Disease-Associated Prion Protein in Neural and Lymphoid Tissues of Mink (Mustela vison) Inoculated with Transmissible Mink Encephalopathy

PubMed Central

Schneider, D. A.; Harrington, R. D.; Zhuang, D.; Yan, H.; Truscott, T. C.; Dassanayake, R. P.; O'Rourke, K. I.

2012-01-01

Summary Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrPd). The distribution of PrPd within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrPTME and of which only the HY strain is associated with accumulation of PrPTME in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrPTME in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrPTME was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrPTME was detected readily in the brain and retropharyngeal lymph node during preclinical infection with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrPTME in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrPTME accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrPTME in the lymphoid tissues of

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina.

PubMed

Yoshinaga, Kousuke; Akahira, Jun-Ichi; Niikura, Hitoshi; Ito, Kiyoshi; Moriya, Takuya; Murakami, Takashi; Kameoka, Jun-Ichi; Ichinohasama, Ryo; Okamura, Kunihiro; Yaegashi, Nobuo

2004-09-01

We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms.

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

PubMed

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 < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in 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.

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

PubMed

Nakamura, Shotaro; Matsumoto, Takayuki

2015-09-01

Recent trends and current knowledge on the diagnosis and treatment strategy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are reviewed. Helicobacter pylori infection plays the causative role in the pathogenesis, and H pylori eradication is the first-line treatment of this disease, which leads to complete remission in 60% to 90% of cases. A Japanese multicenter study confirmed that the long-term outcome of gastric MALT lymphoma after H pylori eradication is excellent. Treatment strategies for patients not responding to H pylori eradication including "watch and wait" strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and combination of these should be tailored in consideration of the disease extent in each patient. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

PubMed

Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

2016-03-01

The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. Copyright © 2016 by The American Association of Immunologists, Inc.

Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling

PubMed Central

Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

2015-01-01

The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. Here we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a non-cell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

Precocious development of lectin (Ulex europaeus agglutinin I) receptors in dome epithelium of gut-associated lymphoid tissues.

PubMed

Roy, M J

1987-06-01

Dome epithelium (DE), the tissue covering lymphoid domes of gut-associated lymphoid tissues, was examined in both adult and neonatal rabbit appendix or sacculus rotundus to determine if dome epithelial cells matured earlier than epithelial cells covering adjacent villi. The localization of well-differentiated epithelial cells in rabbit gut-associated lymphoid tissues (GALT) was accomplished histochemically by use of molecular probes: fluorescein isothiocyanate or horseradish peroxidase conjugates of Ulex europaeus agglutinin I (UEA), a lectin specific for terminal L-fucose molecules on certain glycoconjugates. The villus epithelial cells of newborn and 2-, 5-, or 10-day-old rabbits did not bind UEA, but between the twelfth and fifteenth days of postnatal life, UEA receptors were expressed by well-differentiated villus epithelial cells. In contrast to villus epithelium, DE in appendix and sacculus rotundus of neonatal rabbits expressed UEA receptors two days after birth, a feature that distinguished the DE of neonatal GALT for the next two weeks. In adult rabbits, UEA receptors were associated with dome epithelial cells extending from the mouths of glandular crypts to the upper domes; in contrast to the domes, UEA receptors were only present on well-differentiated epithelial cells at the villus tips. Results suggested that in neonatal rabbits most dome epithelial cells developed UEA receptors shortly after birth, reflecting precocious development of DE as compared to villus epithelium. In adult rabbit dome epithelium UEA receptors appeared on dome epithelial cells as they left the glandular crypts, representing accelerated epithelial maturation.

Association of T-Zone Reticular Networks and Conduits with Ectopic Lymphoid Tissues in Mice and Humans

PubMed Central

Link, Alexander; Hardie, Debbie L.; Favre, Stéphanie; Britschgi, Mirjam R.; Adams, David H.; Sixt, Michael; Cyster, Jason G.; Buckley, Christopher D.; Luther, Sanjiv A.

2011-01-01

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node–like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin+ T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell–rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter–CXCL13–transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell–rich zone. PMID:21435450

Morphologic observation of mucosa-associated lymphoid tissue in the large intestine of Bactrian camels (Camelus bactrianus).

PubMed

ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai

2014-07-01

The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P < 0.05). The germinal centers of the lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. © 2014 Wiley Periodicals, Inc.

Histology and immunohistochemistry of the gut-associated lymphoid tissue of the eastern grey kangaroo, Macropus giganteus.

PubMed

Old, J M; Deane, E M

2001-12-01

Mesenteric lymph nodes and gut-associated lymphoid tissue (GALT) from juvenile eastern grey kangaroos were investigated. The mesenteric nodes had a similar structure to that described for eutherian mammals. They contained distinct regions of medulla and cortex, with prominent follicles and germinal centres. Gut associated lymphoid tissue consisted of areas of submucosal follicles. These varied from areas of densely packed lymphocytes with darkly staining, prominent coronas to areas with no defined follicles. The distribution of T cells in these tissues was documented by use of species-crossreactive antibodies to the surface markers CD3 and CD5; B cells were identified by antibodies to CD79b. Within the lymph nodes T cells were located mainly in the paracortex and cortex, with limited numbers observed in the follicles; B cells were located on the marginal zone of the follicles. In GALT, T cells were located in the peripheral regions of the germinal centres of secondary follicles, while B cells were abundant in primary follicles. These observations are consistent with those made in a range of other marsupials (metatherian) and eutherian mammals and are indicative of the capacity to respond to antigens entering via the mouth.

Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

PubMed Central

Pereira, Marta-Isabel; Medeiros, José Augusto

2014-01-01

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care. PMID:24574742

Expression of lymphocyte antigenic determinants in developing gut-associated lymphoid tissue of the sea bass Dicentrarchus labrax (L.).

PubMed

Picchietti, S; Terribili, F R; Mastrolia, L; Scapigliati, G; Abelli, L

1997-12-01

The monoclonal antibodies DLT15 and DLIg3, which recognize antigenic determinants expressed by T cells and Ig-bearing cells, respectively, allowed the development of gut-associated lymphoid tissue of the teleost fish Dicentrarchus labrax (L.) to be studied. DLT15-immunoreactive cells were first detected in the epithelium of the stomach and intestine at day 30 post-hatching of fish maintained at 16 degrees C. At that age, positive cells were found only in the thymus. Between day 44 and day 81 post-hatching, DLT15-immunoreactive cells became numerous, both in and under the gut epithelium. A gradient in the number of lymphocytes was present, concentrating them towards the anus. Until day 81 post-hatching, DLIg3-immunoreactive cells were not found in the gut, although they were present in the kidney, spleen and thymus earlier. Infrequent Ig-bearing cells were found in the gut mucosa of -year-old sea bass. This study showed that the gut-associated lymphoid tissue developed earlier than other lymphoid compartments. It also provided evidence of the predominance of T cells in the gut immune system of the sea bass.

Lymphoid microenvironments and innate lymphoid cells in the gut.

PubMed

Pearson, Claire; Uhlig, Holm H; Powrie, Fiona

2012-06-01

Gut-associated lymphoid tissue (GALT) is a sensor region for luminal content and plays an important role in lymphoid maturation, activation and differentiation. It comprises isolated and aggregated lymphoid follicles, cryptopatches (CPs) and tertiary lymphoid tissue. Innate lymphoid cells (ILCs) play a central role within GALT. Prenatal GALT development is dependent on ILC lymphoid-inducer function. Postnatally, these cells rapidly respond to commensal and pathogenic intestinal bacteria, parasites and food components by polarized cytokine production [such as interleukin (IL)-22, IL-17 or IL-13] and further contribute to GALT formation and function. Here, we discuss how ILCs shape lymphoid intestinal microenvironments and act as amplifier cells for innate and adaptive immune responses. Copyright © 2012. Published by Elsevier Ltd.

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

PubMed Central

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

Recurrence after radiotherapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma with trisomy 18.

PubMed

Ishikawa, Hisashi; Iwamuro, Masaya; Okada, Hiroyuki; Hori, Keisuke; Kita, Masahide; Kawano, Seiji; Kawahara, Yoshiro; Tanaka, Takehiro; Kondo, Eisei; Yoshino, Tadashi; Yamamoto, Kazuhide

2015-01-01

A 36-year-old Japanese woman presented with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the stomach. The gastric lesions only partially improved after eradication therapy for Helicobacter pylori. A fluorescence in situ hybridization analysis revealed no fusion genes of API2-MALT1, although trisomy of chromosome 18 was identified. Radiation therapy was initiated to treat the gastric lymphoma lesions, resulting in complete remission. However, MALT lymphoma recurred in the stomach 16 months later. This case indicates that intensive follow-up is required for MALT lymphoma associated with chromosomal aberrations in order to detect early relapse.

Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma

PubMed Central

Park, Jeong Bae; Koo, Ja Seol

2014-01-01

Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma. Despite its increasing incidence, diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings, and, thus, a high index of suspicion, and multiple, deep, repeated biopsies at abnormally and normally appearing sites in the stomach are needed. In addition, testing for Helicobacter pylori (H. pylori) infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H. pylori eradication and for assessment of disease progression. In addition, H. pylori infection and MALT lymphoma development are associated, and complete regression of low-grade MALT lymphomas after H. pylori eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used in cases that show poor response to H. pylori eradication, negativity for H. pylori infection, or high-grade lymphoma. PMID:24659867

Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Park, Jeong Bae; Koo, Ja Seol

2014-03-21

Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma. Despite its increasing incidence, diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings, and, thus, a high index of suspicion, and multiple, deep, repeated biopsies at abnormally and normally appearing sites in the stomach are needed. In addition, testing for Helicobacter pylori (H. pylori) infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H. pylori eradication and for assessment of disease progression. In addition, H. pylori infection and MALT lymphoma development are associated, and complete regression of low-grade MALT lymphomas after H. pylori eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used in cases that show poor response to H. pylori eradication, negativity for H. pylori infection, or high-grade lymphoma.

Distribution of the lingual lymphoid tissue in domestic ruminants.

PubMed

Breugelmans, S; Casteleyn, C; Simoens, P; Van den Broeck, W

2011-12-01

The distribution and organisation of the intralingual lymphoid tissue was studied in sheep, goat and cattle. For each species, the tongues of two animals were harvested and divided in sample blocks extending over the total surface of the tongue. With 2.5 mm intervals, ten serial histological sections were made for conventional histological staining (haematoxylin-eosin, Van Gieson, Masson's trichrome) and immunohistochemical staining of lymphoid cells (anti-CD3, anti-CD21, anti-CD45). Lymphocytes were scattered in the subepithelial propria-submucosa and in the connective tissue cores of the lingual papillae. The connective tissue cores of fungiform papillae, including those located on the lingual apex, and vallate papillae showed relatively more lymphocytes than the propria-submucosa. Lymphoid cell aggregations were even more abundant beneath the grooves surrounding the vallate papillae in small ruminants. In cattle, a well-organised lingual tonsil was additionally found at the root of the tongue. CD3-positive lymphocytes were observed in all species examined. CD21-positive lymphocytes were numerous in the lymphoid nodules of the bovine lingual tonsil but very scarce in the ovine and caprine tongues. Therefore, the lymphoid cell aggregations in the tongues of small ruminants should not be referred to by the term 'lingual tonsil'. © 2011 Blackwell Verlag GmbH.

PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer

PubMed Central

Davenport, Kristen A.; Hoover, Clare E.; Bian, Jifeng; Telling, Glenn C.; Mathiason, Candace K.; Hoover, Edward A.

2017-01-01

The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs. PMID:28880938

Establishment and function of tissue-resident innate lymphoid cells in the skin.

PubMed

Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na

2017-07-01

Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

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

PubMed

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.

Nasal immunization with M cell-targeting ligand-conjugated ApxIIA toxin fragment induces protective immunity against Actinobacillus pleuropneumoniae infection in a murine model.

PubMed

Park, Jisang; Seo, Ki-Weon; Kim, Sae-Hae; Lee, Ha-Yan; Kim, Bumseok; Lim, Chae Woong; Kim, Jin-Hee; Yoo, Han Sang; Jang, Yong-Suk

2015-05-15

Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and severe economic loss in the swine industry has been caused by the infection. Therefore, the development of an effective vaccine against the bacteria is necessary. ApxII toxin, among several virulence factors expressed by the bacteria, is considered to be a promising vaccine candidate because ApxII toxin not only accompanies cytotoxic and hemolytic activities, but is also expressed in all 15 serotypes of bacteria except serotypes 10 and 14. In this study, we identified the peptide ligand capable of targeting the ligand-conjugated ApxIIA #5 fragment antigen to nasopharynx-associated lymphoid tissue. It was found that nasal immunization with ligand-conjugated ApxIIA #5 induced efficient mucosal and systemic immune responses measured at the levels of antigen-specific antibodies, cytokine-secreting cells after antigen exposure, and antigen-specific lymphocyte proliferation. More importantly, the nasal immunization induced protective immunity against nasal challenge infection of the bacteria, which was confirmed by histopathological studies and bacterial clearance after challenge infection. Collectively, we confirmed that the ligand capable of targeting the ligand-conjugated antigen to nasopharynx-associated lymphoid tissue can be used as an effective nasal vaccine adjuvant to induce protective immunity against A. pleuropneumoniae infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population.

PubMed

Lugthart, Gertjan; Melsen, Janine E; Vervat, Carly; van Ostaijen-Ten Dam, Monique M; Corver, Willem E; Roelen, Dave L; van Bergen, Jeroen; van Tol, Maarten J D; Lankester, Arjan C; Schilham, Marco W

2016-07-01

Knowledge of human NK cells is based primarily on conventional CD56(bright) and CD56(dim) NK cells from blood. However, most cellular immune interactions occur in lymphoid organs. Based on the coexpression of CD69 and CXCR6, we identified a third major NK cell subset in lymphoid tissues. This population represents 30-60% of NK cells in marrow, spleen, and lymph node but is absent from blood. CD69(+)CXCR6(+) lymphoid tissue NK cells have an intermediate expression of CD56 and high expression of NKp46 and ICAM-1. In contrast to circulating NK cells, they have a bimodal expression of the activating receptor DNAX accessory molecule 1. CD69(+)CXCR6(+) NK cells do not express the early markers c-kit and IL-7Rα, nor killer cell Ig-like receptors or other late-differentiation markers. After cytokine stimulation, CD69(+)CXCR6(+) NK cells produce IFN-γ at levels comparable to CD56(dim) NK cells. They constitutively express perforin but require preactivation to express granzyme B and exert cytotoxicity. After hematopoietic stem cell transplantation, CD69(+)CXCR6(+) lymphoid tissue NK cells do not exhibit the hyperexpansion observed for both conventional NK cell populations. CD69(+)CXCR6(+) NK cells constitute a separate NK cell population with a distinct phenotype and function. The identification of this NK cell population in lymphoid tissues provides tools to further evaluate the cellular interactions and role of NK cells in human immunity. Copyright © 2016 by The American Association of Immunologists, Inc.

[Gastric Mucosa-associated Lymphoid Tissue Lymphoma Based on Outcome of Domestic Treatment].

PubMed

Jung, Jin Tae

2016-10-25

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection. H. pylori eradication can be performed as a primary therapy regardless of H. pylori status. In Korea, six articles were published about low-grade gastric MALT lymphoma with H. pylori . Complete regression rate after H. pylori eradication is reported at 74.5% to 94.4%. Radiotherapy results in favorable clinical long-term outcomes in patients with early-stage gastric MALT lymphoma who fail H. pylori eradication therapy and those who are H. pylori negative. Chemotherapy could be reserved for patients with metastatic or high-grade lymphoma. In gastric MALT lymphoma, patients with polypoid type on initial endoscopy had a higher likelihood of recurrence than those with diffuse infiltration or ulceration types. The depth of invasion, location of lesions, and chromosomal abnormality with t(11;18) together are predictive factors for failure to remission by H. pylori eradication.

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

PubMed

Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

2018-01-16

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Human natural killer cell development in secondary lymphoid tissues

PubMed Central

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

Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology

PubMed Central

Suzuki, Ayana; Hirokawa, Mitsuyoshi; Ito, Aki; Takada, Nami; Higuchi, Miyoko; Hayashi, Toshitetsu; Kuma, Seiji; Miyauchi, Akira

2018-01-01

Objective To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). Study Design We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. Results In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p < 0.001). Moreover, the nuclear sizes in LBC specimens were larger than those in conventional specimens. In 62.9% of the MALT-L and all DLBCL specimens, large nuclei were present in > 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Conclusions Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. PMID:29597203

Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

NASA Technical Reports Server (NTRS)

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.

Artificial engineering of secondary lymphoid organs.

PubMed

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.

Characteristics of Helicobacter pylori-positive and Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma and their influence on clinical outcome.

PubMed

Choi, Yoon Jin; Kim, Nayoung; Paik, Jin Ho; Kim, Jung Mogg; Lee, Sang Hyub; Park, Young Soo; Hwang, Jin-Hyeok; Kim, Jin-Wook; Jeong, Sook-Hyang; Lee, Dong Ho; Jung, Hyun Chae

2013-06-01

To compare clinicopathologic and molecular characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma depending on Helicobacter pylori positivity and to find out a predictive factor for unresponsiveness to Helicobacter pylori eradication therapy in Korea. A total of 53 Helicobacter pylori-positive and 13 negative mucosa-associated lymphoid tissue lymphoma patients were enrolled, and tissues from 21 patients were investigated to examine the presence of t(11;18)(q21;q21) with fluorescence in situ hybridization. Clinicopathologic features such as the endoscopic appearance, dominant site of lesion, depth of invasion, clinical stage, and the existence of MALT1 gene rearrangement were compared between these two groups. Fifty-six patients who underwent H. pylori eradication therapy were divided into responder and nonresponder groups. The two groups were analyzed to calculate odds ratios for resistance to the eradication. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma patients averaged a more advanced clinical stage than H. pylori-positive (p = .023) patients. The frequency of t(11;18)/API2-MALT1 did not differ between H. pylori-positive (45.5%) and H. pylori-negative cases (55.6%). Thirty-eight of 51 (74.5%) H. pylori-positive patients achieved complete regression after the eradication, while 2 of 5 (40%) H. pylori-negative patients obtained regression. Presence of lesions in both distal and proximal parts of stomach (p = .041) and bearing of t(11;18)(q21;q21) (p = .007) were predictors for nonresponsiveness for H. pylori eradication. Helicobacter pylori eradication could be performed as a primary therapy regardless of H. pylori status, and assessing t(11;18)/API2-MALT1 would be considered after failure to remission by H. pylori eradication. © 2013 John Wiley & Sons Ltd.

Rhinovirus inactivation by nasal tissues treated with virucide.

PubMed

Hayden, G F; Gwaltney, J M; Thacker, D F; Hendley, J O

1985-04-01

Rhinovirus colds may be transmitted by hand-to-hand contact followed by self-inoculation of nasal and/or conjunctival mucosa with virus contaminating the fingertips. The purpose of this study was to determine whether impregnation of nasal tissues with virucidal compounds could prevent rhinovirus from passing through the tissue and thus provide a means of preventing hand contamination during nose blowing. Paper tissues treated with a combination of citric acid, malic acid, and sodium laruryl sulfate were compared to placebo tissues containing sodium saccharin. Recovery of infectious virus was significantly reduced by passage of the virus-containing medium through virucidal versus placebo tissue (1/18 vs. 17/18 respectively, P less than 0.001, Fisher exact test). The virucidal effect of treated tissues was demonstrated for multiple rhinovirus serotypes suspended in either cell culture medium or nasal mucus. Virus contained in mucus from infected volunteers was also inactivated.

Inflammation-induced formation of fat-associated lymphoid clusters

PubMed Central

Bénézech, Cécile; Kruglov, Andrei A.; Loo, Yunhua; Nakamura, Kyoko; Zhang, Yang; Nayar, Saba; Jones, Lucy H.; Flores-Langarica, Adriana; McIntosh, Alistair; Marshall, Jennifer; Barone, Francesca; Besra, Gurdyal; Miles, Katherine; Allen, Judith E.; Gray, Mohini; Kollias, George; Cunningham, Adam F.; Withers, David R.; Toellner, Kai Michael; Jones, Nick D.; Veldhoen, Marc; Nedospasov, Sergei A.; McKenzie, Andrew N.J.; Caamaño, Jorge H.

2015-01-01

Fat-associated lymphoid clusters (FALCs) are a recently discovered type of lymphoid tissue associated with visceral fat. Here we show that distribution of FALCs was heterogeneous with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 B cells in the peritoneal cavity through high expression of the chemokine CXCL13 and supported B cell proliferation and germinal center differentiation during peritoneal immune challenges. FALC formation was induced by inflammation, which triggered recruitment of myeloid cells that express tumor necrosis factor (TNF) necessary for TNF receptor-signaling in stromal cells. CD1d-restricted Natural killer T (NKT) cells were likewise required for inducible formation of FALCs. Thus, FALCs support and coordinate innate B and T cell activation during serosal immune responses. PMID:26147686

Salivary gland mucosa-associated lymphoid tissue lymphoma in 2 patients with Sjögren's syndrome: clinical and sonographic features with pathological correlation.

PubMed

Lewis, Khari; Vandervelde, Clive; Grace, Richard; Ramesar, Keith; Williams, Michael; Howlett, David C

2007-02-01

We report 2 cases of mucosa-associated lymphoid tissue lymphoma of the salivary glands, complicating Sjögren's syndrome. The sonographic and histological features are described in depth. The use of sonography as a diagnostic aid in such patients is discussed. (c) 2006 Wiley Periodicals, Inc.

Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue and signet ring cell carcinoma, synchronous collision tumour of the stomach: a case report.

PubMed

George, Smiley Annie; Junaid, T A

2014-01-01

To report a rare case of synchronous marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) signet ring cell carcinoma occurring as a collision tumour in the stomach. A 53-year-old man was diagnosed initially with signet ring cell carcinoma of the stomach. The microscopy of the subsequent total gastrectomy revealed a collision tumour of MALT lymphoma and signet ring cell carcinoma associated with Helicobacter pylori gastritis. This case highlighted the importance of a careful evaluation of the accompanying lymphoid population in the biopsy samples of gastric adenocarcinoma and underlined the need for multiple endoscopic biopsies to detect these rare synchronous tumours. © 2013 S. Karger AG, Basel.

Gastric Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue and Signet Ring Cell Carcinoma, Synchronous Collision Tumour of the Stomach: A Case Report

PubMed Central

George, Smiley Annie; Junaid, T.A.

2014-01-01

Objective To report a rare case of synchronous marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) signet ring cell carcinoma occurring as a collision tumour in the stomach. Clinical Presentation and Intervention A 53-year-old man was diagnosed initially with signet ring cell carcinoma of the stomach. The microscopy of the subsequent total gastrectomy revealed a collision tumour of MALT lymphoma and signet ring cell carcinoma associated with Helicobacter pylori gastritis. Conclusion This case highlighted the importance of a careful evaluation of the accompanying lymphoid population in the biopsy samples of gastric adenocarcinoma and underlined the need for multiple endoscopic biopsies to detect these rare synchronous tumours. PMID:24247357

Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

PubMed

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.

Primary Mucosa-associated Lymphoid Tissue Lymphoma Metachronously Involving Esophagus and Stomach.

PubMed

Byun, Seung Joo; Kang, Hyoun Woo; Cha, Joo Kyoung; Ryoo, Soo Ryeong; Lee, Jeong Hyeon; Kim, Do Yeon; Kim, Eo Jin

2016-05-25

Mucosa-associated lymphoid tissue (MALT) lymphoma is found in various organs as extranodal B cell lymphoma. The gastro-intestinal tract is the most commonly involved extranodal site in MALT lymphoma. However, primary esophageal MALT lymphoma is very rare. In addition, few cases with metachronous gastric involvement have been reported. A 55-year-old man was diagnosed with MALT lymphoma by surveillance esop hagogastroduodenoscopy. A 5 cm esophageal submucosal tumor-like lesion was incidentally revealed by screening esophagogastroduodenoscopy two years prior. Esophagogastroduodenoscopy showed a cylin-drically elongated submucosal mass with normal overlying mucosa in the mid esophagus. He underwent surgery to confirm the diagnosis. The pathologic diagnosis was esophageal MALT lymp homa. He was treated with radiation, which achieved complete remission. Esophagogastroduodenoscopy and chest computed tomography were performed every three to six months, with no evidence of recurrence for 18 months. After 21 months, severa l elevated gastric erosions were found on the great curvature and posterior sides of the midbody and confirmed as MALT lymphoma pathologically. Here we report a case with MALT lymphoma metachronously involving the esophagus and stomach.

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

NASA Technical Reports Server (NTRS)

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.

Innate lymphoid cells in tissue homeostasis and diseases

PubMed Central

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

2017-01-01

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. PMID:28878863

Innate lymphoid cells in tissue homeostasis and diseases.

PubMed

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.

Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

PubMed

Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

2014-12-01

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma

PubMed Central

Wang, Hong-Ping; Zhu, Yong-Liang; Shao, Wei

2013-01-01

Helicobacter pylori (H. pylori) infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue (MALT). Increasing evidence shows that eradication of H. pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission. The eradication of H. pylori is the standard care for patients with gastric MALT lymphoma. Cytotoxin-associated gene A (CagA) protein, one of the most extensively studied H. pylori virulence factors, is strongly associated with the gastric MALT lymphoma. CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races. After being translocated into B lymphocytes via type IV secretion system, CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and -independent manners and/or some other pathways, and thereby promotes lymphomagenesis. A variety of proteins including p53 and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA. Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma. PMID:24363512

Different T-bet expression patterns characterize particular reactive lymphoid tissue lesions.

PubMed

Jöhrens, K; Anagnostopoulos, I; Dürkop, H; Stein, H

2006-03-01

To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels. Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection. In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes. Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.

Suppression of HIV Replication by Lymphoid Tissue CD8+ Cells Correlates with the Clinical State of HIV-Infected Individuals

NASA Astrophysics Data System (ADS)

Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.

1996-11-01

Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

Viral-associated lymphoid proliferations☆

PubMed Central

Pittaluga, Stefania

2013-01-01

The histological spectrum of viral-associated lymphoid proliferations is quite broad, ranging from reactive lymphadenitis to atypical proliferations mimicking classical Hodgkin lymphoma or non-Hodgkin lymphoma. Virally associated reactive lesions can appear quite alarming on histological examination, because of direct (cytopathic) and indirect viral-induced changes eliciting a polymorphic cellular host response. In addition, the atypical lymphoid proliferation may show aberrant phenotypic features as well as restricted/clonal gene immunoglobulin or T-cell receptor rearrangements, further complicating the interpretation. In order to achieve an accurate diagnosis, it is important to be aware of the clinical history, including family history and ethnic background, clinical presentation, symptoms, and extent of the disease. Among the clinical data, particular emphasis should be placed on serology and viral load studies, and the use of immunosuppressive drugs. The clinical course and outcome vary greatly, from an indolent, self-limited to aggressive clinical course, blurring at times the distinction between neoplastic and reactive proliferations. It is now recognized that immunosenescence also plays a significant role in the development of these viral-associated lymphoid proliferations, and new entities have been described in recent years. In this review we discuss mostly Epstein–Barr virus-associated viral proliferations that may be confused with lymphomas, which the practicing pathologist may encounter. PMID:23537914

Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

PubMed Central

Todorovic, Milena; Balint, Bela; Jevtic, Miodrag; Suvajdzic, Nada; Ceric, Amela; Stamatovic, Dragana; Markovic, Olivera; Perunicic, Maja; Marjanovic, Slobodan; Krstic, Miodrag

2008-01-01

AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%. CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival. PMID:18416467

Primary esophageal mucosa-associated lymphoid tissue lymphoma diagnosed by using stacked forceps biopsy.

PubMed

Lee, D S; Ahn, Y C; Eom, D W; Lee, S J

2016-10-01

Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case. © 2015 International Society for Diseases of the Esophagus.

Low lymphatic vessel density associates with chronic rhinosinusitis with nasal polyps.

PubMed

Luukkainen, A; Seppälä, M; Renkonen, J; Renkonen, R; Hagstrő M, J; Huhtala, H; Rautiainen, M; Myller, J; Paavonen, T; Ranta, A; Torkkeli, T; Toppila-Salmi, S

2017-06-01

Chronic rhinosinusitis with and without nasal polyps (CRSwNP and CRSsNP) and antrochoanal polyps (ACP) are different upper airway inflammation phenotypes with different pathomechanisms. In order to understand the development of tissue edema, the present study aimed to evaluate lymphatic vessel density in CRSsNP, CRSwNP and ACP. 120 retrospective nasal and maxillary sinus specimens were stained immunohistochemically with a von Willebrand factor polyclonal antibody recognizing vascular and lymphatic endothelium, and with a podoplanin monoclonal antibody recognizing lymphatic endothelium. Vessels were studied by microscopy in a blinded fashion, and the vessel density and the relative density of lymphatic vessels were calculated. Patient characteristic factors and follow-up data of in average 9 years were collected from patient records. In the nasal cavity, the low absolute and relative density of vessels and of lymphatic vessels was associated with CRSwNP and ACP tissues compared to control inferior turbinate. This was observed also in the inflammatory hotspot area. In the maxillary sinus, lower absolute and relative density of lymphatic vessels associated with the CRSwNP phenotype. High lymphatic vessel density in polyp tissue associated with the need for revision CRS-surgery. As a conclusion, low density of lymphatic vessels distinguished patients with CRSwNP not only in the hotspot area of polyp tissue, but also in maxillary sinus mucosa. Yet, higher lymphatic vessel density seems to associate with polyp recurrence. Further studies are still needed to explore if formation of nasal polyps could be diminished by intranasal therapeutics affecting lymphangiogenesis.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with amyloid deposition: a clinicopathologic case series.

PubMed

Ryan, Russell J H; Sloan, J Mark; Collins, A Bernard; Mansouri, Jaleh; Raje, Noopur S; Zukerberg, Lawrence R; Ferry, Judith A

2012-01-01

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature B-cell neoplasm that typically follows an indolent clinical course. Amyloid deposition associated with MALT lymphoma is uncommon. We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of similar clinical stage.

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

PubMed

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.

Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Wang, Hong-Ping; Zhu, Yong-Liang; Shao, Wei

2013-12-07

Helicobacter pylori (H. pylori) infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue (MALT). Increasing evidence shows that eradication of H. pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission. The eradication of H. pylori is the standard care for patients with gastric MALT lymphoma. Cytotoxin-associated gene A (CagA) protein, one of the most extensively studied H. pylori virulence factors, is strongly associated with the gastric MALT lymphoma. CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races. After being translocated into B lymphocytes via type IV secretion system, CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and -independent manners and/or some other pathways, and thereby promotes lymphomagenesis. A variety of proteins including p53 and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA. Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.

Recurrent gastric perforation as a late complication of radiotherapy for mucosa-associated lymphoid tissue lymphoma of the stomach.

PubMed

Otsuka, Taiga; Noda, Takahiro; Yokoo, Masako; Ibaraki, Kazuo

2008-01-01

Radiation therapy can be used to treat Helicobacter pylori-negative or eradication-refractory extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of the stomach. We report a case of gastric perforation which occurred more than 1 year after the completion of radiotherapy for H. pylori eradication-refractory gastric MALT lymphoma, and then recurred shortly afterwards. This was considered to be a late complication of radiation toxicity. Although gastric perforation due to radiotherapy has been reported very rarely in the past, even in advanced disease, this case shows that perforation can develop in patients with superficial disease and can relapse.

Migration and Tissue Tropism of Innate Lymphoid Cells

PubMed Central

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

Innate lymphoid cells in secondary lymphoid organs.

PubMed

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.

Livestock-Associated, Antibiotic-Resistant Staphylococcus aureus Nasal Carriage and Recent Skin and Soft Tissue Infection among Industrial Hog Operation Workers

PubMed Central

Nadimpalli, Maya; Stewart, Jill R.; Pierce, Elizabeth; Pisanic, Nora; Love, David C.; Hall, Devon; Larsen, Jesper; Carroll, Karen C.; Tekle, Tsigereda; Perl, Trish M.

2016-01-01

Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (≤3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers’ use of face masks to prevent nasal carriage of these bacteria warrant further investigation. PMID:27851746

Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue.

PubMed

Steere, A C; Duray, P H; Butcher, E C

1988-04-01

Using monoclonal antibodies to spirochetal antigenes and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer subset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD-bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present. Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA-DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.

[A case of mucosa-associated lymphoid tissue lymphoma with penicillin allergy successfully treated with levofloxacin, minomycin and rabeprazole].

PubMed

Konno, Tomoko; Motoori, Shigeatsu; Iwamoto, Nozomi; Miyazawa, Tomoe; Saito, Shigeyo; Kitagawa, Naoko; Saisho, Hiromitsu; Furuse, Junji; Itabashi, Masayuki

2010-10-01

A 52-year-old Japanese woman was referred to our Institute because of Helicobacter pylori(H. pylori)-positive gastric mucosa-associated lymphoid tissue(MALT)lymphoma. Since she had a penicillin allergy, we could not eradicate H. pylori using the standard triple therapy including amoxicillin. Additionally, H. pylori was resistant to both clarithromycin and metronidazole. So she was treated with minomycin (MINO), levofloxacin (LVFX), and rabeprazole (RPZ) based on a drug sensitivity test. MINO+LVFX+RPZ appear to be a promising, appropriate, and well-tolerated eradication regimen for H. pylori demonstrating resistance to both clarithromycin and metronidazole, and for patients who are allergic to penicillin.

[A case of a collision tumor comprising mucosa-associated lymphoid tissue lymphoma and early gastric cancer].

PubMed

Isosaka, Mai; Adachi, Takeya; Iida, Tomoya; Mitsuhashi, Kei; Tanaka, Michihiro; Kondou, Yoshihiro; Suzuki, Takashi; Tanuma, Tokuma; Kasai, Kiyoshi

2014-07-01

A 60-year-old woman underwent upper gastrointestinal endoscopy for an abnormality identified during routine examination. The lower gastric corpus showed a type 0-I elevated lesion with a faded mucosa and an area of converging mucosal folds in contact with the lesion. Biopsy indicated the former to be a high-grade adenoma and the latter to be a mucosa-associated lymphoid tissue (MALT) lymphoma. At the same time, Helicobacter pylori infection was diagnosed. Eradication therapy was administered to manage the MALT lymphoma; this resulted in improvement after 3 months. Endoscopic submucosal dissection was performed for the elevated lesion, and subsequent histopathology showed contact between the MALT lymphoma and gastric cancer. Therefore, the patient was diagnosed with a collision tumor. Concurrent cancers are increasingly reported and should be considered during examination.

The interbranchial lymphoid tissue likely contributes to immune tolerance and defense in the gills of Atlantic salmon.

PubMed

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.

Soft tissue nasal asymmetry as an indicator of orofacial cleft predisposition.

PubMed

Zhang, Charles; Miller, Steven F; Roosenboom, Jasmien; Wehby, George L; Moreno Uribe, Lina M; Hecht, Jacqueline T; Deleyiannis, Frederic W B; Christensen, Kaare; Marazita, Mary L; Weinberg, Seth M

2018-06-01

The biological relatives of offspring with nonsyndromic orofacial clefts have been shown to exhibit distinctive facial features, including excess asymmetry, which are hypothesized to indicate the presence of genetic risk factors. The significance of excess soft tissue nasal asymmetry in at-risk relatives is unclear and was examined in the present study. Our sample included 164 unaffected parents from families with a history of orofacial clefting and 243 adult controls. Geometric morphometric methods were used to analyze the coordinates of 15 nasal landmarks collected from three-dimensional facial surface images. Following generalized Procrustes analysis, Procrustes ANOVA and MANOVA tests were applied to determine the type and magnitude of nasal asymmetry present in each group. Group differences in mean nasal asymmetry were also assessed via permutation testing. We found that nasal asymmetry in both parents and controls was directional in nature, although the magnitude of the asymmetry was greater in parents. This was confirmed with permutation testing, where the mean nasal asymmetry was significantly different (p < .0001) between parents and controls. The asymmetry was greatest for midline structures and the nostrils. When subsets of parents were subsequently analyzed and compared (parents with bilateral vs. unilateral offspring; parents with left vs. right unilateral offspring), each group showed a similar pattern of asymmetry and could not be distinguished statistically. Thus, the side of the unilateral cleft (right vs. left) in offspring was not associated with the direction of the nasal asymmetry in parents. © 2018 Wiley Periodicals, Inc.

Collision of EBV-associated gastric carcinoma and primary gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in the remnant stomach.

PubMed

Akiba, Jun; Nakane, Tomoyuki; Arakawa, Fumiko; Ohshima, Koichi; Yano, Hirohisa

2010-02-01

Reported herein is a case of EBV-associated gastric carcinoma with primary gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 69-year-old Japanese man was found to have an ulcer lesion in his stomach on endoscopy, and a biopsy indicated malignancy. He underwent gastrectomy. Microscopically the tumor had features typical of lymphoepithelioma-like carcinoma. The neoplastic epithelial cells proliferated in a trabecular fashion. On in situ hybridization for EBV-encoded RNA, positive signals were observed in most neoplastic epithelial cells. Numerous lymphocytes surrounded the neoplastic epithelial cells. In the stroma, numerous lymphocytes with mild atypia were positive for CD20 and CD79a. In addition, monoclonal proliferation of B cells was confirmed on polymerase chain reaction for IgH. These findings supported MALT lymphoma. The coexistence of EBV-associated gastric carcinoma and MALT lymphoma is extremely rare.

Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

PubMed

Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

2018-06-26

The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells.

PubMed

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.

[Peculiarities of surgical interventions in the nasopharynx of patients presenting with lymphoid tissue hypertrophy and exudative otitis media].

