Granuloma Formation (granuloma + formation)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Granuloma formation in ANCA-associated vasculitides

APMIS, Issue 2009
PETER LAMPRECHT
Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg,Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ,NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [source]


Injecting 1000 Centistoke Liquid Silicone With Ease and Precision

DERMATOLOGIC SURGERY, Issue 3 2003
Anthony V. Benedetto DO, FACP
BACKGROUND Since the Food and Drug Administration approved the use of the 1000 centistoke liquid silicone, Silikon 1000, for intraocular injection, the off-label use of this injectable silicone oil as a permanent soft-tissue filler for facial rejuvenation has increased in the United States. Injecting liquid silicone by the microdroplet technique is the most important preventive measure that one can use to avoid the adverse sequelae of silicone migration and granuloma formation, especially when injecting silicone to improve small facial defects resulting from acne scars, surgical procedures, or photoaging. OBJECTIVE To introduce an easy method for injecting a viscous silicone oil by the microdroplet technique, using an inexpensive syringe and needle that currently is available from distributors of medical supplies in the United States. METHOD We suggest the use of a Becton Dickinson 3/10 cc insulin U-100 syringe to inject Silikon 1000. This syringe contains up to 0.3 mL of fluid, and its barrel is clearly marked with an easy-to-read scale of large cross-hatches. Each cross-hatch marking represents either a unit value of 0.01 mL or a half-unit value of 0.005 mL of fluid, which is the approximate volume preferred when injecting liquid silicone into facial defects. Because not enough negative pressure can be generated in this needle and syringe to draw up the viscous silicone oil, we describe a convenient and easy method for filling this 3/10 cc diabetic syringe with Silikon 1000. RESULTS We have found that by using the Becton Dickinson 3/10 cc insulin U-100 syringe, our technique of injecting minute amounts of Silikon 1000 is facilitated because each widely spaced cross-hatch on the side of the syringe barrel is easy to read and measures exact amounts of the silicone oil. These lines of the scale on the syringe barrel are so large and clearly marked that it is virtually impossible to overinject the most minute amount of silicone. CONCLUSION Sequential microdroplets of 0.01 cc or less of Silikon 1000 can be measured and injected with the greatest ease and precision so that inadvertent overdosing and complications can be avoided. [source]


Case of eosinophilic granulomatous enterocolitis caused by Strongyloides stercoralis infection with marked hypoalbuminemia and ascites

DIGESTIVE ENDOSCOPY, Issue 3 2004
Nuthapong Ukarapol
We report a 10-year-old boy presenting with generalized pitting edema, ascites, abdominal pain, and chronic mucous diarrhea for 4 weeks. He had underlying diseases of hemoglobin E and juvenile rheumatoid arthritis and had been treated with immunosuppressive agents for a long period of time, including prednisolone and methotrexate. After extensive investigations, Strongyloides stercoralis infection, leading to protein-losing enteropathy and eosinophilic granulomatous enterocolitis, was diagnosed. In the present report, we demonstrate early colonoscopic findings, revealing patchy erythema and small raised mucosal nodules with erosions at the cecum. Histopathological study showed open ulceration with cryptitis, intense infiltration of eosinophils and histiocytes with granuloma formation, in which Strongyloides stercoralis larvae were noted. [source]


Innate, antigen-independent role for T cells in the activation of the immune system by Propionibacterium acnes

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2010
Sandrine Tchaptchet
Abstract Propionibacterium acnes is a human commensal but also an opportunistic pathogen. In mice, P. acnes exerts strong immunomodulatory activities, including formation of intrahepatic granulomas and induction of LPS hypersensitivity. These activities are dependent on P. acnes recognition via TLR9 and subsequent IL-12-mediated IFN-, production. We show that P. acnes elicits IL-12p40 and p35 mRNA expression in macrophages, and IFN-, mRNA in liver CD4+ T cells and NK cells. After priming with P. acnes, CD4+ T cells serve as the major IFN-, mRNA source. In the absence of CD4+ T cells, CD8+ T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN-, to induce the P. acnes -driven immune effects. Moreover, in the absence of ,,T cells, ,,T cells also enable the development of strongly enhanced TNF-, and IFN-, responses to LPS and intrahepatic granuloma formation. Thus, under microbial pressure, different T-cell types, independent of their antigen specificity, exert NK-cell-like functions, which contribute decisively to the activation of the innate immune system. [source]


