patients (SB 2.5 ± 0.8%, TB 8.5 ± 4.3%) and that of 20 control subjects (SB 1.9 ± 1.2%, TB 9.3 ± 6.4%) (P 0.05). The serum GH and PRL level was also significantly increased in active patients of SLE (P<0.05). Conclusion: The increase of GHR and PRLR in the PBMCs of SLE was certainly associated with pathogenesis of SLE

  20. Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells.

    Science.gov (United States)

    Marotel, Marie; Hasan, Uzma; Viel, Sébastien; Marçais, Antoine; Walzer, Thierry

    2016-09-01

    Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111-2120] characterized human hepatic NK-cell subsets. The authors report that hepatic CD56(bright) NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype. However, unlike mouse ILC1s, they express high levels of Eomes and low levels of T-bet, and upon stimulation with tumor cells, secrete low amounts of cytokines. These unexpected findings further support the differences between human and mouse immune populations and prompt the study of the role of hepatic ILC subsets in immune responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Science.gov (United States)

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  2. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

    Science.gov (United States)

    Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

  3. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  4. Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

    Science.gov (United States)

    da Costa Monsanto, Rafael; Erdil, Mehmet; Pauna, Henrique F; Kwon, Geeyoun; Schachern, Patricia A; Tsuprun, Vladimir; Paparella, Michael M; Cureoglu, Sebahattin

    2016-09-01

    To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. Comparative human temporal bone study. Otopathology laboratory. To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  5. Clinical indications for high-resolution MRI diagnostics of the peripheral nervous system; Klinische Indikationen hochaufloesender MRT-Diagnostik des peripheren Nervensystems

    Energy Technology Data Exchange (ETDEWEB)

    Godel, T. [Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany); Weiler, M. [Universitaetsklinikum Heidelberg, Neurologische Klinik, Heidelberg (Germany)

    2017-03-15

    Peripheral neuropathies are common and diagnostically often challenging disorders. Difficulties particularly exist in lesion localization and recognition of complex spatial lesion patterns. Medical history taking, neurological examination, neurophysiological tests and nerve ultrasonography represent the gold standard in the diagnosis of peripheral nerve lesions but have known methodical limitations. The use of 3 Tesla magnetic resonance neurography (MRN) is an additional diagnostic imaging tool recently developed for the high-resolution visualization of long segments of peripheral nerves. Reasonable clinical indications for MRN are exemplarily presented. Using MRN a direct visualization and thus precise localization of focal and non-focal peripheral nerve lesions of various origins can be achieved with high spatial resolution down to the anatomical level of nerve fascicles. Using MRN large anatomical areas of the peripheral nervous system (PNS) can be covered in a single examination session, spatial nerve lesion patterns can be evaluated and the underlying causes can often be detected. The MRN is a valuable supplement to the diagnostic work-up of the PNS, especially in cases that cannot be clarified with standard diagnostic methods. Evaluation of the spatial nerve lesion pattern gives additional information on the origin of the underlying disease. Reasonable indications for MRN are the assessment of proximal nerve structures including the brachial and lumbosacral nerve plexi, the clarification of inconclusive diagnostic results, preoperative, postoperative and posttraumatic assessments, the identification of fascicular nerve lesions and the differential diagnosis of an alleged somatoform disorder. (orig.) [German] Periphere Neuropathien sind haeufige und diagnostisch mitunter anspruchsvolle Erkrankungen. Schwierigkeiten bestehen v. a. bei der Laesionslokalisation und Erkennung komplexer Laesionsmuster. Anamnese, klinisch-neurologische Untersuchung

  6. Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

    Science.gov (United States)

    Smith, Alec S T; Passey, Samantha L; Martin, Neil R W; Player, Darren J; Mudera, Vivek; Greensmith, Linda; Lewis, Mark P

    2016-01-01

    Effective models of mammalian tissues must allow and encourage physiologically (mimetic) correct interactions between co-cultured cell types in order to produce culture microenvironments as similar as possible to those that would normally occur in vivo. In the case of skeletal muscle, the development of such a culture model, integrating multiple relevant cell types within a biomimetic scaffold, would be of significant benefit for investigations into the development, functional performance, and pathophysiology of skeletal muscle tissue. Although some work has been published regarding the behaviour of in vitro muscle models co-cultured with organotypic slices of CNS tissue or with stem cell-derived neurospheres, little investigation has so far been made regarding the potential to maintain isolated motor neurons within a 3D biomimetic skeletal muscle culture platform. Here, we review the current state of the art for engineering neuromuscular contacts in vitro and provide original data detailing the development of a 3D collagen-based model for the co-culture of primary muscle cells and motor neurons. The devised culture system promotes increased myoblast differentiation, forming arrays of parallel, aligned myotubes on which areas of nerve-muscle contact can be detected by immunostaining for pre- and post-synaptic proteins. Quantitative RT-PCR results indicate that motor neuron presence has a positive effect on myotube maturation, suggesting neural incorporation influences muscle development and maturation in vitro. The importance of this work is discussed in relation to other published neuromuscular co-culture platforms along with possible future directions for the field. © 2016 S. Karger AG, Basel.

  7. Lymphoid Aggregates That Resemble Tertiary Lymphoid Organs Define a Specific Pathological Subset in Metal-on-Metal Hip Replacements

    Science.gov (United States)

    Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.

    2013-01-01

    Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985

  8. The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration.

    Science.gov (United States)

    Bankvall, Maria; Östberg, Anna-Karin; Jontell, Mats; Wold, Agnes; Östman, Sofia

    2016-09-01

    The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace(™) Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. © 2016 John Wiley & Sons Ltd.

  9. Epigenomic Views of Innate Lymphoid Cells.

    Science.gov (United States)

    Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O'Shea, John J

    2017-01-01

    The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.

  10. Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Cai, X.Z. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang (China); Huang, W.Y.; Qiao, Y.; Chen, Y.; Du, S.Y.; Chen, D.; Yu, S. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Liu, N. [Department of Nephrology, First Affiliated Hospital, China Medical University, Shenyang (China); Dou, L.Y. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Jiang, Y. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang (China); Department of Dermatology, First Affiliated Hospital, China Medical University, Shenyang (China)

    2014-10-17

    The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (r{sub s}=0.283, P=0.049) and serum albumin (r{sub s}=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; r{sub s}=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

  11. Qualitative alteration of peripheral motor system begins prior to appearance of typical sarcopenia syndrome in middle-aged rats

    Directory of Open Access Journals (Sweden)

    Tetsuro eTamaki

    2014-10-01

    Full Text Available Qualitative changes in the peripheral motor system were examined using Young, Adult, Middle-aged and Old-aged rats in order to assess before and after the appearance of sarcopenia symptoms. Significant loss of muscle mass and strength, and slow-type fiber grouping with a loss of innervated nerve fibers were used as typical markers of sarcopenia. Dynamic twitch and tetanus tension and evoked electromyogram (EEMG were measured via electrical stimulation through the sciatic nerve under anesthesia using our force-distance transducer system before and after sciatectomy. Digital and analogue data sampling was performed and shortening and relaxing velocity of serial twitches was calculated with tension force. Muscle tenderness in passive stretching was also measured as stretch absorption ability, associated with histological quantitation of muscle connective tissues. The results indicated the validity of the present model, in which Old-aged rats clearly showed the typical signs of sarcopenia, specifically in the fast-type plantaris muscles, while the slow-type soleus showed relatively mild syndromes. These observations suggest the following qualitative alterations as the pathophysiological mechanism of sarcopenia: 1 reduction of shortening and relaxing velocity of twitch; 2 decline of muscle tenderness following an increase in the connective tissue component; 3 impaired recruitment of motor units (sudden depression of tetanic force and EEMG in higher stimulation frequencies over 50-60 Hz; and 4 easy fatigability in the neuromuscular junctions. These findings are likely to be closely related to significant losses in fast-type motor units, muscle strength and contraction velocity, which could be a causative factor in falls in the elderly. Importantly, some of these symptoms began in Middle-aged rats that showed no other signs of sarcopenia. Thus, prevention should be started in middle age that could be retained relatively higher movement ability.