PubMed

Zav'ialov, F N; Salikov, A V

2011-01-01

A total of 118 patients presenting with exudative otitis media and lymphoid tissue hypertrophy in the nasopharynx were examined and treated. A classification of different variants of lymphoid tissue hypertrophy and pharyngeal tonsil hypertrophy was developed and used as a basis to plan the strategy of surgical interventions in the nasopharynx.

Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

PubMed

Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

2016-12-01

H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Distinct gene expression profiles characterize the histopathological stages of disease in Helicobacter-induced mucosa-associated lymphoid tissue lymphoma

PubMed Central

Mueller, Anne; O'Rourke, Jani; Grimm, Jan; Guillemin, Karen; Dixon, Michael F.; Lee, Adrian; Falkow, Stanley

2003-01-01

Long-term colonization of humans with Helicobacter pylori can cause the development of gastric B cell mucosa-associated lymphoid tissue lymphoma, yet little is known about the sequence of molecular steps that accompany disease progression. We used microarray analysis and laser microdissection to identify gene expression profiles characteristic and predictive of the various histopathological stages in a mouse model of the disease. The initial step in lymphoma development is marked by infiltration of reactive lymphocytes into the stomach and the launching of a mucosal immune response. Our analysis uncovered molecular markers of both of these processes, including genes coding for the immunoglobulins and the small proline-rich protein Sprr 2A. The subsequent step is characterized histologically by the antigen-driven proliferation and aggregation of B cells and the gradual appearance of lymphoepithelial lesions. In tissues of this stage, we observed increased expression of genes previously associated with malignancy, including the laminin receptor-1 and the multidrug-resistance channel MDR-1. Finally, we found that the transition to destructive lymphoepithelial lesions and malignant lymphoma is marked by an increase in transcription of a single gene encoding calgranulin A/Mrp-8. PMID:12552104

Nattokinase, profibrinolytic enzyme, effectively shrinks the nasal polyp tissue and decreases viscosity of mucus.

PubMed

Takabayashi, Tetsuji; Imoto, Yoshimasa; Sakashita, Masafumi; Kato, Yukinori; Tokunaga, Takahiro; Yoshida, Kanako; Narita, Norihiko; Ishizuka, Tamotsu; Fujieda, Shigeharu

2017-10-01

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often comorbid with asthma and resistant to therapeutic interventions. We recently reported that excessive fibrin deposition caused by impairment of fibrinolysis might play pivotal role in forming nasal polyp. Nattokinase (NK), a serine protease produced by Bacillus subtilis, has been reported to be a strong fibrinolytic enzyme. NK could be a promising drug candidate for use in the treatment of both CRSwNP and asthma. The objective of this study was to investigate the effects of NK on nasal polyp tissues from patients with CRSwNP. The nasal discharge from patients with CRSwNP and sputum from subjects with asthma were also used to investigate whether NK influences the viscosity of mucus. To examine the effects on NK on nasal polyp tissues, pieces of nasal polyps were incubated either with saline or NK (10-1000 FU/ml) at 37 °C for 24 h. We assessed the presence of fibrin in nasal polyp tissue incubated with NK by means of immunohistochemistry. To examine the effects of NK on nasal discharge and sputum from patients with CRSwNP and asthma, respectively, were incubated with NK solution at 37 °C for 1 h. NK effectively shrinks the nasal polyp tissue through fibrin degradation. We also found that the viscosity of the nasal discharge and sputum from patients with CRSwNP and asthma, respectively, was significantly reduced by incubation with NK solution. NK may be an effective alternative therapeutic option in patients with CRSwNP and comorbid asthma by causing fibrin degradation. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

The Innate Lymphoid Cell Precursor.

PubMed

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.

Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues

PubMed Central

Rhee, Ki-Jong; Jasper, Paul J.; Sethupathi, Periannan; Shanmugam, Malathy; Lanning, Dennis; Knight, Katherine L.

2005-01-01

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express VHn allotype immunoglobulin (Ig)M. Within weeks, the number of VHn B cells decreases, whereas VHa allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from VHn to VHa B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the VHn to VHa repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of VHa B cells. By comparing amino acid sequences of VHn and VHa Ig, we identified a putative VH ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with VHa B cells results in their selective expansion. PMID:15623575

Bone marrow involvement is rare in superficial gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Park, Jae Yong; Kim, Sang Gyun; Kim, Joo Sung; Jung, Hyun Chae

2016-01-01

The initial staging work-up of gastric mucosa-associated lymphoid tissue (MALT) lymphoma includes bone marrow examination. Since gastric MALT lymphoma is mostly detected in early stages with the national cancer screening programme in Korea, bone marrow is rarely involved. To investigate the incidence of bone marrow involvement in gastric MALT lymphomas and the role of bone marrow examination for an initial staging work-up. Patients diagnosed with gastric MALT lymphoma at Seoul National University Hospital from January 2005 to July 2014 were enrolled. Clinical databases of the patients were retrospectively reviewed. Out of 105 patients, 91 (86.7%) were classified as stage IE1. Among these patients, 78 patients with Helicobacter pylori infection underwent eradication therapy, and complete remission was achieved in 74 cases (94.9%). Twelve out of 13 patients (92.3%) without H. pylori infection underwent radiotherapy or surgery and all achieved complete remission. Bone marrow involvement was proven in only one patient (1.0%). Bone marrow involvement was rare in patients with only superficial gastric MALT lymphoma without extragastric invasion. Further studies are warranted to identify the risk factors of bone marrow involvement in gastric MALT lymphoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Neonatal thymectomy favors Helicobacter pylori-promoted gastric mucosa-associated lymphoid tissue lymphoma lesions in BALB/c mice.

PubMed

Chrisment, Delphine; Dubus, Pierre; Chambonnier, Lucie; Hocès de la Guardia, Anaïs; Sifré, Elodie; Giese, Alban; Capone, Myriam; Khairallah, Camille; Costet, Pierre; Rousseau, Benoît; Hubert, Christophe; Burlen-Defranoux, Odile; Varon, Christine; Bandeira, Antonio; Mégraud, Francis; Lehours, Philippe

2014-08-01

Neonatal thymectomy in BALB/c mice has been described as a model of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). By using this experimental system, we screened, for the first time to our knowledge, Helicobacter pylori GML-associated strains for their capacity to promote disease. A cohort of BALB/c mice underwent thymectomy at day 3 after birth (d3Tx). Successful thymic ablation was evaluated by the degree of lymphopenia in blood samples collected at 4 weeks of age. d3Tx and non-thymectomized controls were infected with either GML strains (B38 or B47) or control strains (SS1 or TN2GF4). Gastric samples collected at 6, 12, and 18 months after infection were studied for bacteria content, and submitted to histological, immunochemical, molecular, and immunological analyses. Severe gastric inflammation was only observed in d3Tx mice. In these animals, the gastric lamina propria was infiltrated with lymphoid cells organized in follicles composed of B cells with few infiltrating T cells. PCR of D/J IgH gene segments proved the monoclonality of infiltrating B cells, which strongly correlated with the presence of lymphoepithelial lesions. B-cell infiltrates were particularly prominent in mice infected with the B47-GML strain. No pathological changes were detected in noninfected d3Tx mice. We identified new H. pylori isolates adapted to the mouse stomach with high potential of GML development, which is only revealed in hosts rendered lymphopenic by neonatal thymic ablation. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Absence of tissue factor is characteristic of lymphoid malignancies of both T- and B-cell origin

PubMed Central

Cesarman-Maus, Gabriela; Braggio, Esteban; Lome-Maldonado, Carmen; Morales-Leyte, Ana Lilia; Fonseca, Rafael

2014-01-01

Summary Background Thrombosis is a marker of poor prognosis in individuals with solid tumors. The expression of tissue factor (TF) on the cell surface membrane of malignant cells is a pivotal molecular link between activation of coagulation, angiogenesis, metastasis, aggressive tumor behavior and poor survival. Interestingly, thrombosis is associated with shortened survival in solid, but not in lymphoid neoplasias. Objectives We sought to study whether the lack of impact of thrombosis on survival in lymphoid neoplasias could be due to a lack of tumor-derived TF expression. Methods We analyzed TF gene (F3) expression in lymphoid (N=114), myeloid (N=49) and solid tumor (N=856) cell lines using the publicly available dataset from the Broad-Novartis Cancer Cell Line Encyclopedia (http://www.broadinstitute.org/ccle/home), and in 90 patient-derived lymphoma samples. TF protein expression was studied by immunohistochemistry (IHC). Results In sharp contrast to wide F3 expression in solid tumors (74.2%), F3 was absent in all low and high grade T- and B-cell lymphomas, and in most myeloid tumors, except for select acute myeloid leukemias with monocytic component. IHC confirmed the absence of TF protein in all indolent and high-grade B-cell (0/90) and T-cell (0/20) lymphomas, and acute leukemias (0/11). Conclusions We show that TF in lymphomas does not derive from the malignant cells, since these do not express either F3 or TF protein. Therefore, it is unlikely that thrombosis in patients with lymphoid neoplasms is secondary to tumor-derived tissue factor. PMID:24491425

The airway antigen sampling system: respiratory M cells as an alternative gateway for inhaled antigens.

PubMed

Kim, Dong-Young; Sato, Ayuko; Fukuyama, Satoshi; Sagara, Hiroshi; Nagatake, Takahiro; Kong, Il Gyu; Goda, Kaoru; Nochi, Tomonori; Kunisawa, Jun; Sato, Shintaro; Yokota, Yoshifumi; Lee, Chul Hee; Kiyono, Hiroshi

2011-04-01

In this study, we demonstrated a new airway Ag sampling site by analyzing tissue sections of the murine nasal passages. We revealed the presence of respiratory M cells, which had the ability to take up OVA and recombinant Salmonella typhimurium expressing GFP, in the turbinates covered with single-layer epithelium. These M cells were also capable of taking up respiratory pathogen group A Streptococcus after nasal challenge. Inhibitor of DNA binding/differentiation 2 (Id2)-deficient mice, which are deficient in lymphoid tissues, including nasopharynx-associated lymphoid tissue, had a similar frequency of M cell clusters in their nasal epithelia to that of their littermates, Id2(+/-) mice. The titers of Ag-specific Abs were as high in Id2(-/-) mice as in Id2(+/-) mice after nasal immunization with recombinant Salmonella-ToxC or group A Streptococcus, indicating that respiratory M cells were capable of sampling inhaled bacterial Ag to initiate an Ag-specific immune response. Taken together, these findings suggest that respiratory M cells act as a nasopharynx-associated lymphoid tissue-independent alternative gateway for Ag sampling and subsequent induction of Ag-specific immune responses in the upper respiratory tract.

Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

PubMed

Macías, J; Japón, M A; Leal, M; Sáez, C; Pineda, J A; Segura, D I; Ortega, J; Lissen, E

2001-12-07

The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

Blood Flukes Exploit Peyer's Patch Lymphoid Tissue to Facilitate Transmission from the Mammalian Host

PubMed Central

Turner, Joseph D.; Narang, Priyanka; Coles, Mark C.; Mountford, Adrian P.

2012-01-01

Schistosomes are blood-dwelling parasitic helminths which produce eggs in order to facilitate transmission. Intestinal schistosomes lay eggs in the mesenteries, however, it is unclear how their eggs escape the vasculature to exit the host. Using a murine model of infection, we reveal that Schistosoma mansoni exploits Peyer's Patches (PP) gut lymphoid tissue as a preferential route of egress for their eggs. Egg deposition is favoured within PP as a result of their more abundant vasculature. Moreover, the presence of eggs causes significant vascular remodeling leading to an expanded venule network. Egg deposition results in a decrease in stromal integrity and lymphoid cellularity, including secretory IgA producing lymphocytes, and the focal recruitment of macrophages. In mice lacking PP, egg excretion is significantly impaired, leading to greater numbers of ova being entrapped in tissues and consequently, exacerbated morbidity. Thus, we demonstrate how schistosomes directly facilitate transmission from the host by targeting lymphoid tissue. For the host, PP-dependency of egg egress represents a trade-off, as limiting potentially life-threatening morbidity is balanced by loss of PP structure and perturbed PP IgA production. PMID:23308064

The Role of Antigenic Drive and Tumor-Infiltrating Accessory Cells in the Pathogenesis of Helicobacter-Induced Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Mueller, Anne; O’Rourke, Jani; Chu, Pauline; Chu, Amanda; Dixon, Michael F.; Bouley, Donna M.; Lee, Adrian; Falkow, Stanley

2005-01-01

Gastric B-cell lymphoma of mucosa-associated lymphoid tissue type is closely linked to chronic Helicobacter pylori infection. Most clinical and histopathological features of the tumor can be reproduced by prolonged Helicobacter infection of BALB/c mice. In this study, we have addressed the role of antigenic stimulation in the pathogenesis of the lymphoma by experimental infection with Helicobacter felis, followed by antibiotic eradication therapy and subsequent re-infection. Antimicrobial therapy was successful in 75% of mice and led to complete histological but not “molecular” tumor remission. Although lympho-epithelial lesions disappeared and most gastric lymphoid aggregates resolved, transcriptional profiling revealed the long-term mucosal persistence of residual B cells. Experimental re-introduction of Helicobacter led to very rapid recurrence of the lymphomas, which differed from the original lesions by higher proliferative indices and more aggressive behavior. Immunophenotyping of tumor cells revealed massive infiltration of lesions by CD4+ T cells, which express CD28, CD69, and interleukin-4 but not interferon-γ, suggesting that tumor B-cell proliferation was driven by Th 2-polarized, immunocompetent, and activated T cells. Tumors were also densely colonized by follicular dendritic cells, whose numbers were closely associated with and predictive of treatment outcome. PMID:16127158

Promoter methylation, mRNA expression of goat tumor‑associated genes and mRNA expression of DNA methyltransferase in enzootic nasal tumors.

PubMed

Quan, Zifang; Ye, Ni; Hao, Zhongxiang; Wen, Caifang; Liao, Hong; Zhang, Manli; Luo, Lu; Cao, Sanjie; Wen, Xintian; Wu, Rui; Yan, Qigui

2015-10-01

The aim of the present study was to investigate the promoter methylation status and mRNA expression of goat tumor‑associated genes, in addition to the mRNA expression of DNA methyltransferase genes in enzootic nasal tumors (ENT). Methylation‑specific polymerase chain reaction and SYBR Green reverse transcription‑quantitative polymerase chain reaction were used to detect the methylation status and the mRNA expression levels of DNA methyltransferases (DNMTs), O6‑methylguanine‑DNA methyltransferase (MGMT), the tumor suppressor genes P73, P53, GADD45G, CHFR and THBS1, the transcription factor CEBPA, the proto‑oncogenes KRAS, NRAS and C‑myc and EGFR in 24 nasal tumor tissue samples and 20 normal nasal epithelia tissue samples. The associations between promoter methylation and DNMT, and promoter methylation and mRNA expression of the genes were analyzed. The results indicated that the expression levels of DNMT1 increased by 56% compared with those in normal nasal epithelial tissues, while MGMT, DNMT3a and DNMT3b had similar expression levels in the two tissue types. The expression levels of P53 decreased by 36.8% and those of THBS1 by 43%, while C‑myc increased by 2.9‑fold and CEBPA by 2‑fold compared with that in normal nasal epithelial tissues. GADD45G, P73, CHFR and NRAS were observed to have similar expression levels in the two tissue types. However, no expression was observed for EGFR and KRAS. CHFR, GADD45G and THBS1 were identified to be methylated in tumor suppressor genes. The methylation expression rate of the CHFR gene was ~60% in the two tissue types and for THBS1 it was 100% in the nasal tumor tissues as opposed to 20% in the normal nasal epithelial tissues. The exhaustive methylation expression rate of GADD45G was 62.5% and the partial methylation expression rate was 37.5% in nasal tumor tissue, while no methylation was observed in normal nasal epithelial tissues. C‑myc was the only gene identified to be methylated amongst proto�

Neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terasawa, Masao; Nagata, Kisaburo; Kobayashi, Yoshiro

2008-12-12

Antigen-transporting cells take up pathogens, and then migrate from sites of inflammation to secondary lymphoid tissues to induce an immune response. Among antigen-transporting cells, dendritic cells (DCs) are believed to be the most potent and professional antigen-presenting cells that can stimulate naive T cells. However, the cells that transport antigens, tumor cell antigens in particular, have not been clearly identified. In this study we have analyzed what types of cells transport tumor cell antigens to secondary lymphoid tissues. We show that neutrophils, monocytes and macrophages but not DCs engulf X-irradiated P388 leukemic cells after their injection into the peritoneal cavity,more » and that neutrophils and monocytes but not macrophages migrate to the parathymic lymph nodes (pLN), the blood, and then the spleen. The monocytes in the pLN comprise Gr-1{sup -} and Gr-1{sup +} ones, and some of these cells express CD11c. Overall, this study demonstrates that neutrophils and monocytes transport tumor cell antigens from the peritoneal cavity to secondary lymphoid tissues.« less

[Prognostic impact of Helicobacter pylori infection and eradication therapy in gastric mucosa-associated lymphoid tissue lymphoma].

PubMed

Park, Sang Hyuk; Chi, Hyun-Sook; Park, Seo-Jin; Jang, Seongsoo; Park, Chan-Jeoung; Huh, Joo Ryung

2010-12-01

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is associated with Helicobacter pylori infection and H. pylori eradication is used as its first-line therapy. However, controversies exist about the prognostic value of H. pylori infection in these patients. We evaluated the prognostic impact of H. pylori infection and eradication therapy in gastric MALT lymphoma. A total of 292 patients diagnosed with MALT lymphoma since 2000 were analysed. MALT lymphoma was diagnosed with tissue biopsy and H. pylori infection was diagnosed with hematoxylin-eosin and additional Warthin-Starry stains on tissue sections. Clinical variables such as bone marrow (BM) involvement, multiorgan involvement, tumor stage at diagnosis, and remission were obtained with retrospective review of electronic medical records. Non-gastric MALT lymphoma patients showed higher multiorgan involvement rates (26.6% vs. 9.6%, P<0.001) and higher proportion of stage ≥ 3 (27.7% vs. 16.7%, P=0.029) than gastric cases. Regarding gastric MALT lymphoma, patients with H. pylori infection at diagnosis showed significantly less BM (2.1% vs. 21.8%, P<0.001) and multiorgan involvement rates (6.3% vs. 18.2%, P=0.011) than those without infection. But there was no significant difference in remission rates between them. In contrast, those with successful H. pylori eradication therapy showed significantly higher remission rates (81.0% vs. 30.8%, P<0.001) than those with failure. Non-gastric MALT lymphoma patients showed worse prognosis compared to gastric cases. As for remission rates in patients with gastric MALT lymphoma, successful H. pylori eradication therapy could be a good prognostic factor even if H. pylori infection was present at diagnosis.

Impaired airway mucociliary function reduces antigen-specific IgA immune response to immunization with a claudin-4-targeting nasal vaccine in mice.

PubMed

Suzuki, Hidehiko; Nagatake, Takahiro; Nasu, Ayaka; Lan, Huangwenxian; Ikegami, Koji; Setou, Mitsutoshi; Hamazaki, Yoko; Kiyono, Hiroshi; Yagi, Kiyohito; Kondoh, Masuo; Kunisawa, Jun

2018-02-13

Vaccine delivery is an essential element for the development of mucosal vaccine, but it remains to be investigated how physical barriers such as mucus and cilia affect vaccine delivery efficacy. Previously, we reported that C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) targeted claudin-4, which is expressed by the epithelium associated with nasopharynx-associated lymphoid tissue (NALT), and could be effective as a nasal vaccine delivery. Mice lacking tubulin tyrosine ligase-like family, member 1 (Ttll1-KO mice) showed mucus accumulation in nasal cavity due to the impaired motility of respiratory cilia. Ttll1-KO mice nasally immunized with C-CPE fused to pneumococcal surface protein A (PspA-C-CPE) showed reduced PspA-specific nasal IgA responses, impaired germinal center formation, and decreased germinal center B-cells and follicular helper T cells in the NALT. Although there was no change in the expression of claudin-4 in the NALT epithelium in Ttll1-KO mice, the epithelium was covered by a dense mucus that prevented the binding of PspA-C-CPE to NALT. However, administration of expectorant N-acetylcysteine removed the mucus and rescued the PspA-specific nasal IgA response. These results show that the accumulation of mucus caused by impaired respiratory cilia function is an interfering factor in the C-CPE-based claudin-4-targeting nasal vaccine.

Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination.

PubMed

Li, Hui-Shan; Singh, Bijay; Park, Tae-Eun; Hong, Zhong-Shan; Kang, Sang-Kee; Cho, Chong-Su; Choi, Yun-Jaie

2015-12-01

Mucosal vaccination of protein as an antigen requires appropriate delivery or adjuvant systems to deliver antigen to mucosal immune cells efficiently and generate valid immune responses. For successful nasal immunization, the obstacles imposed by the normal process of mucociliary clearance which limits residence time of applied antigens and low antigen delivery to antigen presenting cells (APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain efficient immune responses. The potential adjuvant ability of Man-TEM for intranasal immunization was confirmed by in vitro and in vivo experiments. In mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and mucosal sIgA than the soluble OVA group due to the specific recognition of MR of APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit systemic and mucosal immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Tandem alternative polyadenylation events of genes in non-eosinophilic nasal polyp tissue identified by high-throughput sequencing analysis

PubMed Central

TIAN, PENG; LI, JIE; LIU, XIANG; LI, YUXI; CHEN, MEIHENG; MA, YUN; ZHENG, YI QING; FU, YONGGUI; ZOU, HUA

2014-01-01

Nasal polyps (NP) is highly associated with the disorder of immune cells. Alternative polyadenylation (APA) produces mRNA isoforms with different length of 3′-untranslated region (UTR) and regulates gene expression. It has been proven that this APA-mediated regulation of 3′UTR length is an immune-associated phenomenon. The aim of this study was to investigate the genome-wide alternative tandem 3′UTR length switching events in non-eosinophilic nasal polyp tissue. Thirteen patients diagnosed as having non-eosinophilic nasal polyps were included in this study. Nasal polyp tissue and control mucosa were collected during surgery. The 3′ end library of cDNA was constructed. The recovered libraries were sequenced with second sequencing technology, and the sequencing data were analyzed by an in-house bioinformatics pipeline. Tandem 3′UTR length switching between samples was detected by a test of linear trend alternative to independence. We found a significant alteration in the tandem 3′UTR length in 1,920 genes in nasal polyp samples. Functional annotation results showed that several gene ontology (GO) terms were enriched in the list of genes with switched APA sites, including regulation of transcription, macromolecule catabolic localization and mRNA processing. The results suggested that APA-mediated alternative 3′UTR regulation plays an important role in the post-transcriptional regulation of gene expression in non-eosinophilic nasal polyps. PMID:24715051

Naegleria fowleri immunization modifies lymphocytes and APC of nasal mucosa.

PubMed

Carrasco-Yepez, M M; Campos-Rodríguez, R; Reséndiz-Albor, A A; Peña-Juárez, C; Contis-Montes de Oca, A; Arciniega-Martínez, I M; Bonilla-Lemus, P; Rojas-Hernandez, S

2018-03-01

We investigated whether intranasal immunization with amoebic lysates plus cholera toxin modified the populations of T and B lymphocytes, macrophages and dendritic cells by flow cytometry from nose-associated lymphoid tissue (NALT), cervical lymph nodes (CN), nasal passages (NP) and spleen (SP). In all immunized groups, the percentage of CD4 was higher than CD8 cells. CD45 was increased in B cells from mice immunized. We observed IgA antibody-forming cell (IgA-AFC) response, mainly in NALT and NP. Macrophages from NP and CN expressed the highest levels of CD80 and CD86 in N. fowleri lysates with either CT or CT alone immunized mice, whereas dendritic cells expressed high levels of CD80 and CD86 in all compartment from immunized mice. These were lower than those expressed by macrophages. Only in SP from CT-immunized mice, these costimulatory molecules were increased. These results suggest that N. fowleri and CT antigens are taking by APCs, and therefore, protective immunity depends on interactions between APCs and T cells from NP and CN. Consequently, CD4 cells stimulate the differentiation from B lymphocytes to AFC IgA-positive; antibody that we previously found interacting with trophozoites in the nasal lumen avoiding the N. fowleri attachment to nasal epithelium. © 2017 John Wiley & Sons Ltd.

Positive selection of the peripheral B cell repertoire in gut-associated lymphoid tissues.

PubMed

Rhee, Ki-Jong; Jasper, Paul J; Sethupathi, Periannan; Shanmugam, Malathy; Lanning, Dennis; Knight, Katherine L

2005-01-03

Gut-associated lymphoid tissues (GALTs) interact with intestinal microflora to drive GALT development and diversify the primary antibody repertoire; however, the molecular mechanisms that link these events remain elusive. Alicia rabbits provide an excellent model to investigate the relationship between GALT, intestinal microflora, and modulation of the antibody repertoire. Most B cells in neonatal Alicia rabbits express V(H)n allotype immunoglobulin (Ig)M. Within weeks, the number of V(H)n B cells decreases, whereas V(H)a allotype B cells increase in number and become predominant. We hypothesized that the repertoire shift from V(H)n to V(H)a B cells results from interactions between GALT and intestinal microflora. To test this hypothesis, we surgically removed organized GALT from newborn Alicia pups and ligated the appendix to sequester it from intestinal microflora. Flow cytometry and nucleotide sequence analyses revealed that the V(H)n to V(H)a repertoire shift did not occur, demonstrating the requirement for interactions between GALT and intestinal microflora in the selective expansion of V(H)a B cells. By comparing amino acid sequences of V(H)n and V(H)a Ig, we identified a putative V(H) ligand binding site for a bacterial or endogenous B cell superantigen. We propose that interaction of such a superantigen with V(H)a B cells results in their selective expansion.

Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

PubMed

Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

2012-06-01

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

Why Innate Lymphoid Cells?

PubMed

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.

Breathing life into dinosaurs: tackling challenges of soft-tissue restoration and nasal airflow in extinct species.

PubMed

Bourke, Jason M; Porter, W M Ruger; Ridgely, Ryan C; Lyson, Tyler R; Schachner, Emma R; Bell, Phil R; Witmer, Lawrence M

2014-11-01

The nasal region plays a key role in sensory, thermal, and respiratory physiology, but exploring its evolution is hampered by a lack of preservation of soft-tissue structures in extinct vertebrates. As a test case, we investigated members of the "bony-headed" ornithischian dinosaur clade Pachycephalosauridae (particularly Stegoceras validum) because of their small body size (which mitigated allometric concerns) and their tendency to preserve nasal soft tissues within their hypermineralized skulls. Hypermineralization directly preserved portions of the olfactory turbinates along with an internal nasal ridge that we regard as potentially an osteological correlate for respiratory conchae. Fossil specimens were CT-scanned, and nasal cavities were segmented and restored. Soft-tissue reconstruction of the nasal capsule was functionally tested in a virtual environment using computational fluid dynamics by running air through multiple models differing in nasal soft-tissue conformation: a bony-bounded model (i.e., skull without soft tissue) and then models with soft tissues added, such as a paranasal septum, a scrolled concha, a branched concha, and a model combining the paranasal septum with a concha. Deviations in fluid flow in comparison to a phylogenetically constrained sample of extant diapsids were used as indicators of missing soft tissue. Models that restored aspects of airflow found in extant diapsids, such as appreciable airflow in the olfactory chamber, were judged as more likely. The model with a branched concha produced airflow patterns closest to those of extant diapsids. These results from both paleontological observation and airflow modeling indicate that S. validum and other pachycephalosaurids could have had both olfactory and respiratory conchae. Although respiratory conchae have been linked to endothermy, such conclusions require caution in that our re-evaluation of the reptilian nasal apparatus indicates that respiratory conchae may be more widespread

Bioengineering of Artificial Lymphoid Organs.

PubMed

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.

Immunological Characterization of Intraocular Lymphoid Follicles in a Spontaneous Recurrent Uveitis Model.

PubMed

Kleinwort, Kristina J H; Amann, Barbara; Hauck, Stefanie M; Feederle, Regina; Sekundo, Walter; Deeg, Cornelia A

2016-08-01

Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues. Ectopic lymphoid tissues were located preferentially in the iris, ciliary body, and retina at the ora serrata of horses with naturally-occurring ERU. The majority of cells in the tertiary lymphoid follicles were T cells with a scattered distribution of B cells and PNA+ cells interspersed. A fraction of T cells was additionally positive for memory cell marker CD45RO. Almost all cells coexpressed CD166, a molecule associated with activation and transmigration of T cells into inflamed tissues. Several transcription factors that govern immune cell responses were detectable in the tertiary lymphoid follicles, among them Zap70, TFIIB, GATA3, and IRF4. A high expression of the phosphorylated signal transducers and activators of transcription (STAT) proteins 1 and 5 were found at the margin of the structures. Cellular composition and structural organization of these inflammation-associated tertiary lymphoid tissue structures and the expression of markers of matured T and B cells point to highly organized adaptive immune responses in these follicles in spontaneous recurrent uveitis.

Innate lymphoid cells and their stromal microenvironments.

PubMed

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.

Bioengineering of Artificial Lymphoid Organs

PubMed Central

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. PMID:27437136

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

PubMed Central

Powell, J J; Ainley, C C; Harvey, R S; Mason, I M; Kendall, M D; Sankey, E A; Dhillon, A P; Thompson, R P

1996-01-01

Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:8675092

Bone and Soft Tissue Nasal Angles Discrepancies and Overlying Skin Thickness: A Computed Tomography Study.

PubMed

Alharethy, Sami; Alohali, Sama; Alquniabut, Ibrahim; Jang, Yong Ju

2018-04-11

The aim of this study was to derive the normal values for bone and soft tissue nasal angles as well as the overlying skin thickness and to attempt to determine the correlation between differences in bone and soft tissue angles and overlying skin thickness in Middle Eastern patients. Three-dimensional cephalometric analysis was performed for 100 patients who underwent computed tomography of the paranasal sinuses. The nasofrontal angle, pyramidal angle-nasal root, pyramidal angle-tip of the nasal bone, and overlying skin thickness were measured, and the results were analyzed according to sex, age, and body mass index (BMI). All soft tissue angles were significantly larger than the bone angles, with the mean difference being 11.62°, 30.80°, and 27.05° for the nasofrontal angle (P = 0.000), pyramidal angle-nasal root (P = 0.000), and pyramidal angle-tip of the nasal bone (P = 0.000), respectively. The mean overlying skin thickness was 3.89 ± 1.48 mm at the nasion, 1.16 ± 0.6 mm at the rhinion, and 2.93 ± .97 mm at the nasal tip. Differences in the nasofrontal angle were strongly correlated with the skin thickness at the nasion (P = 0.001). A simple clinical exam of the soft tissue nasal angles does not reflect the underlying bone angles that will be encountered during rhinoplasty. BMI does not influence nasal shape, and rhinoplasty surgery should take into account the ethnic group, age, and sex of the patient. Surgeons should leave a minor skeletal hump at the end of the nasal bone for Middle Eastern patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

PubMed

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.

Efficacy of Positron Emission Tomography/Computed Tomography in Gastric Mucosa-associated Lymphoid Tissue Lymphoma.

PubMed

Hwang, Jin Won; Jee, Sam Ryong; Lee, Sang Heon; Kim, Ji Hyun; Seol, Sang Yong; Lee, Seok Mo

2016-04-25

This study evaluated the diagnostic efficacy of fluorine-18 fluorodeoxyglucose PET/CT (F-18 FDG PET/CT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma and examined the association between FDG avidity and the clinical factors affecting lesions. Among the patients diagnosed with gastric MALT lymphoma, 16 who underwent a PET/CT for gastric MALT lymphoma were semi-quantitatively and qualitatively tested for FDG avidity of lesions in the stomach. Retrospectively collected data was analyzed to investigate the clinicoradiological factors and endoscopic findings between the patients with positive F-18 FDG PET/CT scans and those with negative scans. Eight of the 16 patients showed FDG avidity. When comparing the size of lesions in the stomach, the patients with FDG avidity had significantly larger lesions than those without (28.8 mm vs. 15.0 mm, p=0.03). The FDG-avid group has a significantly higher rate of positive CT scans than the non-avid group (75% vs. 13%, p=0.03). According to the endoscopic finding of the lesions, FDG avidity was pronounced with 75% of the protruding tumors, and 100% of the erosive-ulcerative types, which are a type of depressed tumors. When gastric MALT lymphoma is large, when lesions are found using abdominal CT scans, and the macroscopic appearance of a lesion is that of a protruding tumor or erosive-ulcerative type of depressed tumor, there is a high probability that such patients may have a positive F-18 FDG PET/CT scan.

Implications of Airflow Dynamics and Soft-Tissue Reconstructions for the Heat Exchange Potential of Dinosaur Nasal Passages

NASA Astrophysics Data System (ADS)

Bourke, Jason Michael

This study seeks to restore the internal anatomy within the nasal passages of dinosaurs via the use of comparative anatomical methods along with computational fluid dynamic simulations. Nasal airway descriptions and airflow simulations are described for extant birds, crocodylians, and lizards. These descriptions served as a baseline for airflow within the nasal passages of diapsids. The presence of shared airflow and soft-tissue properties found in the nasal passages of extant diapsids, were used to restore soft tissues within the airways of dinosaurs under the assumption that biologically unfeasible airflow patterns (e.g., lack of air movement in olfactory recess) can serve as signals for missing soft tissues. This methodology was tested on several dinosaur taxa. Restored airways in some taxa revealed the potential presence and likely shape of nasal turbinates. Heat transfer efficiency was tested in two dinosaur species with elaborated nasal passages. Results of that analysis revealed that dinosaur noses were efficient heat exchangers that likely played an integral role in maintaining cephalic thermoregulation. Brain cooling via nasal expansion appears to have been necessary for dinosaurs to have achieved their immense body sizes without overheating their brains.

Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

PubMed Central

Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

2013-01-01

Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

PubMed

Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-12-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.

Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells

PubMed Central

Cautivo, Kelly M.; Molofsky, Ari B.

2016-01-01

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 (T2DM). In contrast, recent studies have highlighted the regulation and function of immune cells in lean, healthy adipose tissue, 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, adipose tissue “browning”, and systemic insulin sensitivity, protecting against obesity-induced metabolic dysfunction and T2DM. In particular, group 2 innate lymphoid cells (ILC2s) are integral regulators of AT type 2 immunity, producing the cytokines IL-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 ILC2 cells and type 2 immunity in adipose tissue metabolism and homeostasis. PMID:27120716

Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

PubMed Central

Mindt, Barbara C.; Fritz, Jörg H.; Duerr, Claudia U.

2018-01-01

Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung. PMID:29760695

Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.

PubMed

Mindt, Barbara C; Fritz, Jörg H; Duerr, Claudia U

2018-01-01

Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

Subcutaneous dissemination pattern in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma.

PubMed

Jonak, Constanze; Troch, Marlene; Kiesewetter, Barbara; Lukas, Julius; Müllauer, Leonhard; Jäger, Ulrich; Chott, Andreas; Raderer, Markus

2012-05-01

Mucosa-associated lymphoid tissue (MALT) lymphoma is among the most common forms of extranodal lymphomas, but little is known about subcutaneous involvement in patients with non-primary cutaneous marginal zone lymphomas. Patients with MALT lymphoma diagnosed and treated at our institution between 1999 and 2010 were analyzed for subcutaneous deposits from MALT lymphoma diagnosed in another organ. Histological, clinical and genetic findings were assessed. Among 216 patients with MALT lymphoma, 12 had subcutaneous deposits from MALT lymphoma (5.5%). In two patients, these lesions were present at diagnosis, while they constituted the site of relapse at an interval between 5 to 144 months in the remaining cases. Interestingly, nine of the 12 patients with subcutaneous deposits had originally been diagnosed with MALT lymphoma of the ocular adnexa (total number=51; 20%), and the other three had MALT lymphoma in the breast (total number=5; 60%). None of the patients with gastric (n=86), salivary gland (n=32) or pulmonary (n=19) MALT lymphomas had subcutaneous involvement during a median follow-up time of 87 months (range; 4 to 119 months). Our data show that subcutaneous MALT lymphoma involvement is a rare event in patients with prior non-cutaneous extranodal marginal zone lymphoma. However, it seems to be almost exclusively associated with MALT lymphoma of the ocular adnexa and the breast, suggesting as yet undefined interactions between potentially embryonically related organ systems.

Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells.

PubMed

Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J

2013-01-01

After scald burn-injury, the intestinal immune system responds to maintain immune balance. In this regard CD4+T cells in Gut-Associated Lymphoid Tissues (GALT), like mesenteric lymph nodes (MLN) and Peyer's patches (PP) respond to avoid immune suppression following major injury such as burn. Therefore, we hypothesized that the gut CD4+T cells become dysfunctional and turn the immune homeostasis towards depression of CD4+ T cell-mediated adaptive immune responses. In the current study we show down regulation of mucosal CD4+ T cell proliferation, IL-2 production and cell surface marker expression of mucosal CD4+ T cells moving towards suppressive-type. Acute burn-injury lead to up-regulation of regulatory marker (CD25+), down regulation of adhesion (CD62L, CD11a) and homing receptor (CD49d) expression, and up-regulation of negative co-stimulatory (CTLA-4) molecule. Moreover, CD4+CD25+ T cells of intestinal origin showed resistance to spontaneous as well as induced apoptosis that may contribute to suppression of effector CD4+ T cells. Furthermore, gut CD4+CD25+ T cells obtained from burn-injured animals were able to down-regulate naïve CD4+ T cell proliferation following adoptive transfer of burn-injured CD4+CD25+ T cells into sham control animals, without any significant effect on cell surface activation markers. Together, these data demonstrate that the intestinal CD4+ T cells evolve a strategy to promote suppressive CD4+ T cell effector responses, as evidenced by enhanced CD4+CD25+ T cells, up-regulated CTLA-4 expression, reduced IL-2 production, tendency towards diminished apoptosis of suppressive CD4+ T cells, and thus lose their natural ability to regulate immune homeostasis following acute burn-injury and prevent immune paralysis.