TLR9 activation is a key event for the maintenance of a mycobacterial antigen-elicited pulmonary granulomatous response

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2007
Toshihiro Ito
Abstract Type 1 (Th1) granulomas can be studied in mice sensitized with mycobacterium antigens followed by challenge of agarose beads covalently coupled to purified protein derivative. TLR9 is known to play a role in the regulation of Th1 responses; thus, we investigated the role of TLR9 in granuloma formation during challenge with mycobacterium antigens and demonstrated that mice deficient in TLR9 had increased granuloma formation, but a dramatically altered cytokine phenotype. Th1 cytokine levels of IFN-, and IL-12 in the lungs were decreased in TLR9,/, mice when compared to wild-type mice. In contrast, Th2 cytokine levels of IL-4, IL-5, and IL-13 were increased in TLR9,/, mice. The migration of CD4+ T cells in the granuloma was impaired, while the number of F4/80+ macrophages was increased in TLR9,/, mice. Macrophages in the lungs of the TLR9-deficient animals with developing granulomas expressed significantly lower levels of the classically activated macrophage marker, nitric oxide synthase, but higher levels of the alternatively activated macrophage markers such as ,found in inflammatory zone-1, antigen and Arginase-1. These results suggest that TLR9 plays an important role in maintaining the appropriate phenotype in a Th1 granulomatous response. [source]


Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology

EXPERIMENTAL DERMATOLOGY, Issue 9 2009
Franziska Buback
Abstract:, Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-, secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases. [source]


Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2002
D. A. LAMMAS
Summary Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFN, production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFN, (Fig. 9). At one pole of this spectrum, represented by the complete IFN,R1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFN,R1/2, complete IL-12p40 and complete IL-12R,1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFN, responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited. Figure 9. ,Spectrum of genetic susceptibility to intracellular bacteria. At one pole of this spectrum complete IFN,R deficiencies are found; at the other pole are healthy resistant individuals. Partial IFN,R1 deficiencies, and complete IL-12R,1 and IL-12p40 deficiencies can be positioned in between, albeit closer to the former end of the spectrum, with clinical outcome also depending on pathogen virulence and host compensatory immune mechanism(s). Abbreviations: IFN,R , interferon gamma receptor, IL-12R,1 , interleukin 12 receptor-1 (modified from Ottenhoff et al. (1998)). [source]


Management of complications after implantation of fillers

JOURNAL OF COSMETIC DERMATOLOGY, Issue 1 2004
Koenraad De Boulle
Summary Soft tissue augmentation is widely practised by a variety of different practitioners. A new classification of filler substances and procedures, taking into account long-term safety and reversibility of side effects, is proposed: i non-permanent and biodegradable, ii,semi-permanent and biodegradable, iii,permanent and reversible, iv,permanent and non-reversible. Complications and adverse effects occur with all fillers and all filler procedures. Insufficient experience is an important contributory factor. Underreporting is probably common. Commonest are haematomas, ecchymoses, infections, papulopustular or acneiform lesions, non-hypersensitivity related swelling and oedema, erythema, changes in pigmentation, palpability of the implant and necrosis of overlying tissue. Specific therapeutic approaches for these complications and practical recommendations to minimize or avoid them are discussed. Hypersensitivity reactions and granuloma formation are the most distressing adverse effects. They can occur with most fillers. Mostly these hypersensitivity reactions are local granulomas but, rarely, generalized reactions also occur. Case reports of systemic reactions after injection of hyaluronic acid are documented. Treatments include steroids, minocycline and immunomodulatory agents, such as cyclosporin, tacrolimus and ascomycin. In selected cases, surgical procedures are necessary to elimirate granulomatous reactions. Implant migration and facial lipoatrophy are encountered with certain compounds. Extreme caution is therefore advocated before using permanent and non-reversible products for soft tissue augmentation. Those who use fillers need to be familiar with the complications of fillers and with the treatment of those complications. [source]