  12. The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

    Directory of Open Access Journals (Sweden)

    Ira Ekmekciu

    2017-05-01

    Full Text Available There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and

  13. Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Cai, X.Z.; Huang, W.Y.; Qiao, Y.; Chen, Y.; Du, S.Y.; Chen, D.; Yu, S.; Liu, N.; Dou, L.Y.; Jiang, Y.

    2014-01-01

    The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (r s =0.283, P=0.049) and serum albumin (r s =0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; r s =-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE

  14. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

    Directory of Open Access Journals (Sweden)

    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  15. Concurrent colonic mucosa-associated lymphoid tissue lymphoma and adenoma diagnosed after a positive fecal occult blood test: a case report.

    Science.gov (United States)

    Lin, Pei-Chiang; Chen, Jinn-Shiun; Deng, Po; Wang, Chih-Wei; Huang, Chiung-Huei; Tang, Reiping; Chiang, Jy-Ming; Yeh, Chien-Yuh; Hsieh, Pao-Shiu; Tsai, Wen-Sy; Chiang, Sum-Fu

    2016-01-27

    Colonic lymphoma is an uncommon presentation of extranodal lymphoma. Colonic mucosa-associated lymphoid tissue lymphoma is a different entity from gastric mucosa-associated lymphoid tissue lymphoma, and very rare. The presentation and management of colonic mucosa-associated lymphoid tissue are highly variable in the literature. We report the case of a 59-year-old Taiwanese man who underwent a colonoscopy after a positive test for fecal occult blood. His past history included hypertension and hyperthyroidism. The colonoscopy revealed an adenomatous polyp and mucosa-associated lymphoid tissue lymphoma. We successfully performed a polypectomy and endoscopic mucosal resection. The lymphoma was staged according to the Ann Arbor system modified by Musshoff as E-I. Our patient showed no lymphoma recurrence over a 3-year follow-up. Endoscopic mucosal resection for colonic mucosa-associated lymphoid tissue lymphoma without disseminated disease may be feasible. We successfully used colonoscopic treatment without adjuvant therapy to treat early-stage pathogen-free colonic mucosa-associated lymphoid tissue lymphoma.

  16. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    Science.gov (United States)

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how

  17. Role of the gut-associated and secondary lymphoid tissue in the induction of chronic colitis.

    Science.gov (United States)

    Takebayashi, Koichi; Koboziev, Iurii; Ostanin, Dmitry V; Gray, Laura; Karlsson, Fridrik; Robinson-Jackson, Sherry A; Kosloski-Davidson, Melissa; Dooley, Angela Burrows; Zhang, Songlin; Grisham, Matthew B

    2011-01-01

    It is well known that enteric bacterial antigens drive the development of chronic colitis in a variety of different mouse models of the inflammatory bowel diseases (IBD). The objective of this study was to evaluate the role of gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes (MLNs) and spleen in the pathogenesis of chronic colitis in mice. Surgical as well as genetic approaches were used to generate lymphopenic mice devoid of one or more of these lymphoid tissues. For the first series of studies, we subjected recombinase activating gene-1-deficient mice (RAG(-/-) ) to sham surgery (Sham), mesenteric lymphadenectomy (MLNx), splenectomy (Splx) or both (MLNx/Splx). In a second series of studies we intercrossed lymphotoxinβ-deficient (LTβ(-/-) ) mice with RAG(-/-) animals to generate LTβ(-/-) x RAG(-/-) offspring that were anticipated to contain functional MLNs but be devoid of GALT and most peripheral lymph nodes. Flow purified naïve (CD4(+) CD45RB(high) ) T-cells were adoptively transferred into the different groups of RAG(-/-) recipients to induce chronic colitis. We found that at 3-5 wks following T-cell transfer, all four of the surgically-manipulated RAG(-/-) groups (Sham, MLNx, Splx and MLNx/Splx) developed chronic colitis that was similar in onset and severity. Flow cytometric analysis revealed no differences among the different groups with respect to surface expression of different gut-homing markers nor were there any differences noted in IFN-γ and IL-17 generation by mononuclear cells isolated among these surgically-manipulated mice. Although we anticipated that LTβ(-/-) x RAG(-/-) mice would contain functional MLNs but be devoid of GALT and peripheral lymph nodes (PLNs), we found that LTβ(-/-) x RAG(-/-) mice were in fact devoid of MLNs as well as GALT and PLNs. Adoptive transfer of CD45RB(high) T-cells into LTβ(-/-) x RAG(-/-) mice or their littermate controls (LTβ(+/+) x RAG

  18. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-01-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis

  19. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-07-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.

  20. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation

    Directory of Open Access Journals (Sweden)

    Nancy H Ruddle

    2016-11-01

    Full Text Available High endothelial venules (HEVs and lymphatic vessels (LVs are essential for the function of the immune system, by providing communication between the body and lymph nodes (LNs, specialized sites of antigen presentation and recognition. HEVs bring in naïve and central memory cells and LVs transport antigen, antigen presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs (TLOs are accumulations of lymphoid and stromal cells that arise and organize at ectopic sites in response to chronic inflammation in autoimmunity, microbial infection, graft rejection, and cancer. TLOs are distinguished from primary lymphoid organs-the thymus and bone marrow, and secondary lymphoid organs (SLOs-the LNs, spleen, and Peyer’s patches, in that they arise in response to inflammatory signals, rather than in ontogeny. TLOs usually do not have a capsule, but are rather contained within the confines of another organ. Their structure, cellular composition, chemokine expression, and vascular and stromal support resemble SLOs and are the defining aspects of TLOs. T and B cells, antigen presenting cells, fibroblast reticular cells and other stromal cells and vascular elements including HEVs and LVs are all typical components of TLOS. A key question is whether the HEVs and LVs play comparable roles and are regulated similarly to those in LNs. Data are presented that support this concept, especially with regard to TLO HEVs. Emerging data suggest that the functions and regulation of TLO LVs are also similar to those in LNs. These observations support the concept that TLOs are not merely cellular accumulations, but are functional entities that provide sites to generate effector cells, and that their HEVs and LVs are crucial elements in those activities.

  1. Peripheral nervous system topics

    NARCIS (Netherlands)

    Marani, Enrico; Lakke, E.A.J.F.; Mai, J.K.; Paxinos, G.

    2011-01-01

    *Adopts standard nomenclature following the new scheme by Paxinos, Watson, and Puelles and aligned with the Mai et al. Atlas of the Human Brain (new edition in 2007) * Provides essential reference information for users in conjunction with brain atlases for the identification of brain structures, the

  2. Morphological and functional development of the interbranchial lymphoid tissue (ILT) in Atlantic salmon (Salmo salar L).

    Science.gov (United States)

    Dalum, Alf Seljenes; Griffiths, David James; Valen, Elin Christine; Amthor, Karoline Skaar; Austbø, Lars; Koppang, Erling Olaf; Press, Charles McLean; Kvellestad, Agnar

    2016-11-01

    The interbranchial lymphoid tissue (ILT) of Atlantic salmon originates from an embryological location that in higher vertebrates gives rise to both primary and secondary lymphoid tissues. Still much is unknown about the morphological and functional development of the ILT. In the present work a standardized method of organ volume determination was established to study its development in relation to its containing gill and the thymus. Based on morphological findings and gene transcription data, the ILT shows no signs of primary lymphoid function. In contrast to the thymus, an ILT-complex first became discernible after the yolk-sac period. After its appearance, the ILT-complex constitutes 3-7% of the total volume of the gill (excluding the gill arch) with the newly described distal ILT constituting a major part, and in adult fish it is approximately 13 times larger than the thymus. Confined regions of T-cell proliferation are present within the ILT. Communication with systemic circulation through the distal ILT is also highly plausible thus offering both internal and external recruitment of immune cells in the growing ILT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  4. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  5. Total lymphoid irradiation for multiple sclerosis

    International Nuclear Information System (INIS)

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one

  6. Close Encounters of Lymphoid Cells and Bacteria

    Science.gov (United States)

    Cruz-Adalia, Aranzazu; Veiga, Esteban

    2016-01-01

    During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter. PMID:27774092

  7. Effect of central nervous system radiotherapy in children with acute lymphoblastic leukaemia on lymphocyte subpopulations and indicators of leucocyte migration inhibition in the peripheral blood

    International Nuclear Information System (INIS)

    Cesarz-Kruz, E.; Lukas, A; Sroczynska, M.; Lukas, W; Sonta-Jakimczyk, D.

