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Systemic Response (systemic + response)
Selected AbstractsThe zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin-mediated inflammatory responses in the lungEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Jianmin Jin Abstract Gfi1 is a 55-kD nuclear zinc finger protein that is differentially expressed in lymphoid and myeloid cells. Gfi1,/, mice show a very strong systemic response to the endotoxin LPS and die rapidly within 36,h with symptoms of septic shock. Here we report that the pathohysiological processes for this exaggerated inflammatory response take place in the lung. After LPS treatment, lungs of Gfi1,/, mice showed a rapid accumulation of mononuclear cells and a significant overproduction of inflammatory cytokines such as TNF, IL-1, and IL-6. Increased cytokine production was also observed in blood-free perfused lungs from Gfi1,/, mice exposed to either LPS or overventilation. Alveolar macrophages but not airway epithelial cells from Gfi1,/, mice were found to be responsible for the enhanced cytokine production. Strikingly, when the TNF gene was deleted, Gfi1,/, animals were completely rescued from LPS hypersensitivity and had significantly lower IL-1, and IL-6 levels. We conclude that the unrestrained endotoxin response of Gfi1,/, mice occurs mainly in the lung and that Gfi1 represents a novel factor limiting the inflammatory immune response of this organ, and propose that Gfi1 exerts its regulatory function in alveolar macrophages downstream of the LPS receptor (TLR4) and upstream of TNF. [source] A Systemic Approach to Culturally Responsive Assessment Practices and EvaluationHIGHER EDUCATION QUARTERLY, Issue 3 2010June Slee In an earlier paper, Slee and Keenan demonstrated that it was possible for tertiary education institutions to design culturally responsive assessment procedures that complied with standardised assessment policy. The authors' paper described Growing Our Own, an initiative between Charles Darwin University and Northern Territory Catholic Education, which in 2009 began preparing in situ Indigenous teacher assistants for teacher qualification in very remote schools in the Northern Territory, Australia. The paper demonstrated that the university assessment policy accommodated Indigenous learning, reflecting students' culture, remote learning context, world experience, primary language, family and community values and entry-level competencies. This article is a systemic response to recommendations arising from a recent external evaluation of Growing Our Own and seeks to demonstrate how the project's approaches meet university assessment rules yet fit within a culturally valid framework. [source] Epithelial barrier disruption allows nondisease-causing bacteria to initiate and sustain IBD in the IL-10 gene-deficient mouse,INFLAMMATORY BOWEL DISEASES, Issue 8 2007Beate C. Sydora PhD Abstract Background: In the IL-10 gene-deficient mouse model, development of intestinal inflammation is associated with a defect in epithelial barrier integrity that is thought to allow sufficient passage of bacteria or bacterial antigens to initiate a mucosal immune response. Microbial monoassociation experiments into axenic animals have shown that some, but not all, endogenous bacteria will initiate an intestinal inflammatory response. For instance, Bacteroides vulgatus does not initiate intestinal inflammation in axenic IL-10 gene-deficient mice. We investigated whether B. vulgatus requires concomitant disruption of the intestinal epithelial barrier integrity in order to initiate an inflammatory response. Methods: We first identified a dose of the indomethacin that would cause a primary disruption of the epithelial barrier without causing intestinal inflammation. IL-10 axenic mice were then administered this dose of indomethacin in their drinking water for 7 days and concomitantly monoassociated, by oral gavage, with B. vulgatus. Results: Indomethacin treatment (2 ,g/g/d) for 7 days resulted in disruption of epithelial barrier integrity, but it caused neither a systemic inflammatory response nor a mucosal inflammatory response in the colon or cecum. Monoassociation with B. vulgatus alone did not lead to a mucosal inflammatory response, despite a measurable systemic response. In contrast, administration of indomethacin plus B. vulgatus -monoassociation resulted in a marked intestinal inflammatory response in colon and cecum. Conclusions: Our data show that, in a genetically predisposed animal model, the nondisease-causing endogenous bacteria, B. vulgatus, is able to cause an intestinal inflammatory response provided that disruption of the intestinal epithelial barrier has occurred. (Inflamm Bowel Dis 2007) [source] Systemic and local effects of long-term exposure to alkaline drinking water in ratsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2001Marina E.T. Merne Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. [source] Serum IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis and healthy subjectsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2000A. C. R. Tanner Abstract Background/aims: Established periodontal diseases may be associated with antibody responses to periodontal pathogens, but it is not known at which stage of