Comparison of serologic evaluation via agar gel immunodiffusion and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs.

PubMed

Pomrantz, Jill S; Johnson, Lynelle R; Nelson, Richard W; Wisner, Erik R

2007-05-01

To compare the sensitivity and specificity of serologic evaluation and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs. Prospective study. 58 dogs with nasal discharge and 26 healthy dogs. Dogs with nasal discharge were anesthetized and underwent computed tomography and rhinoscopy; nasal tissues were collected for histologic examination and fungal culture. Sera were assessed for antibodies against Aspergillus spp (healthy dog sera were used as negative control specimens). Nasal aspergillosis was diagnosed in dogs that had at least 2 of the following findings: computed tomographic characteristics consistent with aspergillosis, fungal plaques detected during rhinoscopy, and histologically detectable fungal hyphae in nasal tissue. Histologic characteristics of malignancy were diagnostic for neoplasia. Without evidence of neoplasia or fungal disease, nonfungal rhinitis was diagnosed. Among the 58 dogs, 21 had nasal aspergillosis, 25 had nonfungal rhinitis, and 12 had nasal neoplasia. Fourteen aspergillosis-affected dogs and 1 dog with nonfungal rhinitis had serum antibodies against Aspergillus spp. Fungal culture results were positive for Aspergillus spp only for 17 dogs with aspergillosis. With regard to aspergillosis diagnosis, sensitivity, specificity, and positive and negative predictive values were 67%, 98%, 93%, and 84%, respectively, for serum anti-Aspergillus antibody determination and 81%, 100%, 100%, and 90%, respectively, for fungal culture. Results suggest that seropositivity for Aspergillus spp and identification of Aspergillus spp in cultures of nasal tissue are highly suggestive of nasal aspergillosis in dogs; however, negative test results do not rule out nasal aspergillosis.

Co-Occurrence of Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Long-Standing Hashimoto Thyroiditis

PubMed Central

Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-01-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

PubMed Central

Ager, Ann

2017-01-01

The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

PubMed

Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

2015-11-01

Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

PubMed Central

Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

1995-01-01

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

ClinicalTrials.gov

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

Distinguishing rhinitis and nasal neoplasia by radiography.

PubMed

Russo, M; Lamb, C R; Jakovljevic, S

2000-01-01

To compare the incidence of radiographic signs in dogs with rhinitis and primary nasal neoplasia and to assess the performance of observers for distinguishing these conditions, the nasal radiographs of 72 dogs with either rhinitis (n = 42) or primary nasal neoplasia (n = 30) were examined by two independent observers using custom-designed forms to record their interpretations. Rhinitis was associated with a higher incidence of focal or multifocal lesions, localised soft tissue opacities, lucent foci, and a lack of frontal sinus involvement. Neoplasia was associated with soft tissue opacities and loss of turbinate detail that affected the entire ipsilateral nasal cavity, signs of invasion of the bones surrounding the nasal cavity, and soft tissue/fluid opacities within the ipsilateral frontal sinus. The signs with the highest positive predictive value (PPV) for rhinitis were absence of frontal sinus lesions and lucent foci in nasal cavity (PPV of each 82%), and invasion of surrounding bones for neoplasia (PPV 88%). There were no significant differences in the position of the lesion within the nasal cavity, incidence of unilateral versus bilateral lesions, calcified lesions, or absence of teeth. There was moderate agreement between observers about the diagnosis (kappa 0.59). Areas (SE) under ROC curves were 0.94 (0.03) and 0.96 (0.03) for observers A and B, respectively (not significantly different; P = 0.68). These results indicate a high accuracy for radiologists examining dogs with nasal diseases. Differentiation of rhinitis and nasal neoplasia should be based on finding combinations of radiologic signs that together have a high PPV. Differences in interpretation between experienced observers in this study suggest that certain signs are potential sources of error.

Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients.

PubMed Central

Castrillo, J M; Montalban, C; Obeso, G; Piris, M A; Rivas, M C

1992-01-01

Clinico-pathological features of 56 patients with primary gastric lymphoma were evaluated retrospectively. All cases were regraded according to a classification of Isaacson et al into high grade and low grade B-cell mucosa associated lymphoid tissue lymphoma. A third group of mixed grade was recognised in 11 patients with low grade who also had occasional areas of high grade. Low grade and mixed grade patients had a 100% actuarial survival at 156 months, which was significantly better (p < 0.01) than that of 52% for patients with high grade disease. Different treatment methods--surgery, chemotherapy, or a combination of both--did not significantly affect survival. Low grade tumours occurred mainly in men with a history of several years, and who presented with non-specific gastric symptoms without remarkable exploratory or laboratory findings: most patients were in stage IE-IIE and achieved remission and cure. High grade can have a shorter history, systemic symptoms, abnormal exploratory and laboratory findings, gastric tumour masses, stage IV disease, and a worse outcome. The only significant prognostic factors for survival were the type of lymphoma and stage IV disease. These findings support the Isaacson classification system which separates two extreme groups of gastric lymphomas with different morphology, behaviour, and outcome. The presence of limited areas of high grade in a specimen showing low grade does not change the outcome but suggests that primary gastric lymphoma forms a continuum between these extreme types. PMID:1446850

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

PubMed Central

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

Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps.

PubMed

Tan, Bruce K; Li, Quan-Zhen; Suh, Lydia; Kato, Atsushi; Conley, David B; Chandra, Rakesh K; Zhou, Jinchun; Norton, James; Carter, Roderick; Hinchcliff, Monique; Harris, Kathleen; Peters, Anju; Grammer, Leslie C; Kern, Robert C; Mohan, Chandra; Schleimer, Robert P

2011-12-01

Chronic rhinosinusitis (CRS) with nasal polyps is an inflammatory condition of the nasal passage and paranasal sinuses characterized by T(H)2-biased inflammation with increased levels of B-cell activating factor of the TNF family (BAFF), B lymphocytes, and immunoglobulins. Because high levels of BAFF are associated with autoimmune diseases, we assessed for evidence of autoimmunity in patients with CRS. The objective of this study was to investigate the presence of autoantibodies in sinonasal tissue from patients with CRS. Standardized nasal tissue specimens were collected from patients with CRS and control subjects and assayed for immunoglobulin production, autoantibody levels, tissue distribution of immunoglobulins, and binding potential of antibodies in nasal tissue with a multiplexed autoantibody microarray, ELISA, and immunofluorescence. Increased levels of several specific autoantibodies were found in nasal polyp tissue in comparison with levels seen in control tissue and inflamed tissue from patients with CRS without nasal polyps (P < .05). In particular, nuclear-targeted autoantibodies, such as anti-dsDNA IgG and IgA antibodies, were found at increased levels in nasal polyps (P < .05) and particularly in nasal polyps from patients requiring revision surgery for recurrence. Direct immunofluorescence staining demonstrated diffuse epithelial and subepithelial deposition of IgG and increased numbers of IgA-secreting plasma cells not seen in control nasal tissue. Autoantibodies, particularly those against nuclear antigens, are present at locally increased levels in nasal polyps. The presence of autoantibodies suggests that the microenvironment of a nasal polyp promotes the expansion of self-reactive B-cell clones. Although the pathogenicity of these antibodies remains to be elucidated, the presence of increased anti-dsDNA antibody levels is associated with a clinically more aggressive form of CRS with nasal polyps requiring repeated surgery. Copyright © 2011

A definitive diagnosis of mucosa-associated lymphoid tissue lymphoma made at a second biopsy.

PubMed

Igarashi, Tsutomu; Shimizu, Akira; Yamaguchi, Hiroki; Fukushima, Yoshimitsu; Igarashi, Toru; Takahashi, Hiroshi

2013-01-01

A case of mucosa-associated lymphoid tissue (MALT) lymphoma, the most frequent of the various conjunctival lymphoproliferative disorders, in which the initial biopsy was inconclusive but the second biopsy provided a definitive diagnosis, is reported. A 26-year-old woman with a 3-month history of bilateral conjunctival swelling was referred by a local physician for suspected MALT lymphoma. A salmon-pink elastic swelling was found to involve both eyes and to extend from the lower palpebral conjunctiva to the bulbar conjunctiva. Tonsillar swelling was also found, and ophthalmologic (left eye) and otolaryngologic biopsies were therefore performed simultaneously under general anesthesia. The otolaryngologic diagnosis was chronic tonsillitis. Light microscope examination of the conjunctival tissue showed proliferation of lymphocytes and small aggregates of small to medium-sized atypical lymphocytes. On immunohistochemical studies, atypical lymphocytes were positive for CD20 and CD79a, but differentiation to plasmacytes was not prominent, and neither Dutcher bodies nor evidence of immunoglobulin light chain restriction was found. The results were not incompatible with MALT lymphoma but were not definitive. A second biopsy of the right eye was therefore performed 3 months later. Staining with hematoxylin and eosin showed proliferation of small lymphocytes and monocytoid B cells and differentiation to plasmacytes. The hyperplastic cells were positive for CD19, CD79a, and CD20, and their cytoplasm were positive for Bcl-2 and slightly positive for Bcl-6. Cells positive for CD38 were noted where differentiation to plasmacytes and immunoglobulin light chain κ restriction was evident on immunohistochemical studies and in situ hybridization. The Ki-67-positivity rate was approximately 5%. The results of paraffin-embedded tissue section fluorescence in situ hybridization were negative for MALT-1 (18q21). A diagnosis of MALT lymphoma was made, and treatment with rituximab was

F-18 FDG PET/CT findings in a patient with bilateral orbital and gastric mucosa-associated lymphoid tissue lymphomas.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Hiyama, Atsuto; Takeda, Koumei; Matsunaga, Naofumi

2009-09-01

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma is an uncommon disease, while the incidence is recently increasing. We describe the F-18 fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET/CT) findings in a case of bilateral orbital MALT lymphomas with a coexisting gastric lesion. Although only the lesion in the left orbit was initially identified on MR imaging, FDG PET/CT scan unexpectedly and additionally could identify the tiny lesion of the contralateral orbit and the gastric lesion. This patient received radiotherapy to all these lesions, with a combination of rituximab monoclonal antibody therapy. The follow-up PET/CT studies at 3, 6, and 9 months and 1.5 years after treatment showed regression or disappearance of all these FDG-avid lesions. Accurate localization and staging are crucial to select an adequate treatment in MALT lymphoma at any location. This case indicates the feasibility of FDG PET/CT scan for accurate localization and staging and also for monitoring treatment in patients with orbital MALT lymphoma.

Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station

PubMed Central

Fitzgerald, Wendy; Chen, Silvia; Walz, Carl; Zimmerberg, Joshua; Margolis, Leonid

2013-01-01

The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction. PMID:19609626

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis

PubMed Central

Donaldson, David S.; Else, Kathryn J.

2015-01-01

ABSTRACT Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the

Immunome differences between porcine ileal and jejunal Peyer's patches revealed by global transcriptome sequencing of gut-associated lymphoid tissues.

PubMed

Maroilley, T; Berri, M; Lemonnier, G; Esquerré, D; Chevaleyre, C; Mélo, S; Meurens, F; Coville, J L; Leplat, J J; Rau, A; Bed'hom, B; Vincent-Naulleau, S; Mercat, M J; Billon, Y; Lepage, P; Rogel-Gaillard, C; Estellé, J

2018-06-13

The epithelium of the intestinal mucosa and the gut-associated lymphoid tissues (GALT) constitute an essential physical and immunological barrier against pathogens. In order to study the specificities of the GALT transcriptome in pigs, we compared the transcriptome profiles of jejunal and ileal Peyer's patches (PPs), mesenteric lymph nodes (MLNs) and peripheral blood (PB) of four male piglets by RNA-Seq. We identified 1,103 differentially expressed (DE) genes between ileal PPs (IPPs) and jejunal PPs (JPPs), and six times more DE genes between PPs and MLNs. The master regulator genes FOXP3, GATA3, STAT4, TBX21 and RORC were less expressed in IPPs compared to JPPs, whereas the transcription factor BCL6 was found more expressed in IPPs. In comparison between IPPs and JPPs, our analyses revealed predominant differential expression related to the differentiation of T cells into Th1, Th2, Th17 and iTreg in JPPs. Our results were consistent with previous reports regarding a higher T/B cells ratio in JPPs compared to IPPs. We found antisense transcription for respectively 24%, 22% and 14% of the transcripts detected in MLNs, PPs and PB, and significant positive correlations between PB and GALT transcriptomes. Allele-specific expression analyses revealed both shared and tissue-specific cis-genetic control of gene expression.

Morphological and functional development of the interbranchial lymphoid tissue (ILT) in Atlantic salmon (Salmo salar L).

PubMed

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.

Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy.

PubMed

Yang, Hyo-Joon; Lim, Seon Hee; Lee, Changhyun; Choi, Ji Min; Yang, Jong In; Chung, Su Jin; Choi, Seung Ho; Im, Jong Pil; Kim, Sang Gyun; Kim, Joo Sung

2016-07-01

It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy.

IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.

PubMed

Briend, Emmanuel; Ferguson, G John; Mori, Michiko; Damera, Gautam; Stephenson, Katherine; Karp, Natasha A; Sethi, Sanjay; Ward, Christine K; Sleeman, Matthew A; Erjefält, Jonas S; Finch, Donna K

2017-08-22

Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.

Mouse Models for Assessing the Protective Efficacy of Lactobacillus gasseri SBT2055 against Helicobacter suis Infection Associated with the Development of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

PubMed

Matsui, Hidenori; Takahashi, Tetsufumi; Øverby, Anders; Murayama, Somay Yamagata; Yoshida, Haruno; Yamamoto, Yuji; Nishiyama, Keita; Seto, Yasuyuki; Takahashi, Takashi; Mukai, Takao; Nakamura, Masahiko

2015-08-01

Helicobacter suis strain TKY infection has been strongly associated with the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in a C57BL/6J mouse model. 1. C57BL/6J mice were intragastrically administered Lactobacillus strains once daily with 10(8)-10(9) colony-forming units (CFU), starting 2 days before intragastric infection with H. suis TKY (approximately 1 × 10(4) copies of 16S rRNA genes) or H. pylori Sydney strain 1 (SS1; 3 × 10(8) CFU) and continuing for 14 days after infection. 2. C57BL/6J mice were given powdered feed mixed with lyophilized L. gasseri SBT2055 (LG2055) cells (5 × 10(8) CFU/g), starting 2 weeks before intragastric infection with H. suis TKY and continuing 12 months after infection. 1. Among the 5 Lactobacillus strains that we examined, only LG2055 exhibited significantly preventive efficacy against both H. suis TKY and H. pylori SS1 at day 15 after infection. 2. Dietary supplementation with LG2055 protected mice from the formation of round protrusive lesions in the gastric fundus 12 months after infection with H. suis TKY, whereas such lesions had developed in the gastric fundus of nonsupplemented mice 12 months after infection. In addition, the formation of lymphoid follicles in gastric mucus layers was suppressed by dietary LG2055 at 3 months after infection. LG2055 administration is effective for suppressing the progression of gastric MALT lymphoma by reducing H. suis colonization. © 2015 John Wiley & Sons Ltd.

Multiparametric flow cytometry in the diagnosis and characterization of low-grade pulmonary mucosa-associated lymphoid tissue lymphomas.

PubMed

Zaer, F S; Braylan, R C; Zander, D S; Iturraspe, J A; Almasri, N M

1998-06-01

Primary mucosa associated lymphoid tissue (MALT) lymphomas are rare neoplasms that seem to have a better prognosis than nodal lymphomas. Morphologic diagnosis of these lesions may be difficult because of features that overlap with those of benign lymphoid infiltrates. In this study, we assessed the contribution of multi-parametric flow cytometry in demonstrating clonality and further characterizing pulmonary MALT lymphomas. Based on a clinical or pathologic suspicion of MALT-lymphoma, 3 transbronchial biopsies, 4 fine needle aspirates, 1 core needle biopsy, and 13 wedge excisions of lung were submitted fresh (unfixed) to our laboratory for evaluation. Among the 13 cases diagnosed as MALT lymphomas, B-cell monoclonality was established by identifying expression of a single immunoglobulin light chain on CD20 or CD19-positive cells in 12 cases. One case lacked expression of both light chains on B-cells. Of 11 lymphoma cases in which CD5 and CD10 surface antigens were assessed, no cases expressed CD10, and 1 case demonstrated weak CD5 expression. Nine of 10 cases studied were diploid and 1 case was hyperdiploid. All of the lymphomas displayed low (< or = 3%) S-phase fractions consistent with low grade processes. In 10 patients with short follow-up, none died of their disease and the majority had no evidence of lymphoma dissemination. In seven of the remaining eight cases, B-cells were polyclonal consistent with reactive processes. In one morphologically reactive case, flow cytometric analysis was unsuccessful because of poor cell viability. The pulmonary MALT lymphomas in this study represent a group of B-cell tumors with distinctive morphologic, immunophenotypic, and cell kinetic characteristics. Multi-parametric flow cytometry is useful for confirming B-cell monoclonality and illustrating an antigenic profile compatible with this diagnosis. Flow cytometry can be particularly helpful when working with small biopsies and cytologic samples with limited diagnostic

Whole blood and tissue fungal DNA quantification in the diagnosis of canine sino-nasal aspergillosis.

PubMed

Peeters, Dominique; Peters, Iain R; Helps, Chris R; Dehard, Sandrine; Day, Michael J; Clercx, Cécile

2008-04-01

Various combinations of tests are used to confirm the diagnosis of canine sino-nasal aspergillosis (SNA) because false-positive and false-negative results can occur with each test. Therefore, the aim of this study was to evaluate whether detection of fungal DNA in blood and nasal tissue samples was of value in the clinical diagnosis of this disease. Four groups were included in the study (dogs with SNA, lymphoplasmacytic rhinitis or nasal neoplasia, and control animals). Real-time PCR assays detecting DNA from all Penicillium and Aspergillus species (PenAsp assay) or species-specific DNA from A. fumigatus, A. terreus, A. flavus and A. niger were applied to whole blood and nasal tissue samples. Results obtained by PCR were compared between the groups. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) for fungal DNA detection were compared with those for alternative diagnostic procedures including histopathology, serology and fungal culture. Significantly more fungal DNA was detected by the PenAsp assay in tissue biopsies from dogs with SNA than in the three other groups. Sensitivity, specificity, PPV and NPV for this method were 1.00, 0.06, 0.32 and 1.00. A. fumigatus DNA was detected in seven tissue biopsies from dogs with SNA and in one biopsy from a dog with a nasal tumour. Sensitivity, specificity, PPV and NPV for this diagnostic test were 0.50, 0.97, 0.87 and 0.82. No significant difference was found between the groups with respect to the amount of DNA detected in blood by the PenAsp assay. Sensitivity, specificity, PPV and NPV for this method were 0.71, 0.24, 0.31 and 0.64. A. fumigatus DNA was detected in the blood of three dogs with SNA and sixteen dogs without SNA. Sensitivity, specificity, PPV and NPV for this diagnostic tool were 0.21, 0.45, 0.15 and 0.54. Detection of A. fumigatus DNA in nasal tissue had the highest specificity, PPV and NPV but sensitivity of this method was low. Detection of fungal DNA in whole blood was of

Radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma: long-term outcomes over 10 years.

PubMed

Ohkubo, Yu; Saito, Yoshihiro; Ushijima, Hiroki; Onishi, Masahiro; Kazumoto, Tomoko; Saitoh, Jun-Ichi; Kubota, Nobuko; Kobayashi, Hirofumi; Maseki, Nobuo; Nishimura, Yu; Kurosumi, Masafumi

2017-07-01

This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31-84). Fifteen patients were Helicobacter pylori-negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30-39.5 Gy). The median follow-up period was 121 months (range: 8-176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases. © Oxford University Press 2017.

Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps.

PubMed

Fritz, Stephen B; Terrell, Jeffrey E; Conner, Edward R; Kukowska-Latallo, Jolanta F; Baker, James R

2003-12-01

Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder. We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype. We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks. Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps. These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.

Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer

PubMed Central

Katakai, Tomoya

2012-01-01

The architecture of secondary lymphoid organs (SLOs) is supported by several non-hematopoietic stromal cells. Currently it is established that two distinct stromal subsets, follicular dendritic cells and fibroblastic reticular cells, play crucial roles in the formation of tissue compartments within SLOs, i.e., the follicle and T zone, respectively. Although stromal cells in the anlagen are essential for SLO development, the relationship between these primordial cells and the subsets in adulthood remains poorly understood. In addition, the roles of stromal cells in the entry of antigens into the compartments through some tissue structures peculiar to SLOs remain unclear. A recently identified stromal subset, marginal reticular cells (MRCs), covers the margin of SLOs that are primarily located in the outer edge of follicles and construct a unique reticulum. MRCs are closely associated with specialized endothelial or epithelial structures for antigen transport. The similarities in marker expression profiles and successive localization during development suggest that MRCs directly descend from organizer stromal cells in the anlagen. Therefore, MRCs are thought to be a crucial stromal component for the organization and function of SLOs. PMID:22807928

Bone marrow involvement is not associated with the clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma.

PubMed

Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Jung, Kyoungwon; Cho, Charles J; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho; Yoon, Dok Hyun

2016-08-01

Objective Bone marrow (BM) examination is recommended as part of the initial staging work-up in patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the clinical significance of BM involvement in gastric MALT lymphoma patients has not been evaluated. Materials and methods From November 1995 to September 2014, 496 subjects who were diagnosed with gastric MALT lymphoma and underwent BM examination were eligible to be included in this study. BM involvement was found in 33 patients (6.7%) by retrospective review, and after exclusions, the clinical outcomes of 28 patients with BM involvement and 412 patients without BM involvement were evaluated. Results When comparing the characteristics of patients, age (median 60 vs. 53 years, p = 0.007) and Helicobacter pylori infection rate (71.0% vs. 85.5%, p = 0.040) were different between patients with and without BM involvement, while the location, macroscopic findings, and depth of invasion were similar. The overall complete remission (CR) rate was 85.2% during a median follow-up period of 42 months (interquartile range, 23-66 months) and did not differ between the two groups (78.6 and 85.7%, p = 0.280). Eradication therapy was performed as the first-line treatment in 18 of the 28 patients (64.3%) with BM involvement, and CR was achieved in 13 patients (72.2%). Logistic regression analysis showed that age and location in the upper part of the stomach were factors related to remission failure. Conclusion Gastric MALT lymphoma has a favorable outcome, and eradication therapy can be justified in selected cases even with BM involvement, when these patients are closely monitored.

Reconstruction of Nasal Cleft Deformities Using Expanded Forehead Flaps: A Case Series.

PubMed

Ramanathan, Manikandhan; Sneha, Pendem; Parameswaran, Ananthnarayanan; Jayakumar, Naveen; Sailer, Hermann F

2014-12-01

Reconstruction of the nasal clefts is a challenging task considering the nasal anatomic complexity and their possible association with craniofacial defects. The reconstruction of these defects needs extensive amounts of soft tissue that warrant the use of forehead flaps. Often presence of cranial defects and low hairline compromise the amount of tissue available for reconstruction warrenting tissue expansion. To evaluate the efficacy of tissue expansion in reconstruction of congenital nasal clefts. 9 patients with congenital nasal clefts involving multiple sub units were taken up for nasal reconstruction with expanded forehead flaps. The average amount of expansion needed was 200 ml. The reconstruction was performed in 3 stages. Expanded forehead flaps proved to be best modality for reconstruction providing the skin cover needed for ala, columella and dorsum with minimal scarring at the donor site. Expansion of the forehead flap is a viable option for multiple sub unit reconstruction in congenital nasal cleft deformities.

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

PubMed

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

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

PubMed Central

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) F4 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 F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 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 F4 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 a

CD8 down-regulation and functional impairment of SIV-specific cytotoxic T lymphocytes in lymphoid and mucosal tissues during SIV infection.

PubMed

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

2013-06-01

Functional impairment of virus-specific T cells is a hallmark of HIV/SIV infection, but the underlying mechanisms of this dysfunction are not well understood. To address this, we simultaneously analyzed the expression and intensity of CD8 and inhibitory PD-1 on CTL in blood and lymphoid tissues in SIV-infected rhesus macaques. The intensity (mean channel fluorescence) of CD8 expression was transiently down-regulated in early SIV infection (10-14 dpi), despite an increase in CD8(+) T cell proliferation. In chronic infection, CD8 expression was maintained at low levels on CD8(+) T cells in all tissues. Interestingly, Gag-specific CTLs were clearly divided into CD8high- and CD8low-expressing populations in SIV-infected macaques, and CD8low Gag-specific cells increased with disease progression, especially in lymphoid tissues when compared with peripheral blood or in Gag-vaccinated controls. Moreover, the CD8low CTL population secreted lower levels of cytokines upon SIV antigen stimulation and exhibited lower proliferative capacity during infection compared with the CD8high CTL population. Meanwhile, intensity of PD-1 expression on Gag-specific CTL in chronic infection was significantly higher than in acute SIV infection, although the frequencies of PD-1+ Gag-specific cells were similar in acute and chronic stages. In summary, down-regulation of CD8 expression and higher expression of PD-1 on SIV-specific CTLs could coordinately attenuate SIV-specific CTL responses and their ability to recognize virus-infected target cells, especially in lymphoid tissues, resulting in failure to contain viremia, and continued persistence and replication of HIV in lymphoid tissue reservoirs.

Virological and immunological responses to raltegravir and dolutegravir in the gut-associated lymphoid tissue of HIV-infected men and women.

PubMed

Weber, Michael D; Andrews, Elizabeth; Prince, Heather A; Sykes, Craig; Rosen, Elias P; Bay, Camden; Shaheen, Nicholas J; Madanick, Ryan D; Dellon, Evan S; De Paris, Kristina; Nelson, Julie Ae; Gay, Cynthia L; Kashuba, Angela Dm

2018-05-01

Raltegravir (RTG) and dolutegravir (DTG) have different pharmacokinetic patterns in the gastrointestinal tract. To determine if this results in pharmacodynamic differences, we compared HIV RNA, HIV DNA, and immunological markers in gut-associated lymphoid tissue (GALT) of HIV-infected participants receiving RTG or DTG with tenofovir+emtricitabine (TDF/FTC). GALT specimens from the terminal ileum, splenic flexure, and rectum were obtained by colonoscopy at a single time point in 20 adults treated with RTG (n=10) or DTG (n=10) with HIV RNA <50 copies/mL. Flow cytometry, drug concentrations, and HIV RNA and DNA were analyzed in tissue. CD4/8 + T cells were tested for γδ TCR, and markers of T cell activation and exhaustion. Data are reported as median (Q1,Q3). 15 men and 5 women were enrolled. There was no difference in time since HIV diagnosis for those on RTG [9.5 (4-22) yr] and DTG [17 (1-24) yr] (p = 0.6), although time on RTG [5.4 (2.3-6.7) yr] was greater than DTG [1.0 (0.1-1.5) yr] (P < 0.001). Concentrations of RTG and DTG in rectal tissue (RT) were similar to previous reports: median tissue:plasma ratio was 11.25 for RTG and 0.44 for DTG. RNA:DNA ratios were [1.14 (0.18-5.10)] for the RTG group and [0.90 (0.30-18.87)] for the DTG group (p = 0.95). No differences (p ≥ 0.1) between CD4 + and CD8 + T cell markers were found. RTG produced higher tissue exposures than DTG, but no significant differences in GALT HIV RNA, DNA, or most immunologic markers were observed.

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

ClinicalTrials.gov

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

Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells

PubMed Central

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. PMID:29467768

Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

PubMed

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.

Hypogammaglobulinemia associated with nodular lymphoid hyperplasia of the intestine and pernicious anaemia.

PubMed

Ouakaa-Kchaou, Asma; Trad, Dorra; Boussourra, Houda; Bibani, Norsaf; Elloumi, Héla; Kochlef, Asma; Gargouri, Dalila; Kharrat, Jamel

2015-11-01

Nodular lymphoid hyperplasia of the gastrointestinal tract, recurrent acute pulmonary infections and autoimmune disease are well-recognized complications of common variable immunodeficiency. We aimed to focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid and hyperplasia of the gastrointestinal tract coexisting with hypogammaglobulinemia. We report the case of nodular lymphoid hyperplasia associated with pernicious anaemia in a young man with hypogammaglobulinemia and a long history of pulmonary infections. The considerable point was a mismatch primary clinical diagnosis of familial adenomatous polyposis, due to prominent polyplike endoscopic appearance of the lesions throughout the digestive tract.

Isolation of Human Innate Lymphoid Cells.

PubMed

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.

Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo

NASA Technical Reports Server (NTRS)

Fitzgerald, Wendy; Sylwester, Andrew W.; Grivel, Jean-Charles; Lifson, Jeffrey D.; Margolis, Leonid B.

2004-01-01

Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

2014-03-01

Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortalmore » time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.« less

Leukaemia Evoked with 7,8,12-Trimethylbenz(a)Anthracene in Rat. III. Changes in Lymphoid Tissues

PubMed Central

Bird, C. C.; Mainzer, K.

1972-01-01

Profound changes in the level of certain dehydrogenase enzymes were observed in lymphoid tissues of rats involved by erythroblastic stem cell leukaemia. In lymphoid tissues free of leukaemic involvement, activity of malate dehydrogenase (MDH) always exceeded that of lactate dehydrogenase (LDH). In those which contained substantial infiltrates of leukaemic cells, activity of LDH was increased while MDH activity was reduced. In leukaemic spleen significant changes were observed in the molecular forms of LDH; the proportion of LDH-5 (muscle-type LDH) was greatly increased while the other molecular forms were reduced. The spleen of rats with leukaemia exhibited a marked increase in the normal level of aerobic and anaerobic glycolysis but the rate of respiration was unchanged. The terminal stages of stem cell leukaemia in the rat are characterized by wide-spread leukaemic infiltration of liver and other tissues. Lymph node involvement, however, was found to be selective. Coeliac lymph nodes greatly exceeded other lymph node groups in their incidence of leukaemic involvement. It is considered that the selective nature of lymph node involvement in stem cell leukaemia derives from topographical considerations. PMID:5085676

Role of the Lymphotoxin/LIGHT System in the Development and Maintenance of Reticular Networks and Vasculature in Lymphoid Tissues

PubMed Central

Lu, Theresa T.; Browning, Jeffrey L.

2014-01-01

Lymphoid organs are meeting zones where lymphocytes come together and encounter antigens present in the blood and lymph or as delivered by cells migrating from the draining tissue bed. The exquisite efficiency of this process relies heavily on highly specialized anatomy to direct and position the various players. Gated entry and exit control access to these theaters and reticular networks and associated chemokines guide cells into the proper sections. Lymphoid tissues are remarkably plastic, being able to expand dramatically and then involute upon resolution of the danger. All of the reticular scaffolds and vascular and lymphatic components adapt accordingly. As such, the lymph node (LN) is a wonderful example of a physiologic remodeling process and is potentially a guide to study such elements in pathological settings such as fibrosis, chronic infection, and tumor metastasis. The lymphotoxin/LIGHT axis delivers critical differentiation signals that direct and hone differentiation of both reticular networks and the vasculature. Considerable progress has been made recently in understanding the mesenchymal differentiation pathways leading to these specialized networks and in the remodeling that occurs in reactive LNs. In this article, we will review some new advances in the area in terms of developmental, differentiation, and maintenance events mediated by this axis. PMID:24575096

Incidence of Staphylococcus aureus nasal colonization and soft tissue infection among high school football players.

PubMed

Lear, Aaron; McCord, Gary; Peiffer, Jeffrey; Watkins, Richard R; Parikh, Arpan; Warrington, Steven

2011-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections have been documented with increasing frequency in both team and individual sports in recent years. It also seems that the level of MRSA skin and soft tissue infections in the general population has increased. One hundred ninety athletes from 6 local high school football teams were recruited for this prospective observational study to document nasal colonization and the potential role this plays in skin and soft tissue infections in football players and, in particular, MRSA infections. Athletes had nasal swabs done before their season started, and they filled out questionnaires regarding potential risk factors for skin and soft tissue infections. Those enrolled in the study were then observed over the course of the season for skin and soft tissue infections. Those infected had data about their infections collected. One hundred ninety of 386 available student athletes enrolled in the study. Forty-four of the subjects had nasal colonization with methicillin-susceptible S. aureus, and none were colonized with MRSA. There were 10 skin and soft tissue infections (8 bacterial and 2 fungal) documented over the course of the season. All were treated as outpatients with oral or topical antibiotics, and none were considered serious. Survey data from the preseason questionnaire showed 21% with skin infection, 11% with methicillin-susceptible S. aureus, and none with MRSA infection during the past year. Three reported a remote history of MRSA infection. We documented an overall skin infection rate of 5.3% among high school football players over a single season. Our results suggest that skin and soft tissue infection may not be widespread among high school athletes in northeast Ohio.

Systems approaches evaluating the perturbation of xenobiotic metabolism in response to cigarette smoke exposure in nasal and bronchial tissues.

PubMed

Iskandar, Anita R; Martin, Florian; Talikka, Marja; Schlage, Walter K; Kostadinova, Radina; Mathis, Carole; Hoeng, Julia; Peitsch, Manuel C

2013-01-01

Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue.

Systems Approaches Evaluating the Perturbation of Xenobiotic Metabolism in Response to Cigarette Smoke Exposure in Nasal and Bronchial Tissues

PubMed Central

Iskandar, Anita R.; Martin, Florian; Talikka, Marja; Schlage, Walter K.; Mathis, Carole; Hoeng, Julia; Peitsch, Manuel C.

2013-01-01

Capturing the effects of exposure in a specific target organ is a major challenge in risk assessment. Exposure to cigarette smoke (CS) implicates the field of tissue injury in the lung as well as nasal and airway epithelia. Xenobiotic metabolism in particular becomes an attractive tool for chemical risk assessment because of its responsiveness against toxic compounds, including those present in CS. This study describes an efficient integration from transcriptomic data to quantitative measures, which reflect the responses against xenobiotics that are captured in a biological network model. We show here that our novel systems approach can quantify the perturbation in the network model of xenobiotic metabolism. We further show that this approach efficiently compares the perturbation upon CS exposure in bronchial and nasal epithelial cells in vivo samples obtained from smokers. Our observation suggests the xenobiotic responses in the bronchial and nasal epithelial cells of smokers were similar to those observed in their respective organotypic models exposed to CS. Furthermore, the results suggest that nasal tissue is a reliable surrogate to measure xenobiotic responses in bronchial tissue. PMID:24224167

[Effects of prebiotics and probiotics on gastrointestinal tract lymphoid tissue in hiv infected patients].

PubMed

Feria, Manuel G; Taborda, Natalia A; Hernandez, Juan C; Rugeles, María T

2017-02-01

HIV infection induces alterations in almost all immune cell populations, mainly in CD4+ T cells, leading to the development of opportunistic infections. The gut-associated lymphoid tissue (GALT) constitutes the most important site for viral replication, because the main target cells, memory T-cells, reside in this tissue. It is currently known that alterations in GALT are critical during the course of the infection, as HIV-1 induces loss of tissue integrity and promotes translocation of microbial products from the intestinal lumen to the systemic circulation, leading to a persistent immune activation state and immune exhaustion. Although antiretroviral treatment decreases viral load and substantially improves the prognosis of the infection, the alterations in GALT remains, having a great impact on the ability to establish effective immune responses. This emphasizes the importance of developing new therapeutic alternatives that may promote structural and functional integrity of this tissue. In this regard, therapy with probiotics/prebiotics has beneficial effects in GALT, mainly in syndromes characterized by intestinal dysbiosis, including the HIV-1 infection. In these patients, the consumption of probiotics/prebiotics decreased microbial products in plasma and CD4+ T cell activation, increased CD4+ T cell frequency, in particular Th17, and improved the intestinal flora. In this review, the most important findings on the potential impact of the probiotics/prebiotics therapy are discussed.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type arising in the pleura with pleural fibrous plaques in a lathe worker.

PubMed

Nakatsuka, Shin-ichi; Nagano, Teruaki; Kimura, Hayato; Hanada, Shoji; Inoue, Hidetoshi; Iwata, Takashi

2012-06-01

Our patient was an 86-year-old man who had worked as a lathe operator for 40 years. He had no history of tuberculosis, pyothorax, or autoimmune disease. He had not been exposed to asbestos. He was asymptomatic, but an imaging study showed gradually increasing pleural plaques. A biopsy specimen of a pleural lesion showed sclerosis of the pleura and diffuse infiltration of small- to medium-sized B lymphocytes. Polymerase chain reaction-based analysis detected monoclonal rearrangement of immunoglobulin heavy-chain genes. Histologic diagnosis was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). The lymphoma was negative for Epstein-Barr virus. We report a rare case of a metal worker with MALT lymphoma arising in the pleura with pleural fibrous plaques. It is speculated that MALT lymphoma might develop in the background of pneumoconiosis. Inflammatory and/or immunologic reactions to metal particles might contribute to the oncogenesis of this tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

PubMed

Bodel, P

1974-01-01

The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

The histological characteristics of the aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus) of different ages.