    1981-01-01

    The reported investigations of changes in lymphocyte subpopulations and indicators of leycocyte migration inhibition in the peripheral blood were carried out in 17 children with acute lymphoblastic leukaemia subjected to prophylactic irradiation of the central nervous system. It was found that the depressive effect of radioprophylaxis affected mostly lymphocytes B. The usefulness of immunomodulation application in children with this leukaemia immediately after completion of radiotherapy is considered. (author)

  8. The interbranchial lymphoid tissue likely contributes to immune tolerance and defense in the gills of Atlantic salmon.

    Science.gov (United States)

    Aas, Ida Bergva; Austbø, Lars; Falk, Knut; Hordvik, Ivar; Koppang, Erling Olaf

    2017-11-01

    Central and peripheral immune tolerance is together with defense mechanisms a hallmark of all lymphoid tissues. In fish, such tolerance is especially important in the gills, where the intimate contact between gill tissue and the aqueous environment would otherwise lead to continual immune stimulation by innocuous antigens. In this paper, we focus on the expression of genes associated with immune regulation by the interbranchial lymphoid tissue (ILT) in an attempt to understand its role in maintaining immune homeostasis. Both healthy and virus-challenged fish were investigated, and transcript levels were examined from laser-dissected ILT, gills, head kidney and intestine. Lack of Aire expression in the ILT excluded its involvement in central tolerance and any possibility of its being an analogue to the thymus. On the other hand, the ILT appears to participate in peripheral immune tolerance due to its relatively high expression of forkhead box protein 3 (Foxp3) and other genes associated with regulatory T cells (Tregs) and immune suppression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Role of innate lymphoid cells in obesity and metabolic disease

    Science.gov (United States)

    Saetang, Jirakrit; Sangkhathat, Surasak

    2018-01-01

    The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

  10. Winter to summer change in vitamin D status reduces systemic inflammation and bioenergetic activity of human peripheral blood mononuclear cells.

    Science.gov (United States)

    Calton, Emily K; Keane, Kevin N; Raizel, Raquel; Rowlands, Jordan; Soares, Mario J; Newsholme, Philip

    2017-08-01

    Vitamin D status [25(OH)D] has recently been reported to be associated with altered cellular bioenergetic profiles of peripheral blood mononuclear cells (PBMCs). No study has tracked the seasonal variation of 25(OH)D and its putative influence on whole body energy metabolism, cellular bioenergetic profiles, inflammatory markers and clinical chemistry. Whole body energy metabolism and substrate utilisation were measured by indirect calorimetry. PBMCs obtained from the same subjects were isolated from whole blood, counted and freshly seeded. Bioenergetic analysis (mitochondrial stress test and glycolysis stress test) was performed using the Seahorse XF e 96 flux analyser. 25(OH)D was assessed using the Architect immunoassay method. 25(OH)D increased by a median (IQR) of 14.40 (20.13)nmol/L (pwinter to summer and was accompanied by significant improvements in indices of insulin sensitivity, McAuley's index (p=0.019) and quantitative insulin sensitivity check index (p=0.028). PBMC mitochondrial parameters basal respiration, non-mitochondrial respiration, ATP production, proton leak, and maximal respiration decreased in summer compared to winter. Similarly, PBMC glycolytic parameters glycolytic activity, glucose response, and glycolytic capacity were all reduced in summer compared to winter. There was also a trend for absolute resting metabolic rate (RMR) to decrease (p=0.066). Markers of systemic inflammation MCP-1, IL-6, IL-8, IL-10, and IL-12p70 decreased significantly in summer compared to winter. Participants who entered winter with a low 25(OH)D (winter 25(OH)D concentrations of 50-75nmol/L or >75nmol/L. The absolute change in 25(OH)D was not associated with altered bioenergetics. Seasonal improvements in 25(OH)D was associated with reduced systemic inflammation, PBMC bioenergetic profiles and whole body energy metabolism. These observational changes in PBMC bioenergetics were most pronounced in those who had insufficient 25(OH)D in winter. The data warrants

  11. [Rectal tonsil or lymphoid follicular hyperplasia of the rectum].

    Science.gov (United States)

    Trillo Fandiño, L; Arias González, M; Iglesias Castañón, A; Fernández Eire, M P

    2014-01-01

    The rectal tonsil is a reactive proliferation of lymphoid tissue located in the rectum. The morphology of the lymphoid proliferation of the colon is usually polypoid or, less commonly, nodular. Only in exceptional cases does lymphoid proliferation of the colon present as a mass in the rectum (rectal tonsil), although this is the most common presentation in middle-aged patients. It is important to be familiar with the rectal tonsil because in cases of exuberant growth it can be difficult to distinguish it from other types of masses. We present the case of rectal tonsil in a four-year-old girl. We describe the magnetic resonance imaging findings and review the literature. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  12. Induction and Analysis of Bronchus-Associated Lymphoid Tissue.

    Science.gov (United States)

    Fleige, Henrike; Förster, Reinhold

    2017-01-01

    Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Intranasal administration of both pathogens induces highly organized BALT but distinct pathways and molecules are used to promote the development of BALT. Here, we describe the induction and phenotype of the distinct types of BALT as well as the immunofluorescence microscopy-based analysis of the induced lymphoid tissue in the lung.

  13. World Health Organisation Classification of Lymphoid Tumours in Veterinary and Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61 Cats.

    Science.gov (United States)

    Wolfesberger, B; Fuchs-Baumgartinger, A; Greß, V; Hammer, S E; Gradner, G; Knödl, K; Tichy, A; Rütgen, B C; Beham-Schmid, C

    2018-02-01

    To diagnose and classify the various entities of lymphomas, the World Health Organisation (WHO) classification is applied in human as well as in veterinary medicine. We validated the concordance of these classification systems by having a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from 61 cats. In 59% of all cases, there was a match between their respective diagnoses of the lymphoma subtype. A complete consensus between the two evaluators was obtained for all samples with a diagnosis of diffuse large B-cell lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also made in the majority of samples with enteropathy associated T-cell lymphoma (EATL) type II, although this subtype in cats has similarities to the 'indolent T-cell lymphoproliferative disorder of the gastrointestinal tract', a provisional entity newly added to the revised human WHO classification in 2016. Very little consensus has been found with cases of EATL type I due to the fact that most did not meet all of the criteria of human EATL I. Hence, the human pathologist assigned them to the heterogeneous group of peripheral T-cell lymphomas (not otherwise specified). Consequently, concrete guidelines and advanced immunophenotyping based on the model of human medicine are essential to differentiate these challenging entities in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Immmunohistochemical study of the blood and lymphatic vasculature and the innervation of mouse gut and gut-associated lymphoid tissue.