disease this antibody response is initiated. This study aimed to characterize the host systemic response in initial periodontitis, gingivitis, and periodontal health, to evaluate whether elevated serum antibodies to subgingival species could be detected in initial periodontitis. Method: Human systemic immune response were evaluated to 40 subgingival bacterial species in 16 healthy, 21 gingivitis, 11 initial periodontitis and 5 progressing recession adults. Subjects had minimal periodontal attachment level (AL) loss at baseline. Disease categories were determined after 12 months monitoring at three-month intervals. Increased AL loss 1.5 mm (disease activity) at interproximal sites defined initial periodontitis, recession was characterized by AL loss at buccal sites. Serum IgG antibodies were evaluated semi-quantitatively by immunoblot from blood taken at baseline, active and final visits. Results: No antibody was detected from 55% of reactions. When detected, levels were below those reported for advanced periodontitis subjects. There were no major differences in serum antibody levels between healthy, gingivitis and initial periodontitis subjects, despite differences in the subgingival microbiota. Serum antibodies for more species were detected in recession subjects, compared with the other study subjects. No changes in antibody levels were detected between baseline, active, and final visits. No systematic association between species colonization and presence of systemic antibody was observed. Conclusions: This study did not detect differential elevation of mean serum antibody levels in initial periodontitis subjects, suggesting that serum antibody levels are not sensitive risk markers for initial periodontitis. [source] The effects of Pierce's disease on leaf and petiole hydraulic conductance in Vitis vinifera cv. ChardonnayPHYSIOLOGIA PLANTARUM, Issue 4 2009Brendan Choat In this study, we test the hypothesis that the symptoms of Pierce's Disease (PD) result from the occlusion of xylem conduits by the bacteria Xylella fastidiosa (Xf ). Four treatments were imposed on greenhouse-grown Vitis vinifera cv. Chardonnay: well-watered and deficit-irrigated plants with and without petiole inoculation with Xf. The hydraulic conductance of the stem-petiole junction (kjun) and leaves (kleaf) were measured, and Xf concentrations were established by quantitative polymerase chain reaction (qPCR). Leaf hydraulic conductance decreased with increasing leaf scorch symptoms in both irrigation treatments. The positive relationship between Xf concentration and symptom formation in deficit-irrigated plants suggests that water-stress increases susceptibility to PD. In field-grown vines, water relations of symptomatic leaves were similar to naturally senescing leaves but differed from green control leaves. Overall, these results suggest that the development of PD symptoms represents a form of accelerated senescence as part of a systemic response of the plant to Xf infection. [source] Inflammatory protein profile during systemic high dose interleukin-2 administrationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2006Leonardo Rossi Abstract Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein,A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were down-regulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers. [source] Low doses of silver nitrate induce pleurodesis with a limited systemic responseRESPIROLOGY, Issue 6 2009Evaldo MARCHI ABSTRACT Background and objective: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. Methods: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. Results: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-, and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-, at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. Conclusions: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate. [source] ORIGINAL ARTICLE: Activation of TLR3 in the Trophoblast is Associated with Preterm DeliveryAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009Kaori Koga Problem, Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response. Method of study, C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-,B pathway was evaluated in vivo and in vitro. Results, Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-,B pathway was activated by Poly[I:C] in human and mice trophoblast cells. Conclusion, We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface. [source] Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanomaCANCER, Issue 8 2008A phase II Cytokine Working Group study Abstract BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population. Cancer 2008. © 2008 American Cancer Society. [source] Temozolomide in advanced malignant melanoma with small brain metastasesCANCER, Issue 2 2007Can we Withhold Cranial Irradiation? Abstract BACKGROUND. The efficacy of radiotherapy (RT) in patients who have brain metastases from melanoma is limited. In this study, the authors evaluated the efficacy of treatment with temozolomide in patients with metastatic melanoma, including small brain metastases, who did not require immediate RT and investigated the feasibility of deferring RT. METHODS. Patients with brain metastasis were identified from 3 prospective studies of temozolomide (with or without