PubMed

Zhang, Wang-Dong; Wang, Wen-Hui; Xu, Xiao-Hong; Zhaxi, Ying-Pai; Zhang, Lin-Jiang; Qi, Shan-Shan; Li, Hang; Tan, Xue-Fen

2012-06-30

The aggregated lymphoid nodules area (ALNA) in abomasum of Bactrian camels is a special immune structure discovered only in Bactrian camels in recent years (2003). The anatomy research found that there was a close relationship between degree of development, anatomical characteristics and age. To further establish the relationship between histological characteristics of this special structure and animal age, 24 Alashan Bactrian camels of the following four age groups were studied: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). Mucosal-associated lymphoid tissue (MALT) of ALNA in abomasum was particularly observed and analyzed by histology, histochemistry and statistical methods. The results showed that the average number of lymphoid nodules in reticular mucosal folds region of ALNA in abomasum from young group to old group was in order of 26.8, 32.7, 17.6 and 7.8, and in longitudinal mucosal folds region was 20.1, 26.0, 10.3 and 5.1. The number of lymphoid nodules in the four experimental groups first increased and then decreased with increasing age (P<0.01). In young and pubertal camels lymphoid nodules were distributed evenly on both sides of the axis of mucosal folds and mostly displayed round, oval or wedge shape. The number of lymphoid nodules, follicle-associated epithelium (FAE), reticular fibers and plasmocytes in mucosal folds gradually increased from 1 to 2 years and peaked at puberty. There were up to 37 visible lymphoid nodules in a mucosal fold. However, ALNA of middle-aged and old camels gradually degenerated as aging. Lymphoid nodules were unevenly distributed on both sides of the axis of mucosal folds, which mostly displayed oval or irregular shape. Lymphoid tissue in old camels mostly existed as diffuse form. Although germinal centers of the lymphoid nodules were still obvious, the number of reticular fiber and plasmocyte and lymphoid nodules gradually decreased. The results indicated that in accord with the

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

PubMed

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.

Malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers.

PubMed

Gluzman, Daniel; Imamura, Nobutaka; Sklyarenko, Lylia; Nadgornaya, Valentina; Zavelevich, Michael; Machilo, Vasily

2005-01-01

The question as to whether the incidence of leukemias and malignant lymphomas among the clean-up workers increased in 18 years after the catastrophe is still a point of much controversy. Precise diagnosis of the main forms of hematopoietic malignancies and comparison of these data with those in the general population will be helpful in estimating thr relative contribution of the radiation factor to the overall incidence of such pathologies. In all, 187 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers were analyzed in Ukrainian Reference Laboratory in 1996-2003. A total of 1942 consecutive patients of general population, mainly the residents of Kyiv city and district, diagnosed in References Laboratory at the same period comprised the group of comparison. The morphology and cytochemistry of bone marrow and peripheral blood cells were studied. Immunocytochemical techniques (PAP, APAAP, ABC) and the panel of monoclonal antibodies to differentiation antigens of leukocytes were employed for immunophenotyping leukemic cells. Various types of malignant disease of hematopoietic and lymphoid tissues were registered in Chernobyl clean-up workers under study including myelodysplastic syndromes (nine patients), acute lymphoblastic leukemia (eight) and acute myeloblastic leukemia (31), chromic myeloid leukemia (17), multiple myeloma (17) and other forms of chromic myeloproliferative and lymphoproliferative disease including B-cell chromic lymphocytic leukemia (49 patients). The verified diagnosis of tumors of hematopoietic malignancies according to modern classification (EGIL, WHO) could be the prerequisite for further analytical epidemiology study of leukemias that may be related to the Chernobyl accident.

Prevalence and Implications of Bone Marrow Involvement in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Choi, Sang Il; Kook, Myeong-Cherl; Hwang, Sanghyun; Kim, Young-Il; Lee, Jong Yeul; Kim, Chan Gyoo; Choi, Il Ju; Lee, Hyewon; Eom, Hyeon Seok

2018-01-01

Background/Aims Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. PMID:29409307

Association of magnetic resonance imaging findings and histologic diagnosis in dogs with nasal disease: 78 cases (2001-2004).

PubMed

Miles, Macon S; Dhaliwal, Ravinder S; Moore, Michael P; Reed, Ann L

2008-06-15

OBJECTIVE-To determine whether magnetic resonance imaging (MRI) features correlated with histologic diagnosis in dogs with nasal disease. DESIGN-Retrospective case series. ANIMALS-78 Dogs undergoing MRI for evaluation of nasal disease. PROCEDURES-Medical records and MRI reports of dogs were reviewed to identify MRI features associated with histologic diagnosis. Features evaluated were presence of a mass effect, frontal sinus involvement, sphenoid sinus involvement, maxillary recess involvement, nasopharyngeal infiltration by soft tissue, nasal turbinate destruction, vomer bone lysis, paranasal bone destruction, cribriform plate erosion, and lesion extent (ie, unilateral vs bilateral). RESULTS-33 Dogs had neoplastic disease, 38 had inflammatory rhinitis, and 7 had fungal rhinitis. Lesion extent was not significantly associated with histologic diagnosis. Absence of a mass effect was significantly associated with inflammatory disease. However, presence of a mass was not specific for neoplasia. In dogs with evidence of a mass on magnetic resonance (MR) images, nasal turbinate destruction, frontal sinus invasion, and maxillary recess invasion were not useful in distinguishing neoplastic from nonneoplastic disease, but cribriform plate erosion, vomer bone lysis, paranasal bone destruction, sphenoid sinus invasion, and nasopharyngeal invasion were. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that in dogs with nasal disease, the lack of a mass effect on MR images was significantly associated with inflammatory disease. In dogs with a mass effect on MR images, vomer bone lysis, cribriform plate erosion, paranasal bone destruction, sphenoid sinus invasion by a mass, and nasopharyngeal invasion by a mass were significantly associated with a diagnosis of neoplasia.

Lymphoid organs function as major reservoirs for human immunodeficiency virus.

PubMed Central

Pantaleo, G; Graziosi, C; Butini, L; Pizzo, P A; Schnittman, S M; Kotler, D P; Fauci, A S

1991-01-01

The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection. Images PMID:1682922

Innate Lymphoid Cells in Tumor Immunity.

PubMed

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.

Innate Lymphoid Cells in Tumor Immunity

PubMed Central

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

2016-01-01

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. PMID:28536374

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

PubMed

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.

Conjunctival lymphoma arising from reactive lymphoid hyperplasia.

PubMed

Fukuhara, Junichi; Kase, Satoru; Noda, Mika; Ishijima, Kan; Yamamoto, Teppei; Ishida, Susumu

2012-09-18

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.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis.

PubMed

Suzuki, Hidekazu; Saito, Yoshimasa; Hibi, Toshifumi

2009-06-01

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

PubMed Central

Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

2014-01-01

Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

Innate lymphoid cells: the new kids on the block.

PubMed

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.

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

PubMed

Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

2016-11-01

Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The activity of N-acetyl-β-d-hexosaminidase A and B and β-glucuronidase in nasal polyps and hypertrophic nasal concha.

PubMed

Chojnowska, Sylwia; Minarowska, Alina; Waszkiewicz, Napoleon; Kępka, Alina; Zalewska-Szajda, Beata; Gościk, Elżbieta; Kowal, Krzysztof; Olszewska, Ewa; Konarzewska-Duchnowska, Emilia; Minarowski, Łukasz; Zwierz, Krzysztof; Ładny, Jerzy Robert; Szajda, Sławomir Dariusz

2014-01-01

Nasal polyps and hypertrophic lower nasal conchae are common disorders of nasal cavity. The majority of etiopathogenetic theories indicate inflammatory background of polyps and hypertrophic concha. N-acetyl-β-D-hexosaminidase and β-glucuronidase are lysosomal exoglycosidases revealing accelerated activity in inflammatory processes. The aim of the study was to evaluate the catabolism of glycoconjugates in nasal polyps and hypertrophic nasal concha basing on the activity of N-acetyl-β-D-hexosaminidase (HEX) and β-glucuronidase (GLU). Material consisted of nasal polyps taken from 40 patients during polypectomy in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and hypertrophic lower nasal conchae taken from 20 patients during mucotomy. The activity of HEX, HEX A, HEX B and GLU in supernatant of homogenates of nasal polyps and hypertrophic lower nasal concha tissues has been estimated using colorimetric method. Statistically significant decrease has been observed in concentration of the activity (per 1mg of tissue) of HEX (p<0.05), HEX B (p<0.001) and specific activity (per 1mg of protein) of HEX B (p<0.001) in nasal polyps tissue in comparison to hypertrophic lower nasal conchae tissue. Decrease in the activity and specific activity concentration of the majority of examined lysosomal exoglycosidases (increasing in inflammations) in comparison to hypertrophic lower nasal conchae suggests electrolytes disorders and questions the inflammatory background of nasal polyps. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Molecular detection of microbes in nasal tissue of dogs with idiopathic lymphoplasmacytic rhinitis.

PubMed

Windsor, Rebecca C; Johnson, Lynelle R; Sykes, Jane E; Drazenovich, Tracy L; Leutenegger, Christian M; De Cock, Hilde E V

2006-01-01

Lymphoplasmacytic rhinitis (LPR) is a common histologic finding in dogs with chronic nasal disease; however, potential etiologies of this disorder have not been examined. We investigated the hypothesis that specific microbes contribute to clinical disease in dogs with LPR. Paraffin-embedded nasal biopsies were obtained from 19 dogs with LPR, 10 dogs with nasal neoplasia, and 10 dogs with nasal aspergillosis. Nucleic acids were extracted from paraffin blocks, and real-time quantitative polymerase chain reaction (PCR) was employed for detection of target genes for bacterial and fungal DNA, canine adenovirus 2 (CAV-2), parainfluenza virus 3 (PI-3), Chlamydial Chlamydophila spp., and Bartonella spp. Conventional PCR was used for detection of Mycoplasma spp. Statistical analysis was performed using the Mann-Whitney U-test for nonparametric data, and significance was set at P < 0.05. DNA or RNA for CAV-2, PI-3, Bartonella, Mycoplasma, and Chlamydophila was not detected in any nasal biopsy. DNA loads for bacterial DNA did not differ among disease groups. Detection of fungal DNA in nasal biopsies was highest in dogs with aspergillosis (P < 0.0001); however, nasal biopsies of LPR dogs also displayed higher fungal DNA levels than samples from dogs with nasal neoplasia (P = 0.016). Detection of high levels of fungal DNA in nasal biopsies of dogs with LPR suggests that fungal organisms may be causally associated with the inflammation observed, although the possibility of entrapment or accumulation of fungi in the nasal cavity due to chronic inflammation cannot be excluded. Further investigations are required to elucidate the underlying etiopathogenesis of LPR.

Declining lymphoid progenitor fitness promotes aging-associated leukemogenesis.

PubMed

Henry, Curtis J; Marusyk, Andriy; Zaberezhnyy, Vadym; Adane, Biniam; DeGregori, James

2010-12-14

Aging is associated with the functional decline of cells, tissues, and organs. At the same time, age is the single most important prognostic factor in the development of most human cancers, including chronic myelogenous and acute lymphoblastic leukemias initiated by Bcr-Abl oncogenic translocations. Prevailing paradigms attribute the association between aging and cancers to the accumulation of oncogenic mutations over time, because the accrual of oncogenic events is thought to be the rate-limiting step in initiation and progression of cancers. Conversely, aging-associated functional decline caused by both cell-autonomous and non-cell-autonomous mechanisms is likely to reduce the fitness of stem and progenitor cell populations. This reduction in fitness should be conducive for increased selection of oncogenic mutations that can at least partially alleviate fitness defects, thereby promoting the initiation of cancers. We tested this hypothesis using mouse hematopoietic models. Our studies indicate that the dramatic decline in the fitness of aged B-lymphopoiesis coincides with altered receptor-associated kinase signaling. We further show that Bcr-Abl provides a much greater competitive advantage to old B-lymphoid progenitors compared with young progenitors, coinciding with restored kinase signaling pathways, and that this enhanced competitive advantage translates into increased promotion of Bcr-Abl-driven leukemias. Moreover, impairing IL-7-mediated signaling is sufficient to promote selection for Bcr-Abl-expressing B progenitors. These studies support an unappreciated causative link between aging and cancer: increased selection of oncogenic mutations as a result of age-dependent alterations of the fitness landscape.

Innate lymphoid cells, precursors and plasticity.

PubMed

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.

Is narrow-band imaging useful for histological evaluation of gastric mucosa-associated lymphoid tissue lymphoma after treatment?

PubMed

Nonaka, Kouichi; Ohata, Ken; Matsuhashi, Nobuyuki; Shimizu, Michio; Arai, Shin; Hiejima, Yoshimitsu; Kita, Hiroto

2014-05-01

Endoscopic diagnosis of stomach mucosa-associated lymphoid tissue (MALT) lymphoma is often difficult because few specific findings are indicated. Even when MALT lymphoma is suspected by endoscopy, it is still difficult to make a definitive diagnosis by biopsy because lymphoma cells sometimes distribute unevenly. We previously reported that a tree-like appearance (TLA) is a characteristic finding of MALT lymphoma by narrow-band imaging (NBI) magnifying endoscopy and it is valuable in the selection of an optimal biopsy site in MALT lymphoma. Here, we study the frequency of TLA and evaluate the relationship between the response to eradication therapy and TLA in MALT lymphoma. We retrospectively examined the clinical background, endoscopic findings, response to eradication therapy, and Helicobacter pylori infection status of 16 patients diagnosed with MALT lymphoma who were referred to our hospital from April 2007 to August 2012. The regimen for eradicationtherapy consisted of rabeprazole, with amoxicillin and clarithromycin, all given for 7 days. TLA was found in 75% (12/16) and H. pylori infection in 75% (12/16) of patients diagnosed with MALT lymphoma by NBI magnifying endoscopy. In all complete regression (CR) patients after eradication treatment, the TLA finding had disappeared (100%); however, in the non-CR patients, TLA remained the same as before the eradication therapy (P=0.002). These results suggest that NBI magnifying endoscopy may be useful not only in the diagnosis but also in the evaluation of the response to eradication therapy of MALT lymphoma of the stomach. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

PubMed

Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

2016-03-15

Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients.

PubMed

Girinsky, Theodore; Paumier, Amaury; Ferme, Christophe; Hanna, Colette; Ribrag, Vincent; Leroy-Ladurie, François; Ghalibafian, Mithra

2012-07-01

To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 × 2 Gy) delivered exclusively to tumor sites. Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma. Copyright © 2012 Elsevier Inc. All rights reserved.

‘Trained immunity’: consequences for lymphoid malignancies

PubMed Central

Stevens, Wendy B.C.; Netea, Mihai G.; Kater, Arnon P.; van der Velden, Walter J.F.M.

2016-01-01

In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity. Restoring dysfunction or enhancing responsiveness of the innate immune system might therefore represent a new angle for the prevention and treatment of hematological malignancies, in particular lymphoid malignancies and associated infections. Recently, it has been shown that cells of the innate immune system, such as monocytes/macrophages and natural killer cells, harbor features of immunological memory and display enhanced functionality long-term after stimulation with certain microorganisms and vaccines. These functional changes rely on epigenetic reprogramming and have been termed ‘trained immunity’. In this review the concept of ‘trained immunity’ is discussed in the setting of lymphoid malignancies. Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis. PMID:27903713

Tertiary lymphoid structures in cancer and beyond.

PubMed

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.

Phenotype and function of nasal dendritic cells

PubMed Central

Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

2015-01-01

Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

Treatment outcome for gastric mucosa-associated lymphoid tissue lymphoma according to Helicobacter pylori infection status: a single-center experience.

PubMed

Ryu, Kwang Duck; Kim, Gwang Ha; Park, Seong Oh; Lee, Kwang Jae; Moon, Jung Youn; Jeon, Hye Kyung; Baek, Dong Hoon; Lee, Bong Eun; Song, Geun Am

2014-07-01

Helicobacter pylori eradication therapy has been used as a first-line treatment for H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the management strategy for H. pylori-negative MALT lymphoma remains controversial. Therefore, the aim of this study was to examine the success rate of each treatment option for H. pylori-positive and H. pylori-negative gastric MALT lymphomas. In total, 57 patients with gastric MALT lymphoma diagnosed between December 2000 and June 2012 were enrolled in the study. The treatment responses were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphomas. Of the 57 patients, 43 (75%) had H. pylori infection. Forty-eight patients received H. pylori eradication as a first-line treatment, and complete remission was achieved in 31 of the 39 patients (80%) with H. pylori-positive MALT lymphoma and in five (56%) of the nine patients with H. pylori-negative MALT lymphoma; no significant difference was observed between the groups (p=0.135). The other treatment modalities, including radiation therapy, chemotherapy, and surgery, were effective irrespective of H. pylori infection status, with no significant difference in the treatment response between H. pylori-positive and H. pylori-negative MALT lymphomas. H. pylori eradication therapy may be considered as a first-line treatment regardless of H. pylori infection status.

Treatment Outcome for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to Helicobacter pylori Infection Status: A Single-Center Experience

PubMed Central

Ryu, Kwang Duck; Kim, Gwang Ha; Park, Seong Oh; Lee, Kwang Jae; Moon, Jung Youn; Jeon, Hye Kyung; Baek, Dong Hoon; Lee, Bong Eun; Song, Geun Am

2014-01-01

Background/Aims Helicobacter pylori eradication therapy has been used as a first-line treatment for H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the management strategy for H. pylori-negative MALT lymphoma remains controversial. Therefore, the aim of this study was to examine the success rate of each treatment option for H. pylori-positive and H. pylori-negative gastric MALT lymphomas. Methods In total, 57 patients with gastric MALT lymphoma diagnosed between December 2000 and June 2012 were enrolled in the study. The treatment responses were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphomas. Results Of the 57 patients, 43 (75%) had H. pylori infection. Forty-eight patients received H. pylori eradication as a first-line treatment, and complete remission was achieved in 31 of the 39 patients (80%) with H. pylori-positive MALT lymphoma and in five (56%) of the nine patients with H. pylori-negative MALT lymphoma; no significant difference was observed between the groups (p=0.135). The other treatment modalities, including radiation therapy, chemotherapy, and surgery, were effective irrespective of H. pylori infection status, with no significant difference in the treatment response between H. pylori-positive and H. pylori-negative MALT lymphomas. Conclusions H. pylori eradication therapy may be considered as a first-line treatment regardless of H. pylori infection status. PMID:25071906

Functional anatomy of the nasal bones and adjacent structures. Consequences for nasal surgery.

PubMed

Popko, M; Verlinde-Schellekens, S A M W; Huizing, E H; Bleys, R L A W

2018-03-01

The periosteum of the nasal bones, the periosteal-perichondrial nasal envelope, and the cartilaginous support of the bony vault were studied in serial coronal sections of four human cadaver noses. To differentiate between the various tissue components, the sections were stained according to Mallory-Cason and Verhoeff-Van Gieson stain. The results demonstrated: 1. the presence of clearly distinguishable layers of the periosteum covering the nasal bones; 2. the presence of a continuous periosteal-perichondrial covering of the bony and cartilaginous nasal vaults; 3. the way the cartilaginous support of the bony vault is constructed. The findings described in the present study may have clinical relevance in nasal surgery.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

PubMed

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

2016-10-22

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

Detection of Foot-and-mouth Disease Virus RNA and Capsid Protein in Lymphoid Tissues of Convalescent Pigs Does Not Indicate Existence of a Carrier State.

PubMed

Stenfeldt, C; Pacheco, J M; Smoliga, G R; Bishop, E; Pauszek, S J; Hartwig, E J; Rodriguez, L L; Arzt, J

2016-04-01

A systematic study was performed to investigate the potential of pigs to establish and maintain persistent foot-and-mouth disease virus (FMDV) infection. Infectious virus could not be recovered from sera, oral, nasal or oropharyngeal fluids obtained after resolution of clinical infection with any of five FMDV strains within serotypes A, O and Asia-1. Furthermore, there was no isolation of live virus from tissue samples harvested at 28-100 days post-infection from convalescent pigs recovered from clinical or subclinical FMD. Despite lack of detection of infectious FMDV, there was a high prevalence of FMDV RNA detection in lymph nodes draining lesion sites harvested at 35 days post-infection, with the most frequent detection recorded in popliteal lymph nodes (positive detection in 88% of samples obtained from non-vaccinated pigs). Likewise, at 35 dpi, FMDV capsid antigen was localized within follicles of draining lymph nodes, but without concurrent detection of FMDV non-structural protein. There was a marked decline in the detection of FMDV RNA and antigen in tissue samples by 60 dpi, and no antigen or viral RNA could be detected in samples obtained at 100 dpi. The data presented herein provide the most extensive investigation of FMDV persistence in pigs. The overall conclusion is that domestic pigs are unlikely to be competent long-term carriers of infectious FMDV; however, transient persistence of FMDV protein and RNA in lymphoid tissues is common following clinical or subclinical infection. © Published 2014. This article is a US Government work and is in the public domain in the USA.

Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication

PubMed Central

Saito, Yoshimasa; Suzuki, Hidekazu; Tsugawa, Hitoshi; Imaeda, Hiroyuki; Matsuzaki, Juntaro; Hirata, Kenro; Hosoe, Naoki; Nakamura, Masahiko; Mukai, Makio; Saito, Hidetsugu; Hibi, Toshifumi

2012-01-01

microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma. PMID:23209550

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

PubMed Central

Lim, Hyeon Woo; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong

2016-01-01

Purpose To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys. PMID:27730803

RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY

PubMed Central

Wakefield, J. D.; Thorbecke, G. J.

1968-01-01

The fate, proliferation, and developmental potentialities of cell suspensions made from white pulp containing large germinal centers have been studied in the mouse by transfer of cells labeled with thymidine-3H to lethally irradiated, syngeneic recipients. Radioautographic analyses were made using both smears and sections of a variety of tissues. Thymidine-3H-labeling patterns of white pulp showed that, initially, labeling occurred in a majority of blast and "intermediate cells" but in very few or no small lymphocytes. After intravenous transfer, most of the labeled cells localized in the lymphoid tissues of spleen, lymph nodes, and Peyer's patches. Few cells migrated to the thymus, lung, liver, and intestinal mucosa. Both after intravenous and after intraperitoneal transfer there was a rapid increase in the incidence of labeled small lymphocytes and a decrease of labeled blasts and intermediate cells. This was accompanied by an increase in the grain count of the small lymphocytes and a progressive decrease in the grain counts of the blast cells. Exposure of nonlabeled donor cells to thymidine-3H at various time intervals after transfer indicated that dividing cells were present early after transfer but that their incidence progressively decreased. Between 24 and 48 hr, very little cell division was detectable. PMID:5662013

Human innate lymphoid cells.

PubMed

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.

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study.

PubMed

Donahue, Robert E; Srinivasula, Sharat; Uchida, Naoya; Kim, Insook; St Claire, Alexis; Duralde, Gorka; DeGrange, Paula; St Claire, Marisa; Reba, Richard C; Bonifacino, Aylin C; Krouse, Allen E; Metzger, Mark E; Paik, Chang H; Lane, H Clifford; Tisdale, John F; Di Mascio, Michele

2015-12-10

Ionizing irradiation is used routinely to induce myeloablation and immunosuppression. However, it has not been possible to evaluate the extent of ablation without invasive biopsy. For lymphoid recovery, peripheral blood (PB) lymphocytes (PBLs) have been used for analysis, but they represent <2% of cells in lymphoid tissues (LTs). Using a combination of single-photon emission computed tomography imaging and a radiotracer ((99m)Tc-labeled rhesus immunoglobulin G1 anti-CD4R1 (Fab')2), we sequentially imaged CD4(+) cell recovery in rhesus macaques following total body irradiation (TBI) and reinfusion of vector-transduced, autologous CD34(+) cells. Our results present for the first time a sequential, real-time, noninvasive method to evaluate CD4(+) cell recovery. Importantly, despite myeloablation of circulating leukocytes following TBI, total depletion of CD4(+) lymphocytes in LTs such as the spleen is not achieved. The impact of TBI on LTs and PBLs is discordant, in which as few as 32.4% of CD4(+) cells were depleted from the spleen. In addition, despite full lymphocyte recovery in the spleen and PB, lymph nodes have suboptimal recovery. This highlights concerns about residual disease, endogenous contributions to recovery, and residual LT damage following ionizing irradiation. Such methodologies also have direct application to immunosuppressive therapy and other immunosuppressive disorders, such as those associated with viral monitoring.

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study

PubMed Central

Srinivasula, Sharat; Uchida, Naoya; Kim, Insook; St. Claire, Alexis; Duralde, Gorka; DeGrange, Paula; St. Claire, Marisa; Reba, Richard C.; Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Paik, Chang H.; Lane, H. Clifford; Tisdale, John F.; Di Mascio, Michele

2015-01-01

Ionizing irradiation is used routinely to induce myeloablation and immunosuppression. However, it has not been possible to evaluate the extent of ablation without invasive biopsy. For lymphoid recovery, peripheral blood (PB) lymphocytes (PBLs) have been used for analysis, but they represent <2% of cells in lymphoid tissues (LTs). Using a combination of single-photon emission computed tomography imaging and a radiotracer (99mTc-labeled rhesus immunoglobulin G1 anti-CD4R1 (Fab′)2), we sequentially imaged CD4+ cell recovery in rhesus macaques following total body irradiation (TBI) and reinfusion of vector-transduced, autologous CD34+ cells. Our results present for the first time a sequential, real-time, noninvasive method to evaluate CD4+ cell recovery. Importantly, despite myeloablation of circulating leukocytes following TBI, total depletion of CD4+ lymphocytes in LTs such as the spleen is not achieved. The impact of TBI on LTs and PBLs is discordant, in which as few as 32.4% of CD4+ cells were depleted from the spleen. In addition, despite full lymphocyte recovery in the spleen and PB, lymph nodes have suboptimal recovery. This highlights concerns about residual disease, endogenous contributions to recovery, and residual LT damage following ionizing irradiation. Such methodologies also have direct application to immunosuppressive therapy and other immunosuppressive disorders, such as those associated with viral monitoring. PMID:26492933

Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids.

PubMed

Hansen, Rodney A; Anderson, Christine; Fettman, Martin J; Larue, Susan M; Davenport, Deborah J; Gross, Kathleen L; Richardson, Kristine L; Ogilvie, Gregory K

2011-12-01

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or menhaden oil may reduce inflammatory eicosanoids (prostaglandin E₂, thromboxane B₂, leukotriene B₄, and 11-dehydro thromboxane B₂), matrix metalloproteinases (MMPs), and blood lactate in dogs with nasal carcinomas receiving radiation therapy. We hypothesized that menhaden oil would reduce inflammation from radiation damage and lower blood lactate levels in dogs with nasal carcinoma. In a randomized, double-blind, placebo-controlled clinical study, 12 dogs with malignant carcinomas of the nasal cavity were given dietary menhaden oil (DHA and EPA) or soybean oil (control) and then received radiation therapy. Megavoltage radiation was delivered in 18 fractions to a total dose of 56 Gy. Blood levels of DHA, EPA, insulin, glucose, lactic acid, and MMPs 2 and 9; resting energy expenditure; and inflammatory eicosanoids from nasal biopsies were measured throughout radiation therapy. Samples were obtained from each patient 1 week before the start of radiation therapy, at start of radiation, and 7, 18 (end of radiation therapy), and 42 days after radiation was initiated. Dogs that are fed with menhaden oil had significantly (P < .05) higher plasma concentration of DHA by 500% and EPA by 200% and had significantly lower tissue inflammatory eicosanoids and decreased resting energy expenditure by 20% when compared with controls. Increased plasma DHA was significantly associated (P < .05) with decreased plasma lactic acid and MMPs. These data may suggest that dietary fish oil could reduce some detrimental inflammatory eicosanoids and metabolic consequences of radiation therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

PubMed

Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

2015-01-01

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

Prenatal Diagnosis of Nasal Glioma Associated with Metopic Craniosynostosis: Case Report and Review of the Literature

PubMed Central

Boyer, Andrew C; Krishnan, Anant; Goncalves, Luis F; Williams, Lindsay; Chaiyasate, Kongkrit

2015-01-01

Nasal gliomas (nasal glial heterotopia) are rare benign congenital frontonasal lesions occurring in approximately 1: 20.000 – 40,000 live births. The diagnosis is rarely reported prenatally. Nasal gliomas are typically isolated lesions, with syndromic association being exceedingly rare. Metopic craniosynostosis can occur as an isolated abnormality or in association with multiple syndromes. This case is the first reported case of nasal glioma in association with craniosynostosis in the published literature. PMID:26622922

Conjunctiva-Associated Lymphoid Tissue (CALT) Reactions to Antiglaucoma Prostaglandins with or without BAK-Preservative in Rabbit Acute Toxicity Study

PubMed Central

Liang, Hong; Baudouin, Christophe; Labbe, Antoine; Riancho, Luisa; Brignole-Baudouin, Françoise

2012-01-01

Conjunctiva-associated lymphoid tissue (CALT) is closely associated with ocular surface immunity. This study investigated the effects of antiglaucoma prostaglandin analogs with or without benzalkonium chloride (BAK) preservative on organized CALT using an acute toxic model. A total of 48 albino rabbits were used and seven groups of treatments were constituted. Solutions (50 µl) of PBS, 0.02%BAK, 0.02%BAK+latanoprost, 0.015%BAK+travoprost, 0.005%BAK+bimatoprost, BAK-freetravoprost preserved with the SofZia® system or BAK-freetafluprost were instilled 15 times at 5-min intervals in both eyes. CALT changes were analyzed using in vivo confocal microscopy (IVCM), immunohistology in cryosections for detecting MUC-5AC+ mucocytes and CD45+ hematopoietic cells. Antiglaucoma eye drops stimulated inflammatory cell infiltration in the CALT, and seemed to be primarily related to the concentration of their BAK content. The CALT reaction after instillation of BAK-containing eye drops was characterized by inflammatory cell infiltration in the dome and intrafollicular layers and by cell circulation inside the lymph vessels. CD45 was strongly expressed in the CALT after instillation of all BAK-containing solutions at 4 h and decreased at 24 h. The number of MUC-5AC+ mucocytes around the CALT structure decreased dramatically after instillation of BAK-containing solutions. This study showed for the first time the in vivo aspect of rabbit CALT after toxic stimuli, confirming the concentration-dependent toxic effects of BAK. IVCM-CALT analysis could be a pertinent tool in the future for understanding the immunotoxicologic challenges in the ocular surface and would provide useful criteria for evaluating newly developed eye drops. PMID:22442734

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene.

PubMed

Iwamuro, Masaya; Takenaka, Ryuta; Nakagawa, Masahiro; Moritou, Yuki; Saito, Shunsuke; Hori, Shinichiro; Inaba, Tomoki; Kawai, Yoshinari; Toyokawa, Tatsuya; Tanaka, Takehiro; Yoshino, Tadashi; Okada, Hiroyuki

2017-09-07

To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1. This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated. Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10). Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1.

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

PubMed Central

Iwamuro, Masaya; Takenaka, Ryuta; Nakagawa, Masahiro; Moritou, Yuki; Saito, Shunsuke; Hori, Shinichiro; Inaba, Tomoki; Kawai, Yoshinari; Toyokawa, Tatsuya; Tanaka, Takehiro; Yoshino, Tadashi; Okada, Hiroyuki

2017-01-01

AIM To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1. METHODS This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated. RESULTS Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10). CONCLUSION Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1. PMID:28970731

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

PubMed

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.

Hyperactive gp130/STAT3‐driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

PubMed Central

Hill, David G.; Yu, Liang; Gao, Hugh; Balic, Jesse J.; West, Alison; Oshima, Hiroko; McLeod, Louise; Oshima, Masanobu; Gallimore, Awen; D'Costa, Kimberley; Bhathal, Prithi S.; Sievert, William; Ferrero, Richard L.

2018-01-01

Tertiary lymphoid structures (TLSs) display phenotypic and functional characteristics of secondary lymphoid organs, and often develop in tissues affected by chronic inflammation, as well as in certain inflammation‐associated cancers where they are prognostic of improved patient survival. However, the mechanisms that govern the development of tumour‐associated TLSs remain ill‐defined. Here, we observed tumour‐associated TLSs in a preclinical mouse model (gp130 F/F) of gastric cancer, where tumourigenesis is dependent on hyperactive STAT3 signalling through the common IL‐6 family signalling receptor, gp130. Gastric tumourigenesis was associated with the development of B and T cell‐rich submucosal lymphoid aggregates, containing CD21+ cellular networks and high endothelial venules. Temporally, TLS formation coincided with the development of gastric adenomas and induction of homeostatic chemokines including Cxcl13, Ccl19 and Ccl21. Reflecting the requirement of gp130‐driven STAT3 signalling for gastric tumourigenesis, submucosal TLS development was also STAT3‐dependent, but independent of the cytokine IL‐17 which has been linked with lymphoid neogenesis in chronic inflammation and autoimmunity. Interestingly, upregulated lymphoid chemokine expression and TLS formation were also observed in a chronic gastritis model induced by Helicobacter felis infection. Tumour‐associated TLSs were also observed in patients with intestinal‐type gastric cancer, and a gene signature linked with TLS development in gp130 F/F mice was associated with advanced clinical disease, but was not prognostic of patient survival. Collectively, our in vivo data reveal that hyperactive gp130‐STAT3 signalling closely links gastric tumourigenesis with lymphoid neogenesis, and while a TLS gene signature was associated with advanced gastric cancer in patients, it did not indicate a favourable prognosis. PMID:29417587

Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization.

PubMed

Coffin, S E; Clark, S L; Bos, N A; Brubaker, J O; Offit, P A

1999-09-15

Parenterally administered immunizations have long been used to induce protection from mucosal pathogens such as Bordetella pertussis and influenza virus. We previously found that i.m. inoculation of mice with the intestinal pathogen, rotavirus, induced virus-specific Ab production by intestinal lymphocytes. We have now used adoptive transfer studies to identify the cell types responsible for the generation of virus-specific Ab production by gut-associated lymphoid tissue (GALT) after i.m. immunization. Three days after i.m. immunization with rotavirus, cells obtained from the draining peripheral lymph nodes of donor mice were transferred into naive recipient mice. We found that intestinal lymphocytes produced rotavirus-specific Igs (IgM, IgA, and IgG) 2 wk after transfer of either unfractionated cells, or unfractionated cells rendered incapable of cellular division by mitomycin C treatment. Additional studies demonstrated that rotavirus-specific IgA, but not IgG, was produced by intestinal lymphocytes after transfer of purified B cells. Ig allotype analysis revealed that rotavirus-specific IgA was produced by intestinal B cells of recipient origin, suggesting that migration of Ag-presenting B cells from peripheral lymphoid tissues to GALT may contribute to the generation of mucosal IgA responses after parenteral immunization. Strategies that promote Ag uptake and presentation by B cells may enhance mucosal IgA production following parenteral immunization.

Dynamics of CCR5 Expression by CD4+ T Cells in Lymphoid Tissues during Simian Immunodeficiency Virus Infection

PubMed Central

Veazey, Ronald S.; Mansfield, Keith G.; Tham, Irene C.; Carville, Angela C.; Shvetz, Daniel E.; Forand, Amy E.; Lackner, Andrew A.

2000-01-01

Early viral replication and profound CD4+ T-cell depletion occur preferentially in intestinal tissues of macaques infected with simian immunodeficiency virus (SIV). Here we show that a much higher percentage of CD4+ T cells in the intestine express CCR5 compared with those found in the peripheral blood, spleen, or lymph nodes. In addition, the selectivity and extent of the CD4+ T-cell loss in SIV infection may depend upon these cells coexpressing CCR5 and having a “memory” phenotype (CD45RA−). Following intravenous infection with SIVmac251, memory CD4+ CCR5+ T cells were selectively eliminated within 14 days in all major lymphoid tissues (intestine, spleen, and lymph nodes). However, the effect on CD4+ T-cell numbers was most profound in the intestine, where cells of this phenotype predominate. The CD4+ T cells that remain after 14 days of infection lacked CCR5 and/or were naive (CD45RA+). Furthermore, when animals in the terminal stages of SIV infection (with AIDS) were examined, virtually no CCR5-expressing CD4+ T cells were found in lymphoid tissues, and all of the remaining CD4+ T cells were naive and coexpressed CXCR4. These findings suggest that chemokine receptor usage determines which cells are targeted for SIV infection and elimination in vivo. PMID:11069995

Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

PubMed Central

Bombardieri, Michele; Greenhill, Claire J.; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S.; Pitzalis, Costantino; Jenkins, Brendan J.

2015-01-01

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. PMID:26417004

Nasal septal abscess in association with pediatric acute rhinosinusitis.

PubMed

Tien, Duc A; Krakovitz, Paul; Anne, Samantha

2016-12-01

Nasal septal abscess (NSA) in the pediatric population is rare and can result in devastating complications. Objective of this study is to review a case series of pediatric patients presenting with NSA in association with acute rhinosinusitis (ARS) for possible risk factors and predisposing conditions. This is a retrospective review of pediatric patients that presented to a tertiary care hospital with nasal septal abscess associated with ARS. Patient demographics, presence of ARS, sinuses involved, and other potential risk factors were recorded. In addition, a literature review was conducted to evaluate other reported cases of NSA in association with ARS. Cases of NSA associated with trauma or other causes were excluded from analysis. Five patients with NSA were treated by the pediatric otolaryngology department of a tertiary care center from 2003 to 2014. Three of these cases were associated with ARS. Of these cases, the average age at diagnosis was 9.7 years. Two were male and one was female. In these cases, the bilateral frontal, maxillary and ethmoid sinuses were involved. Sphenoid involvement occurred in two patients. One case was associated with ipsilateral middle turbinate concha bullosa. The cartilaginous septum was compromised in all three cases. All patients were treated with incision and drainage. This is the largest case series of NSA described in the pediatric population. NSA is exceedingly rare but may be associated with ARS. While the etiology of NSA is not always clear, identifying and treating nasal septal abscesses early is imperative to reduce potentially devastating complications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ocular surface reconstruction with a tissue-engineered nasal mucosal epithelial cell sheet for the treatment of severe ocular surface diseases.