    Science.gov (United States)

    Ma, B; von Wasielewski, R; Lindenmaier, W; Dittmar, K E J

    2007-02-01

    The blood and lymphatic vascular system of the gut plays an important role in tissue fluid homeostasis, nutrient absorption and immune surveillance. To obtain a better understanding of the anatomic basis of these functions, the blood and lymphatic vasculature of the lower segment of mouse gut and several constituents of gut-associated lymphoid tissue (GALT) including Peyer's patch, specialized lymphoid nodules in the caecum, small lymphoid aggregates and lymphoid nodules in the colon were studied by using confocal microscopy. Additionally, the innervation and nerve/immune cell interactions in the gut and Peyer's patch were investigated by using cell surface marker PGP9.5 and Glial fibrillary acidic protein (GFAP). In the gut and Peyer's patch, the nerves have contact with B cell, T cell and B220CD3 double-positive cells. Dendritic cells, the most important antigen-presenting cells, were closely apposed to some nerves. Some dendritic cells formed membrane-membrane contact with nerve terminals and neuron cell body. Many fine nerve fibres, which are indirectly detected by GFAP, have contact with dendritic cells and other immune cells in the Peyer's patch. Furthermore, the expression of Muscarinic Acetylcholine receptor (subtype M2) was characterized on dendritic cells and other cell population. These findings are expected to provide a route to understand the anatomic basis of neuron-immune regulation/cross-talk and probably neuroinvasion of prion pathogens in the gut and GALT.

  15. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system.

    Science.gov (United States)

    Zimmermann, Katharina; Lennerz, Jochen K; Hein, Alexander; Link, Andrea S; Kaczmarek, J Stefan; Delling, Markus; Uysal, Serdar; Pfeifer, John D; Riccio, Antonio; Clapham, David E

    2011-11-01

    Detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (>10-15 °C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. Here we report that TRP cation channel, subfamily C member 5 (TRPC5), but not TRPC1/TRPC5 heteromeric channels, are highly cold sensitive in the temperature range 37-25 °C. We found that TRPC5 is present in mouse and human sensory neurons of dorsal root ganglia, a substantial number of peripheral nerves including intraepithelial endings, and in the dorsal lamina of the spinal cord that receives sensory input from the skin, consistent with a potential TRPC5 function as an innocuous cold transducer in nociceptive and thermosensory nerve endings. Although deletion of TRPC5 in 129S1/SvImJ mice resulted in no temperature-sensitive behavioral changes, TRPM8 and/or other menthol-sensitive channels appear to underpin a much larger component of noxious cold sensing after TRPC5 deletion and a shift in mechanosensitive C-fiber subtypes. These findings demonstrate that highly cold-sensitive TRPC5 channels are a molecular component for detection and regional adaptation to cold temperatures in the peripheral nervous system that is distinct from noxious cold sensing.

  16. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis

    NARCIS (Netherlands)

    Cantaert, Tineke; Kolln, Johanna; Timmer, Trieneke; van der Pouw Kraan, Tineke C.; Vandooren, Bernard; Thurlings, Rogier M.; Cañete, Juan D.; Catrina, Anca I.; Out, Theo; Verweij, Cor L.; Zhang, Yiping; Tak, Paul P.; Baeten, Dominique

    2008-01-01

    B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may

  17. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    Directory of Open Access Journals (Sweden)

    Iraklis C Kourtis

    Full Text Available Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d. compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

  18. Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

    OpenAIRE

    Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasma...

  19. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    Science.gov (United States)

    Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

  20. Antinociception by systemically-administered acetaminophen (paracetamol) involves spinal serotonin 5-HT7 and adenosine A1 receptors, as well as peripheral adenosine A1 receptors.

    Science.gov (United States)

    Liu, Jean; Reid, Allison R; Sawynok, Jana

    2013-03-01

    Acetaminophen (paracetamol) is a widely used analgesic, but its sites and mechanisms of action remain incompletely understood. Recent studies have separately implicated spinal adenosine A(1) receptors (A(1)Rs) and serotonin 5-HT(7) receptors (5-HT(7)Rs) in the antinociceptive effects of systemically administered acetaminophen. In the present study, we determined whether these two actions are linked by delivering a selective 5-HT(7)R antagonist to the spinal cord of mice and examining nociception using the formalin 2% model. In normal and A(1)R wild type mice, antinociception by systemic (i.p.) acetaminophen 300mg/kg was reduced by intrathecal (i.t.) delivery of the selective 5-HT(7)R antagonist SB269970 3μg. In mice lacking A(1)Rs, i.t. SB269970 did not reverse antinociception by systemic acetaminophen, indicating a link between spinal 5-HT(7)R and A(1)R mechanisms. We also explored potential roles of peripheral A(1)Rs in antinociception by acetaminophen administered both locally and systemically. In normal mice, intraplantar (i.pl.) acetaminophen 200μg produced antinociception in the formalin test, and this was blocked by co-administration of the selective A(1)R antagonist DPCPX 4.5μg. Acetaminophen administered into the contralateral hindpaw had no effect, indicating a local peripheral action. When acetaminophen was administered systemically, its antinociceptive effect was reversed by i.pl. DPCPX in normal mice; this was also observed in A(1)R wild type mice, but not in those lacking A(1)Rs. In summary, we demonstrate a link between spinal 5-HT(7)Rs and A(1)Rs in the spinal cord relevant to antinociception by systemic acetaminophen. Furthermore, we implicate peripheral A(1)Rs in the antinociceptive effects of locally- and systemically-administered acetaminophen. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  2. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  3. The influence of recovery and training phases on body composition, peripheral vascular function and immune system of professional soccer players.

    Directory of Open Access Journals (Sweden)

    Simon Reinke

    Full Text Available Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4+/-4.2 kg to 72.2+/-3.9 kg was observed, but an increase of fat mass from 10.3+/-5.6 kg to 11.1+/-5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3+/-3.4 and 26.0+/-6.3 ml/100 ml/min respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0+/-2.7 and 33.9+/-7.6 ml/100 ml/min during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by i

  4. Apparent clusters of childhood lymphoid malignancy in Northern England

    International Nuclear Information System (INIS)

    Craft, A.W.; Openshaw, S.; Birch, J.

    1984-01-01

    The authors have reanalysed their previous data on the incidence of childhood malignancy in the North of England by very small geographical areas. Seascale, which ranks first by Poisson probability for all lymphoid malignancies is the village closest to the Sellafield plant. However, it is not unique in the region; nor are wards of apparent excess confined to coastal areas of Cumbria. The highest rate of lymphoid malignancies is in Whittingham, a village in north Northumberland. For other varieties of childhood cancer, there is a similar spread of 'Highly ranked', but different, wards throughout the region. (U.K.)

  5. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  6. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    International Nuclear Information System (INIS)

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-01-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

  7. Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation.

    Science.gov (United States)

    Friedmann, David; Keller, Baerbel; Harder, Ina; Schupp, Jonas; Tanriver, Yakup; Unger, Susanne; Warnatz, Klaus

    2017-11-01

    Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc). We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype. Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21 low B cells, but we could not detect an association of the altered ILC phenotype with a T H 1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients. We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21 low B cells, but not overtly with the relative expansion of T H 1-like T cells. Given the relative abundance of T H 1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.

  8. Gut-associated lymphoid tissues for the development of oral vaccines.

    Science.gov (United States)

    Kunisawa, Jun; Kurashima, Yosuke; Kiyono, Hiroshi

    2012-05-01

    Oral vaccine has been considered to be a prospective vaccine against many pathogens especially invading across gastrointestinal tracts. One key element of oral vaccine is targeting efficient delivery of antigen to gut-associated lymphoid tissue (GALT), the inductive site in the intestine where antigen-specific immune responses are initiated. Various chemical and biological antigen delivery systems have been developed and some are in clinical trials. In this review, we describe the immunological features of GALT and the current status of antigen delivery system candidates for successful oral vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Alteraciones del sistema nervioso periférico en la drepanocitosis Abnormalities of peripheral nervous system in drepanocytosis

    Directory of Open Access Journals (Sweden)

    Mirta C Campos Díaz

    2000-04-01

    Full Text Available Se realizó la evaluación clínica y electromiográfica de la función de los nervios periféricos en un grupo de 40 pacientes (20 adultos y 20 niños con anemia drepanocítica en condiciones basales. Los resultados obtenidos evidencian la existencia de neuropatía periférica en un elevado número de enfermos, más frecuentemente en los adultosAuthors performed a clinical and electromyographic evaluation of peripheral nerves function in a group of 40 patients (20 adults and 20 children presenting sickle cell anemia in basal conditions. Results obtained demonstrate existence of peripheral neuropathy in a significant number of patients, more frequently in adults ones

  10. Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment

    International Nuclear Information System (INIS)

    Hanly, J.G.; Hassan, J.; Moriarty, M.; Barry, C.; Molony, J.; Casey, E.; Whelan, A.; Feighery, C.; Bresnihan, B.