Atypical Aeromonas salmonicida infection in naturally and experimentally infected cod, Gadus morhua L.

JOURNAL OF FISH DISEASES, Issue 10 2002
B Magnadóttir
Abstract Cod, Gadus morhua L., of wild origin, were reared at different temperatures for 12 months. During this period, moribund and newly dead fish were examined and samples collected for bacteriology and histopathology. Atypical Aeromonas salmonicida was isolated from 10 individuals reared at or above 7 °C. The isolates were homogeneous with respect to biochemical and antibiogram characters and similar to the ssp. achromogenes National Collection of Industrial and Marine Bacteria, UK, type strain 1110 and reference strains that have been isolated from salmonids and haddock in Iceland. Histopathological analysis of the naturally infected cod showed typical ulceration associated with atypical A. salmonicida infection and also widespread granulomatous formations. One-year-old cod of farmed origin, kept at 9 °C, received intraperitoneal or intramuscular injection with different doses of atypical A. salmonicida, isolated from the above wild cod. Mortalities were monitored for 28 days and the LD50 calculated. The route of bacterial injection influenced the mortality rate and LD50 value and affected, to some extent, the pathological changes observed and humoral immune parameters. Pathological changes, including haemorrhage, early stages of granuloma formation and necrotic changes, were seen in several organs. Infection appeared to induce non-specific antibody activity against trinitrophenyl (TNP)-haptenated protein and may have activated the complement system. Specific antibody response against atypical A. salmonicida was not detected. [source]


Effector memory T cells as driving force of granuloma formation and autoimmunity in Wegener's granulomatosis

JOURNAL OF INTERNAL MEDICINE, Issue 3 2006
P. Lamprecht
First page of article [source]


Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti

MOLECULAR MICROBIOLOGY, Issue 3 2002
Alexander S. Pym
Summary Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M. bovis BCG and M. microti. Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli. Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants. The BCG::RD1 and M. microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation. Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared. Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development. [source]


Intrathecal inflammatory masses: is the yearly opioid dose increase an early indicator?

NEUROMODULATION, Issue 2 2010
Rui V. Duarte BSc
Objectives:, The objective of this study is to investigate the association between intrathecal drug, flow rate, drug concentration, and drug dose with the formation of intrathecal inflammatory masses. Methods:, A retrospective longitudinal study of 56 consecutive patients receiving long-term intrathecal analgesic administration was undertaken through screening of medical records. Data regarding drug flow rate, dose per day, and concentration of drugs administered were recorded for morphine, diamorphine, bupivicaine, clonidine and baclofen and averages computed. Results:, The average follow-up time post-implant was 91 ± 55 months (range: 9,209). Four of the 56 patients were diagnosed with intrathecal granuloma indicating a rate of 7%, the equivalent to 0.009 events per patient year. Twenty-one of the patients had received morphine either alone or combined; 22 had received diamorphine either alone or mixed; and 13 crossed over from morphine to diamorphine or the inverse. None of the patients with granuloma crossed over before diagnosis. A significant correlation was found between opioid dose (r= 0.275, p < 0.05), yearly increase of the opioid dose (r= 0.433, p < 0.05), and granuloma formation. Clonidine appeared to have a protective effect for the non-granuloma patients. No association was found with flow rate (r= 0.056) or opioid concentration (r= 0.214). Conclusion:, This is the first detailed study showing an association of diamorphine with granulomas. This study supports the previous finding of intrathecal opioid dose being a risk factor for intrathecal granulomas and clonidine being protective. In addition we have found that the yearly increase in opioid dose is a risk factor for granulomas and could serve as an indicator for closer surveillance. [source]