PubMed

Kobayashi, Masakazu; Nakamura, Takahiro; Yasuda, Makoto; Hata, Yuiko; Okura, Shoki; Iwamoto, Miyu; Nagata, Maho; Fullwood, Nigel J; Koizumi, Noriko; Hisa, Yasuo; Kinoshita, Shigeru

2015-01-01

Severe ocular surface diseases (OSDs) with severe dry eye can be devastating and are currently some of the most challenging eye disorders to treat. To investigate the feasibility of using an autologous tissue-engineered cultivated nasal mucosal epithelial cell sheet (CNMES) for ocular surface reconstruction, we developed a novel technique for the culture of nasal mucosal epithelial cells expanded ex vivo from biopsy-derived human nasal mucosal tissues. After the protocol, the CNMESs had 4-5 layers of stratified, well-differentiated cells, and we successfully generated cultured epithelial sheets, including numerous goblet cells. Immunohistochemistry confirmed the presence of keratins 3, 4, and 13; mucins 1, 16, and 5AC; cell junction and basement membrane assembly proteins; and stem/progenitor cell marker p75 in the CNMESs. We then transplanted the CNMESs onto the ocular surfaces of rabbits and confirmed the survival of this tissue, including the goblet cells, up to 2 weeks. The present report describes an attempt to overcome the problems of treating severe OSDs with the most severe dry eye by treating them using tissue-engineered CNMESs to supply functional goblet cells and to stabilize and reconstruct the ocular surface. The present study is a first step toward assessing the use of tissue-engineered goblet-cell transplantation of nonocular surface origin for ocular surface reconstruction. ©AlphaMed Press.

RT-PCR analysis of RNA extracted from Bouin-fixed and paraffin-embedded lymphoid tissues.

PubMed

Gloghini, Annunziata; Canal, Barbara; Klein, Ulf; Dal Maso, Luigino; Perin, Tiziana; Dalla-Favera, Riccardo; Carbone, Antonino

2004-11-01

In the present study, we have investigated whether RNA can be efficiently isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue specimens. To this aim, we applied a new and simple method that includes the combination of proteinase K digestion and column purification. By this method, we demonstrated that the amplification of long fragments could be accomplished after a pre-heating step before cDNA synthesis associated with the use of enzymes that work at high temperature. By means of PCR using different primers for two examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we amplified segments of cDNA obtained by reverse transcription of the isolated RNA extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues. Amplified fragments of the expected sizes were obtained for both genes tested indicating that this method is suitable for the isolation of high-quality RNA. To explore the possibility for giving accurate real time quantitative RT-PCR results, cDNA obtained from matched frozen, Bouin-fixed and formalin-fixed neoplastic samples (two diffuse large cell lymphomas, one plasmacytoma) was tested for the following target genes: CD40, Aquaporin-3, BLIMP1, IRF4, Syndecan-1. Delta threshold cycle (DeltaC(T)) values for Bouin-fixed and formalin-fixed paraffin-embedded tissues and their correlation with those for frozen samples showed an extremely high correlation (r > 0.90) for all of the tested genes. These results show that the method of RNA extraction we propose is suitable for giving accurate real time quantitative RT-PCR results.

Case report and surgical solution for nasal spine agenesis in a woman with Binder syndrome.

PubMed

Kansu, Leyla; Akkuzu, Babur; Avci, Suat

2008-07-01

Binder syndrome is an uncommon disorder of unknown etiology. It is characterized by hypoplasia of the nose and maxilla and altered morphology of the associated soft tissue. We report a 19-year-old Binder syndrome patient with short-nose deformity and anterior nasal spine agenesis. We present a surgical technique for nasal spine agenesis treatment. We used a titanium screw without a graft, which supported the nasal tip and increased tip projection. As there is good soft-tissue coverage over the screw, infection or extrusion was not encountered, and the patient had no complaints 1 year after surgery.

Persistence and responsiveness of immunologic memory in the absence of secondary lymphoid organs.

PubMed

Moyron-Quiroz, Juan E; Rangel-Moreno, Javier; Hartson, Louise; Kusser, Kim; Tighe, Michael P; Klonowski, Kimberly D; Lefrançois, Leo; Cauley, Linda S; Harmsen, Allen G; Lund, Frances E; Randall, Troy D

2006-10-01

Secondary lymphoid organs (SLOs) promote primary immune responses by recruiting naive lymphocytes and activated APCs. However, their role in the persistence or responsiveness of memory lymphocytes is unclear. We tested whether memory cells were maintained and could respond to challenge in the absence of SLOs. We found that influenza-specific CD8 cells in the lung acquired a memory phenotype, underwent homeostatic proliferation, recirculated through nonlymphoid tissues, and responded to and cleared a challenge infection in the complete absence of SLOs. Similarly, influenza-specific virus-neutralizing antibody was generated and maintained in the absence of SLOs. Inducible bronchus-associated lymphoid tissue (iBALT) was also formed in the lungs of previously infected mice and may provide a niche for the maintenance of memory cells at the local level. These data show that SLOs are dispensable for the maintenance of immunologic memory and directly demonstrate the utility of local tissues, such as iBALT, in secondary immune responses.

Chromosomal imbalances are associated with outcome of Helicobacter pylori eradication in t(11;18)(q21;q21) negative gastric mucosa-associated lymphoid tissue lymphomas.

PubMed

Fukuhara, Noriko; Nakamura, Tsuneya; Nakagawa, Masao; Tagawa, Hiroyuki; Takeuchi, Ichiro; Yatabe, Yasushi; Morishima, Yasuo; Nakamura, Shigeo; Seto, Masao

2007-08-01

Approximately 70% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas can be successfully treated with H. pylori eradication. The translocation t(11;18)(q21;q21) characteristic of MALT lymphoma is recognized as a marker for H. pylori independency, but this marker is found in only a half of the MALT lymphomas resistant to H. pylori eradication. Detailed analyses of the genomic features of eradication resistant as well as responsive groups are important for understanding their molecular basis. We performed array-based comparative genomic hybridization (array-CGH) for 29 gastric MALT lymphomas treated with H. pylori eradication. These comprised ten cases of t(11;18) positive MALT, nine cases of t(11;18) negative MALT with H. pylori dependency, and ten cases of t(11;18) negative MALT with H. pylori independency. Array-CGH analysis demonstrated that no significant genetic alterations were found in t(11;18) positive MALT lymphomas, but numerous genomic alterations were detected in t(11;18) negative MALT lymphomas. Many of these alterations were similar to those found in diffuse large B-cell lymphoma with trisomy 3 being the most recurrent alteration. Within the t(11;18) negative MALT lymphoma without large cell components group, genomic imbalances occurred more frequently in the H. pylori independent than in the H. pylori dependent group (P = 0.02). Genomic imbalances are associated with H. pylori independency in t(11;18) negative gastric MALT lymphomas. They may thus play an important role in the development of H. pylori independency.

PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.

PubMed

Wang, Y; Zhou, J; Zhang, Y; Wang, L; Liu, Y; Fan, L; Zhu, J; Xu, X; Huang, G; Li, X; Xun, W

2015-05-01

To determine the role of PRDM1, a key molecule for modulating the immune cells, in Warthin tumour (WT) pathogenesis. Forty paraffin-embedded parotid tissues of patients (mean age: 62.08 ± 11.90) with WT were retrieved from the pathology archives of Qindu Hospital from January 2012 to December 2012. The PRDM1 expression was investigated in a cohort of WT by immunohistochemistry. PRDM1 was expressed only on the epithelial component but not on ectopic lymphoid tissue of the tumour. Statistically, PRDM1 expression rates between WT glandular epithelial cells (40/40 cases) and the tumour-adjacent tissues (0/9 cases), and WT germinal centres (0/34 cases) and tonsil tissues (10/10 cases) were significantly different (P < 0.001), respectively. The PRDM1 expression appeared to play an essential role in WT pathogenesis. A better understanding of it might give options for revealing possible novel management strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nasal erosion as an uncommon sign of child abuse.

PubMed

Culotta, Paige A; Isaac, Reena; Sarpong, Kwabena; Chandy, Binoy; Cruz, Andrea; Donaruma-Kwoh, Marcella

2018-05-01

While various forms of facial trauma, bruising, burns, and fractures are frequently seen in cases of child abuse, purposeful nasal erosion has rarely been identified as a form of abusive injury. Progressive destruction of nasal tissue in children provokes a wide differential diagnosis crossing multiple subspecialties: infectious, primary immunodeficiencies, inflammatory conditions, malignancy, and genetic disorders. Progressive nasal erosion also can be a manifestation of child abuse. The proposed mechanism is repetitive mechanical denudation of the soft tissue and cartilage resulting in chronic inflammation, bleeding, and ultimately destruction of the insulted tissue. We report 6 cases of child abuse manifesting as overt nasal destruction. Copyright © 2018 Elsevier B.V. All rights reserved.

[The clinical characteristics and prognostic analysis of gastric mucosa-associated lymphoid tissue lymphoma of 103 cases].

PubMed

Li, Xiao-wu; Xia, Bing; Guo, Qing; Jin, Xin; Yu, Yong; Zhao, Zhi-gang; Wang, Xiao-fang; Wang, Ya-fei; Zhang, Yi-zhuo

2012-10-01

To analyze the clinical characteristics and prognosis of the patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The clinical characteristics and prognostic factors of 103 gastric MALT lymphoma patients admitted to our hospital from April 2001 to August 2011 were retrospectively analyzed. The onset of gastric MALT lymphoma was often insidious without specific clinical manifestation, the most common complaints were abdominal pain or discomfort, weight loss, poor appetite, nausea and vomiting. According to Musshoff staging system, 75(72.8%) patients were at early stages (I/II) and 28 (27.2%) patients at advanced stages (III/IV). There was no significant difference in five-year overall survival (OS) between the patients in surgery group and non-surgery group (60.4% vs 78.9%, respectively, P = 0072), while there was statistical difference in five-year progression-free survival (PFS) between the two groups (31.7% vs 52.8%, respectively, P = 0.023). Helicobacter pylori (Hp) was detected in 94 patients (91.2%). Anti-Hp treatment was effective with 100% overall response rate. In 94 patients with complete follow-up data, the 5-year OS rate was 75%, 5-year PFS rate was 46%. Univariate survival analysis showed that the B symptoms, Musshoff staging, performance staging, stage-modified IPI, levels of LDH, nodal involvement and levels of β(2)-microglobulin were correlated with OS and PFS (P < 0.05). The Cox regression analysis showed that Musshoff-III/IV stage, stage-modified IPI score > 2 and B symptoms were independent factor for OS (P < 0.05), whereas Musshoff-III/IV stage was independent factor for PFS (P = 0.027). The gastric MALT lymphoma had a favorable outcome with high OS rate. The anti-Hp therapy was an effective treatment for the gastric MALT lymphoma, which avoid the surgical trauma and improve the quality of life. The prognostic analysis showed that Musshoff staging, B symptoms or stage-modified IPI score were independent factors for OS and

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anacak, Yavuz, E-mail: yavuz.anacak@ege.edu.tr; Miller, Robert C.; Constantinou, Nikos

2012-01-01

Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIEmore » in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease

Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2

PubMed Central

Zanussi, S; Simonelli, C; Bortolin, M T; D'Andrea, M; Crepaldi, C; Vaccher, E; Nasti, G; Politi, D; Barzan, L; Tirelli, U; De Paoli, P

1999-01-01

This study presents the immunophenotypic and functional analysis of lymphocyte subsets obtained from peripheral blood and lymphoid tissue from HIV+ individuals treated with highly active anti-retroviral therapy (HAART) alone or in combination with 6 million units international (MUI) s.c. IL-2. Before treatment, the HIV+ patients had reduced CD4 and increased CD8 values in the peripheral blood and lymphoid tissue and impaired cytokine production by peripheral blood mononuclear cells (PBMC). After 24 weeks of treatment, all the HIV+ patients demonstrated increased CD4 values in peripheral blood and lymphoid tissue. The use of IL-2 did not promote an additional CD4 expansion compared with HAART alone; increased ‘naive’ and CD26+ CD4 cells and reduced CD8 cells were found in the peripheral blood and lymphoid tissue of the IL-2-treated, but not of the HAART-treated patients. Both types of treatment induced a significant reduction of the CD8/CD38+ cells. While HAART alone had negligible effects on cytokine production by PBMC, the combined use of HAART + IL-2 was unable to increase the endogenous production of IL-2, but caused an increase of IL-4, IL-13 and interferon-gamma (IFN-γ) and a reduction of monocyte chemoattractant protein-1 (MCP-1) production. These data suggest that, although in this schedule IL-2 has minimal efficacy on CD4 recovery when compared with HAART alone, it produces an increase of ‘naive’ and CD26+CD4 cells and a partial restoration of cytokine production. These data may be used to better define clinical trials aiming to improve the IL-2-dependent immunological reconstitution of HIV-infected subjects. PMID:10361239

Lymphoid disorders associated with HHV-8/KSHV infection: facts and contentions.

PubMed

Gaidano, G; Castaños-Velez, E; Biberfeld, P

1999-04-01

Following the demonstration in 1994, that Kaposi's sarcoma (KS) was associated with a novel virus (KSHV or HHV-8) belonging to the lymphotropic herpes family, this virus was also found in certain lymphoid neoplasias of immunodeficient (HIV+) and immune competent hosts. The association of HHV-8/KSHV infection is now well established with primary effusion lymphoma (PEL) or body cavity based lymphoma (BCBL) and multicentric Castleman's disease (MCD) of the plasma cell type. A possible pathogenic role of HHV-8/KSHV in other lymphoid tumours including primary central nervous system lymphoma (PCNSL) and multiple myeloma (MM) as well as some atypical lymphoproliferations and sarcoidosis has also been suggested, but this is at present a controversial matter, or not confirmed. Several HHV-8/KSHV genes, including potential oncogenes, genes homologous to various cellular genes and growth factors have been incriminated in the pathogenesis of KS and PEL/BCBL, but a common pathogenic mechanism for the clearly diverse proliferations represented by PEL, MCD and KS is at present not evident.

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer.

PubMed

Hoover, Clare E; Davenport, Kristen A; Henderson, Davin M; Denkers, Nathaniel D; Mathiason, Candace K; Soto, Claudio; Zabel, Mark D; Hoover, Edward A

2017-05-15

Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrP CWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrP CWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrP CWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrP CWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrP CWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrP CWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

Pathways of Prion Spread during Early Chronic Wasting Disease in Deer

PubMed Central

Hoover, Clare E.; Davenport, Kristen A.; Henderson, Davin M.; Denkers, Nathaniel D.; Mathiason, Candace K.; Soto, Claudio; Zabel, Mark D.

2017-01-01

ABSTRACT Among prion infections, two scenarios of prion spread are generally observed: (i) early lymphoid tissue replication or (ii) direct neuroinvasion without substantial antecedent lymphoid amplification. In nature, cervids are infected with chronic wasting disease (CWD) prions by oral and nasal mucosal exposure, and studies of early CWD pathogenesis have implicated pharyngeal lymphoid tissue as the earliest sites of prion accumulation. However, knowledge of chronological events in prion spread during early infection remains incomplete. To investigate this knowledge gap in early CWD pathogenesis, we exposed white-tailed deer to CWD prions by mucosal routes and performed serial necropsies to assess PrPCWD tissue distribution by real-time quaking-induced conversion (RT-QuIC) and tyramide signal amplification immunohistochemistry (TSA-IHC). Although PrPCWD was not detected by either method in the initial days (1 and 3) postexposure, we observed PrPCWD seeding activity and follicular immunoreactivity in oropharyngeal lymphoid tissues at 1 and 2 months postexposure (MPE). At 3 MPE, PrPCWD replication had expanded to all systemic lymphoid tissues. By 4 MPE, the PrPCWD burden in all lymphoid tissues had increased and approached levels observed in terminal disease, yet there was no evidence of nervous system invasion. These results indicate the first site of CWD prion entry is in the oropharynx, and the initial phase of prion amplification occurs in the oropharyngeal lymphoid tissues followed by rapid dissemination to systemic lymphoid tissues. This lymphoid replication phase appears to precede neuroinvasion. IMPORTANCE Chronic wasting disease (CWD) is a universally fatal transmissible spongiform encephalopathy affecting cervids, and natural infection occurs through oral and nasal mucosal exposure to infectious prions. Terminal disease is characterized by PrPCWD accumulation in the brain and lymphoid tissues of affected animals. However, the initial sites of prion

Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.

PubMed

Zeng, Ming; Paiardini, Mirko; Engram, Jessica C; Beilman, Greg J; Chipman, Jeffrey G; Schacker, Timothy W; Silvestri, Guido; Haase, Ashley T

2012-08-30

Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.

Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution

PubMed Central

Zeng, Ming; Paiardini, Mirko; Engram, Jessica C.; Beilman, Greg J.; Chipman, Jeffrey G.; Schacker, Timothy W.; Silvestri, Guido

2012-01-01

Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1–infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution. PMID:22613799

Computed tomography as an aid in the diagnosis of chronic nasal disease in dogs.

PubMed

Lefebvre, J; Kuehn, N F; Wortinger, A

2005-06-01

To assess the use of computed tomography (CT) in the diagnosis of chronic nasal disease in dogs. A retrospective study of 85 dogs with chronic nasal discharge due to primary nasal disease, which had undergone nasal CT and biopsy, was carried out. Medical records were reviewed for signalment, clinical signs, CT findings, endoscopic findings and histopathology. The results obtained via CT were correlated with nasal histopathology and gross anatomical observations were recorded at the time of rhinoscopy. Neoplasia was diagnosed in 37 dogs for which CT typically revealed a soft tissue density associated with extensive turbinate destruction. Inflammatory rhinitis was diagnosed in 40 dogs. CT disclosed either normal turbinate structures or mild to moderate turbinate destruction, with or without the presence of soft tissue densities (mucopus) within the nasal passages. Fungal rhinitis was diagnosed in seven dogs for which CT disclosed extensive turbinate destruction with hyperlucency of the nasal passages. One dog had normal CT and histopathology findings. CT greatly enhanced the ability to diagnose chronic nasal disease in dogs, providing detailed Information regarding the extent of the disease, accurate discrimination of neoplastic versus non-neoplastic diseases, and identification of areas of the nose to examine rhinoscopically and suspicious regions to target for biopsy.

Treatment of gastric marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue with rituximab, cyclophosphamide, vincristine and prednisone.

PubMed

Aguiar-Bujanda, David; Llorca-Mártinez, Ignacio; Rivero-Vera, José C; Blanco-Sánchez, María J; Jiménez-Gallego, Pedro; Mori-De Santiago, Marta; Limeres-Gonzalez, Miguel A; Cabrera-Marrero, José C; Hernández-Sosa, María; Galván-Ruíz, Saray; Hernández-Sarmiento, Samuel; Saura Grau, Salvador; Bohn-Sarmiento, Uriel

2014-09-01

There is no standard treatment for patients with gastric marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who are resistant to, or ineligible for, anti-Helicobacter pylori (anti-HP) therapy. In this study, we investigated the activity of the rituximab, cyclophosphamide, vincristine and prednisone (R-CVP) regimen in patients with gastric MALT lymphoma. Patients were included provided they had untreated gastric MALT lymphoma (except for anti-HP therapy) and were resistant to, or ineligible for, anti-HP therapy. Treatment plan consisted of six to eight 21-day cycles of the R-CVP chemotherapy regimen. Toxicity, response, relapse and survival were evaluated. Twenty patients (12 women and 8 men) were included in the analyses with median age of 59 years. Thirteen patients (65%) had stage I tumours, and seven patients (35%) had stages II-IV tumours. The overall response rate was 100%, with 19 (95%) complete responses and one (5%) partial response. Regimen toxicity was mild and mainly hematological, and no cases of gastric bleeding or perforation occurred. After a median follow-up of 56.3 months, three patients had relapsed, and 19 patients remained alive (specific lymphoma survival 100%), of whom 17 had no evidence of disease. In our experience, the R-CVP regimen is a well-tolerated and effective treatment for patients with gastric MALT lymphoma who are resistant to, or ineligible for, anti-HP therapy. Copyright © 2013 John Wiley & Sons, Ltd.

Anatomy of nasal complex in the southern right whale, Eubalaena australis (Cetacea, Mysticeti).

PubMed

Buono, Mónica R; Fernández, Marta S; Fordyce, R Ewan; Reidenberg, Joy S

2015-01-01

The nasal region of the skull has undergone dramatic changes during the course of cetacean evolution. In particular, mysticetes (baleen whales) conserve the nasal mammalian pattern associated with the secondary function of olfaction, and lack the sound-producing specializations present in odontocetes (toothed whales, dolphins and porpoises). To improve our understanding of the morphology of the nasal region of mysticetes, we investigate the nasal anatomy, osteology and myology of the southern right whale, Eubalaena australis, and make comparisons with other mysticetes. In E. australis external deflection surfaces around the blowholes appear to divert water off the head, and differ in appearance from those observed in balaenopterids, eschrichtiids and cetotherids. In E. australis the blowholes are placed above hypertrophied nasal soft tissues formed by fat and nasal muscles, a pattern also observed in balaenopterids (rorqual mysticetes) and a cetotherid (pygmy right whale, Caperea marginata). Blowhole movements are due to the action of five nasofacial muscles: dilator naris superficialis, dilator naris profundus, depressor alae nasi, constrictor naris, and retractor alae nasi. The dilator naris profundus found in E. australis has not been previously reported in balaenopterids. The other nasofacial muscles have a similar arrangement in balaenopterids, with minor differences. A novel structure, not reported previously in any mysticete, is the presence of a vascular tissue (rete mirabile) covering the lower nasal passage. This vascular tissue could play a role in warming inspired air, or may engorge to accommodate loss of respiratory space volume due to gas compression from increased pressure during diving. © 2014 Anatomical Society.

Anatomy of nasal complex in the southern right whale, Eubalaena australis (Cetacea, Mysticeti)

PubMed Central

Buono, Mónica R; Fernández, Marta S; Fordyce, R Ewan; Reidenberg, Joy S

2015-01-01

The nasal region of the skull has undergone dramatic changes during the course of cetacean evolution. In particular, mysticetes (baleen whales) conserve the nasal mammalian pattern associated with the secondary function of olfaction, and lack the sound-producing specializations present in odontocetes (toothed whales, dolphins and porpoises). To improve our understanding of the morphology of the nasal region of mysticetes, we investigate the nasal anatomy, osteology and myology of the southern right whale, Eubalaena australis, and make comparisons with other mysticetes. In E. australis external deflection surfaces around the blowholes appear to divert water off the head, and differ in appearance from those observed in balaenopterids, eschrichtiids and cetotherids. In E. australis the blowholes are placed above hypertrophied nasal soft tissues formed by fat and nasal muscles, a pattern also observed in balaenopterids (rorqual mysticetes) and a cetotherid (pygmy right whale, Caperea marginata). Blowhole movements are due to the action of five nasofacial muscles: dilator naris superficialis, dilator naris profundus, depressor alae nasi, constrictor naris, and retractor alae nasi. The dilator naris profundus found in E. australis has not been previously reported in balaenopterids. The other nasofacial muscles have a similar arrangement in balaenopterids, with minor differences. A novel structure, not reported previously in any mysticete, is the presence of a vascular tissue (rete mirabile) covering the lower nasal passage. This vascular tissue could play a role in warming inspired air, or may engorge to accommodate loss of respiratory space volume due to gas compression from increased pressure during diving. PMID:25440939

Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis.

PubMed

Hayashi, Seishu; Imamura, Jun; Kimura, Kiminori; Saeki, Shunichi; Hishima, Tsunekazu

2015-01-01

Small, round, yellowish-white nodules (YWN) are frequently observed in Helicobacter pylori-associated gastritis. The aim of the present study was to investigate the clinical significance of these YWN. Participants comprised 211 patients with H. pylori-associated gastritis, ranging in age from 23 to 86 years. YWN were detected in 23% of participants, more frequently in women (33%) than in men (12%; P < 0.01). YWN were observed on the antral mucosa in 4.7% of cases, lesser curvature of the corpus mucosa in 20%, greater curvature of the corpus mucosa in 0.9%, and fundic mucosa in 12%. Most YWN located on the antral mucosa showed nodular type, and most YWN located on the corpus mucosa and fundic mucosa showed flat type. On magnifying endoscopy with narrow-band imaging, YWN appeared as round whitish lesions with radial or branching microvessels on the surface and hypovascular globe structures just beneath the surface of the mucosa. Targeted biopsies of YWN revealed lymphoid follicles with lymphocyte infiltration or intense inflammatory cell infiltration. The endoscopic finding of YWN could be observed at any site of the gastric mucosa in H. pylori-associated gastritis, and represented histological lymphoid follicles. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by Salmonella

PubMed Central

Lim, Chee Han; Voedisch, Sabrina; Wahl, Benjamin; Rouf, Syed Fazle; Geffers, Robert

2014-01-01

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. PMID:25079958

Nasal packing and stenting

PubMed Central

Weber, Rainer K.

2011-01-01

Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

The development of the immune tissues in marsupial pouch young.

PubMed

Borthwick, Casey R; Young, Lauren J; Old, Julie M

2014-07-01

Current knowledge of the development of the marsupial immune system, particularly in the context of lymphoid tissue development and the appearance of lymphocytes, has been examined and limitations identified. While primary lymphoid tissues like the thymus have been extensively studied, secondary lymphoid tissues such as the spleen and lymph nodes have been examined to a lesser extent, partly due to the difficulty of macroscopically identifying these structures, particularly in very small neonates. In addition, little research has been conducted on the mucosal-associated lymphoid tissues; tissues that directly trap antigens and play an important role in the maturity of adaptive immune responses. Research on the development of the marsupial immune tissues to date serves as a solid foundation for further research, particularly on the mechanisms behind the development of the immune system of marsupials. With the recent sequencing and annotation of whole marsupial genomes, the current wealth of sequence data will be essential in the development of marsupial specific reagents, including antibodies, that are required to widen our specific knowledge of the complex marsupial immune system and its development. © 2014 Wiley Periodicals, Inc.

Cellular changes in tears associated with keratoconjunctival responses induced by nasal allergy.

PubMed

Pelikan, Z

2014-04-01

Allergic keratoconjunctivitis occurs in a primary form, caused by an allergic reaction localized in the conjunctiva, and in a secondary form, induced by an allergic reaction originating in the nasal mucosa. Various hypersensitivity mechanisms involved in the keratoconjunctivitis forms result in different keratoconjunctival response types. To investigate the cytologic changes in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed (SDYKCR) keratoconjunctival responses. In 61 patients, comprising 20 SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens and 61 phosphate-buffered control challenges were repeated and supplemented with cell counting in the tears. The SIKCR (P<0.01), appearing 10-120 min after the NPT, was associated with increased eosinophil and mast cell counts in tears. The SLKCR (P<0.01), appearing 5-12 h after the NPT, was accompanied by increased counts of eosinophils, neutrophils, basophils, and conjunctival epithelial and goblet cells. The SDYKCR (P<0.05), appearing 24-48 h after NPT, was associated with increased counts of lymphocytes, neutrophils, monocytes, basophils, conjunctival epithelial, corneal epithelial and goblet cells. The SIKCR, SLKCR, and SDYKCR, induced by nasal allergy, were associated with different cellular profiles in the tears. The cells, except mast, epithelial and goblet cells, displaying no intracellular changes, migrated probably from the conjunctival capillaries, in response to the factors released during the primary allergic reaction in the nasal mucosa and subsequently penetrating into the conjunctiva. These results demonstrate a causal role of nasal allergy and diagnostic value of NPT combined with recording of ocular features and cellular profiles in tears in some keratoconjunctivitis patients.

Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor

PubMed Central

Kuzin, Igor; Sun, Hongliang; Moshkani, Safiekhatoon; Feng, Changyong; Mantalaris, Athanasios; Wu, JH David; Bottaro, Andrea

2011-01-01

Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g. T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three-dimensional bioreactor system for long-term, functional culture of human bone marrow cells on macroporous microspheres in a packed-bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell-enriched areas. Strikingly, these cultures generated a significant number of antibody-producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three-dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. PMID:21309085

Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor.

PubMed

Kuzin, Igor; Sun, Hongliang; Moshkani, Safiekhatoon; Feng, Changyong; Mantalaris, Athanasios; Wu, J H David; Bottaro, Andrea

2011-06-01

Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g., T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological, and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three-dimensional bioreactor system for long-term, functional culture of human bone marrow cells on macroporous microspheres in a packed-bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell-enriched areas. Strikingly, these cultures generated a significant number of antibody-producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three-dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. Copyright © 2011 Wiley Periodicals, Inc.

Measuring and Characterizing the Human Nasal Cycle

PubMed Central

Kahana-Zweig, Roni; Geva-Sagiv, Maya; Weissbrod, Aharon; Secundo, Lavi; Soroker, Nachum; Sobel, Noam

2016-01-01

Nasal airflow is greater in one nostril than in the other because of transient asymmetric nasal passage obstruction by erectile tissue. The extent of obstruction alternates across nostrils with periodicity referred to as the nasal cycle. The nasal cycle is related to autonomic arousal and is indicative of asymmetry in brain function. Moreover, alterations in nasal cycle periodicity have been linked to various diseases. There is therefore need for a tool allowing continuous accurate measurement and recording of airflow in each nostril separately. Here we provide detailed instructions for constructing such a tool at minimal cost and effort. We demonstrate application of the tool in 33 right-handed healthy subjects, and derive several statistical measures for nasal cycle characterization. Using these measures applied to 24-hour recordings we observed that: 1: subjects spent slightly longer in left over right nostril dominance (left = 2.63 ± 0.89 hours, right = 2.17 ± 0.89 hours, t(32) = 2.07, p < 0.05), 2: cycle duration was shorter in wake than in sleep (wake = 2.02 ± 1.7 hours, sleep = 4.5 ± 1.7 hours, (t(30) = 5.73, p < 0.0001). 3: slower breathing was associated with a more powerful cycle (the extent of difference across nostrils) (r = 0.4, p < 0.0001), and 4: the cycle was influenced by body posture such that lying on one side was associated with greater flow in the contralateral nostril (p < 0.002). Finally, we provide evidence for an airflow cycle in each nostril alone. These results provide characterization of an easily obtained measure that may have diagnostic implications for neurological disease and cognitive state. PMID:27711189

A new concept of skin-associated lymphoid tissue (SALT): UVB light impaired cutaneous immunity reveals a prominent role for cutaneous nerves.

PubMed

Streilein, J W; Alard, P; Niizeki, H

1999-03-01

More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part on evidence that cutaneous contact hypersensitivity (CH) reactions are closely correlated with Langerhans cells (LC). Recent reports have demonstrated that LC have neural connectivity with cutaneous nerve termini containing calcitonin gene-related peptide (CGRP), suggesting that a link exists between innervation and immune responses in the skin. Here we discuss the neural components which have recently been found to be participants in skin-associated lymphoid tissue (SALT). In part, discovery of a functional link between the nervous system and SALT is based on studies in which cutaneous immunity was impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on cutaneous immunity include failed CH induction and promotion of hapten-specific tolerance, effects that are mediated by tumor necrosis factor-alpha and interleukin-10, respectively. The source of these cytokines after UVR appears to be dermal mast cells. Evidence indicates that mast cells are triggered to release these cytokines in response to CGRP, which is released from UVR-damaged cutaneous nerve endings. Moreover, a substance P agonist was able to reverse the deleterious effects of UVR on CH induction, rendering the mice able to develop intense CH. These observations indicate that two cell types not originally included in the SALT concept are critical to the functional integrity of cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous nerves dictate whether antigen applied to or arising within skin will lead to sensitivity or tolerance.

Comparison between endoscopic macroscopic classification and F-18 FDG PET findings in gastric mucosa-associated lymphoid tissue lymphoma patients.

PubMed

Hirose, Yasumitsu; Kaida, Hayato; Ishibashi, Masatoshi; Uozumi, Jun; Arikawa, Shunji; Kurata, Seiji; Hayabuchi, Naofumi; Nakahara, Keita; Ohshima, Koichi

2012-02-01

The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis-like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis-like tumors and 40% for depressed-type tumors. F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.

Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia in nasal polyps.

PubMed

Yu, Xue Min; Li, Chun Wei; Li, Ying Ying; Liu, Jing; Lin, Zhi Bin; Li, Tian Ying; Zhao, Li; Pan, Xin Liang; Shi, Li; Wang, De Yun

2013-11-01

The aim of this study was to assess protein and mRNA expression of epithelial membrane protein 1 (EMP1) in the nasal mucosa of patients with nasal polyps (NP), and to determine what changes occur in response to glucocorticosteroid (GC) treatment. NP tissue was obtained from 55 patients, 18 of whom were treated with nasal GCs (i.e. these 18 patients had NP biopsies taken before and after treatment). Biopsies of inferior turbinate mucosa from 30 healthy subjects were used as controls. Quantitative PCR and immunohistochemistry were performed to determine the expression levels of EMP1. EMP1 mRNA expression was significantly lower (2.77-fold) in tissues from NP patients before GC treatment when compared to controls, but was increased in these patients after GC treatment. EMP1 staining in nasal epithelium co-localized with both basal (p63(+)) and differentiated (CK18(+)) epithelial cells. Their immunoreactivity was significantly greater in controls than NP patients. EMP1 mRNA levels were lower in the epithelium with severe hyperplasia (1.79-fold) or with metaplasia (1.85-fold) as compared to those with mild to moderate hyperplasia or non-metaplastic epithelium, respectively. Positive correlations between EMP1 and other epithelial cell-related gene (e.g. JUN, PTGS2, AREG etc.) mRNAs were observed. EMP1 could be a biomarker for aberrant epithelial remodelling and metaplasia in chronic inflammatory upper airway mucosa (e.g. NP). © 2013 John Wiley & Sons Ltd.

Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers.

PubMed

Liu, Xia; Tsang, Julia Y S; Hlaing, Thazin; Hu, Jintao; Ni, Yun-Bi; Chan, Siu Ki; Cheung, Sai Yin; Tse, Gary M

2017-11-01

The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival. In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined. Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated with hormone receptors negativity, HER2 positivity, and c-kit expression. Tertiary lymphoid structures were significantly related to better disease-free survival (DFS) in HER2 positive (HER2+) breast cancers (log-rank = 4.054), which was not dependent on high TIL status. The combined TLS and TIL status was an independent favorable factor associated with DFS in those cases. Interestingly, tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It was associated with LVI in HER2 negative (HER2-) TLS positive (particularly estrogen receptor positive [ER+] HER2-) cases. In the ER+ HER2- cases, tumor cell infiltration into TLS was also associated with increased pathologic nodal stage (pN) stage and nodal involvement. Tertiary lymphoid structures showed a similar relationship with clinicopathologic features and biomarkers as TIL. The presence of TLS, irrespective of TIL level, could be an important favorable prognostic indicator in HER2+ breast cancer patients. Given the significance of TLS in promoting effective antitumor immunity, further understanding of its organization and induction may provide new opportunities to improve the current immunotherapy strategies. Despite recent interest on the clinical value of tumor infiltrating lymphocyte (TIL), little was known on the clinical significance on their spatial organization as tertiary lymphoid structures (TLS

Blindness associated with nasal/paranasal lymphoma in a stallion.

PubMed

Sano, Yuto; Okamoto, Minoru; Ootsuka, Youhei; Matsuda, Kazuya; Yusa, Shigeki; Taniyama, Hiroyuki

2017-03-23

A 29-year-old stallion presented with bilateral blindness following the chronic purulent nasal drainage. The mass occupied the right caudal nasal cavity and right paranasal sinuses including maxillary, palatine and sphenoidal sinuses, and the right-side turbinal and paranasal septal bones, and cribriform plate of ethmoid bone were destructively replaced by the mass growth. The right optic nerve was invaded and involved by the mass, and the left optic nerve and optic chiasm were compressed by the mass which was extended and invaded the skull base. Histologically, the optic nerves and optic chiasm were degenerated, and the mass was diagnosed as lymphoma which was morphologically and immunohistochemically classified as a diffuse large B-cell lymphoma. Based on these findings, the cause of the blindness in the stallion was concluded to be due to the degeneration of the optic nerves and chiasm associated with lymphoma occurring in the nasal and paranasal cavities. To the best of our knowledge, this is the first report of the equine blindness with optic nerve degeneration accompanied by lymphoma.

Cellular changes in tears associated with keratoconjunctival responses induced by nasal allergy

PubMed Central

Pelikan, Z

2014-01-01

Background Allergic keratoconjunctivitis occurs in a primary form, caused by an allergic reaction localized in the conjunctiva, and in a secondary form, induced by an allergic reaction originating in the nasal mucosa. Various hypersensitivity mechanisms involved in the keratoconjunctivitis forms result in different keratoconjunctival response types. Purpose To investigate the cytologic changes in tears during the secondary immediate (SIKCR), late (SLKCR), and delayed (SDYKCR) keratoconjunctival responses. Methods In 61 patients, comprising 20 SIKCRs, 23 SLKCRs, and 18 SDYKCRs, nasal provocation tests (NPTs) with allergens and 61 phosphate-buffered control challenges were repeated and supplemented with cell counting in the tears. Results The SIKCR (P<0.01), appearing 10–120 min after the NPT, was associated with increased eosinophil and mast cell counts in tears. The SLKCR (P<0.01), appearing 5–12 h after the NPT, was accompanied by increased counts of eosinophils, neutrophils, basophils, and conjunctival epithelial and goblet cells. The SDYKCR (P<0.05), appearing 24–48 h after NPT, was associated with increased counts of lymphocytes, neutrophils, monocytes, basophils, conjunctival epithelial, corneal epithelial and goblet cells. Conclusions The SIKCR, SLKCR, and SDYKCR, induced by nasal allergy, were associated with different cellular profiles in the tears. The cells, except mast, epithelial and goblet cells, displaying no intracellular changes, migrated probably from the conjunctival capillaries, in response to the factors released during the primary allergic reaction in the nasal mucosa and subsequently penetrating into the conjunctiva. These results demonstrate a causal role of nasal allergy and diagnostic value of NPT combined with recording of ocular features and cellular profiles in tears in some keratoconjunctivitis patients. PMID:24434662

Premalignant gastric lesions in patients with gastric mucosa-associated lymphoid tissue lymphoma and metachronous gastric adenocarcinoma: a case-control study.