    1986-01-01

    Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis

  11. Functional differences between human NKp44(-) and NKp44(+) RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    Hoorweg, Kerim; Peters, Charlotte P.; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M.; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human

  12. File list: InP.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: ALL.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: ALL.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

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  15. File list: InP.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

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  17. File list: InP.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: His.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Lymphoid_cells mm9 Histone Blood Lymphoid cells SRX658419,SRX65840...5,SRX658389,SRX658437,SRX971603,SRX971602 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Lymphoid_cells.bed ...

  19. Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

    Science.gov (United States)

    Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

    2017-04-01

    Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The effect of acrylamide on alpha-naphthyl acetate esterase enzyme in blood circulating lymphocytes and gut associated lymphoid tissues in rats.

    Science.gov (United States)

    Yener, Y; Sur, E; Telatar, T; Oznurlu, Y

    2013-01-01

    The aim of this study is to determine the functional effects of the acrylamide (AA) administrated by oral gavage on the peripheral blood lymphocytes (PBL) and the Gut Associated Lymphoid Tissue (GALT) in male Sprague-Dawley rats using alpha-naphthyl acetate esterase (ANAE) demonstration. For this purpose, two separate experiments were performed with Sprague Dawley rats. In Experiment-I rats were gavaged with 0, 30, 45 and 60 mg/kgb.w. AA for five consecutive days and in Experiment-II rats were gavaged with 0, 125, 150, and 175 mg/kg/b.w. AA for single oral dose. Animals were sacrificed 24 h after the last treatments in both experiments by servical dislocations under ether anaesthesia. Blood samples were collected from the heart in heparinized (10 UI heparin/ml(-1) of the blood) tubes before sacrification and lymphoid tissue samples from the ileal Peyer's patches (IPPs) were taken and processed for histochemical demonstration of ANAE following the sacrification. The lymphoid follicles of the IPPs of animals given 125, 150 and 175 mg/kgb.w. AA were markedly reduced in size. Germinal centres (GCs) markedly regressed in AA-treated animals compared with those of controls. ANAE-positive lymphocyte depletion of IPPs was very prominent in the high doses AA-treated animals. In the animals treated with 30, 45, and 60 mg/kg b.w. AA, the IPPs had similar histology to those of the controls. ANAE-positive peripheral blood lymphocyte levels significantly decreased in AA exposed groups in a dose dependent manner (pAssociated Lymphoid Tissue (GALT) in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. THE EXTENT OF CLONAL STRUCTURE IN DIFFERENT LYMPHOID ORGANS

    NARCIS (Netherlands)

    HERMANS, MHA; WUBBENA, A; KROESE, FGM; HUNT, SV; COWAN, R; OPSTELTEN, D

    1992-01-01

    To gain insight into the clonal organization of lymphoid organs, we studied the distribution in situ of donor-derived cells in near-physiological chimeras. We introduced RT7b fetal liver cells into nonirradiated congenic RT7a neonatal rats. The chimerism 6-20 wk after injection ranged from 0.3 to

  2. Innate lymphoid cells and parasites: Ancient foes with shared history.

    Science.gov (United States)

    Neill, D R; Fallon, P G

    2018-02-01

    This special issue of Parasite Immunology charts the rapid advances made in our understanding of the myriad interactions between innate lymphoid cells and parasites and how these interactions have shaped our evolutionary history. Here, we provide an overview of the issue and highlight key findings from studies in mice and man. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  3. Developmental acquisition of regulomes underlies innate lymphoid cell functionality

    Science.gov (United States)

    Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...

  4. Innate lymphoid cells--a proposal for uniform nomenclature

    NARCIS (Netherlands)

    Spits, Hergen; Artis, David; Colonna, Marco; Diefenbach, Andreas; Di Santo, James P.; Eberl, Gerard; Koyasu, Shigeo; Locksley, Richard M.; McKenzie, Andrew N. J.; Mebius, Reina E.; Powrie, Fiona; Vivier, Eric

    2013-01-01

    Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly

  5. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  6. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases

    NARCIS (Netherlands)

    Shikhagaie, Medya M.; Germar, Kristine; Bal, Suzanne M.; Ros, Xavier Romero; Spits, Hergen

    2017-01-01

    Innate lymphoid cells (ILCs) are important in the regulation of barrier homeostasis. These cells do not express T cell receptors but share many functional similarities with T helper cells and cytotoxic CD8(+) T lymphocytes. ILCs are divided into three groups, namely group 1 ILCs, group 2 ILCs and

  7. Occurrence of lymphoid cells in the intestine of the Goldfish

    NARCIS (Netherlands)

    Weinberg, Steven

    1975-01-01

    The Goldfish intestine normally contains a large number of lymphocytes, many of them being present in the epithelial layer. After stimulation with antigen, the number of lymphoid cells does not increase, but the proportion of large pyroninophilic cells and plasma cells does. It seems therefore that

  8. Induction of secondary and tertiary lymphoid structures in the skin.

    NARCIS (Netherlands)

    Cupedo, T.; Jansen, W.; Kraal, G.; Mebius, R.E.

    2004-01-01

    During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells.

  9. Clinical impact of the immunome in lymphoid malignancies: the role of Myeloid-Derived Suppressor Cells

    Directory of Open Access Journals (Sweden)

    Calogero eVetro

    2015-05-01

    Full Text Available The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of myeloid-derived suppressor cells in the settings of lymphoid malignancies.

  10. Gut microbiota and probiotics in modulation of epithelium and gut-associated lymphoid tissue function.

    Science.gov (United States)

    Sanz, Yolanda; De Palma, Giada

    2009-01-01

    The intestinal tract mucosa is exposed to a vast number of environmental antigens and a large community of commensal bacteria. The mucosal immune system has to provide both protection against pathogens and tolerance to harmless bacteria. Immune homeostasis depends on the interaction of indigenous commensal and transient bacteria (probiotics) with various components of the epithelium and the gut-associated lymphoid tissue. Herein, an update is given of the mechanisms by which the gut microbiota and probiotics are translocated through the epithelium, sensed via pattern-recognition receptors, and activate innate and adaptive immune responses.

  11. Peripherally Placed Totally Implantable Venous-access Port Systems of the Forearm: Clinical Experience in 763 Consecutive Patients

    International Nuclear Information System (INIS)

    Goltz, Jan P.; Scholl, Anne; Ritter, Christian O.; Wittenberg, Guenther; Hahn, Dietbert; Kickuth, Ralph

    2010-01-01

    The aim of this study is to evaluate the effectiveness and safety of percutaneously placed totally implantable venous-access ports (TIVAPs) of the forearm. Between January 2006 and October 2008, peripheral TIVAPs were implanted in 763 consecutive patients by ultrasound and fluoroscopic guidance. All catheters were implanted under local anesthesia and were tunneled subcutaneously. Indication, technical success, and complications were retrospectively analyzed according to Society of Interventional Radiology (SIR) criteria. Presence of antibiotic prophylaxis, periprocedurally administered drugs (e.g., sedation), and laboratory results at the time of implantation were analyzed. Maintenance during the service interval was evaluated. In total, 327,499 catheter-days were analyzed. Technical success rate was 99.3%. Reasons for initial failure of implantation were either unexpected thrombosis of the subclavian vein, expanding tumor mass of the mediastinum, or failure of peripheral venous access due to fragile vessels. Mean follow-up was 430 days. There were 115 complications observed (15.1%, 0.03 per 100 catheter-days), of which 33 (4.3%) were classified as early (within 30 days from implantation) and 82 (10.7%) as late. Catheter-related venous thrombosis was found in 65 (8.5%) of 763 (0.02 per 100 catheter-days) TIVAPs. Infections were observed in 41 (5.4%) of 763 (0.01 per 100 catheter-days) devices. Other complications observed included dislocation of the catheter tip (0.8%), occlusion (0.1%), or rupture (0.1%) of the port catheter. Dislocated catheters were corrected during a second interventional procedure. In conclusion, implantation of percutaneously placed peripheral TIVAPs shows a high technical success rate and low risk of early complications when ultrasound and fluoroscopic guidance are used. Late complications are observed three times as often as early complications.