immunotherapy) for metastatic melanoma. Patients with brain metastasis that measured >2 cm, extensive edema, and localization in the brain stem were excluded from the study. For the current analysis, patients with leptomeningeal metastasis and patients who received previous stereotactic RT were excluded. In patients who achieved a systemic response or stabilization to temozolomide, the response of brain metastasis and the necessity for palliative cranial RT were evaluated. RESULTS. Among 179 patients who received temozolomide for advanced melanoma, 52 patients with brain metastasis were evaluable. Stabilization of systemic metastasis was noted in 7 of 52 patients (13%), and there were 6 responses (5 partial responses and 1 complete response; 11%); thus, in those 13 patients, 6 had stabilization of brain metastasis (11%) and 5 had a response (2 partial responses and 3 complete responses; 9%). Immunotherapy did not influence the neurologic response. The median time to neurologic progression was 7 months (range 2,15, months). RT for cerebral recurrence was required in 2 patients. The median survival of patients with brain metastases was 5.6 months (95% confidence interval, 4.4,6.8 months). Intracranial hemorrhagic complications were not observed. CONCLUSIONS. The current results indicated that it is feasible to treat patients who have advanced melanoma and small brain metastasis with temozolomide as the single treatment. The small subset of patients with systemic response usually showed durable stabilization or a response of brain metastasis. With this approach, neurologic disease can be controlled, and cranial irradiation may be deferred and even withheld in most of patients. Cancer 2007. © 2006 American Cancer Society. [source] Comparison of intranasal with targeted lymph node immunization using PR8-Flu ISCOM adjuvanted HIV antigens in macaquesJOURNAL OF MEDICAL VIROLOGY, Issue 5 2007G. Koopman Abstract The rapidly spreading HIV epidemic requires a vaccine that elicits potent mucosal immunity to halt or slow transmission. Induction of these responses will depend on the use of appropriate adjuvants and targeting of the mucosal immune system. Previously, immune stimulating complexes (ISCOM) have shown great potency as adjuvant in the induction of mucosal responses in mice and systemic responses in non-human primates. In this study, HIV formulated in PR8-Flu ISCOM adjuvant was applied to immunize rhesus macaques against HIV; targeting the mucosa either via intranasal (IN) application or via targeted lymph node immunization (TLNI). While, strong systemic, HIV specific, cytokine, lymphoproliferative, and antibody responses were induced via the TLNI route, the IN application generated only low responses. Furthermore, all four animals immunized via TLNI developed vaginal IgA antibodies against gp120. In conclusion, in contrast to what has been demonstrated in mice, the IN application of PR8-Flu ISCOM did not induce strong immune responses in rhesus macaques unlike those immunized by the TLNI route. J. Med. Virol. 79:474,482, 2007. © 2007 Wiley-Liss, Inc. [source] Implementing Equal Justice for Parents in Washington: A Dual ApproachJUVENILE AND FAMILY COURT JOURNAL, Issue 4 2002JUSTICE BOBBE J. BRIDGE ABSTRACT In many states, legal representation for parents of dependent children is inadequate and can be a source of delays in securing permanency for children and unnecessarily protracted court proceedings. Often, such parents also face barriers to accessing services and independent evaluators. These issues are being addressed in the state of Washington through two approaches. The first is a successful enhanced legal representation program that has substantially improved case outcomes. The second is a statewide committee using innovative means to examine systemic responses to the challenges of the Adoption and Safe Families Act. [source] Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized studyLIVER TRANSPLANTATION, Issue 6 2006Luca Aldrighetti Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. Liver Transpl 12:941,949, 2006. © 2006 AASLD. [source] Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by AnisakisALLERGY, Issue 9 2009N. Nieuwenhuizen Background:, Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease. Objective:, To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4R, in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins. Methods:, BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4R, expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization. Results:, In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4R, or with impaired IL-4R, expression on CD4+ T cells. Conclusions:, Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock. [source] Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunitMOLECULAR ORAL MICROBIOLOGY, Issue 6 2007Y. Takahashi Introduction:, Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice. Methods:, Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis -induced periodontitis in mice was evaluated by measuring alveolar bone loss. Results:, The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 ,g) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 ,g fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis -mediated alveolar bone loss. Conclusion:, Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis -mediated periodontitis. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] Herbivory-induced signalling in plants: perception and actionPLANT CELL & ENVIRONMENT, Issue 9 2009JIANQIANG WU ABSTRACT Plants and herbivores have been interacting for millions of years. Over time, plants have evolved mechanisms to defend against herbivore attacks. Herbivore-challenged plants reconfigure their metabolism to produce compounds that are toxic, repellant or anti-digestive for the herbivores. Some compounds are volatile signals that attract the predators of herbivores. All these responses are tightly regulated by a signalling network triggered by the plant's perception machinery. Several compounds that specifically elicit herbivory-induced responses in plants have been isolated from herbivore oral secretions and oviposition fluids. Elicitor perception is rapidly followed by cell membrane depolarization, calcium influx and mitogen-activated protein kinase (MAPK) activation; plants also elevate the concentrations of reactive oxygen and nitrogen species, and modulate phytohormone levels accordingly. In addition to these reactions in the herbivore-attacked regions of a leaf, defence responses are also mounted in unattacked parts of the attacked leaf and as well in unattacked leaves. In this review, we summarize recent progress in understanding how plants recognize herbivory, the involvement of several important signalling pathways that mediate the responses to herbivore attack and the signals that transduce local into systemic responses. [source] Proteomic analysis of bacterial-blight defense-responsive proteins in rice leaf bladesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2006Tariq Mahmood Abstract Plants exhibit resistance against incompatible pathogens, via localized and systemic responses as part of an integrated defense mechanism. To study the compatible and incompatible interactions between rice and bacteria, a proteomic approach was applied. Rice cv. Java 14 seedlings were inoculated with compatible (Xo7435) and incompatible (T7174) races of Xanthomonasoryzae pv. oryzae (Xoo). Cytosolic and membrane proteins were fractionated from the leaf blades and separated by 2-D PAGE. From 366 proteins analyzed, 20 were differentially expressed in response to bacterial inoculation. These proteins were categorized into classes related to energy (30%), metabolism (20%), and defense (20%). Among the 20 proteins, ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (RuBisCO LSU) was fragmented into two smaller proteins by T7174 and Xo7435 inoculation. Treatment with jasmonic acid (JA), a signaling molecule in plant defense responses, changed the level of protein accumulation for 5 of the 20 proteins. Thaumatin-like protein and probenazole-inducible protein (PBZ) were commonly up-regulated by T7174 and Xo7435 inoculation and JA treatment. These results suggest that synthesis of the defense-related thaumatin-like protein and PBZ are stimulated by JA in the defense response pathway of rice against bacterial blight. [source] In situ photoimmunotherapy: a tumour-directed treatment for melanomaBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2006M.F. Naylor Summary We report a new immunological treatment for advanced cutaneous melanoma which combines laser stimulation with topical application of a toll-like receptor agonist. This treatment, in situ photoimmunotherapy (ISPI), provides an alternative to traditional therapies for melanoma patients with cutaneous metastases. A 6-week cycle of ISPI is carried out on cutaneous metastases located in a designated 20 × 20 cm treatment area: 2 weeks of pretreatment with twice-daily topical applications of imiquimod (5% cream under plastic occlusion), with a laser treatment session at week 2 and again at week 4. Topical imiquimod is continued for the entire 6-week cycle. Two patients with late-stage melanoma were treated with ISPI. Patient 1 had the primary tumour and local metastases on the left arm, as well as metastatic tumours in the lungs [American Joint Committee on Cancer (AJCC) stage IV]. Patient 2 had a head and neck melanoma with multiple local metastases (AJCC stage IIIC), which had failed repeated attempts at surgical resection and high-dose radiation therapy. Patient 1 is now free of all clinically detectable tumours (including the lung metastases) >20 months after the first treatment cycle. Patient 2 has been free of any clinical evidence of the tumour for over 6 months. These two cases demonstrate that ISPI can clear local tumour and trigger beneficial systemic responses, with a side-effect profile that compares favourably with other treatments for advanced melanoma. [source] Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009K. Kulhankova Summary Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. Objective We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. Methods C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. Results Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG1, and IgG2a production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG1, lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. Conclusions Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures. [source] | |||||||||||||||||||||||||