PubMed

Capelle, Lisette G; den Hoed, Caroline M; de Vries, Annemarie C; Biermann, Katharina; Casparie, Mariel K; Meijer, Gerrit A; Kuipers, Ernst J

2012-01-01

Patients with gastric mucosa-associated lymphoid tissue lymphoma or diffuse large B-cell lymphoma have an increased risk of developing gastric carcinoma (GC). Identifying patients at high GC risk may lead to improved survival and prognosis. The aim of this case-control study was to evaluate whether premalignant gastric lesions are more prevalent and severe in gastric lymphoma (GL) patients with a subsequent diagnosis of GC than in those without GC. Patients with a first GL diagnosis from 1991-2008 were identified in the Dutch histopathology registry (PALGA). Cases were patients with a diagnosis of GL and a subsequent diagnosis of GC. Controls were patients with a diagnosis of GL without GC development. In total, eight cases (mean follow-up 5.5 years) and 31 controls (mean follow-up 5.3 years) were included (mean age 60 years). At lymphoma diagnosis, six (75%) cases were diagnosed with premalignant lesions, whereas in the control group, 21 (68%) had histological evidence for premalignant lesions (P=0.69). At GC diagnosis, five (63%) cases showed intestinal metaplasia in the surrounding gastric mucosa. In 22 (71%) controls premalignant lesions were present at the end of follow-up (P=0.47). No differences were demonstrated in the prevalence of premalignant lesions of cases and controls at GL diagnosis or the end of follow-up. As the prevalence of premalignant lesions is substantial in both the groups of patients, careful endoscopic surveillance of GL patients is warranted not only for recurrence of lymphoma, but also for progression to adenocarcinoma.

Long-Term Outcomes of 107 Cases of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma at a Single Medical Institution in Japan.

PubMed

Watanabe, Natsuko; Narimatsu, Hiroto; Noh, Jaeduk Yoshimura; Iwaku, Kenji; Kunii, Yo; Suzuki, Nami; Ohye, Hidemi; Suzuki, Miho; Matsumoto, Masako; Yoshihara, Ai; Kameyama, Kaori; Kobayashi, Kazuhiko; Kami, Masahiro; Sugino, Kiminori; Ito, Koichi

2018-02-01

Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis. To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma. Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed. Overall and event-free survival (EFS). Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively. Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities. Copyright © 2017 Endocrine Society

Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

PubMed

Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

2011-01-18

Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea piglymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Group 2 innate lymphoid cells in disease

PubMed Central

2016-01-01

Abstract Group 2 innate lymphoid cells (ILC2) are now recognized as an important innate source of type-2 effector cytokines. Although initially associated with mucosal tissues, it is clear that ILC2 are present in diverse anatomical locations. The function of ILC2 at these sites is equally varied, and although ILC2 represent a relatively minor population, they are fundamentally important regulators of innate and adaptive immune processes. As such, there is much interest to understand the role of ILC2 in diseases with a type-2 inflammatory component. This review explores the known roles of ILC2 in disease, and the diseases that show associations or other strong evidence for the involvement of ILC2. PMID:26306498

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

PubMed

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.

Human nasal polyp microenvironments maintained in a viable and functional state as xenografts in NOD-scid IL2rgamma(null) mice.

PubMed

Bernstein, Joel M; Brooks, Stephen P; Lehman, Heather K; Pope, Liza; Sands, Amy; Shultz, Leonard D; Bankert, Richard B

2009-12-01

The objective was to develop a model with which to study the cellular and molecular events associated with nasal polyp progression. To accomplish this, we undertook to develop a system in which nondisrupted human nasal polyp tissue could be successfully implanted into severely immunocompromised mice, in which the histopathology of the original nasal polyp tissue, including inflammatory lymphocytes, epithelial and goblet cell hyperplasia, and subepithelial fibrosis, could be preserved for prolonged periods. Small, non-disrupted pieces of human nasal polyp tissues were subcutaneously implanted into NOD-scid IL2rgamma(null) mice. Xenografts at 8 to 12 weeks after implantation were examined histologically and immunohistochemically to identify human inflammatory leukocytes and to determine whether the characteristic histopathologic characteristics of the nasal polyps were maintained for a prolonged period. The xenografts, spleen, lung, liver, and kidneys were examined histologically and immunohistochemically and were evaluated for changes in volume. The sera of these mice were assayed for human cytokines and immunoglobulin. Xenografts of human nasal polyp tissues were established after their subcutaneous implantation into NOD-scid IL2rgamma(null) mice. The xenografts were maintained in a viable and functional state for up to 3 months, and retained a histopathologic appearance similar to that of the original tissue, with a noticeable increase in goblet cell hyperplasia and marked mucus accumulation in the submucosal glands compared to the original nasal polyp tissue. Inflammatory lymphocytes present in the polyp microenvironment were predominantly human CD8+ T cells with an effector memory phenotype. Human CD4+ T cells, CD138+ plasma cells, and CD68+ macrophages were also observed in the xenografts. Human immunoglobulin and interferon-gamma were detected in the sera of xenograft-bearing mice. The polyp-associated lymphocytes proliferated and were found to migrate from

Immunohistochemical investigation of the cross-reactivity of selected cell markers in formalin-fixed, paraffin-embedded lymphoid tissues of Franciscana (Pontoporia blainvillei).

PubMed

Díaz-Delgado, J; Ressio, R; Groch, K R; Catão-Dias, J L

2018-06-01

A considerable amount of knowledge on natural and anthropogenic pathologic conditions affecting different cetacean species has been gained over the last decades. Nonetheless, the immunopathological bases for most of these processes have been poorly documented or remain unknown. Comparative immunopathological investigations in these species are precluded by the limited number of specific antibodies, most of which are not commercially available, and the reduced spectrum of validated and/or cross-reactive ones. To partially fill in this gap of knowledge, a set of commercially available primary antibodies were tested for cross-reactivity against leukocytes and cytokines in formalin-fixed, paraffin-embedded (FFPE) lymphoid tissues (lymph nodes, spleen and thymus) of three bycaught, apparently healthy and fresh Franciscanas (Pontoporia blainvillei) using immunohistochemistry. On the basis of similar region specificity within the lymphoid organs, cellular morphology and staining pattern with human control tissues, 13/19 primary antibodies (caspase 3, CD3, CD57, CD68, FoxP3, HLA-DRα, IFNγ, IgG, IL4, IL10, Lysozyme, TGFβ and PAX-5) exhibited satisfactory cross-reactivity. Our results expand the spectrum of suitable cross-reactive primary antibodies in FFPE cetacean tissues. Further comparative immunopathological studies focused on infectious diseases and ecotoxicology may benefit from establishment of baseline expression of immunologically relevant molecules in various cetaceans species. Copyright © 2018 Elsevier B.V. All rights reserved.

Innate lymphoid cells in normal and disease: An introductory overview.

PubMed

Moretta, Lorenzo; Locatelli, Franco

2016-11-01

Innate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-γ. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL-4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORγt TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells [1]. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Extranodal NK÷T-cell lymphoma, nasal type with cutaneous involvement - a rare case associated with chronic C hepatitis and occupational metal dust exposure.

PubMed

Ştefănescu, Eugen Horaţiu; Balica, Nicolae Constantin; Horhat, Ioana Delia; Baderca, Flavia; Pricop, Marius Octavian; Urechescu, Horaţiu Constantin; Lighezan, Daniel Florin; Sarău, Cristian Andrei

2017-01-01

Extranodal natural killer (NK)÷T-cell lymphomas, nasal type are rare and aggressive non-Hodgkin's lymphomas (NHLs), with unknown etiology, rapid evolution and poor prognosis, due to midline tissue destruction and rapid spreading of the tumor. These lymphomas occur commonly in the nasal cavity and upper aerodigestive tract, but can also present involvement of the skin, salivary gland, and testis. We describe a case of nasal type T-cell NHL involving the nasal cavity and determining right thigh cutaneous metastases in a 47-year-old female associated with liver comorbidities and occupational dust exposure. The patient was suffering from chronic type C hepatitis and cirrhosis and she has been occupationally exposed to metal dust for 10 years. Clinical and laboratory investigations were performed. Essential for diagnosis and treatment protocol was nasal endoscopy and biopsy of nasal and cutaneous lesions. The histopathological exam was consistent with NK÷T-cell lymphoma. Patient was diagnosed in Ann Arbor stage IVA. Chemotherapy was initiated with Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine and Prednisone, but it was stopped after two cycles because of the liver condition. The treatment plan also included radiotherapy, but soon after initiation, the patient died because of a liver complication. We present a rare case of extranodal NK÷T-cell lymphoma, nasal type, with cutaneous involvement to which the treatment could not be properly applied because of the late diagnosis and liver comorbidities.

Treatment of nasal burns: analysis of 150 cases

PubMed Central

Prousskaia, E.; El-Muttardi, N.; Philp, B.; Dziewulski, P.; Shelley, O.P.

2015-01-01

Summary Nasal burns present a challenge for the plastic surgeon in terms of immediate management, choice of primary treatment and secondary reconstruction with the goals of good aesthetic and functional outcome. We present a retrospective analysis of the management of 150 patients with nasal burns treated in our center between July 2005 and July 2011. We rationalized our conservative and all surgical treatments of this subset of burns patients and organized them in a simple and structured way. The reconstructive options for most complex full thickness nasal injury is determined by the integrity of adjacent facial tissues which would always be preferred when available. Microsurgical free tissue transfer is dependent upon the fitness of the patient and the availability of unburned skin at the donor site. Secondary nasal reconstruction is based on an assessment of the residual functional and cosmetic problems. Airways narrowing from scar contracture or loss of support are managed using standard plastic surgical and rhinoplasty principles. Cosmetic refinements range from flap debulking to the importation of new tissue on to the nose. Our experience with this challenging group of patients has led us to develop a simple treatment algorithm for the management of nasal burns. PMID:27252610

Three-dimensional Evaluation of Nasal Surgery in Patients with Obstructive Sleep Apnea.

PubMed

Cui, Dan-Mo; Han, De-Min; Nicolas, Busaba; Hu, Chang-Long; Wu, Jun; Su, Min-Min

2016-03-20

Obstructive sleep apnea (OSA) is a common sleep disorder and is characterized by airway collapse at multiple levels of upper airway. The effectiveness of nasal surgery has been discussed in several studies and shows a promising growing interest. In this study, we intended to evaluate the effects of nasal surgery on the upper airway dimensions in patients with OSA using three-dimensional (3D) reconstruction of cone-beam computed tomography (CT). Twelve patients with moderate to severe OSA who underwent nasal surgery were included in this study. All patients were diagnosed with OSA using polysomnography (PSG) in multi sleep health centers associated with Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary and the Partners Health Care from May 31, 2011 to December 14, 2013. The effect of nasal surgery was evaluated by the examination of PSG, subjective complains, and 3D reconstructed CT scan. Cross-sectional area was measured in eleven coronal levels, and nasal cavity volume was evaluated from anterior nasal spine to posterior nasal spine. The thickness of soft tissue in oral pharynx region was also measured. Five out of the 12 patients were successfully treated by nasal surgery, with more than 50% drop of apnea-hypopnea index. All the 12 patients showed significant increase of cross-sectional area and volume postoperatively. The thickness of soft tissue in oral pharynx region revealed significant decrease postoperatively, which decreased from 19.14 ± 2.40 cm 2 and 6.11 ± 1.76 cm 2 to 17.13 ± 1.91 cm 2 and 5.22 ± 1.20 cm 2 . Nasal surgery improved OSA severity as measured by PSG, subjective complaints, and 3D reconstructed CT scan. 3D assessment of upper airway can play an important role in the evaluation of treatment outcome.

Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Naoki; Sasaki, Ryohei, E-mail: rsasaki@med.kobe-u.ac.jp; Nishimura, Hideki

2012-03-15

Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66more » months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.« less

Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with multiple pure ground-glass opacities: a case report.

PubMed

Ding, Xuebing; Makino, Takashi; Koezuka, Satoshi; Azumi, Takashi; Otsuka, Hajime; Hata, Yoshinobu; Shinya, Yuichi; Tochigi, Naobumi; Shibuya, Kazutoshi; Iyoda, Akira

2017-01-25

Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell lymphoma that is a type of non-Hodgkin lymphoma and a type of primary pulmonary malignant lymphoma. MALT lymphomas affecting the lung show various findings on chest computed tomography, which range from typical nodules or areas of consolidation to findings that are extremely rare in pulmonary MALT lymphomas, such as pure ground-glass opacities throughout the lung. A 35-year-old woman was found to have a few shadows with ground glass opacities on chest computed tomography (CT) in 2012. A shadow in right S10 that was initially very small increased in size over time, and was 14 × 8 mm in 2015. Other shadows also appeared. Because lung adenocarcinoma was suspected, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Histopathological examination of the right S10 and other lesions revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact. Immunohistochemical staining showed that tumor cells were positive for CD20, CD79a, and BCL2 expression. The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT. We think that the ground glass opacities on CT were accounted for by MALT lesions that contained intact alveolar air spaces. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

PubMed

Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

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

PubMed Central

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

Nasal Chondromesenchymal Hamartoma in a Child

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finitsis, Stefanos; Giavroglou, Constantinos; Potsi, Stamatia, E-mail: matinapotsi@hotmail.co

Nasal chondromesenchymal hamartoma (NCMH) is a benign tumor that was described in 1998. The occurrence of this lesion in the nasal cavity of infants and children is especially rare, with only 21 cases reported in the international literature. We report a 12-month-old boy with respiratory distress due to nasal obstruction. Computed tomographic scan and magnetic resonance imaging examination demonstrated a soft-tissue mass obstructing the left nasal cavity. Digital subtraction angiography and preoperative superselective embolization with microparticles were also performed. The tumor was completely resected surgically. Histopathology and immunohistochemical analyses of the tumor disclosed a NCMH. The imaging characteristics of themore » tumor are described and the radiology literature is reviewed.« less

Type two innate lymphoid cells; the Janus cells in health and disease

PubMed Central

Maazi, Hadi; Akbari, Omid

2017-01-01

Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

Type two innate lymphoid cells: the Janus cells in health and disease.

PubMed

Maazi, Hadi; Akbari, Omid

2017-07-01

Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pathoadaptation of the Intracellular Bacteria Shigella and Chlamydia: Virulence, Antivirulence, and Tissue Tropism

DTIC Science & Technology

2015-04-27

innate immune mechanisms, the bacteria must also prevent or avoid adaptive immune responses such as B cell antibody production and, in the case of...residing in the intestinal lumen and 13 present them to immune cells in the underlying lymphoid tissue. M cells are situated in the region of the...Peyer‟s Patches (or gut-associated lymphoid tissue (GALT)), enteric bacteria transcytosed through M cells must then contend with macrophages, T

Anatomy of the nasal profile

PubMed Central

Anderson, K J; Henneberg, M; Norris, R M

2008-01-01

There is a lack in the understanding of the variation within the thickness of the soft tissue structures (muscle, skin and fat) overlying the cartilaginous skeleton of the nose and their relationship to the dorsum shape. We examined such relationships by dissecting noses of six adult female and six adult male cadavers, comparing the internal anatomical structures to the external nasal profile. We found that the soft tissue structures differ in thickness along the dorsum and that these differences are individualized. Specifically, continuous presence of subcutaneous fat from root to tip was found in half the sample, one nose had fat only on the tip, another one only on the root, the four others at both positions. The nasalis muscle was identifiable in nine of the 12 noses, transversing the nose in half the sample, and in the remaining three, only the lateral section of the muscle was identified. The superior border of the septal cartilage does not form a linear extension of the profile contour of the nasal bones but angles downwards. The actual profile contour of the dorsum does not follow the profile of the nasal bones or the septal cartilage. These results may influence the current use of nasal guidelines in forensic facial approximation. PMID:19172735

Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire

NASA Technical Reports Server (NTRS)

Miracle, A. L.; Anderson, M. K.; Litman, R. T.; Walsh, C. J.; Luer, C. A.; Rothenberg, E. V.; Litman, G. W.

2001-01-01

Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

Prion pathogenesis and secondary lymphoid organs (SLO)

PubMed Central

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

Nasal Cavity Masses Resembling Chondro-osseous Respiratory Epithelial Adenomatoid Hamartomas in 3 Dogs.

PubMed

LaDouceur, E E B; Michel, A O; Lindl Bylicki, B J; Cifuentes, F F; Affolter, V K; Murphy, B G

2016-05-01

Chondro-osseous respiratory epithelial adenomatoid hamartomas (COREAHs) are rare tumors in the nasal cavity of people, which have not been described in other species. COREAHs in people are minimally invasive and rarely recur following excision. Histologically, these tumors are composed of disorganized, mature, nasal turbinate tissue that is organized into polypoid growths. These growths are lined by respiratory epithelium, contain glandular elements, and are organized around central cores of chondro-osseous matrix. This report describes 3 cases of dogs with nasal tumors that have histomorphology similar to that of COREAH in people. The tumors were all identified within the nasal cavity and were associated with regional bony lysis of the turbinates and surrounding skull bones, a feature that has not been reported in COREAH in people. There was no evidence of metastasis or extension beyond the nasal cavity in any of the 3 cases. © The Author(s) 2015.

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

PubMed

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.

Aberrant Huntingtin interacting protein 1 in lymphoid malignancies.

PubMed

Bradley, Sarah V; Smith, Mitchell R; Hyun, Teresa S; Lucas, Peter C; Li, Lina; Antonuk, Danielle; Joshi, Indira; Jin, Fang; Ross, Theodora S

2007-09-15

Huntingtin interacting protein 1 (HIP1) is an inositol lipid, clathrin, and actin binding protein that is overexpressed in a variety of epithelial malignancies. Here, we report for the first time that HIP1 is elevated in non-Hodgkin's and Hodgkin's lymphomas and that patients with lymphoid malignancies frequently had anti-HIP1 antibodies in their serum. Moreover, p53-deficient mice with B-cell lymphomas were 13 times more likely to have anti-HIP1 antibodies in their serum than control mice. Furthermore, transgenic overexpression of HIP1 was associated with the development of lymphoid neoplasms. The HIP1 protein was induced by activation of the nuclear factor-kappaB pathway, which is frequently activated in lymphoid malignancies. These data identify HIP1 as a new marker of lymphoid malignancies that contributes to the transformation of lymphoid cells in vivo.

Reduced nasal growth after primary nasal repair combined with cleft lip surgery.

PubMed

Yoshimura, Y; Okumoto, T; Iijima, Y; Inoue, Y

2015-11-01

Nasal growth after cleft lip surgery with or without primary nasal repair was evaluated using lateral cephalograms. In 14 patients who underwent simultaneous nasal repair with primary cleft lip repair and 12 patients without simultaneous nasal repair, lateral cephalograms were obtained at 5 and 10 years of age. Lateral cephalograms of normal Japanese children were used as a control. At 5 years of age, there were significant differences in the nasal height and columellar angle among the three groups. Children without simultaneous nasal repair had shorter noses with more upward tilt of the columella compared with the controls, while children with simultaneous nasal repair had much shorter noses and more upward tilt than those without repair. At 10 years of age, the children without simultaneous nasal repair showed no differences from the control group, while those with simultaneous repair still had shorter noses and more upward tilt of the columella. These findings suggest that performing nasal repair at the same time as primary cleft lip surgery has an adverse influence on the subsequent growth of the nose. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Innate lymphoid cells and asthma.

PubMed

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.

Innate lymphoid cells in atherosclerosis.

PubMed

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.

Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes.

PubMed

Bardsley, Katie; Kwarciak, Agnieska; Freeman, Christine; Brook, Ian; Hatton, Paul; Crawford, Aileen

2017-01-01

The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5-10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6 fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31-45 μm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed. Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume

Accessory cells in physiological lymphoid tissue from the intestine: an immunohistochemical study.

PubMed

Sarsfield, P; Rinne, A; Jones, D B; Johnson, P; Wright, D H

1996-03-01

We report a study of the organization of accessory cell populations, in normal mucosal lymphoid tissue from small intestine (8 cases), large intestine (6) and appendix (9) using a panel of monoclonal antibodies and polyclonal antisera in paraffin-embedded tissue. Two populations were identified in dome areas, one positive for acid cysteine proteinase inhibitor and HLA class II (WR18) only and the second positive for S-100 protein, CD68, and WR18 and negative for acid cysteine proteinase inhibitor and factor XIIIa. Superficial colonic mucosal and small intestinal villous tip macrophages stained positively with CD68 and WR18 only, while deeper cryptal and submucosal populations exhibited additional positivity for factor XIIIa, but both populations were negative for acid cysteine proteinase inhibitor and S-100 protein. Germinal centre macrophages were positive for CD68, WR18 and acid cysteine proteinase inhibitor and negative for factor XIIIa, and S-100 protein. T zone dendritic cells included a population which stained positively for S-100 protien, WR18 and were negative for factor XIIIa, CD68 and acid cysteine proteinase inhibitor, an immunophenotype typical of interdigitating dendritic reticulum cells. This distribution of phenotypically identifiable accessory cell subpopulations was apparent at all three sites examined. We suggest that the specialized subpopulations of dendritic cells staining for S-100 protein and for acid cysteine proteinase inhibitor which are restricted to the dome areas, may have a potential role in the transfer of antigen across the epithelium to the germinal centres, while factor XIIIa appears to identify a tissue macrophage population with a potential role in stromal modulation distant from direct antigen challenge.

Appraisal of transverse nasal groove: a study.

PubMed

Sathyanarayana, Belagola D; Basavaraj, Halevoor B; Nischal, Kuchangi C; Swaroop, Mukunda R; Umashankar, Puttagangu N; Agrawal, Dhruv P; Swamy, Suchetha S; Okram, Sarda

2012-01-01

Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

PubMed

Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua

2017-01-29

The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.

The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

PubMed

Rumfelt, L L; McKinney, E C; Taylor, E; Flajnik, M F

2002-08-01

Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

PubMed Central

Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.

2014-01-01

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

Inverted papillomas and benign nonneoplastic lesions of the nasal cavity

PubMed Central

Casiano, Roy R.

2012-01-01

Background: Benign lesions of the nasal cavity represent a diverse group of pathologies. Furthermore, each of these disorders may present differently in any given patient as pain and discomfort, epistaxis, headaches, vision changes, or nasal obstruction. Although these nasal masses are benign, many of them have a significant capacity for local tissue destruction and symptomatology secondary to this destruction. Advances in office-based endoscopic nasendoscopy have equipped the otolaryngologist with a safe, inexpensive, and rapid means of directly visualizing lesions within the nasal cavity and the initiation of appropriate treatment. Methods: The purpose of this study is to review the diagnosis, management, and controversies of many of the most common benign lesions of the nasal cavity encountered by the primary care physician or otolaryngologist. Results: This includes discussion of inverted papilloma (IP), juvenile angiofibroma, squamous papilloma, pyogenic granuloma, hereditary hemorrhagic telangiectasia, schwannoma, benign fibro-osseous lesions, and other benign lesions of the nasal cavity, with particular emphasis on IP and juvenile angiofibroma. Conclusion: A diverse array of benign lesions occur within the nasal cavity and paranasal cavities. Despite their inability to metastasize, many of these lesions have significant capability for local tissue destruction and recurrence. PMID:22487294

Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease.

PubMed

Kim, J S; Chung, S J; Choi, Y S; Cheon, J H; Kim, C W; Kim, S G; Jung, H C; Song, I S

2007-05-07

A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2-3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11-125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10-22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication.

Helicobacter pylori eradication for low-grade gastric mucosa-associated lymphoid tissue lymphoma is more successful in inducing remission in distal compared to proximal disease

PubMed Central

Kim, J S; Chung, S J; Choi, Y S; Cheon, J H; Kim, C W; Kim, S G; Jung, H C; Song, I S

2007-01-01

A series of studies has shown that Helicobacter pylori eradication induces remission in most patients with low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, there have been few reports about the effect of bacterial treatment on the gastric MALT lymphoma in Korea, a well-known H. pylori endemic area. A total of 111 H. pylori-infected patients were prospectively enrolled in Seoul National University Hospital and 99 among them were completely followed up according to our protocol. After H. pylori eradication, tumoural response was evaluated by endoscopy and histopathology every 2–3 months till complete remission (CR) and every 6 months after achieving CR. Median follow-up period was 41 months (range, 11–125 months). Helicobacter pylori was successfully eradicated in all 99 patients and CR was obtained in 84 (84.8%) of 99 patients. The median time to reach CR was 3 months and 94% of CR is in continuous complete remission. Five patients with CR relapsed after 10–22 months without the evidence of H. pylori reinfection. Cumulative recurrence rate was 2.3, 7.7 and 9.3% at 1, 2 and 3 years, respectively. Tumours were mainly located in distal stomach (67.7%) and tumours in distal stomach were associated with more favourable response than those in proximal stomach (P=0.001). Majority of patients with low-grade gastric MALT lymphoma treated by exclusive H. pylori eradication have a favourable long-term outcome, offering a real chance of cure. Tumour location could be a predictive factor for remission following H. pylori eradication. PMID:17406363

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

PubMed

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.

Helicobacter pylori Eradication Therapy Is Effective as the Initial Treatment for Patients with H. pylori-Negative and Disseminated Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

PubMed Central

Gong, Eun Jeong; Ahn, Ji Yong; Jung, Hwoon-Yong; Park, Hyungchul; Ko, Young Bo; Na, Hee Kyong; Jung, Kee Wook; Kim, Do Hoon; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

2016-01-01

Background/Aims We investigated the effectiveness of Helicobacter pylori eradication therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma regardless of the H. pylori infection status or disease stage. Methods From November 1995 to September 2014, 345 subjects who were diagnosed with gastric MALT lymphoma and had received eradication therapy as their first-line treatment were eligible for inclusion in this study. A retrospective review was performed using the medical records. Results Of the 345 patients, H. pylori infection was detected in 317 patients (91.9%). The complete remission (CR) rate after eradication therapy was 82.3%, which was higher in H. pylori-positive patients than in H. pylori-negative patients (84.5% vs 57.1%, p=0.001). CR rates after eradication did not present significant differences between stages, and the CR rate was 83.3% for stage IE1 and 74.4% for stage IE2 or above (p=0.167). The overall CR rate was 87.2% after additional treatment, and neither H. pylori infection status nor stage showed differences according to the treatment response. Conclusions Eradication therapy led to CR in 57.1% of H. pylori-negative patients and in 74.4% of patients with stage IE2 or above. Eradication therapy is worthwhile as an initial treatment for gastric MALT lymphoma regardless of the H. pylori infection status and stage. PMID:27114423

Airflow, gas deposition, and lesion distribution in the nasal passages.

PubMed Central

Morgan, K T; Monticello, T M

1990-01-01

The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. Images FIGURE 4. FIGURE 6. FIGURE 7. PMID:2200663

Silicone nasal prosthesis retained by an intranasal stent: a clinical report.

PubMed

Goveas, Reiyal; Puttipisitchet, Ongart; Shrestha, Binit; Thaworanunta, Sita; Srithavaj, M L Theerathavaj

2012-08-01

Nasal defects after tumor excision can leave a patient functionally and esthetically impaired. Loss of nasal septal cartilage support causes the soft tissue to collapse or undergo stenosis, further compounding the problem. Intranasal stents can be used to maintain the patency of such nasal defects. This clinical report describes the use of an acrylic resin nasal stent bonded to a silicone nasal prosthesis to rehabilitate a patient with a nasal defect. Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

The lymphoid cell network in the skin.

PubMed

Tikoo, Shweta; Jain, Rohit; Kurz, Angela Rm; Weninger, Wolfgang

2018-05-01

Cutaneous immunity represents a crucial component of the mammalian immune response. The presence of a large array of commensal microorganisms along with a myriad of environmental stresses necessitates constant immuno-surveillance of the tissue. To achieve a perfect balance between immune-tolerance and immune-activation, the skin harbors strategically localized immune cell populations that modulate these responses. To maintain homeostasis, innate and adaptive immune cells assimilate microenvironmental cues and coordinate cellular and molecular functions in a spatiotemporal manner. The role of lymphoid cells in cutaneous immunity is gaining much appreciation due to their important roles in regulating skin health and pathology. In this review, we aim to highlight the recent advances in the field of cutaneous lymphoid biology. © 2018 Australasian Society for Immunology Inc.

Intranasal tissue necrosis associated with opioid abuse: Case report and systematic review.

PubMed

Morrison, Danielle A; Wise, Sarah K; DelGaudio, John M; Chowdhury, Naweed I; Levy, Joshua M

2017-12-27

Opioid abuse is a common disorder affecting over 2 million Americans. Intranasal tissue necrosis is a previously described sequela of nasal opioid inhalation, with a similar presentation to invasive fungal rhinosinusitis (IFRS). The goal of this case report and systematic review is to evaluate the evidence supporting this uncommon disease, with qualitative analysis of the presentation, management and treatment outcomes. MEDLINE, EMBASE, Google Scholar, Scopus, and Web of Science. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting intranasal mucosal injury associated with prescription opioid abuse. Primary outcomes included clinical presentation, treatment strategies, and outcomes. Systematic review identified 61 patients for qualitative analysis. Common clinical features include facial pain without a history of chronic sinusitis or known immunodeficiency. Diagnostic nasal endoscopy revealed superficial debris with underlying tissue necrosis, consistent with a preliminary diagnosis of IFRS. Characteristic pathologic findings include mucosal ulceration with an overlying acellular substrate, often with polarizable material. Fungal colonization is often reported, with several accounts of angiocentric invasion in immunocompetent patients. Complete symptom resolution is expected following surgical debridement with cessation of intranasal opioid inhalation, with 89% of identified patients experiencing a complete resolution of disease. Intranasal opioid abuse is a prevalent condition associated with chronic pain and tissue necrosis that is clinically concerning for invasive fungal disease. Whereas IFRS must be excluded, even in patients without known immunodeficiency, complete resolution of symptoms can be expected following surgical debridement with cessation of opioid abuse. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Impact assessment of repeated exposure of organotypic 3D bronchial and nasal tissue culture models to whole cigarette smoke.

PubMed

Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C

2015-02-12

Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers.

Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury.

PubMed

Cao, Qi; Wang, Yiping; Niu, Zhiguo; Wang, Chengshi; Wang, Ruifeng; Zhang, Zhiqiang; Chen, Titi; Wang, Xin Maggie; Li, Qing; Lee, Vincent W S; Huang, Qingsong; Tan, Jing; Guo, Minghao; Wang, Yuan Min; Zheng, Guoping; Yu, Di; Alexander, Stephen I; Wang, Hui; Harris, David C H

2018-03-01

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33-treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo -expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo -expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33-ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy. Copyright © 2018 by the American Society of Nephrology.

Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodgers, D.A.; Nikula, K.J.; Avila, K.

1995-12-01

The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models tomore » human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.« less

Clinical manifestations and epigenetic mechanisms of gastric mucosa associated lymphoid tissue lymphoma and long-term follow-up following Helicobacter pylori eradication

PubMed Central

Song, Yan; Jiang, Kui; Su, Shuai; Wang, Bangmao; Chen, Guangxia

2018-01-01

The current study aimed to summarize the clinical manifestations and identify the epigenetic mechanisms of gastric mucosa associated lymphoid tissue (MALT) lymphoma, as well as evaluate the long-term effects of Helicobacter pylori (H. pylori) eradication. A total of 122 patients with marginal zone B-cell lymphoma of primary gastric MALT lymphoma were enrolled in the present study. The clinical manifestations of gastric MALT lymphoma, including symptoms, H. pylori state and endoscopic type, were summarized. The response to therapy was evaluated in patients that underwent H. pylori eradication. Survival analysis was estimated using the Kaplan-Meier method. The expression of microRNA-383 (miR-383) in tumor tissues and cell lines was determined using reverse transcription quantitative polymerase chain reaction. Furthermore, bioinformatic analyses, luciferase reporter assays. and western blot analysis identified zinc finger E-box binding homeobox 2 (ZEB2) as a direct target gene of miR-383. An MTT assay was used to examine the function of miR-383 and ZEB2 in MALT lymphoma. The clinical symptoms of patients with gastric MALT lymphoma were non-specific and included epigastric pain, abdominal discomfort and bleeding. The majority of endoscopic types were classified as ulcer, erosion and mucosa edema. The H. pylori infection rate was 79.5% (97/122) and a total of 47 patients underwent eradication therapy. Lymphoma remission was achieved in 93.6% (44/47) of patients and complete remission (CR) was achieved in 74.4% (35/47). The median follow-up time was 38 months (range, 10–132 months) and the median time taken to achieve CR was 4 months (range, 3–7 months). The estimated 3-year survival rate was 90.3% and the 5-year survival rate was 76.2%. Therefore, it was determined that patients with stage I or II gastric MALT lymphoma are able to undergo H. pylori eradication as a first-line treatment and that the survival rate of patients undergoing this treatment is high

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

PubMed Central

Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

2010-01-01

Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID:18671762

A nasal dermoid sinus in an English bull terrier.

PubMed

Burrow, R D

2004-11-01

A five-year-old, entire female English bull terrier was presented with a six-week history of intermittent facial swelling and nasal pain, following an incident of nasal trauma. A small opening was present at the mucocutaneous junction on the dorsal nasal planum. Examination under general anaesthesia allowed catheterisation of this opening and confirmed the presence of a tract passing caudally. Plain radiographic examination of the region was unremarkable. Positive contrast sinography demonstrated contrast material filling a midline tract that passed caudally and subcutaneously towards the nasal bone. This tract was surgically excised. Histopathological examination of the excised tissue, together with the clinical findings, led to the diagnosis of nasal dermoid sinus.

Nasal dermoid cyst extending through the frontal bone with no sinus tract in a Dalmatian.

PubMed

van der Peijl, G J W; Schaeffer, I G F

2011-02-01

A Dalmatian was presented with a subcutaneous swelling in the dorsal midline between the eyes. No opening in the skin was identified at the dorsal nasal planum and there was no discharge. Positive contrast sinography showed contrast material filling a cyst that extended to the frontal bone. At surgery, the cyst had a tubular shape and was embedded in a fibrous dermal tissue strand running into the bony nasal septum. The nasal dermoid sinus cyst was surgically removed by limited dorsal rhinotomy, followed by excision of the remaining strand from a bony recess in the lamina perpendicularis ethmoidalis. It is proposed that this nasal dermoid cyst that extends through the frontal bone with no sinus tract is classified as a type V subtype c. © 2011 British Small Animal Veterinary Association.

Perception of Better Nasal Patency Correlates with Increased Mucosal Cooling after Surgery for Nasal Obstruction

NASA Astrophysics Data System (ADS)

Garcia, Guilherme; Sullivan, Corbin; Frank-Ito, Dennis; Kimbell, Julia; Rhee, John

2014-11-01

Nasal airway obstruction (NAO) is a common health problem with 340,000 patients undergoing surgery annually in the United States. Traditionally, otolaryngologists have focused on airspace cross-sectional areas and nasal resistance to airflow as objective measures of nasal patency, but neither of these variables correlated consistently with patients' symptoms. Given that the sensation of nasal airflow is also associated with mucosal cooling (i.e., heat loss) during inspiration, we investigated the correlation between the sensation of nasal obstruction and mucosal cooling in 10 patients before and after NAO surgery. Three-dimensional models of the nasal anatomy were created based on pre- and post-surgery computed tomography scans. Computational fluid dynamics (CFD) simulations were conducted to quantify nasal resistance and mucosal cooling. Patient-reported symptoms were measured by a visual analog scale and the Nasal Obstruction Symptom Evaluation (NOSE), a disease-specific quality of life questionnaire. Our results revealed that the subjective sensation of nasal obstruction correlated with both nasal resistance and heat loss, but the strongest correlation was between the NOSE score and the nasal surface area where heat flux exceeds 50 W /m2 . In conclusion, a significant post-operative increase in mucosal cooling correlates well with patients' perception of better nasal patency after NAO surgery.

Cellular comparison of sinus mucosa vs polyp tissue from a single sinus cavity in chronic rhinosinusitis.