  12. Scrapie-specific pathology of sheep lymphoid tissues.

    Directory of Open Access Journals (Sweden)

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases often result in accumulation of disease-associated PrP (PrP(d in the lymphoreticular system (LRS, specifically in association with follicular dendritic cells (FDCs and tingible body macrophages (TBMs of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d within endosomes and lysosomes. In addition, TBMs showed PrP(d in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d/cell membrane interactions occur in different cell types.

  13. Providing straw to allow exploratory behaviour in a pig experimental system does not modify putative indicators of positive welfare: peripheral oxytocin and serotonin.

    Science.gov (United States)

    Marcet Rius, M; Cozzi, A; Bienboire-Frosini, C; Teruel, E; Chabaud, C; Monneret, P; Leclercq, J; Lafont-Lecuelle, C; Pageat, P

    2018-01-22

    Numerous studies have shown that providing straw to pigs can reduce undesirable behaviours such as aggression, tail biting and stereotypy. The measurement of various neuromodulators can be helpful in assessing the development of positive behaviours and overall animal welfare. The oxytocin release is frequently linked to positive emotions and positive welfare. It has been suggested that oxytocin modulates the serotoninergic system. This study aims to investigate the potential effect of straw provision in pigs on peripheral levels of oxytocin and serotonin. In total, 18 mini-pigs were involved in an exploratory study conducted in two parallel groups, Enriched (n=10) and Control (n=8) groups. Pigs were divided by group and housed in pens of two individuals. Straw was provided continuously only in Enriched group and renewed each day for 2 weeks. Two blood samples were drawn from each animal 5 to 10 min before providing the straw, and 15 min after providing straw, during the 1st week, to analyse peripheral changes in oxytocin and serotonin before and after straw provision, and determine the existence of a putative short-term effect. The same procedure was carried out for Control group, without straw provision. Long-term effects of straw provision were also examined using blood samples drawn at the same hour from each animal in the 2nd and 3rd weeks. During this time, animals had the permanent possibility to explore the straw in Enriched group but not in Control group. At the end of each week, one animal-keeper completed two visual analogue scales for each mini-pig regarding the difficulty/ease to work with and handle it and its trust in humans. Results showed peripheral oxytocin increases in both groups after 2 weeks (P=0.02). Results did not demonstrate any effect of providing straw to allow exploratory behaviour on peripheral serotonin. Other results were not significant. This preliminary study explored the relationship between peripheral oxytocin and serotonin and

  14. Evaluation of the effect of duration of diabetes mellitus on peripheral neuropathy using the United Kingdom screening test scoring system, bio-thesiometry and aesthesiometry.

    Science.gov (United States)

    Oguejiofor, O C; Odenigbo, C U; Oguejiofor, C B N

    2010-09-01

    Risk factors predisposing to foot ulceration in diabetic subjects are multiple. Long duration of diabetes mellitus is a major risk factor, likewise peripheral neuropathy (PN), which globally, is recognized as the commonest risk factor for foot disease in diabetic subjects. To evaluate the effect of duration of diabetes mellitus on peripheral neuropathy using the United Kingdom Screening Test (UKST) Scoring System, Bio-thesiometry and Aesthesiometry, in Nigerian diabetic subjects without current or previous foot ulceration. One hundred and twenty (120) diabetes mellitus (DM) subjects with and without symptoms of peripheral neuropathy receiving care at the medical outpatient department (MOPD) and the diabetic clinic of the Nnamdi Azikiwe University Teaching Hospital Nnewi, Nigeria, were recruited consecutively as they presented. Data collected included subjects age (years), gender, age at first diagnosis of DM, duration of DM (years) and baseline fasting venous plasma glucose. The United Kingdom Screening Test (UKST) symptom score was used to separate the participants into two groups those with symptoms of PN and those without and the subjects further assessed by three methods the UKST Signs score, Bio-thesiometry and Aesthesiometry to determine the presence . of PN. Among the 120 diabetic participants, 83(69.2%) had neuropathic symptoms (the symptomatic participants) while 37 (30.8%) were asymptomatic (the asymptomatic participants). The different methods of diagnosing PN increasingly detected PN with increasing duration of diabetes. For the symptomatic group, the UKST method detected PN least in those with duration of DM 15 years while for the asymptomatic group, it detected PN in 25.0% of those with duration of DM 15 years. For the symptomatic group, Aesthesiometry detected PN in 65.2% of those with duration of DM 15 years. For the asymptomatic group, it detected PN in 29.2% of those with duration of DM 15 years. Likewise, for the symptomatic group, Bio

  15. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  17. Stromal cell contributions to the homeostasis and functionality of the immune system.

    Science.gov (United States)

    Mueller, Scott N; Germain, Ronald N

    2009-09-01

    A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response.

  18. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  19. Pairing experimentation and computational modelling to understand the role of tissue inducer cells in the development of lymphoid organs

    Directory of Open Access Journals (Sweden)

    Kieran eAlden

    2012-07-01

    Full Text Available The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signalling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex 3-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically the role of different tissue inducer cell populations in the dynamic formation of Peyer's Patches has been examined. Utilising approaches from critical systems engineering an unbiased model of lymphoid tissue inducer cell function has been developed, that permits the development of emerging behaviours that are statistically not different from that observed in vivo. These results provide the confidence to utilise statistical methods to explore how the simulator predicts cellular behaviour and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine begins to have an influence on observed behaviour, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilising experimental approaches.

  20. The nature of newly-synthesized DNA in irradiated lymphoid cells, measured by a technique sensitive to changes after low doses

    International Nuclear Information System (INIS)

    Olsen, I.; Herbert, L.; Harris, G.; Cramp, W.A.; Hesslewood, I.P.; Parker, J.

    1978-01-01

    We have investigated the post-irradiation synthesis of DNA in a lymphoid cell line (LDV) obtained from normal human peripheral blood and maintained in culture. For doses up to Gy (1 kilorad) the repair of DNA damage in these cells was rapid and complete. However, when DNA strand elongation was assayed in apparently fully repaired cells the new DNA was grossly abnormal. Hydroxapathie chromatography was used to examine lesions in prelabelled DNA as well as strand elongation. Because of the sensitivity of this technique we have been able to show that the repair process is error prone. (orig.) [de

  1. Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.

    Science.gov (United States)

    Boshra, Vivian; Abbas, Amr M

    2017-07-26

    Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH. RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B. RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress. The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

  2. Macro- and microperfusion during application of a new compression system, designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease.