A fish bone embedded in the mobile tongue mimicking a neoplasm

ORAL SURGERY, Issue 4 2008
Yan Wang
Abstract Foreign bodies embedded in a mobile tongue as an enlarged tongue mass are rarely presented to either a laryngologist or a dentist, because such bodies are commonly lodged superficially and are easily removed by the patients themselves or removed by a laryngologist by means of indirect laryngoscope or endoscope. We have described a 63-year-old female with an 8-month history of an enlarged mass in the anterior right tongue. Physical examination demonstrated a mass located in the anterior right tongue without clear margin, with superficially intact mucosa and normal colour. A benign tongue neoplasm was first considered. However, a fish bone totally embedded in the mobile tongue with granuloma formation was encountered during the incisional biopsy operation. Complete removal of the foreign body with granuloma was achieved under general anaesthesia. There was no neuromuscular or neurosensory dysfunction of the tongue in the follow-up period of 2 years. Although an embedded foreign body in the mobile tongue is a rare condition, it should be considered in the work-up of a patient with an enlarged tongue mass, with or without a history of swallowing a foreign body. [source]


Chemokine responses in schistosomal antigen-elicited granuloma formation,

PARASITE IMMUNOLOGY, Issue 6 2002
Bo-Chin Chiu
Summary Host immune systems have evolved specialized responses to multicellular parasites. This is well represented by the type 2 granulomatous response to Schistosoma mansoni egg antigens, which is an eosinophil-rich inflammatory response mediated by Th2-associated cytokines. Using Ag-bead models of pulmonary granuloma formation in mice, we defined characteristic chemokine (CK) profiles in the granulomatous lungs. Our findings point to a role for C-C chemokine receptor-2 (CCR2) and CCR3 agonists such as monocyte chemotactic proteins (MCPs) 1/CCL2, 3/CCL7 and 5/CCL12 as important participants that are subject to regulation by Th2 cytokines interleukin (IL)-4 and IL-13. CCR4 and CCR8 agonists are also likely contributors. Analysis of CK receptor knockout mice revealed that CCR2 ligands (e.g. MCP-1 and 5) promoted early phase granuloma macrophage accumulation, whereas anti-MCP-3 (CCL7) antibody treatment abrogated eosinophil recruitment. CCR8 knockout mice also demonstrated impaired eosinophil recruitment but this appeared to be related to impaired Th2 cell function. Transcript analysis of CD4+ T cells generated during schistosome granuloma formation failed to show biased CCR8 expression but, having a more limited receptor repertoire, these cells were likely more dependent on CCR8 ligands. Together, these studies indicate an intricate involvement of chemokines in various stages and aspects of schistosomal egg Ag-elicited granuloma formation. [source]


Pharmacological studies on Indian black tea (leaf variety) in acute and chronic inflammatory conditions

PHYTOTHERAPY RESEARCH, Issue 6 2008
Dilip K. Roy
Abstract Infusions of Indian black tea (BTI), when administered orally, produced significant inhibition of rat paw oedema, induced with carrageenin (pre and post treatment) and arachidonic acid. BTI was also found to inhibit peritoneal capillary permeability and caused a marked reduction of lipopolysaccharide induced PGE2 generation. In these models, the observed antioedema effect was similar to that of BW755C (a dual inhibitor of cyclooxygenase and 5-lipoxygenase enzymes). BTI was found to scavenge superoxide and hydroxyl radicals, and also protected rat erythrocytes from the damaging effects of hydrogen peroxide. In chronic studies, BTI inhibited granuloma formation along with the reduction of both lipid peroxidation and hydroxyproline content (in the granuloma tissue). Significant antiarthritic activity was observed with regular administration of BTI in the Freund's adjuvant induced model of arthritis. Chronic treatment with BTI (in arthritic rats) resulted in a decrease of paw diameter and tissue lipid peroxidation, along with a restoration of GSH, catalase and superoxide dismutase levels. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Granuloma caused by subcutaneous injection of leuprorelin acetate product: Case report and histopathological findings