PubMed

Ho, Jacqueline; Bailey, Michelle; Zaunders, John; Mrad, Nadine; Sacks, Raymond; Sewell, William; Harvey, Richard J

2015-01-01

Nasal polyposis is a common development in chronic rhinosinusitis (CRS), and sinus mucosa and polyp tissue have been used interchangeably in studies investigating CRS. However, potential differences may exist between these 2 tissue types, which have not been entirely characterized. A cross-sectional study of CRS with nasal polyposis (CRSwNP) patients undergoing endoscopic sinus surgery was conducted. Sinus mucosal biopsies and corresponding polyp tissue were obtained from the same sinus cavity via flow cytometry, single-cell suspensions identified type 2 innate lymphoid cells (ILC2s), CD4 and CD8 T cells, activated CD4 and CD8 T cells, plasma cells, plasmacytoid dendritic cells (pDCs), regulatory T cells, T follicular helper cells, B cells, and immunoglobulin A (IgA)(+) and IgG(+) B cells. Cells were measured as a percentage of CD45(+) cells. Paired nonparametric comparisons between sinus and polyp tissue were performed. Ten patients (50% female; age 48 ± 16 years) were recruited. Significantly elevated ILC2 levels were found in polyp tissue compared to sinus mucosa (0.12 [0.07 to 0.23] vs 0.07 [0.04 to 0.16], p = 0.02), as well as plasma cells (2.25 [0.84 to 3.68] vs 1.18 [0.74 to 2.41], p = 0.01); pDCs (0.15 [0.12 to 0.50[ vs 0.04 [0.02 to 0.17], p = 0.03); activated CD8 T cells (29.22 [17.60 to 41.43] vs 16.32 [10.07 to 36.16], p = 0.04) and IgG(+) B cells (6.96 [0.06 to 11.82] vs 1.51 [0.38 to 5.13], p = 0.04). Other cell populations showed no significant differences. Polyps have a similar cellular composition to that of mucosa. Higher levels of ILC2s, plasma cells, pDCs, activated CD8 T cells, and IgG(+) B cells in polyp tissue may be reflective of cell populations driving nasal polyp development. The cellular machinery of CRS is present in polyps and representative of the disease process. This pilot study strongly suggests that a larger study would provide significant insights into the relationship of sinus mucosa to pathogenesis of nasal polyps. © 2014 ARS

Cancer Immunosurveillance by Tissue-resident Innate Lymphoid Cells and Innate-like T Cells

PubMed Central

Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M.; Franklin, Ruth A.; Luo, Chong T.; Oh, Soyoung A.; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S.; Li, Ming O.

2016-01-01

Summary Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRαβ and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells. PMID:26806130

Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes

PubMed Central

ANDERSSON, A; QVARFORDT, I; LAAN, M; SJÖSTRAND, M; MALMHÄLL, C; RIISE, G C; CARDELL, L-O; LINDÉN, A

2004-01-01

CD4+ and CD8+ lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8+ cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4+ lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4+ or CD8+ lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Rα) protein were also measured in conditioned medium from human blood CD4+ and CD8+ lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription–polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Rα in conditioned medium from CD4+ and CD8+ lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8+ cytokine IL-16, in the airway lumen, in blood CD4+ and CD8+ lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4+ lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD. PMID:15373908

The expression of 11β-hydroxysteroid dehydrogenase type 1 and 2 in nasal polyp-derived epithelial cells and its possible contribution to glucocorticoid activation in nasal polyp.

PubMed

Kook, Jin Ho; Kim, Hyun Jin; Kim, Kyung Won; Park, Se Jin; Kim, Tae Hoon; Lim, Sae Hee; Kang, Sung Hoon; Lee, Sang Hag

2015-01-01

The actions of glucocorticoids in target tissues depend on the local metabolism of glucocorticoids catalyzed by 11β hydroxysteroid dehydrogenase (HSD) 1 and 2. Glucocorticoids are the most effective anti-inflammatory drugs in the treatment of nasal polyps. However, the mechanisms that underlie the anti-inflammatory effects are unclear. The present study analyzed the expression of 11β-HSD1, 11β-HSD2, and steroidogenic enzymes (cytochrome P450, family 11, subfamily B, polypeptide 1 [CYP11B1]; cytochrome P450, family 11, subfamily A, polypeptide 1 [CYP11A1]) in nasal polyp tissues, and endogenous cortisol levels in nasal polyp-derived epithelial cells. The expression levels and distribution pattern of 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1 were determined in nasal polyp tissues or nasal polyp-derived epithelial cells by using real-time polymerase chain reaction, Western blot, and immunohistochemistry testing. The expression levels of cortisol by using enzyme-linked immunosorbent assay were determined in cultured polyp-derived epithelial cells treated with adrenocorticotrophic hormone (ACTH), 11β-HSD1 inhibitor, or small interfering ribonucleic acid technique. The effect of glucocorticoids on the expression levels of these enzymes was investigated in cultured cells. Expressed in nasal polyp tissues and nasal polyp-derived epithelial cells were 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1. Cortisol production in cultured epithelial cells was decreased in cells treated with 11β-HSD1 small interfering ribonucleic acid or inhibitor, compared with nontreated cells. Cultured cells treated with adrenocorticotropic hormone induced increased cortisol production. 11β-HSD1 expression levels were upregulated in cells treated with glucocorticoid. Analysis of these results indicated that 11β-HSD1 expressed in polyp-derived epithelial cells may be involved in the anti-inflammatory function of glucocorticoid in the treatment of nasal polyps, which contributes to increased

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals

PubMed Central

Bailey, Ryan S.; Casey, Kevin P.; Pawar, Sachin S.; Garcia, Guilherme J. M.

2016-01-01

Importance Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. Objective To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy subjects. Design, Setting, and Participants Twenty-two healthy adults were recruited for this study. Subjects first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale (VAS) to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in two locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Results The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (ΔTexp-insp = 6.2 ± 2.6°C) than during resting breathing (ΔTexp-insp = 4.2 ± 2.3°C) in both locations (p < 10−13). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side VAS score (Pearson r = −0.55, p=0.0076) and NOSE score (Pearson r = −0.47, p=0.028). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower in the first cavity to be measured, which was the right cavity in all subjects. Conclusions and Relevance The greater mucosal temperature oscillations during deep breathing is consistent with the common experience that airflow sensation is enhanced during deep breaths, thus supporting the hypothesis that mucosal cooling plays a central role in nasal airflow sensation

Role of innate lymphoid cells in obesity and metabolic disease

PubMed Central

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

The Yin and Yang of Innate Lymphoid Cells in Cancer.

PubMed

Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

2016-11-01

The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

PubMed

Cao, Weiping; Kim, Jin Hyang; Reber, Adrian J; Hoelscher, Mary; Belser, Jessica A; Lu, Xiuhua; Katz, Jacqueline M; Gangappa, Shivaprakash; Plante, Martin; Burt, David S; Sambhara, Suryaprakash

2017-06-05

Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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.

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

PubMed Central

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

Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

PubMed

Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

2017-01-01

Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Occurrence of lymphohaemopoietic tissue in the meninges of the stingray Dasyatis akajei (Elasmobranchii, chondricthyes).

PubMed

Chiba, A; Torroba, M; Honma, Y; Zapata, A G

1988-11-01

The cytoarchitecture of the lymphohaemopoietic masses occurring in the "meninx primitiva" of the stingray Dasyatis akajei (Elasmobranchii, Chondricthyes) has been analyzed by light and scanning and transmission electron microscopy. Lymphohaemopoietic aggregates showing similar morphologies occurred along all the central nervous system, but they were more frequent in the telencephalon, diencephalon, and mesencephalon. In each aggregate, the granulopoietic tissue appeared in a fibroblastic stroma surrounding the large blood vessels, and the lymphoid components were present in a reticular network. Developing and mature eosinophils and heterophils--as well as lymphocytes, monocytes, macrophages, and plasma cells--are the main free cells present in these meningeal aggregates. The remarkable intimate association between macrophages and lymphoid cells to form close cell clusters suggests some immunological capacity for the meningeal lymphohaemopoietic tissue. According to their capacities, presence of lymphoid tissue, and histological organization, the meningeal lymphohemopoietic aggregates of Dasyatis akajei resemble other lymphomyeloid aggregates associated with cranium and choroid plexuses in Holocephali and Ganoidei. The phylogenetical relationships of these aggregates with mammalian bone marrow are discussed.

Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity

PubMed Central

Germain, Claire; Gnjatic, Sacha; Dieu-Nosjean, Marie-Caroline

2015-01-01

It is now admitted that the immune system plays a major role in tumor control. Besides the existence of tumor-specific T cells and B cells, many studies have demonstrated that high numbers of tumor-infiltrating lymphocytes are associated with good clinical outcome. In addition, not only the density but also the organization of tumor-infiltrating immune cells has been shown to determine patient survival. Indeed, more and more studies describe the development within the tumor microenvironment of tertiary lymphoid structures (TLS), whose presence has a positive impact on tumor prognosis. TLS are transient ectopic lymphoid aggregates displaying the same organization and functionality as canonical secondary lymphoid organs, with T-cell-rich and B-cell-rich areas that are sites for the differentiation of effector and memory T cells and B cells. However, factors favoring the emergence of such structures within tumors still need to be fully characterized. In this review, we survey the state of the art of what is known about the general organization, induction, and functionality of TLS during chronic inflammation, and more especially in cancer, with a particular focus on the B-cell compartment. We detail the role played by TLS B cells in anti-tumor immunity, both as antigen-presenting cells and tumor antigen-specific antibody-secreting cells, and raise the question of the capacity of chemotherapeutic and immunotherapeutic agents to induce the development of TLS within tumors. Finally, we explore how to take advantage of our knowledge on TLS B cells to develop new therapeutic tools. PMID:25755654

Innate Lymphoid Cells in HIV/SIV Infections.

PubMed

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.

Innate Lymphoid Cells in HIV/SIV Infections

PubMed Central

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. PMID:29326704

Human innate lymphoid cells.

PubMed

Montaldo, Elisa; Vacca, Paola; Vitale, Chiara; Moretta, Francesca; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

2016-11-01

The interest in innate lymphoid cells (ILC) has rapidly grown during the last decade. ILC include distinct cell types that are collectively involved in host protection against pathogens and tumor cells and in the regulation of tissue homeostasis. Studies in mice enabled a broad characterization of ILC function and of their developmental requirements. In humans all mature ILC subsets have been characterized and their role in the pathogenesis of certain disease is emerging. Nonetheless, still limited information is available on human ILC development. Indeed, only the cell precursors committed toward NK cells or ILC3 have been described. Here, we review the most recent finding on human mature ILC, discussing their tissue localization and function. Moreover, we summarize the available data regarding human ILC development. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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

2014-04-03

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.

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

PubMed

Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Nasal dermoid sinus cysts in the dog.

PubMed

Anderson, Davina M; White, Richard A S

2002-01-01

To describe the clinical and morphologic characteristics of nasal dermoid sinus cysts in the dog. Retrospective clinical study. Six client-owned dogs. Medical records (1995 to 1999) of 6 dogs that had a discharging sinus in the midline of the nose removed surgically were reviewed for signalment, physical examination, surgical and histopathologic findings, and outcome. Three golden retrievers, 1 springer spaniel, 1 cocker spaniel, and 1 Brittany spaniel with a history of intermittent discharge from a small opening in the midline on the bridge of the nose at the junction between the nasal planum and the skin were identified. The condition was unresponsive to antibiotic therapy, and previous surgical excision had been unsuccessful in 3 dogs. None of the dogs had any other congenital defects, and all dogs responded to complete surgical excision of the tract and cyst. On histopathologic examination of excised tissue, there were adnexal structures along a tract lined with stratified squamous epithelium, consistent with a developmental abnormality of ectodermal tissue. The lesions were diagnosed as nasal dermoid sinus cysts, similar to the congenital condition described in humans. Nasal dermoid sinus cysts are rare developmental defects related to abnormal development of the pre-nasal space and may extend into the cranial vault causing cerebral abscesses or recurrent meningitis. Complete surgical excision has a good prognosis. This is a new condition that should be added to the surgical differential diagnosis for a discharging sinus over the external nares in dogs. Copyright 2002 by The American College of Veterinary Surgeons

Correlation of Nasal Mucosal Temperature With Subjective Nasal Patency in Healthy Individuals.

PubMed

Bailey, Ryan S; Casey, Kevin P; Pawar, Sachin S; Garcia, Guilherme J M

2017-01-01

Historically, otolaryngologists have focused on nasal resistance to airflow and minimum airspace cross-sectional area as objective measures of nasal obstruction using methods such as rhinomanometry and acoustic rhinometry. However, subjective sensation of nasal patency may be more associated with activation of cold receptors by inspired air than with respiratory effort. To investigate whether subjective nasal patency correlates with nasal mucosal temperature in healthy individuals. Healthy adult volunteers first completed the Nasal Obstruction Symptom Evaluation (NOSE) and a unilateral visual analog scale to quantify subjective nasal patency. A miniaturized thermocouple sensor was then used to record nasal mucosal temperature bilaterally in 2 locations along the nasal septum: at the vestibule and across from the inferior turbinate head. Nasal mucosal temperature and subjective patency scores in healthy individuals. The 22 healthy adult volunteers (12 [55%] male; mean [SD] age, 28.3 [7.0] years) had a mean (SD) NOSE score of 5.9 (8.4) (range, 0-30) and unilateral VAS score of 1.2 (1.4) (range, 0-5). The range of temperature oscillations during the breathing cycle, defined as the difference between end-expiratory and end-inspiratory temperatures, was greater during deep breaths (mean [SD] change in temperature, 6.2°C [2.6°C]) than during resting breathing (mean [SD] change in temperature, 4.2°C [2.3°C]) in both locations (P < .001). Mucosal temperature measured at the right vestibule had a statistically significant correlation with both right-side visual analog scale score (Pearson r = -0.55; 95% CI, -0.79 to -0.17; P = .008) and NOSE score (Pearson r = -0.47; 95% CI, -0.74 to -0.06; P = .03). No other statistically significant correlations were found between mucosal temperature and subjective nasal patency scores. Nasal mucosal temperature was lower (mean of 1.5°C lower) in the first cavity to be measured, which was the right cavity in all

Nasal cavity ossifying fibrosarcoma: an unusual fibro-osseous neoplasm.

PubMed

Alameda, Yadiel A; Perez-Mitchell, Carlos; Busquets, José M

2010-11-01

We describe the case of a 65-year-old woman who presented with left nasal obstruction. Clinical and radiographic examinations revealed the presence of a soft-tissue mass that had obliterated the left nasal cavity. The mass was completely excised via an endoscopic approach. Histopathologic examination identified the tumor as an ossifying fibrosarcoma. The patient recovered uneventfully and remained free of disease at the 2-year postoperative follow-up. To the best of our knowledge, no case of an ossifying fibrosarcoma of the nasal cavity has been previously reported in the English-language literature. We discuss the features of this case and the clinical presentation, diagnosis, and management of fibrosarcomas of the nasal cavity and paranasal sinuses.

Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

NASA Technical Reports Server (NTRS)

Foster, B. R.

1975-01-01

A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

Cytokine profile of nasal and middle ear polyps in a patient with Woakes' syndrome and eosinophilic otitis media.

PubMed

De Loof, Marie; De Leenheer, Els; Holtappels, Gabriële; Bachert, Claus

2016-05-03

Woakes' syndrome is characterised by severe recurrent nasal polyps in early childhood with broadening of the nose, nasal dyscrinia, frontal sinus aplasia and bronchiectasis. Eosinophilic otitis media (EOM) is an intractable condition that can cause gradual or sudden deterioration of hearing and is associated with comorbid asthma. For these reasons, both diseases must be recognised and treated appropriately. We present a case of a 20-year-old man with Woakes' syndrome complicated by EOM, with polyps in both middle ears; this condition has so far not been described as an entity of eosinophilic disease in the literature. We have, from reviewing the literature, learned that this is the first time that results of tissue examination on nasal polyposis with respect to tissue IgE, eosinophil-cationic protein, interleukin (IL)-17 and IL-5 in a patient with Woakes' syndrome and EOM, has been reported and discussed. 2016 BMJ Publishing Group Ltd.

Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.

PubMed

Buggert, Marcus; Nguyen, Son; Salgado-Montes de Oca, Gonzalo; Bengsch, Bertram; Darko, Samuel; Ransier, Amy; Roberts, Emily R; Del Alcazar, Daniel; Brody, Irene Bukh; Vella, Laura A; Beura, Lalit; Wijeyesinghe, Sathi; Herati, Ramin S; Del Rio Estrada, Perla M; Ablanedo-Terrazas, Yuria; Kuri-Cervantes, Leticia; Sada Japp, Alberto; Manne, Sasikanth; Vartanian, Shant; Huffman, Austin; Sandberg, Johan K; Gostick, Emma; Nadolski, Gregory; Silvestri, Guido; Canaday, David H; Price, David A; Petrovas, Constantinos; Su, Laura F; Vahedi, Golnaz; Dori, Yoav; Frank, Ian; Itkin, Maxim G; Wherry, E John; Deeks, Steven G; Naji, Ali; Reyes-Terán, Gustavo; Masopust, David; Douek, Daniel C; Betts, Michael R

2018-06-01

Current paradigms of CD8 + T cell-mediated protection in HIV infection center almost exclusively on studies of peripheral blood, which is thought to provide a window into immune activity at the predominant sites of viral replication in lymphoid tissues (LTs). Through extensive comparison of blood, thoracic duct lymph (TDL), and LTs in different species, we show that many LT memory CD8 + T cells bear phenotypic, transcriptional, and epigenetic signatures of resident memory T cells (T RMs ). Unlike their circulating counterparts in blood or TDL, most of the total and follicular HIV-specific CD8 + T cells in LTs also resemble T RMs Moreover, high frequencies of HIV-specific CD8 + T RMs with skewed clonotypic profiles relative to matched blood samples are present in LTs of individuals who spontaneously control HIV replication in the absence of antiretroviral therapy (elite controllers). Single-cell RNA sequencing analysis confirmed that HIV-specific T RMs are enriched for effector-related immune genes and signatures compared with HIV-specific non-T RMs in elite controllers. Together, these data indicate that previous studies in blood have largely failed to capture the major component of HIV-specific CD8 + T cell responses resident within LTs. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

PubMed

Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

2016-02-17

The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

Immunoblot analysis of cellular expression of Bcl-2 family proteins, Bcl-2, Bax, Bcl-X and Mcl-1, in human peripheral blood and lymphoid tissues.

PubMed

Ohta, K; Iwai, K; Kasahara, Y; Taniguchi, N; Krajewski, S; Reed, J C; Miyawaki, T

1995-11-01

The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of apoptotic cell death, whereas Bax facilitates it, indicating possible interactions among them in the control of cellular survival. To investigate the in vivo role of expression of bcl-2 gene family products, immunoblot analysis using corresponding specific antisera was performed for peripheral blood cells and some lymphoid tissues in humans. We demonstrated that all Bcl-2 family proteins were expressed at various levels in hematolymphoid cell subpopulations isolated from peripheral blood, tonsil, spleen and thymus. Lymphoid expression of Bcl-2 family proteins tended to increase following activation, but declined with time in culture. Loss of Bcl-2 in cultured lymphoid cells was especially marked. Sole expression of Bax, but not other members of the Bcl-2 family, was observed on neutrophils, seemingly reflecting their shortest life-span among blood leukocytes. The results support the notion that a balance of expression of Bcl-2 family proteins may regulate the life and death of hematolymphoid cells at different stages of cell differentiation and activation.

The golden ratio of nasal width to nasal bone length.

PubMed

Goynumer, G; Yayla, M; Durukan, B; Wetherilt, L

2011-01-01

To calculate the ratio of fetal nasal width over nasal bone length at 14-39 weeks' gestation in Caucasian women. Fetal nasal bone length and nasal width at 14-39 weeks' gestation were measured in 532 normal fetuses. The mean and standard deviations of fetal nasal bone length, nasal width and their ratio to one another were calculated in normal fetuses according to the gestational age to establish normal values. A positive and linear correlation was detected between the nasal bone length and the gestational week, as between the nasal width and the gestational week. No linear growth pattern was found between the gestational week and the ratio of nasal width to nasal bone length, nearly equal to phi, throughout gestation. The ratio of nasal width to nasal bone length, approximately equal to phi, can be calculated at 14-38 weeks' gestation. This might be useful in evaluating fetal abnormalities.

Nasal rhinosporidiosis in a mule.

PubMed

Berrocal, Alexis; López, Alfonso

2007-03-01

A mass was removed from the nostril of a mule that exhibited unilateral epistaxis and nasal discharge. Impression smears revealed oval structures consistent with spores of Rhinosporidium seeberi. Microscopically, the mass was composed of fibrovascular granulomatous tissue containing sporangia R. seeberi. Surgical excision and antifungal treatment proved curative.

Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor.

PubMed

Sathe, Priyanka; Metcalf, Donald; Vremec, David; Naik, Shalin H; Langdon, Wallace Y; Huntington, Nicholas D; Wu, Li; Shortman, Ken

2014-07-17

The relationship between dendritic cells (DCs) and macrophages is often debated. Here we ask whether steady-state, lymphoid-tissue-resident conventional DCs (cDCs), plasmacytoid DCs (pDCs), and macrophages share a common macrophage-DC-restricted precursor (MDP). Using new clonal culture assays combined with adoptive transfer, we found that MDP fractions isolated by previous strategies are dominated by precursors of macrophages and monocytes, include some multipotent precursors of other hematopoietic lineages, but contain few precursors of resident cDCs and pDCs and no detectable common precursors restricted to these DC types and macrophages. Overall we find no evidence for a common restricted MDP leading to both macrophages and FL-dependent, resident cDCs and pDCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Nasal polyps

MedlinePlus

... get rid of nasal polyps. Nasal steroid sprays shrink polyps. They help clear blocked nasal passages and ... is stopped. Corticosteroid pills or liquid may also shrink polyps, and can reduce swelling and nasal congestion. ...

NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

PubMed

Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

2016-01-01

Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

Simulating the nasal cycle with computational fluid dynamics

PubMed Central

Patel, Ruchin G.; Garcia, Guilherme J. M.; Frank-Ito, Dennis O.; Kimbell, Julia S.; Rhee, John S.

2015-01-01

Objectives (1) Develop a method to account for the confounding effect of the nasal cycle when comparing pre- and post-surgery objective measures of nasal patency. (2) Illustrate this method by reporting objective measures derived from computational fluid dynamics (CFD) models spanning the full range of mucosal engorgement associated with the nasal cycle in two subjects. Study Design Retrospective Setting Academic tertiary medical center. Subjects and Methods A cohort of 24 nasal airway obstruction patients was reviewed to select the two patients with the greatest reciprocal change in mucosal engorgement between pre- and post-surgery computed tomography (CT) scans. Three-dimensional anatomic models were created based on the pre- and post-operative CT scans. Nasal cycling models were also created by gradually changing the thickness of the inferior turbinate, middle turbinate, and septal swell body. CFD was used to simulate airflow and to calculate nasal resistance and average heat flux. Results Before accounting for the nasal cycle, Patient A appeared to have a paradoxical worsening nasal obstruction in the right cavity postoperatively. After accounting for the nasal cycle, Patient A had small improvements in objective measures postoperatively. The magnitude of the surgical effect also differed in Patient B after accounting for the nasal cycle. Conclusion By simulating the nasal cycle and comparing models in similar congestive states, surgical changes in nasal patency can be distinguished from physiological changes associated with the nasal cycle. This ability can lead to more precise comparisons of pre and post-surgery objective measures and potentially more accurate virtual surgery planning. PMID:25450411

Smart Polymers in Nasal Drug Delivery

PubMed Central

Chonkar, Ankita; Nayak, Usha; Udupa, N.

2015-01-01

Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

Fabrication of custom PCL scaffold for nasal septal perforation repair

NASA Astrophysics Data System (ADS)

Gadaleta, Dominick; Lee, Daniel Z.; Peng, Matthew W.; Cruickshank, Nicholas; Shinde, Rohit; Hong, Abigail; Pennacchi, Sara; Dawit, Abel; Krein, Howard; Udupa, Jayaram K.; Rajapakse, Chamith S.

2018-03-01

Nasal septal perforations (NSPs) are relatively common. They can be problematic for both patients and head and neck reconstructive surgeons who attempt to repair them. Often, this repair is made using an interpositional graft sandwiched between bilateral mucoperichondrial advancement flaps. The ideal graft is nasal septal cartilage. However, many patients with NSP lack sufficient septal cartilage to harvest. Harvesting other sources of autologous cartilage grafts, such as auricular cartilage, adds morbidity to the surgical case and results in a graft that lacks the ideal qualities required to repair the nasal septum. Tissue engineering has allowed for new reconstructive protocols to be developed. Currently, the authors are unaware of any new literature that looks to improve repair of NSP using custom tissue-engineered cartilage grafts. The first step of this process involves developing a protocol to print the graft from a patient's pre-operative CT. In this study, CT scans were converted into STereoLithography (STL) file format. The subsequent STL files were transformed into 3D printable G-Code using the Slic3r software. This allowed us to customize the parameters of our print and we were able to choose a layer thickness of 0.1mm. A desktop 3D bioprinter (BioBot 1) was then used to construct the scaffold. This method resulted in the production of a PCL scaffold that precisely matched the patient's nasal septal defect, in both size and shape. This serves as the first step in our goal to create patient-specific tissue engineered nasal septal cartilage grafts for NSP repair.

Orbito-nasal cyst in a young European short-haired cat.

PubMed

Zemljič, Tadej; Matheis, Franziska L; Venzin, Claudio; Makara, Mariano; Grest, Paula; Spiess, Bernhard M; Pot, Simon A

2011-09-01

To describe a case of an orbito-nasal cyst in a cat. An 18-month-old male European short-haired cat was presented to the Ophthalmology service of the Vetsuisse Faculty, University of Zurich for a subcutaneous swelling in the medial canthal region of the right eye (OD). Ophthalmologic, ultrasound and CT examinations, and fine needle aspiration were performed. After lesion excision, the removed tissue was submitted for histopathology. CT examination was repeated 5 months after removal of the cyst. Ophthalmologic examination revealed a large fluctuant swelling inferonasal to OD. Despite patent lacrimal puncta, only the first few mm of the lacrimal canaliculi could be cannulated. A normal globe with moderate enophthalmos was present. Ultrasound examination showed a well-defined lobulated cyst-like structure in the right orbit, inferonasal and anterior to the eye. CT examination revealed extension of this lesion through the medial orbital wall into the right nasal cavity. Fine needle aspiration confirmed the cystic nature of the lesion. An orbito-nasal cyst was diagnosed. The orbital part of the cyst was dissected from the surrounding tissue and excised from the periosteum in the medial orbital wall defect. Part of the maxillary bone was removed to allow removal of the cyst from the nasal cavity. Histologically, the cyst wall consisted of a single to multilayered, mostly cuboidal epithelium and surrounding connective tissue. Follow-up revealed a good functional result and no recurrence 7 months after cyst removal. Similar orbito-nasal cystic structures were reported in dogs but not in cats. © 2011 American College of Veterinary Ophthalmologists.

Comparison of Nasal Acceleration and Nasalance across Vowels

ERIC Educational Resources Information Center

Thorp, Elias B.; Virnik, Boris T.; Stepp, Cara E.

2013-01-01

Purpose: The purpose of this study was to determine the performance of normalized nasal acceleration (NNA) relative to nasalance as estimates of nasalized versus nonnasalized vowel and sentence productions. Method: Participants were 18 healthy speakers of American English. NNA was measured using a custom sensor, and nasalance was measured using…

Persistent monoclonality after histological remission in gastric mucosa-associated lymphoid tissue lymphoma treated with chemotherapy and/or surgery: influence of t(11;18)(q21;q21).

PubMed

Santón, Almudena; García-Cosio, Mónica; Bellosillo, Beatriz; Rodríguez, Patricia; Cristóbal, Eva; Serrano, Sergio; Besses, Carlos; Abraira, Victor; Salar, Antonio; Montalbán, Carlos

2008-08-01

The purpose of this work was to study retrospectively the molecular response and outcome of 19 gastric mucosa associated lymphoid tissue (MALT) lymphoma patients achieving histological remission after chemotherapy or surgery. Immunoglobulin heavy chain variable (IgV(H)) gene rearrangements were studied by PCR in biopsies obtained at diagnosis and follow-up. Presence of t(11;18)(q21;q21) was studied by FISH or RT-PCR. Sequencing analysis of three t(11;18)(q21;q21) positive and two negative lymphomas with persistent monoclonal IgV(H) rearrangements was also performed. Long-term IgV(H) monoclonality was demonstrated in 11/19 patients (58%); in five of them monoclonal rearrangements were present in all samples throughout the follow-up. Persistent IgV(H) monoclonality was detected a median of 49 months after the achievement of histological response and did not condition histological relapse in most cases. All three t(11;18)(q21;q21) positive patients had maintained IgV(H) monoclonality and sequencing analyses revealed the same mutated IgV(H) alleles in the diagnostic and the follow-up samples. Over half of the patients with gastric MALT lymphoma with histological response after chemotherapy and/or surgery have long-term persistent monoclonality. The presence of t(11;18)(q21;q21) seems to condition long-term persistence of the initial lymphoma clone.trade mark.

Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

PubMed

Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

2017-10-01

Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

Nasal deposition of ciclesonide nasal aerosol and mometasone aqueous nasal spray in allergic rhinitis patients.

PubMed

Emanuel, Ivor A; Blaiss, Michael S; Meltzer, Eli O; Evans, Philip; Connor, Alyson

2014-01-01

Sensory attributes of intranasal corticosteroids, such as rundown to the back of the throat, may influence patient treatment preferences. This study compares the nasal deposition and nasal retention of a radiolabeled solution of ciclesonide nasal aerosol (CIC-hydrofluoroalkane [HFA]) with a radiolabeled suspension of mometasone furoate monohydrate aqueous nasal spray (MFNS) in subjects with either perennial allergic rhinitis (AR) or seasonal AR. In this open-label, single-dose, randomized, crossover scintigraphy study, 14 subjects with symptomatic AR received a single dose of radiolabeled 74-μg CIC-HFA (37 μg/spray, 1 spray/each nostril) via a nasal metered-dose inhaler or a single dose of radiolabeled 200-μg MFNS (50 μg/spray, 2 sprays/each nostril), with a minimum 5-day washout period between treatments. Initial deposition (2 minutes postdose) of radiolabeled CIC-HFA and MFNS in the nasal cavity, nasopharynx, and on nasal wipes, and retention of radioactivity in the nasal cavity and nasal run-out on nasal wipes at 2, 4, 6, 8, and 10 minutes postdose were quantified with scintigraphy. At 2 and 10 minutes postdose, deposition of radiolabeled CIC-HFA was significantly higher in the nasal cavity versus radiolabeled MFNS (99.42% versus 86.50% at 2 minutes, p = 0.0046; and 81.10% versus 54.31% at 10 minutes, p < 0.0001, respectively; p values unadjusted for multiplicity). Deposition of radioactivity on nasal wipes was significantly higher with MFNS versus CIC-HFA at all five time points, and posterior losses of radiolabeled formulation were significantly higher with MFNS at 6, 8, and 10 minutes postdose. In this scintigraphic study, significantly higher nasal deposition and retention of radiolabeled aerosol CIC-HFA were observed versus radiolabeled aqueous MFNS in subjects with AR.

Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003).

PubMed

Rassnick, Kenneth M; Goldkamp, Carrie E; Erb, Hollis N; Scrivani, Peter V; Njaa, Bradley L; Gieger, Tracy L; Turek, Michelle M; McNiel, Elizabeth A; Proulx, David R; Chun, Ruthanne; Mauldin, Glenna E; Phillips, Brenda S; Kristal, Orna

2006-08-01

To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. Retrospective case series. 139 dogs with histologically confirmed nasal carcinomas. Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.

Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.

PubMed

Kim, Jisu; Kim, Geon; Min, Hyeyoung

2017-11-01

Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets.

Use of laser rhinoscopy to treat a nasal obstruction in a captive California sea lion (Zalophus californianus).

PubMed

Sherrill, Johanna; Peavy, George M; Kopit, Mark J; Garner, Michael M; Gardiner, Chris H; Adams, Lance M

2004-06-01

Laser rhinoscopy was used to treat a nasal obstruction in a captive California sea lion (Zalophus californianus). The rehabilitated, adult, female sea lion developed mucopurulent, intermittent, bilateral nasal discharge and functional nasal obstruction 20 mo after acquisition by the Aquarium of the Pacific in Long Beach, California. A 3-mm-thick soft tissue structure spanning the region between the soft and hard palates, a deviated nasal septum, and several nasopharyngeal polyps were identified. Biopsies and cultures of the obstructive web showed ulcerative granulation tissue with suppurative inflammation, bacterial infection, and a partial section of an arthropod larva (not speciated). Laser rhinoscopy was performed to relieve the caudal nasopharyngeal obstruction and ablate the polyps. The sea lion appeared to breathe through the nares with lessened nasal discharge for a period of 6 wk after laser therapy, but within 8 wk the mucopurulent nasal discharge returned, the obstruction had reformed, and the sea lion was euthanized. Postmortem examination confirmed antemortem diagnoses of caudal nasopharyngeal obstruction secondary to inflammatory tissue; however, no additional sections of arthropod parasites were located microscopically.

Modified Activation Technique for Nasal Stent of Nasoalveolar Molding Appliance for Columellar Lengthening in Bilateral Cleft Lip/Palate.

PubMed

Patil, Pravinkumar G; Nimbalkar-Patil, Smita P

2018-01-01

Bilateral cleft lip/cleft palate is associated with nasal deformities typified by a short columella. The presurgical nasoalveolar molding (NAM) therapy approach includes reduction of the size of the intraoral alveolar cleft as well as positioning of the surrounding deformed soft tissues and cartilages. In a bilateral cleft patient, NAM, along with columellar elongation, eliminates the need for columellar lengthening surgery. Thus the frequent surgical intervention to achieve the desired esthetic results can be avoided. This article proposes a modified activation technique of the nasal stent for a NAM appliance for columellar lengthening in bilateral cleft lip/palate patients. The design highlights relining of the columellar portion of the nasal stent and the wire-bending of the nasal stent to achieve desirable results within the limited span of plasticity of the nasal cartilages. With this technique the vertical taping of the premaxilla to the oral plate can be avoided. © 2016 by the American College of Prosthodontists.

Surgical Approaches to the Nasal Cavity and Sinuses.

PubMed

Weeden, Alyssa Marie; Degner, Daniel Alvin

2016-07-01

The nasal cavity and sinuses may be exposed primarily via a dorsal or ventral surgical approach. Surgical planning involves the use of advanced imaging, such as computed tomography or MRI. Surgical treatment of lesions of the nasal cavity usually is limited to benign lesions or can also be used in combination with adjunctive therapy, such as radiation therapy. Extreme caution must be exercised with a dorsal approach to the nasal cavity to avoid complications of inadvertent penetration into the brain case. Gentle tissue handling and careful closure of the mucoperiosteum must be exercised following a ventral approach to minimize the risk of oronasal fistula formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Complications of Nasal Bone Fractures.

PubMed

Hwang, Kun; Yeom, Seung Han; Hwang, Suk Hyun

2017-05-01

The aim of this study was to perform a systematic review of the treatment of nasal bone fractures. The search terms ("nasal bone fracture" AND complication) and ("nasal bone fracture" AND [anosmia OR olfaction OR olfactory nerve OR smell]) and (anosmia AND ["nasal preparation" OR "nasal antiseptics"]) were used to search PubMed and SCOPUS. Of the 500 titles, 40 full papers were reviewed. One paper was excluded, and 3 mined papers were added. Ultimately, 12 papers were analyzed. The overall deformity rate was 10.4% ± 4.8%. No significant differences were found between patients who underwent closed reduction (14.7% ± 7.3%) and those who underwent open reduction (9.4% ± 4.4%), between those who underwent local anesthesia (5.8% ± 4.5%), and those who underwent general anesthesia (8.8% ± 3.8%), or between those who received timely treatment (5.7%) and those whose treatment was delayed (9.0%). Septal deviation occurred in 10.0% of patients as a sequela of nasal bone fracture. The nasal obstruction rate was 10.5% ± 5.3%. Fewer patients of nasal obstruction occurred in the open reduction patients (6.9% ± 4.4%) than in the closed reduction patients (15.2%). One patient of epiphora and 1 patient of diplopia were reportedAmong the 77 patients with nasal bone fractures, 29 (37.7% ± 11.3%) complained of olfactory disturbances. No significant associations were found between the type of fracture and the presence of olfactory disturbances. It is recommended for providers to explain to patients that approximately one-tenth of nasal bone fractures exhibit deformity, septal deviation, or nasal obstruction after surgery. Surgeons should take considerable care to avoid the olfactory mucosa during reduction surgery.

[Ultrastructural characteristics of mast cells and eosinophils in nasal inverted papilloma].

PubMed

Yokoshima, K; Ohnishi, M; Okuda, M; Okubo, K

1994-12-01

We previously found that an increased number of mast cells and eosinophils accumulated in nasal inverted papilloma and in the nasal mucosa of allergic subjects. Two subtypes of mast cells, i.e., mucosal mast cells and connective tissue mast cells are known to be present in the allergic nasal mucosa. Eosinophils in the allergic nasal mucosa are also heterogeneous. In addition, we demonstrated accumulation of formalin-sensitive mast cells at the tumor site of nasal inverted papilloma. The morphological characteristics and function of mast cells and eosinophils, however, have not yet been identified. The purpose of this study was to determine the ultrastructural characteristics of mast cells and eosinophils in relation to their function in tumor tissue. The results revealed two subtypes of mast cells in nasal inverted papilloma, one distributed mainly in the tumor site, the other mainly in the stromal site. These two subtypes of mast cells had different ultrastructural characteristics. In contrast to stromal mast cells, mast cells in the tumor site were characterized by a smaller cell diameter, fewer specific granules and a higher rate of degranulation. This suggested that they may have played some role in the pathogenesis of the tumor, however, their precise function is still unknown. In comparison with the mast cells in the allergic nasal mucosa, previously reported by Okuda et al, the mast cells in the tumor site were similar to those in the epithelial layer of the allergic nasal mucosa (MMCs), while mast cells in the stromal site resembled those in the lamina propria (CTMCs). There were no marked morphological differences between eosinophils in the tumor site and the stromal site.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nasal glial heterotopia: Clinical and morphological characteristics].