    Science.gov (United States)

    Jünger, Michael; Haase, Hermann; Schwenke, Linda; Bichel, Jens; Schuren, Jan; Ladwig, Andrea

    2013-01-01

    To investigate macro- and microperfusion during 14 days of treatment with a new 2-layer compression system (3M™ Coban™ 2 Lite), designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease. A single-centre, open-label, prospective pilot study was performed with 15 subjects suffering from peripheral arterial occlusive disease with an ankle brachial pressure index (ABPI) of 0.5-0.8, who volunteered to have their 'study leg' bandaged with the new system. Coincident leg ulcer or chronic venous disease was not mandatory. All subjects received the new compression system, which stayed in place from 1 up to 4 days according to scheduled study visits. The system was reapplied by study personnel at each clinical visit (days 1, 2, 3, 4, 7, 10 and 14). The study participation stopped after 14 days. At each clinical visit safety assessments were performed: measurement of acral pulsation to capture macroperfusion; laser Doppler fluxmetry to capture microperfusion; clinical signs of pressure related skin damage, hypoxia-related pain and sub-bandage pressure measurement. In addition, the leg volume was measured and a comfort questionnaire was completed. An average sub-bandage pressure in standing position of approximately 30 mmHg was measured at the B1 location immediately after bandage application. Laser Doppler fluxmetry demonstrated positive effects on microcirculation regarding vasomotion and respiratory reflux. No change of the cardiac signal appeared. For acrale pulsations a high intraindividual variability was found with no clear interference to the bandage application. No pressure-related skin damage or hypoxia-related pain was detected. After application of the new compression system in subjects with moderate PAOD, laser Doppler fluxmetry indicated significant improvements of the microcirculation. High variability and lack of correlation to clinical symptoms was found for the acral pulsation. The new compression system revealed a high

  3. Epigenetic regulation of non-lymphoid cells by Bisphenol-A, a model endocrine disrupter: Potential Implications for Immunoregulation

    Directory of Open Access Journals (Sweden)

    Deena eKhan

    2015-06-01

    Full Text Available Endocrine disrupting chemicals (EDC abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical and consumer product industries. Many of the EDCs such as Bisphenol A (BPA have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  4. Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases.

    Science.gov (United States)

    Sanati, Golshid; Aryan, Zahra; Barbadi, Mehri; Rezaei, Nima

    2015-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express V(D)J-rearranged receptors and play a role in the innate immune system. ILCs are categorized into three groups with respect to their function in the immune system. ILC1 induces production of IFN-γ via T-box expressed on T cells, ILC2 promotes production of type 2 cytokines via GATA-binding protein-3 and ILC3 promotes IL-17 and IL-22 production via retinoic acid receptor-related orphan receptor-γt. ILCs can maintain homeostasis in epithelial surfaces by responding to locally produced cytokines or direct recognition of danger patterns. Altered epithelial barrier function seems to be a key point in inappropriate activation of ILCs to promote inflammatory and allergic responses. ILCs play an essential role in initiation and maintenance of defense against infections as well as immune-mediated diseases. In this paper, we discuss the role of ILCs in inflammatory, allergic and autoimmune diseases.

  5. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    Science.gov (United States)

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  6. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    International Nuclear Information System (INIS)

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years

  7. Beyond NK cells: the expanding universe of innate lymphoid cells.

    Science.gov (United States)

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  8. Beyond NK cells: the expanding universe of Innate Lymphoid Cells.

    Directory of Open Access Journals (Sweden)

    Marina eCella

    2014-06-01

    Full Text Available For a long time NK cells were thought to be the only immune innate lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different Innate Lymphoid Cells found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. ILC populations closely mirror the phenotype of adaptive Thelper subsets in their ability to secrete soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response appropriate to the incoming insult. Here we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  9. Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice

    International Nuclear Information System (INIS)

    Kim, Y.T.; Goidl, E.A.; Samarut, C.; Weksler, M.E.; Thorbecke, G.J.; Siskind, G.W.

    1985-01-01

    After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, the authors show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id

  10. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    International Nuclear Information System (INIS)

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-01-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease

  12. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments

  13. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-01-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  14. Assessment of peripheral vessels and of the lymphatic system by means of gamma-camera scintiscan (gamma-scintigraphy of the whole body)

    Energy Technology Data Exchange (ETDEWEB)

    Ennis, J T

    1981-01-01

    For diagnosing pathologies of the peripheric vessels or of the lymphatic system, albumin aggregates marked with sup(99m) technetium (MAA) or antimonocolloids were used. The radionuclide venography is useful in diagnosing thrombosis, venous insufficiency, and permits a high degree of accuracy, comparable with that of phlebography. In the most cases the radionuclide lymphoscintigraphy is required for the diagnosis of lymphoedema and allows by distribution analysis an adequate morphological representation of the lymphatic ducts and glands. Contrary to lymphography, lymphoscintigraphy presents a completely physiological radionuclide transport and does not cause any reactive lymphatic node hyperplasia by contrast media. Increased capillary perfusion is found in collateral vessel formation in cases of arterial obstruction and ischaemic ulcus, whereas hypoperfusion is seen in obstructions of the larger arteries having no collateral vessels, and in bad circulatory states. Particularly in diabetics with microangiopathy, a peripheral distribution with hyperfusion of the skon presents itself as piece-meal necrosis. The importance and relevance of the perfusion scans of the extremities for the diagnostic assessment within the field of resection surgery is explained.

  15. Analysis of axonal regeneration in the central and peripheral nervous systems of the NG2-deficient mouse

    Directory of Open Access Journals (Sweden)

    Lieberman Alexander R

    2007-09-01

    Full Text Available Abstract Background The chondroitin sulphate proteoglycan NG2 blocks neurite outgrowth in vitro and has been proposed as a major inhibitor of axonal regeneration in the CNS. Although a substantial body of evidence underpins this hypothesis, it is challenged by recent findings including strong expression of NG2 in regenerating peripheral nerve. Results We studied axonal regeneration in the PNS and CNS of genetically engineered mice that do not express NG2, and in sex and age matched wild-type controls. In the CNS, we used anterograde tracing with BDA to study corticospinal tract (CST axons after spinal cord injury and transganglionic labelling with CT-HRP to trace ascending sensory dorsal column (DC axons after DC lesions and a conditioning lesion of the sciatic nerve. Injury to these fibre tracts resulted in no difference between knockout and wild-type mice in the ability of CST axons or DC axons to enter or cross the lesion site. Similarly, after dorsal root injury (with conditioning lesion, most regenerating dorsal root axons failed to grow across the dorsal root entry zone in both transgenic and wild-type mice. Following sciatic nerve injuries, functional recovery was assessed by analysis of the toe-spreading reflex and cutaneous sensitivity to Von Frey hairs. Anatomical correlates of regeneration were assessed by: retrograde labelling of regenerating dorsal root ganglion (DRG cells with DiAsp; immunostaining with PGP 9.5 to visualise sensory reinnervation of plantar hindpaws; electron microscopic analysis of regenerating axons in tibial and digital nerves; and by silver-cholinesterase histochemical study of motor end plate reinnervation. We also examined functional and anatomical correlates of regeneration after injury of the facial nerve by assessing the time taken for whisker movements and corneal reflexes to recover and by retrograde labelling of regenerated axons with Fluorogold and DiAsp. None of the anatomical or functional analyses

  16. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

    Science.gov (United States)

    Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes, Rashade A H; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D

    2016-01-01

    Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. The biology of innate lymphoid cells

    NARCIS (Netherlands)

    Artis, David; Spits, Hergen

    2015-01-01

    The innate immune system is composed of a diverse array of evolutionarily ancient haematopoietic cell types, including dendritic cells, monocytes, macrophages and granulocytes. These cell populations collaborate with each other, with the adaptive immune system and with non-haematopoietic cells to

  18. Toxicity to nasal-associated lymphoid tissue

    NARCIS (Netherlands)

    Kuper, C.F.; Arts, J.H.E.; Feron, V.J.