THE JOURNAL OF DERMATOLOGY, Issue 10 2006
Takeshi OUCHI
ABSTRACT Leuprorelin acetate is a luteinizing hormone-releasing hormone (LH-RH) analog, which is used for chemical castration. Chemical castration treatment has an especially important role for prostate cancer. To ensure ongoing chemical castration, a novel sustained-action injection system using spherical microcapsules has been developed. We report a patient who had granuloma caused by administration of the 11.25 mg leuprorelin acetate product. Histological examination revealed many giant cells with vacuoles. On the basis of reported cases, these vacuoles are characteristic for the granuloma caused by leuprorelin acetate product. The vacuoles in the granuloma are the same size as the microcapsules, and their shape is almost spherical. We assume that the vacuoles in the granuloma are actually the microcapsules. We expect that there will be investigations regarding the procatarctic cause of granuloma formation. [source]


Fragmented QRS Complexes on 12-Lead ECG: A Marker of Cardiac Sarcoidosis as Detected by Gadolinium Cardiac Magnetic Resonance Imaging

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2009
Mohamed Homsi M.D.
Background: Fragmented QRS complexes (fQRS) on a 12-lead ECG are a marker of myocardial scar in patients with coronary artery disease. Cardiac sarcoidosis is also associated with myocardial granuloma formation and scarring. We evaluated the significance of fQRS on a 12-lead ECG compared to Gadolinium-delayed enhancement images (GDE) in cardiac magnetic resonance imaging (CMR). Method and results: The ECGs of patients (n = 17, mean age: 52 ± 11 years, male: 53%) with established diagnosis of sarcoidosis who underwent a CMR for evaluation of cardiac involvement were studied. ECG abnormalities included bundle branch block, Q wave, and fQRS. fQRS, Q wave, and bundle branch block were present in 9 (53%), 1 (6%), and 4 (24%) patients, respectively. The sensitivity and specificity of fQRS for detecting abnormal GDE were 100% and 80%, respectively. Sensitivity and specificity of Q waves were 11% and 100%, respectively. Conclusions: fQRS on a 12-lead ECG in patients with suspected cardiac sarcoidosis are associated with cardiac involvement as detected by GDE on CMR. [source]


Granuloma formation in ANCA-associated vasculitides

APMIS, Issue 2009
PETER LAMPRECHT
Granuloma formation is a key pathologic finding in two of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides: Wegener's granulomatosis (WG) and Churg,Strauss syndrome (CSS). So far, no animal models have been established convincingly reproducing both vasculitic and granulomatous features typical of WG and CSS. In biopsies, granulomatous lesions are found both at distant extravascular sites and in the vicinity of inflamed vessels, e.g. in the lung. Intriguingly, WG-granulomata appear to display features of tertiary lymphoid tissue. Cartilaginous and osseous destruction is caused by granulomatous inflammation invading adjacent tissues. Rhinosinusitis is regularly encountered in WG and CSS. Septal perforation, saddle nose deformity, middle and inner ear symptoms, and granulomatous invasion of the palate, orbita, meninges, or the pituitary gland may complicate WG. Both common (e.g. FCGR3B copy number) and distinct (e.g. HLA-DP, IL-10.2) genetic factors have been identified in AAV potentially favouring inflammation and autoimmunity. The HLA-DPB1/RING1/RXRB region constitutes a quantitative trait locus for ANCA-positive WG with the strongest association to be reported up to now. A profound alteration of the T-cell response including Th1 and Th17 responses, anomalously NK-receptor-expressing ,NK-like' T cells, and dysfunctional regulatory T cells could facilitate and sustain granuloma formation and autoimmunity. [source]


Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model

ARTHRITIS & RHEUMATISM, Issue 2 2010
Philana Ling Lin
Objective An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor , (TNF,),neutralizing agents. In murine models, impaired signaling by TNF causes exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model. Methods Cynomolgus macaques 4 years of age or older were infected with Mycobacterium tuberculosis and subjected to clinical, microbiologic, immunologic, and radiographic examinations. Monkeys were classified as having active or latent disease 6,8 months after infection, based on clinical criteria. Monkeys used in acute infection studies were randomized to receive either adalimumab (prior to and during infection) or no treatment. Monkeys with latent infection that were randomized to receive TNF-neutralizing agent were given either an inhibitor of soluble TNF, recombinant methionyl human soluble TNF receptor I (p55-TNFRI), or adalimumab. Control monkeys with latent infection were given no treatment or saline. Data from previously studied monkeys with active or latent disease were also used for comparison. Results Administration of TNF-neutralizing agents prior to M tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks after infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathologic examination and bacterial burden. A spectrum of dissemination was noted, including extrapulmonary disease. Surprisingly, monkeys that developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition to that of control monkeys with active disease. TNF neutralization was associated with increased levels of interleukin-12, decreased levels of CCL4, increased chemokine receptor expression, and reduced mycobacteria-induced interferon-, production in blood but not in the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes. Conclusion These findings have important clinical implications for determining the mechanism of TNF neutralization,related tuberculosis. [source]


Blockade of parathyroid hormone,related protein prevents joint destruction and granuloma formation in streptococcal cell wall,induced arthritis

ARTHRITIS & RHEUMATISM, Issue 6 2003
J. L. Funk
Objective To determine whether parathyroid hormone,related protein (PTHrP), an interleukin-1,,inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA. Methods PTHrP expression and the effect of PTHrP 1,34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW),induced arthritis, an animal model of RA. Results As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium. Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals. However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone. Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor,positive neutrophils and in SCW-induced neutrophilia. In vitro, neutrophil chemotaxis was stimulated by PTHrP 1,34. Conclusion These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA. Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders. [source]


A case of cutaneous-type adult T-cell leukaemia/lymphoma showing granuloma formation under a parapsoriatic eruption

BRITISH JOURNAL OF DERMATOLOGY, Issue 5 2002
E. Okumura
No abstract is available for this article. [source]


Cicatricial ectropion: repair with myocutaneous flaps and canthopexy

CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 7 2006
Kiran Manku FRANZCO
Abstract Background:, To evaluate the effectiveness of myocutaneous upper eyelid flaps combined with canthopexy to treat cicatricial lower eyelid ectropion. Methods:, A prospective non-comparative case series undertaken in a private practice setting. Consecutive patients with moderate lower eyelid cicatricial ectropion and upper eyelid dermatochalasis underwent transfer of a bipedicle or monopedicle flap from the upper eyelid combined with canthopexy. The main outcome measures included the occurrence of complications, eyelid position and cosmesis. Results:, Sixty-two consecutive cases of cicatricial ectropion repair using myocutaneous flaps and canthopexy. After a mean follow up of 20 months, 58 (93.5%) of the cases had the lower lid punctum facing posterosuperior into the tear lake, showed lid globe apposition and satisfactory eyelid position. There was mild recurrence of cicatricial ectropion in four patients (6.5%). There were no cases of graft failure or granuloma formation. Conclusion:, The use of a myocutaneous flap from the upper eyelid combined with a canthopexy suspension suture for repair of cicatricial ectropion may offer good eyelid position and function. This technique has the advantage of avoiding full thickness blepharotomy and was associated with a low incidence of early recurrence. [source]