PubMed

Bykova, V P; Bakhtin, A A; Polyakov, D P; Yunusov, A S; Daikhes, N A

The paper describes a case of nasal glial heterotopia in a 10-month-old girl with a mixed (intranasal and subcutaneous) localization, which is accompanied by the divergence of the nasal bones. Histological examination supplemented by immunohistochemical reactions with antibodies to vimentin, S100 protein, neuron-specific enolase, as well as Ki-67 and smooth muscle actin confirmed the neural nature of the tumor. Fields of mature astrocytic glia including individual cells with neuronal differentiation were found among the fibrous and fibrovascular tissues. The paper provides a brief overview of the discussed pathology.

Adjuncts to Improve Nasal Reconstruction Results.

PubMed

Gordon, Shayna Lee; Hurst, Eva A

2017-02-01

The final cosmetic appearance of nasal reconstruction scars is of paramount importance to both the patient and surgeon. Ideal postreconstruction nasal scars are flat and indistinguishable from surrounding skin. Unfortunately, even with meticulous surgical execution, nasal scars can occasionally be suboptimal. Abnormal fibroblast response can lead to hypertrophic nasal scars, and excessive angiogenesis may lead to telangiectasias or an erythematous scar. Imperfect surgical closure or poor postoperative management can lead to surgical outcomes with step-offs, depressions, suture marks, or dyspigmentation. Aesthetically unacceptable nasal scars can cause pruritus, tenderness, pain, sleep disturbance, and anxiety and depression in postsurgical patients. Fortunately, there are several minimally invasive or noninvasive techniques that allow for enhancement and improvement of cosmetic results with minimal risk and associated downtime. This article provides an overview of adjuncts to improve nasal reconstruction with a focus on techniques to be used in the postoperative period. Armed with an understanding of relevant available therapies, skillful surgeons may drastically improve the final cosmesis and outcome of nasal reconstruction scars. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A simplified plastic embedding and immunohistologic technique for immunophenotypic analysis of human hematopoietic and lymphoid tissues.

PubMed Central

Casey, T. T.; Cousar, J. B.; Collins, R. D.

1988-01-01

Routine fixation and paraffin embedding destroys many hematopoietic and lymphoid differentiation antigens detected by flow cytometry or frozen section immunohistochemistry. On the other hand, morphologic evaluation is difficult in flow cytometric or frozen section studies. A simplified three-step plastic embedding system using acetone-fixed tissues embedded in glycol-methacrylate (GMA) resin has been found to provide both excellent morphologic and antigenic preservation. With our system, a wide variety of antigens are detected in plastic sections without trypsinization or prolonged embedding procedures; pan-B (CD19, CD22), pan-T (CD7, CD5, CD3, CD2), T-subset (CD4, CD8, CD1, CD25) markers as well as surface immunoglobulin and markers for myeloid and mononuclear-phagocyte cells are preserved. In summary, modifications of plastic embedding techniques used in this study simplify the procedure, apparently achieve excellent antigenic preservation, and facilitate evaluation of morphologic details in relation to immunocytochemical markers. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3282442

Objective Measure of Nasal Air Emission Using Nasal Accelerometry

ERIC Educational Resources Information Center

Cler, Meredith J.; Lien, Yu-An, S.; Braden, Maia N.; Mittleman, Talia; Downing, Kerri; Stepp, Cara, E.

2016-01-01

Purpose: This article describes the development and initial validation of an objective measure of nasal air emission (NAE) using nasal accelerometry. Method: Nasal acceleration and nasal airflow signals were simultaneously recorded while an expert speech language pathologist modeled NAEs at a variety of severity levels. In addition, microphone and…

S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

USDA-ARS?s Scientific Manuscript database

Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

Evaluation of polyvinylidene fluoride nasal sensor to assess deviated nasal septum in comparision with peak nasal inspiratory flow measurements.

PubMed

Manjunatha, Roopa G; Rajanna, K; Mahapatra, D Roy; Prakash, Surya

2014-01-01

Deviated nasal septum (DNS) is one of the major causes of nasal obstruction. Polyvinylidene fluoride (PVDF) nasal sensor is the new technique developed to assess the nasal obstruction caused by DNS. This study evaluates the PVDF nasal sensor measurements in comparison with PEAK nasal inspiratory flow (PNIF) measurements and visual analog scale (VAS) of nasal obstruction. Because of piezoelectric property, two PVDF nasal sensors provide output voltage signals corresponding to the right and left nostril when they are subjected to nasal airflow. The peak-to-peak amplitude of the voltage signal corresponding to nasal airflow was analyzed to assess the nasal obstruction. PVDF nasal sensor and PNIF were performed on 30 healthy subjects and 30 DNS patients. Receiver operating characteristic was used to analyze the DNS of these two methods. Measurements of PVDF nasal sensor strongly correlated with findings of PNIF (r = 0.67; p < 0.01) in DNS patients. A significant difference (p < 0.001) was observed between PVDF nasal sensor measurements and PNIF measurements of the DNS and the control group. A cutoff between normal and pathological of 0.51 Vp-p for PVDF nasal sensor and 120 L/min for PNIF was calculated. No significant difference in terms of sensitivity of PVDF nasal sensor and PNIF (89.7% versus 82.6%) and specificity (80.5% versus 78.8%) was calculated. The result shows that PVDF measurements closely agree with PNIF findings. Developed PVDF nasal sensor is an objective method that is simple, inexpensive, fast, and portable for determining DNS in clinical practice.

ID’ing Innate and Innate-like Lymphoid Cells

PubMed Central

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

Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.

PubMed

O'Sullivan, Timothy E; Sun, Joseph C

2018-01-01

Innate lymphoid cells are a heterogeneous family of tissue-resident and circulating lymphocytes that play an important role in host immunity. Recent studies have profiled the developmental pathways of mature ILCs and have identified ILC progenitors in the bone marrow through the use of transcription factor reporter mice. Here we describe methodology to identify and isolate bone marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker expression for adoptive transfer into lymphopenic mice to track the fate of developing ILCs.

DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

PubMed

Calderón-Garcidueñas, Lilian; Maronpot, Robert R; Torres-Jardon, Ricardo; Henríquez-Roldán, Carlos; Schoonhoven, Robert; Acuña-Ayala, Hilda; Villarreal-Calderón, Anna; Nakamura, Jun; Fernando, Reshan; Reed, William; Azzarelli, Biagio; Swenberg, James A

2003-01-01

Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer

Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue

PubMed Central

Pido-Lopez, Jeffrey; Kwok, William W.; Mitchell, Timothy J.; Heyderman, Robert S.; Williams, Neil A.

2011-01-01

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines. PMID:22144893

In vivo effects of endotoxin on DNA synthesis in rat nasal epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harkema, J.R.; Hotchkiss, J.A.

Airway inflammation in bacterial infections is characterized by the presence of neutrophils and often epithelial injury and repair. Release of endotoxin from bacteria may contribute to these processes. The purpose of this study was to determine the in vivo effects of repeated endotoxin exposure on DNA synthesis in rat nasal epithelium in the presence and absence of neutrophilic influx. Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls). Before the first and third instillations, half of the saline and endotoxin-instilled animals were depleted of circulating blood neutrophils by administering a rabbit anti-rat neutrophil antiserum.more » Rats were sacrificed 6 or 24 h after the last instillation. Two hours prior to sacrifice, rats were intraperitoneally injected with bromodeoxyuridine (BrdU), an analog of thymidine that is incorporated in the nucleus of cells in the S-phase of the cell cycle. Nasal tissues were processed for light microscopy and immunohistochemical detection of BrdU in nasal epithelial cells. The numbers of nasal epithelial cells, BrdU-labeled epithelial nuclei, and neutrophils per millimeter of basal lamina in the epithelium lining the nasal turbinates in the proximal nasal passages were determined by morphometric analysis. The authors did not observe a neutrophilic influx in the nasal tissues of neutrophil-depleted rats at 6 or 24 h after the last endotoxin instillation; however, the numbers of nasal epithelial cells and the BrdU-labeling index were significantly increased compared to saline-instilled controls. In contrast, non-neutrophil-depleted rats instilled with endotoxin had a marked neutrophilic influx, but no significant differences in the number of nasal epithelial cells at 6 or 24 h, compared to controls. In addition, the BrdU-labeling index in neutrophil-sufficient rats was increased only 6 h after the last instillation, compared to controls.« less

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isobe, Koichi; Kagami, Yoshikazu; Higuchi, Keiko

2007-11-15

Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. Themore » median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.« less

IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells.

PubMed

Hashiguchi, Masaaki; Kashiwakura, Yuji; Kojima, Hidefumi; Kobayashi, Ayano; Kanno, Yumiko; Kobata, Tetsuji

2015-03-01

Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. Il5-egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP(+) cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL-33 preferentially expanded EGFP(+) cells and eosinophils in GAT in vivo. EGFP(+) ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL-33Rα, on the other hand, did not impair EGFP(+) ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL-33Rα and IL-33 expanded eosinophil numbers in CD90(+) cell-depleted mice. IL-33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS

PubMed Central

Shao, Jingwei; Kraft, John C; Li, Bowen; Yu, Jesse; Freeling, Jennifer; Koehn, Josefin; Ho, Rodney JY

2016-01-01

Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A ‘systems approach’ has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS. PMID:26892323

Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice.

PubMed Central

Hostetler, K Y; Richman, D D; Sridhar, C N; Felgner, P L; Felgner, J; Ricci, J; Gardner, M F; Selleseth, D W; Ellis, M N

1994-01-01

During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS. PMID:7695264

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

PubMed

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.

Treatment of intractable lupus nephritis with total lymphoid irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1985-04-01

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 serummore » 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.« less

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency

PubMed Central

Maglione, Paul J.; Cols, Montserrat

2018-01-01

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. PMID:28983810

Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

PubMed Central

Takamura, Shiki

2018-01-01

Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

PubMed

Greiser, Eberhard M; Greiser, Karin Halina; Ahrens, Wolfgang; Hagen, Rudolf; Lazszig, Roland; Maier, Heinz; Schick, Bernhard; Zenner, Hans Peter

2012-11-06

There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Similarity and Enhancement: Nasality from Moroccan Arabic Pharyngeals and Nasals

ERIC Educational Resources Information Center

Zellou, Georgia Eve

2012-01-01

Experimental studies of the articulation, acoustics, and perception of nasal and pharyngeal consonants and adjacent vowels were conducted to investigate nasality in Moroccan Arabic (MA). The status of nasality in MA is described as coarticulatorily complex, where two phoneme types (pharyngeal segments and nasal segments) yield similar…

Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.

PubMed

Young, Kira; Borikar, Sneha; Bell, Rebecca; Kuffler, Lauren; Philip, Vivek; Trowbridge, Jennifer J

2016-10-17

Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential. Impaired lymphoid differentiation potential of aged LMPP/MPP4 is not rescued by transplantation into a young bone marrow microenvironment, demonstrating cell-autonomous changes in the MPP compartment with aging. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. © 2016 Young et al.

Differentiating Immune Cell Targets in Gut-Associated Lymphoid Tissue for HIV Cure.

PubMed

Khan, Shahzada; Telwatte, Sushama; Trapecar, Martin; Yukl, Steven; Sanjabi, Shomyseh

2017-11-01

The single greatest challenge to an HIV cure is the persistence of latently infected cells containing inducible, replication-competent proviral genomes, which constitute only a small fraction of total or infected cells in the body. Although resting CD4 + T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4 + T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues. The mechanisms by which latency is established and maintained will likely depend on the location and cytokine milieu surrounding the latently infected cells in each compartment. Therefore, successful HIV cure strategies require identification and characterization of the exact cell types that support viral persistence, particularly in the gut. In this review, we describe the seeding of the latent HIV reservoir in the gut mucosa; highlight the evidence for compartmentalization and depletion of T cells; summarize the immunologic consequences of HIV infection within the gut milieu; propose how the damaged gut environment may promote the latent HIV reservoir; and explore several immune cell targets in the gut and their place on the path toward HIV cure.

Assessment of different protocols for the isolation and purification of gut associated lymphoid cells from the gilthead seabream (Sparus aurata L.)

PubMed Central

2007-01-01

Teleost gut associated lymphoid tissue (GALT) consists of leucocyte populations located both intraepithelially and in the lamina propria with no structural organization. The present study aims to assess different protocols for the isolation of GALT cells from an important fish species in the Mediterranean aquaculture, the gilthead seabream. Mechanical, chemical and enzymatic treatments were assayed. Nylon wool columns and continuous density gradients were used for further separation of cell subpopulations. Light microscopy and flow cytometry showed that the highest density band (HD) consisted of a homogeneous lymphocytic population, whereas the intermediate density band (ID) corresponded to epithelial and secretory cells and some lymphocytes. Respiratory burst activity of total cell suspensions revealed very low numbers of potential phagocytic cells, reflecting results from light microscopy and reports in other teleost species. The present data set up the basis for future functional characterization of GALT in seabream. PMID:18213363

Saline nasal washes

MedlinePlus

... nasal wash helps flush pollen, dust, and other debris from your nasal passages. It also helps remove excess mucus (snot) and adds moisture. Your nasal passages are open spaces behind your nose. Air passes through your nasal ...

Local recurrence as immunoglobulin G4 (IgG4)-related disease 10 years after radiotherapy to ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

PubMed

Matsuo, Toshihiko; Ichimura, Kouichi; Yoshino, Tadashi

2011-01-01

In 2000, a 48-year-old woman developed a left orbital mass with lacrimal gland involvement and then, in 2003, a right orbital mass with lacrimal gland involvement, both of which were diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). She underwent 30 Gy external beam radiation to bilateral orbital lesions. The lymphoma cells in both lesions did not share the same clonality, as shown by amplification by polymerase chain reaction of the immunoglobulin heavy chain gene. Immunoglobulin light chain analysis by immunohistochemistry and messenger RNA in situ hybridization showed λ chain monotype in the left orbital lesion but κ chain monotype in the right orbital lesion. She developed recurrent left orbital mass with high uptake on fluorodeoxyglucose positron emission tomography fused with computed tomography in 2010, and excisional biopsy disclosed the formation of follicles and infiltration with immunoglobulin G4 (IgG4)-positive plasma cells mainly in interfollicular areas. The immunoglobulin light chain analysis showed the λ chain and κ chain bitype. With the immunohistopathological diagnosis of IgG4-related disease, the serum IgG4 level was found to show elevation at 376 mg/dL, and the patient chose observation. This is the first reported case of development of IgG4-related disease after bilataral orbital MALT lymphoma with external beam radiotherapy.

Epidemiological analysis of structural alterations of the nasal cavity associated with obstructive sleep apnea syndrome (OSA).

PubMed

Mekhitarian Neto, Levon; Fava, Antonio Sérgio; Lopes, Hugo Canhete; Stamm, Aldo

2005-01-01

The objective of this paper is to demonstrate that structural alterations of the nasal cavity, e.g. septal deviation and conchal hypertrophy have high incidence in patients with sleep apnea and hypopnea syndrome and must be addressed with associated specific procedures of the syndrome. Clinical retrospective. A retrospective study of 200 patients was performed, with 196 male and 4 female, attended at the otorhinolaryngology ambulatory of Hospital Prof. Edmundo Vasconcelos and Unidade Paulista de Otorrinolaringologia, all of them subjected to polysomnography, otorhinolaryngological physical exam, endoscopy exam, and surgical treatment with nasal and pharyngeal procedures. All of them were subjected to pharyngeal procedure: uvulopalatopharyngoplasty or uvulopalatoplasty and nose procedure: 176 septoplasty with partial turbinectomy (88%) and 24 isolated turbinectomy, with satisfactory results. We can see that structural alterations of the nasal cavity have high incidence in patients with OSA.

Treatment of hyperplastic inferior nasal turbinates by means of a Ho:YAG laser

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Leunig, Andreas; Janda, P.; Rosler, P.; Grevers, G.; Baumgartner, Reinhold

1999-06-01

Although the successful use of the Ho:YAG laser in nasal turbinate surgery had been reported no clinical study had been performed to assess the clinical outcome in longterm. By means of a pulsed Ho:YAG laser emitting at λ=2080nm (1J/pulse, 3-8 Hz) 57 patients suffering from nasal obstruction due to allergic rhinitis and vasomotoric rhinitis were treated under local anesthesia. The study was conducted by standardized questionnaire, photo documentation, allergy test, mucocilliar test, rhinomanometry, radiology and histology. Within 2 weeks after laser treatment a significant improvement of nasal airflow correlating to the extent of the ablated turbinate tissue could be determined. This effect lasted up until 1 year post treatment resulting in an improved quality of life in more than 80 percent of the patients. Side effects like nasal dryness and pain were rare (<4%), no immediate complications were observed. The total treatment time takes 3-8 min and nasal packing was not necessary after the laser procedure. In conclusion Ho:YAG laser treatment can be performed as an outpatient procedure under local anesthesia with excellent ablation of soft tissue in a short treatment time with promising results.

Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

PubMed

Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak

2015-01-01

Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Florid reactive lymphoid hyperplasia of terminal ileum.

PubMed

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 be curative.

ID'ing innate and innate-like lymphoid cells.

PubMed

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.

Effects of topical phenytoin on nasal wound healing after mechanical trauma: An experimental study.

PubMed

Şimşek, Gökçe; Ciftci, Osman; Karadag, Neşe; Karatas, Erkan; Kizilay, Ahmet

2014-12-01

Impaired postoperative wound healing is the second most common morbidity after synechia formation in endoscopic sinus surgery. The aim of this experimental study was to investigate the potential effects of topical phenytoin on wound healing after nasal mucosal trauma in rats. An experimental study at the Inonu University Faculty of Medicine. Twenty-four rats were randomized into three groups: 1) phenytoin group (n = 8), 2) control group (n = 8), and 3) vehicle group (n = 8). After damaging the right nasal cavity, in the phenytoin group, 1% topical phenytoin cream was applied for 7 days. The rats in the control group did not receive any treatment. The vehicle group was treated with daily topical cold cream for 1 week. The rats were sacrificed at the end, and the nasal cavities were excised. Tissue edema and inflammatory cell infiltration were compared among the groups. Additionally, proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) immunoexpression levels were evaluated. Furthermore, in biochemical analysis, the tissue levels of vascular endothelial growth factor and (EGF) of the groups were investigated. In the phenytoin group, tissue edema and inflammatory cell infiltration were significantly decreased, and PCNA and CD31 immunoexpression levels were more prominent (P < .001) and the tissue EGF levels were significantly higher (P < .01). Topical phenytoin treatment may alter the nasal wound healing after mechanical trauma. The potential beneficial effects of topical phenytoin on nasal mucosa should be investigated by further experimental and human trials. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Circulating innate lymphoid cells are unchanged in response to DAC HYP therapy.

PubMed

Gillard, Geoffrey O; Saenz, Steven A; Huss, David J; Fontenot, Jason D

2016-05-15

Innate lymphoid cells (ILCs) play an important role in immunity, inflammation, and tissue remodeling and their dysregulation is implicated in autoimmune and inflammatory disorders. We analyzed the impact of daclizumab, a humanized monoclonal anti-CD25 antibody, on circulating natural killer (NK) cells and ILCs in a cohort of multiple sclerosis patients. An increase in CD56(bright) NK cells and CD56(hi)CD16(intermediate) transitional NK cells was observed. No significant change in total ILCs or major ILC subpopulations was observed. These results refine our understanding of the impact of daclizumab on innate lymphoid cell populations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

PubMed

Wang, Yi Yuen; Srirathan, Vinothan; Tirr, Erica; Kearney, Tara; Gnanalingham, Kanna K

2011-04-01

The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

Emerging concepts and future challenges in innate lymphoid cell biology

PubMed Central

Artis, David

2016-01-01

Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

[Clinical analysis of nasal resistance and pulmonary function testing in patients with chronic nasal-sinusitis and nasal polyps].

PubMed

Liao, Hua; Shen, Ying; Wang, Pengjun

2015-05-01

To study the pulmonary function and nasal resistance characteristics of patients with chronic nose-sinusitis and nasal polyps (CRSwNP), to explore the evaluation role of nasal resistance in nasal ventilation function and the effect of endoscopic sinus surgery on pulmonary function in patients with CRSwNP. Fifty CRSwNP patients that met the study criteria were selected . The patients were performed endoscopic surgeries according to Messerklinger surgical procedures under general anesthesia. Extent of surgery was based on preoperative CT showing the range of the lesion of disease and endoscopic findings. Perioperative treatments contained intranasal corticosteroids, cephalosporin or penicillin antibiotics, nasal irrigation and other treatments. Main outcome measures included visual analog scale (VAS), endoscopic Lind-Kennedy scores, nasal resistence, pulmonary function in patientsone week before and after surgery, three months and six months after surgery. Pulmonary function includes forced expiratory volume in one second (FEV1), forced vital capacity FEV1/FVC and peak expiratory flow (PEF). The study found that there were significantly positive correlations among VAS score, Lund-Kennedy score and nasal resistance (P < 0.05) in CRSwNP patients, but there is a significantly negative correlation between VAS score, Lund-Kennedy score, nasal resistance and pulmonary function indexes of FEV1, FVC and PEF (P < 0.05). The VAS score, Lund-Kennedy score and nasal resistance values of CRSwNP patients were decreased significantly after comprehensive treatments with nasal endoscopic operation as the major one, the difference was statistically different (P < 0.05). And the pulmonary function indexs (FEV1, FVC, PEF) were significantly increased after surgery in CRSwNP patients. The nasal resistance can objectively and reliably reflect the degree of nasal congestion and the recovery of nasal function in CRSwNP patients after endoscopic sinus surgery. The detection method of nasal

Florid reactive lymphoid hyperplasia of terminal ileum

PubMed Central

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 be curative. PMID:22242075

Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

PubMed

Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

2015-08-01

Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spontaneous Nasal Septal Abscess Presenting as a Soft Tissue Mass in a Child.

PubMed

Cai, Yi; Saqi, Anjali; Haddad, Joseph

2017-04-01

Nasal septal abscess (NSA) is a rare condition most commonly seen as a complication of nasal trauma. The diagnosis of NSA requires emergent treatment, because delayed management can result in significant morbidity. Typically, NSA presents as a purulent collection that can be managed with drainage, either surgically or at bedside. We report an unusual presentation of a spontaneous NSA in a 7-year-old boy as a solid nasal mass eroding the nasal septum. The solid, tumor-like nature of the mass necessitated intervention beyond drainage and was ultimately excised. Imaging initiated in the emergency department revealed a partially cystic mass and erosion of the septum, which was key to the diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given the ease with which a diagnosis of NSA may be missed and the need for urgent management upon diagnosis of a NSA, we aim to highlight the clinical, radiologic, and histopathologic aspects that aid in diagnosis of NSA. Imaging, obtaining culture results, and initiation of antibiotics are paramount in management. In addition, NSAs may also necessitate bedside drainage given their emergent nature. Copyright © 2016 Elsevier Inc. All rights reserved.

Retrospective review of 50 canine nasal tumours evaluated by low-field magnetic resonance imaging.

PubMed

Avner, A; Dobson, J M; Sales, J I; Herrtage, M E

2008-05-01

Low-field magnetic resonance imaging machines are being used more often in veterinary practice for the investigation of sinonasal disease. The aim of this retrospective study was to describe and characterise the low-field magnetic resonance imaging features of nasal tumours in dogs. The Queen's Veterinary School Hospital magnetic resonance imaging database (2001-2005) was searched for dogs with a magnetic resonance imaging diagnosis of a nasal tumour. Fifty cases with histological diagnosis of nasal tumour were found. The appearance and extent of the nasal tumour as well as the involvement of adjacent anatomic structures were examined against a checklist. The most common magnetic resonance imaging findings were as follows. (1) Soft tissue mass replacing the destroyed nasal conchae and/or ethmoturbinates (98 per cent of cases). (2) Nasal septum destruction (68 per cent of cases). (3) Retained secretions with or without mass caudally in frontal sinuses (62 per cent of cases). (4) Nasal/frontal bone destruction (52 per cent of cases). Low-field magnetic resonance imaging allowed differentiation of tumour tissue from retained secretions or necrotic tissue. Magnetic resonance imaging was invaluable in assessing the extension of the tumour into the maxillary recesses, caudal recesses, nasopharynx, adjacent bones and cranial cavity. The tumour often extended caudally into the frontal sinuses, nasopharynx and perhaps most importantly into the caudal recesses. Tumour extension into the cranial cavity was not common (16 per cent), and only three of these cases showed neurological signs. However, 54 per cent of cases showed focal meningeal (dural) hyperintensity, although the significance of this is unclear. A significant difference (P<0.05) in tumour signal intensity between the sarcomas and carcinomas was found. The use of a low-field magnetic resonance imaging technique is excellent for the diagnosis and determination of extent of sinonasal tumours.

Saquinavir-mediated inhibition of human immunodeficiency virus (HIV) infection in SCID mice implanted with human fetal thymus and liver tissue: an in vivo model for evaluating the effect of drug therapy on HIV infection in lymphoid tissues.

PubMed Central

Pettoello-Mantovani, M; Kollmann, T R; Raker, C; Kim, A; Yurasov, S; Tudor, R; Wiltshire, H; Goldstein, H

1997-01-01

Treatment with protease inhibitors alone or in combination with inhibitors of reverse transcriptase potently suppresses levels of human immunodeficiency virus (HIV) RNA in plasma and thereby may significantly delay the progression of HIV-mediated disease. To investigate the effect of treatment with the protease inhibitor saquinavir on HIV replication in the lymphoid tissues, we used a SCID-hu mouse model that we developed, in which human thymic and liver tissues (hu-thy/liv) were implanted under both kidney capsules in SCID mice (thy/liv-SCID-hu mice). These mice are populated in the periphery with large numbers of human T cells and develop disseminated HIV infection after intraimplant injection. thy/liv-SCID-hu mice with established HIV infection that were treated for 1 month with saquinavir had a significantly lower viral load present in the implanted hu-thy/liv and mouse spleen than did the untreated HIV-infected thy/liv-SCID-hu mice. To examine the capacity of acute treatment with saquinavir to prevent HIV infection, some thy/liv-SCID-hu mice were inoculated with HIV and then immediately started on saquinavir. Although treated mice had markedly lower viral loads in the thy/liv implants and spleens, HIV infection was not completely prevented. Thus, the effect of antiviral therapy on HIV infection in the major site of HIV replication, the lymphoid tissues, can be readily evaluated in our thy/liv-SCID-hu mice. These mice should prove to be a useful model for determining the in vivo effectiveness of different therapeutic interventions on acute and chronic HIV infection. PMID:9303378

Lymphoid tissue fibrosis is associated with impaired vaccine responses.

PubMed

Kityo, Cissy; Makamdop, Krystelle Nganou; Rothenberger, Meghan; Chipman, Jeffrey G; Hoskuldsson, Torfi; Beilman, Gregory J; Grzywacz, Bartosz; Mugyenyi, Peter; Ssali, Francis; Akondy, Rama S; Anderson, Jodi; Schmidt, Thomas E; Reimann, Thomas; Callisto, Samuel P; Schoephoerster, Jordan; Schuster, Jared; Muloma, Proscovia; Ssengendo, Patrick; Moysi, Eirini; Petrovas, Constantinos; Lanciotti, Ray; Zhang, Lin; Arévalo, Maria T; Rodriguez, Benigno; Ross, Ted M; Trautmann, Lydie; Sekaly, Rafick-Pierre; Lederman, Michael M; Koup, Richard A; Ahmed, Rafi; Reilly, Cavan; Douek, Daniel C; Schacker, Timothy W

2018-05-21

Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection. We found blunted antibody responses to YFV that correlated to the amount of LN fibrosis and loss of T cells, including T follicular helper cells. These data suggest that LN fibrosis is not limited to HIV infection and may be associated with impaired immunologic responses to vaccines. This may have an impact on vaccine development, especially for infectious diseases prevalent in the developing world.

Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-07

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Accumulation of CD69+ tissue‑resident memory T cells in the nasal polyps of patients with chronic rhinosinusitis.

PubMed

Ickrath, Pascal; Kleinsasser, Norbert; Ding, Xin; Ginzkey, Christian; Beyersdorf, Niklas; Hagen, Rudolf; Kerkau, Thomas; Hackenberg, Stephan

2018-08-01

In patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a relative accumulation of cluster of differentiation (CD)8+ T cells over CD4+ T cells occurs in nasal polyps compared with the peripheral blood. Nasal CD8+ T cells and CD4+ T cells predominantly present an effector memory phenotype. Immunological studies have reported that memory T cells recirculate from the tissues to the peripheral blood and a high percentage of these T cells persist within the tissue. The aim of the present study was to characterize CD69+ sphingosine‑1‑phosphate receptor 1 (S1PR1)‑ tissue resident memory T cells (Trm) in the polyps of patients with CRSwNP. Tissue and blood samples were collected from 10 patients undergoing nasal sinus surgery. Expression of specific extra‑ and intracellular molecules were analyzed using multicolor flow cytometry. A significantly higher level of CD8+ T cells than CD4+ T cells was present in nasal polyps, while significantly more CD4+ T cells than CD8+ T cells were detected in the peripheral blood of patients with CRSwNP. The frequency of CD69+ T cells was significantly higher in CD8+ and CD4+ T cells in nasal polyps compared with the peripheral blood. The frequency of CD69+ S1PR1‑ Trm was also significantly higher in CD4+ and CD8+ T cells from nasal polyps compared with the peripheral blood. Within polyps, the frequency of CD69+ S1PR1‑ Trm was again significantly higher in CD8+ compared with CD4+ T cells. In summary, a significantly higher frequency of CD69+ S1PR1‑ T cells was observed in the nasal polyps compared with the peripheral blood in patients with CRSwNP. The results of the present study suggest that local regulation of the immune response occurs within nasal polyps. As such, Trm should be considered a potential stimulus in the pathogenesis of nasal polyps. However, the role of Trm in nasal polyps as a pathogenic trigger of the local inflammatory reaction requires further investigation.

A review of nasal polyposis

PubMed Central

Newton, Jonathan Ray; Ah-See, Kim Wong

2008-01-01

Nasal polyps are common, affecting up to four percent of the population. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, cystic fibrosis, and aspirin sensitivity. They present with nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly facial pain. Clinical examination reveals single or multiple grey polypoid masses in the nasal cavity. Computerized tomography allows evaluation of the extent of the disease and is essential if surgical treatment is to be considered. Management of polyposis involves a combination of medical therapy and surgery. There is good evidence for the use of corticosteroids (systemic and topical) both as primary treatment and as postoperative prophylaxis against recurrence. Surgical treatment has been refined significantly over the past twenty years with the advent of endoscopic sinus surgery and, in general, is reserved for cases refractory to medical treatment. Recurrence of the polyposis is common with severe disease recurring in up to ten percent of patients. PMID:18728843

Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

PubMed Central

Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

2016-01-01

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

Assessment of nasalance and nasality in patients with a repaired cleft palate.

PubMed

Sinko, Klaus; Gruber, Maike; Jagsch, Reinhold; Roesner, Imme; Baumann, Arnulf; Wutzl, Arno; Denk-Linnert, Doris-Maria

2017-07-01

In patients with a repaired cleft palate, nasality is typically diagnosed by speech language pathologists. In addition, there are various instruments to objectively diagnose nasalance. To explore the potential of nasalance measurements after cleft palate repair by NasalView ® , we correlated perceptual nasality and instrumentally measured nasalance of eight speech items and determined the relationship between sensitivity and specificity of the nasalance measures by receiver-operating characteristics (ROC) analyses and AUC (area under the curve) computation for each single test item and specific item groups. We recruited patients with a primarily repaired cleft palate receiving speech therapy during follow-up. During a single day visit, perceptive and instrumental assessments were obtained in 36 patients and analyzed. The individual perceptual nasality was assigned to one of four categories; the corresponding instrumental nasalance measures for the eight specific speech items were expressed on a metric scale (1-100). With reference to the perceptual diagnoses, we observed 3 nasal and one oral test item with high sensitivity. However, the specificity of the nasality indicating measures was rather low. The four best speech items with the highest sensitivity provided scores ranging from 96.43 to 100%, while the averaged sensitivity of all eight items was below 90%. We conclude that perceptive evaluation of nasality remains state of the art. For clinical follow-up, instrumental nasalance assessment can objectively document subtle changes by analysis of four speech items only. Further studies are warranted to determine the applicability of instrumental nasalance measures in the clinical routine, using discriminative items only.

Innate lymphoid cells in the initiation, regulation and resolution of inflammation

PubMed Central

Sonnenberg, Gregory F.; Artis, David

2016-01-01

A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans, and found to profoundly influence the induction, regulation and resolution of inflammation. ILCs play an important role in these processes in murine models of infection, inflammatory disease and tissue repair. Further, disease association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a potential role for these cell populations in human health and disease. In this review, we discuss the emerging family of ILCs, the role of ILCs in inflammation, and how current or novel therapeutic strategies could be employed to selectively modulate ILC responses and limit chronic inflammatory diseases in patients. PMID:26121198

Implantation of Corynebacterium pseudodiphtheriticum for elimination of Staphylococcus aureus from the nasal cavity in volunteers

NASA Astrophysics Data System (ADS)

Viacheslav, Ilyin; Kiryukhina, Nataliya

Nasal carriage of Staphylococcus aureus is a well-documented risk factor of infection and inflammation of the skin, soft tissues and bacteremia. It is also known that most often etiology of these disorders is associated with autoinfection. The present-day methods of opportunistic pathogens eradication from the nasal cavity are based principally on the use of antiseptic and antibacterial agents. For instance, a local antibiotic mupirocin in the form of nasal ointment is considered to be the gold standard for the treatment of S. aureus carriage. The literature describes investigations showing how mupirocin can strengthen antibiotic resistance in S. aureus strains, including those with methicillin resistance (MRSA). It is also common knowledge that recolonization of the nasal mucous membrane takes place within several months after mupirocin treatment. This circumstance dictates the necessity to look for alternative ways of preventing the S. aureus carriage and methods of elimination. One of the methods of nasal S. aureus elimination is implantation of nonpathogenic microorganisms which will extrude opportunistic pathogens without impinging the symbiotic microbiota. Effectiveness of saline suspension of Corynebacterium pseudodiphtheriticum containing spray was assessed in a several chamber experiments with simulation of some spaceflight factors (dry immersion, isolation). Various schemes of application of preparations were applied. In all cases of corynebacteria application the strong inhibiting effect against S. aureus was detected. This fact opens a prospect of using nonpathogenic corynebacteria as a nasal probiotic. Administration of the nasal corynebacteria spray possibly prevented cross-infection by MRSA and appearance of staphylococcal infection. Further pre-clinical and clinical study of this bacterial therapy method is under development.

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma).

PubMed

Fu, Y S; Perzin, K H

1976-06-01

In a study of 256 nonepithelial neoplasms involving the nasal cavity, paranasal sinuses, and nasopharynx, 23 lesions were classified as fibrous tissue tumors, including four cases of "fibroma", six of fibromatosis, and thirteen of fibrosarcoma. The clinical findings associated with these lesions are described, their histologic features illustrated, results of therapy presented and clinicopathologic correlations made. The "fibromas" presented a small localized nodules. None recurred after local excision. Fibromatosis, a locally aggressive tumor, does not metastasize, but may cause considerable morbidity or even death due to local infiltration which may be difficult to control surgically. Fibrosarcoma may cause death either by local infiltration or by metastasis, but has a better prognosis than most other sarcomas of this region. We recommend that a large en block resection be performed initially for fibromatosis and fibrosarcoma growing in this area, after the diagnosis has been made by biopsy. In this series, including patients who had more than one operation, recurrent tumor was seen following 10 of 12 limited local excisions performed for fibromatosis and fibrosarcoma, but in only one of 13 patients after a large bloc resection. The problems involved in histologically differentiating fibrous tissue tumors from other lesions are discussed. A patient with the rare syndrome of multicentric fibromatosis with spontaneous regression of lesions is presented.

Three-Dimensional Soft Tissue Nasal Changes After Nasoalveolar Molding and Primary Cheilorhinoplasty in Infants With Unilateral Cleft Lip and Palate.

PubMed

Mancini, Laura; Gibson, Travis L; Grayson, Barry H; Flores, Roberto L; Staffenberg, David; Shetye, Pradip R

2018-01-01

To quantify 3-dimensional (3D) nasal changes in infants with unilateral cleft lip with or without cleft palate (UCL±P) treated by nasoalveolar molding (NAM) and cheilorhinoplasty and compare to noncleft controls. Retrospective case series of infants treated with NAM and primary cheilorhinoplasty between September, 2012 and July, 2016. Infants were included if they had digital stereophotogrammetric records at initial presentation (T1), completion of NAM (T2), and following primary cheilorhinoplasty (T3). Images were oriented in 3dMD Vultus software, and 16 nasolabial points identified. Twenty consecutively treated infants with UCL±P. Nasoalveolar molding and primary cheilorhinoplasty. Anthropometric measures of nasal symmetry and morphology were compared in the treatment group between time points using paired Student t tests. Postsurgical nasal morphology was compared to noncleft controls. Nasal tip protrusion increased, and at T3 was 2.64 mm greater than noncleft controls. Nasal base width decreased on the cleft side by 4.01 mm after NAM and by 6.73 mm after cheilorhinoplasty. Columellar length of the noncleft to cleft side decreased from 2:1 to 1:1 following NAM. Significant improvements in subnasale, columella, and nasal tip deviations from midsagittal plane were observed. Treatment improved symmetry of the alar morphology angle and the nasal base-columella angle between cleft and noncleft sides. Three-dimensional analysis of UCL±P patients demonstrated significant improvements in nasal projection, columella length, nasal symmetry, and nasal width. Compared to noncleft controls, nasal form was generally corrected, with overcorrection of nasal tip projection, columella angle, and outer nasal widths.