    2003-01-01

    The mucosal membranes form a weak mechanical barrier, but they are provided with an extensive specific and non-specific defence system. Antigenic stimulation of the mucosal immune system of the oronasal passages induces specific, local immune responses, and activates immune components of mucosae

  19. Peripheral facial weakness (Bell's palsy).

    Science.gov (United States)

    Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

    2013-06-01

    Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

  20. Dynamic analysis with a fractional-order chaotic system for estimation of peripheral arterial disease in diabetic foot

    Science.gov (United States)

    Li, Chien-Ming; Du, Yi-Chun; Wu, Jian-Xing; Lin, Chia-Hung; Ho, Yueh-Ren; Chen, Tainsong

    2013-08-01

    Lower-extremity peripheral arterial disease (PAD) is caused by narrowing or occlusion of vessels in patients like type 2 diabetes mellitus, the elderly and smokers. Patients with PAD are mostly asymptomatic; typical early symptoms of this limb-threatening disorder are intermittent claudication and leg pain, suggesting the necessity for accurate diagnosis by invasive angiography and ankle-brachial pressure index. This index acts as a gold standard reference for PAD diagnosis and categorizes its severity into normal, low-grade and high-grade, with respective cut-off points of ≥0.9, 0.9-0.5 and diabetics and 11 healthy adults, with analysis of dynamic errors based on various butterfly motion patterns, and color relational analysis as classifier for pattern recognition. The results show that the classification of PAD severity among these testees was achieved with high accuracy and efficiency. This noninvasive methodology potentially provides timing and accessible feedback to patients with asymptomatic PAD and their physicians for further invasive diagnosis or strict management of risk factors to intervene in the disease progression.

  1. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    OpenAIRE

    Martinet , Kim ,; Bloquet , Stéphane; Bourgeois , Christine

    2014-01-01

    International audience; BackgroundCD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue ...

  2. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

    Science.gov (United States)

    Cautivo, Kelly M; Molofsky, Ari B

    2016-06-01

    Adipose tissue (AT) is home to an abundance of immune cells. With chronic obesity, inflammatory immune cells accumulate and promote insulin resistance and the progression to type 2 diabetes mellitus. In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy AT, including those associated with type 2 or "allergic" immunity. Although traditionally activated by infection with multicellular helminthes, AT type 2 immunity is active independently of infection, and promotes tissue homeostasis, AT "browning," and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and type 2 diabetes mellitus. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines interleukin-5 and IL-13, promoting eosinophils and alternatively activated macrophages, and cooperating with and promoting AT regulatory T (Treg) cells. In this review, we focus on the recent developments in our understanding of group 2 innate lymphoid cell cells and type 2 immunity in AT metabolism and homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

    Science.gov (United States)

    Głobińska, Anna; Kowalski, Marek L

    2017-10-01

    Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

  4. Bronchus-associated lymphoid tissue (BALT and survival in a vaccine mouse model of tularemia.

    Directory of Open Access Journals (Sweden)

    Damiana Chiavolini

    2010-06-01

    Full Text Available Francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant.Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensis and neisserial recombinant PorB as an adjuvant candidate. Then, mice were challenged via the same route with the F. tularensis attenuated live vaccine strain (LVS. Mouse survival and analysis of a number of immune parameters were conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infection presented prominent lymphoid aggregates in peribronchial and perivascular areas, consistent with the location of bronchus-associated lymphoid tissue (BALT. BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs. We also observed local production of antibody generating cells and homeostatic chemokines in BALT areas.These data indicate that PorB might be an optimal adjuvant candidate for improving the protective effect of F. tularensis antigens. The presence of BALT induced after intranasal challenge in vaccinated mice might play a role in regulation of local immunity and long-term protection, but more work is needed to elucidate mechanisms that lead to its formation.

  5. Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and persistence.

    Science.gov (United States)

    Deleage, Claire; Turkbey, Baris; Estes, Jacob D

    2016-08-01

    CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these cells residing within lymphoid tissue compartments throughout the body. Predictably, HIV-1 infection, replication, localization, reservoir establishment and persistence, as well as associated host immune and inflammatory responses and disease pathology principally take place within the tissues of the immune system. By virture of the fact that the virus-host struggle is played out within lymphoid and additional tissues compartments in HIV-1 infected individuals it is critical to understand HIV-1 infection and disease within these relevant tissue sites; however, there are obvious limitations to studying these dynamic processes in humans. Nonhuman primate (NHP) research has provided a vital bridge between basic and preclinical research and clinical studies, with experimental SIV infection of NHP models offering unique opportunities to understand key processes of HIV-1 infection and disease that are either not practically feasible or ethical in HIV-1 infected humans. In this review we will discuss current approaches to studying the tissue based immunopathogenesis of AIDS virus infection in NHPs, including both analyses of tissues obtained at biopsy or necropsy and complementary non-invasive imaging approaches that may have practical utility in monitoring HIV-1 disease in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

    Science.gov (United States)

    Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

    2016-07-01

    Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

  7. Lymphoid tissue inducer cells: pivotal cells in the evolution of CD4 immunity and tolerance?

    Directory of Open Access Journals (Sweden)

    Peter John Lane

    2012-02-01

    Full Text Available Phylogeny suggests that the evolution of placentation in mammals was accompanied by substantial changes in the mammalian immune system: in particular lymph nodes and CD4 high affinity memory antibody responses co-evolved during the same period. Lymphoid tissue inducer cells (LTi are members of an emerging family of innate lymphoid cells (ILCs that are crucial for lymph node development, but our studies have indicated that they also play a pivotal role in the long-term maintenance of memory CD4 T cells in adult mammals through their expression of the tumor necrosis family members, OX40- and CD30-ligands. Additionally, our studies have shown that these two molecules are also key operators in CD4 effector function, as their absence obviates the need for the FoxP3-dependent regulatory T cells (Tregs that prevent CD4 driven autoimmune responses. In this perspective article, we summarize findings from our group over the last 10 years, and focus specifically on the role of LTi in thymus. We suggest that like memory CD4 T cells, LTi also play a role in the selection and maintenance of the Tregs that under normal circumstances are absolutely required to regulate CD4 effector cells.

  8. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2017-10-10

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

    Science.gov (United States)

    2017-05-28

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  10. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    International Nuclear Information System (INIS)

    Najarian, J.S.; Ferguson, R.M.; Sutherland, D.E.; Slavin, S.; Kim, T.; Kersey, J.; Simmons, R.L.

    1982-01-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  11. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K

    2015-01-01

    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

  12. Innate lymphoid cells in inflammatory bowel diseases

    NARCIS (Netherlands)

    Peters, C. P.; Mjösberg, J. M.; Bernink, J. H.; Spits, H.

    2016-01-01

    It is generally believed that inflammatory bowel diseases (IBD) are caused by an aberrant immune response to environmental triggers in genetically susceptible individuals. The exact contribution of the adaptive and innate immune system has not been elucidated. However, recent advances in treatments

  13. Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients.

    Science.gov (United States)

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Andreotti, Mauro; Selvaggi, Carla; Giustini, Noemi; Serafino, Sara; Schietroma, Ivan; Nunnari, Giuseppe; Antonelli, Guido; Vullo, Vincenzo; Scagnolari, Carolina

    2015-01-01

    The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression) into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory) in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

  14. Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated Lymphoid Tissue of Chronic HIV-1 Positive Patients

    Directory of Open Access Journals (Sweden)

    Gabriella d’Ettorre

    2015-01-01

    Full Text Available The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

  15. EDITORIAL MODERN TECHNOLOGY IN PERIPHERAL HEALTH ...

    African Journals Online (AJOL)

    hi-tech

    2004-06-01

    Jun 1, 2004 ... new technology to peripheral health care systems in developing countries. ... and maintenance of medical equipment in Africa, citing information ... operating laboratory equipment, and for emergency lighting for operating ...

  16. Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

    Science.gov (United States)

    Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

    2017-03-17

    The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T-lymphoid

  17. Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

    Science.gov (United States)

    Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

    2012-01-01

    Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

  18. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis.

    Directory of Open Access Journals (Sweden)

    Sambasiva P Rao

    Full Text Available Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs display the highest number while natural killer (NK cells, plasmacytoid dendritic cells (pDCs and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact.

  19. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    Almaraz, R.

    1981-01-01

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  20. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...