A Rare Complication: Development of an Aspergilloma after Endobronchial Coil Placement in a COPD Patient.

Endobronchial coils are a relatively novel endoscopic lung volume reduction modality that aims to increase functional capacity in chronic obstructive pulmonary disease (COPD) patients. Two major trials have studied the safety and efficacy of this therapy, but long-term safety has not been studied. Adverse events reported are mainly periprocedural pneumothoraces and early bacterial infectious complications. We report the case of a patient with severe emphysema (Global Initiative for Chronic Obstructive Lung Disease stage IV COPD) who developed endobronchial coil-associated aspergillomas 3 years after coil placement.

Description of the feeding preferences of triatominae in the Chagas disease surveillance study for the State of Pernambuco, Brazil (Hemiptera: Reduviidae)

Abstract INTRODUCTION: Studying the feeding preferences of triatomines is an important entomological surveillance tool, since continuous surveillance of the disease is necessary. METHODS: The precipitin reaction was used to describe the feeding preferences of triatomines along with their natural infection by flagellates similar to Tyrpanosoma cruzi. Six hundred eighty-seven insects were examined, including Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus lutzi. RESULTS: Sixty-nine (10%) of 687 triatomines examined tested positive for flagellates similar to T. cruzi, and 8 (1.2%) of these fed on human blood. CONCLUSIONS: This study found potential transmitters of Chagas disease both inside and outside the domiciliar environment.

Diagnostic implications of positive avian serology in suspected hypersensitivity pneumonitis.

BACKGROUND: The diagnostic evaluation of patients with interstitial lung disease (ILD) often involves serologic assessment for identifiable causes such as hypersensitivity pneumonitis (HP). While not on its own defining of HP, precipitin serologies are often obtained to support clinical suspicion if other findings are inconclusive. We studied the clinical relevance of positive avian serology in patients undergoing ILD evaluation. MATERIAL AND METHODS: We identified individuals with positive avian serology (>53.3 mg/L) and undifferentiated ILD seen at our institution over a three-year period. Clinical, laboratory, pathologic, and radiologic findings were evaluated for consensus HP diagnosis by two expert pulmonologists, blinded to presenting serology levels. RESULTS: Ninety-one ILD subjects with positive avian serology were identified; mean age was 62.7 ± 15.3 years with a slight male predominance (56%). Forty-nine (54%) received a consensus HP diagnosis. Those with HP had higher mean avian serology titer (95.0 ± 38.7 mg/L vs. 68.3 ± 16.7, (P < 0.0001). Never-smokers also had higher titers compared to prior or active smokers (P = 0.0008). Positive avian protein exposure (P < 0.0001, OR 21.3 (6.4-87)), DLCO% (P = 0.04, unit OR 0.96 (0.92-0.99)), and increasing serology titer (P < 0.015, unit OR 1.03 [1.01-1.06]) were independent predictors of HP diagnosis. CONCLUSION: Among patients with positive avian serology, those with higher titers were more likely to have HP diagnosis. Nonsmokers also manifested higher titers compared to those with smoking history. These results may guide the usage and interpretation of avian serology screening in the initial assessment of suspected HP.

Emphysema in active farmer's lung disease.

BACKGROUND: Farmer's lung (FL) is a common type of hypersensitivity pneumonitis. It is often considered that fibrosis is the most frequent finding in chronic FL. Nevertheless, three cohort studies have suggested that some patients with chronic FL may develop emphysema. We aimed to evaluate the current prevalence of emphysema in active FL, to describe the radiological and functional features of emphysema in active FL, and to identify risk factors associated with emphysema in this population. METHODS: Patients aged over 18 years with active FL were prospectively recruited through the SOPHIA study (CPP Est; P-2009-521), between 2007 and 2015. Each patient had complete medical history screening, clinical examination, high resolution computed tomodensitometry, bronchoalveolar lavage, pulmonary function tests and serum precipitins. RESULTS: Among 33 patients with active FL, the prevalence of emphysema in this series of incident active FL cases was higher (48.5%) than that of fibrosis (12%) and was not dependent on smoking habits. Most patients with emphysema did not have lung hyperinflation. The possible risk factors for emphysema in active FL were a longer duration of exposure to organic dusts, and at a higher level. CONCLUSION: Emphysema is found in half of patients with active FL and may be influenced by exposure patterns.

Comparative study of the accuracy of different technique for the laboratory diagnosis of schistosomiasis mansoni in areas of low endemicity in Barra Mansa City, Rio de Janeiro State, Brazil

Schistosomiasis constitutes a major public health problem, with an estimated 200 million people infected worldwide. Many areas of Brazil show low endemicity of schistosomiasis, and the current standard parasitological techniques are not sufficiently sensitive to detect the low-level helminth infections common in areas of low endemicity (ALEs). This study compared the Kato-Katz (KK); Hoffman, Pons, and Janer (HH); enzyme-linked immunosorbent assay- (ELISA-) IgG and ELISA-IgM; indirect immunofluorescence technique (IFT-IgM); and qPCR techniques for schistosomiasis detection in serum and fecal samples, using the circumoval precipitin test (COPT) as reference. An epidemiological survey was conducted in a randomized sample of residents from five neighborhoods of Barra Mansa, RJ, with 610 fecal and 612 serum samples. ELISA-IgM (21.4%) showed the highest positivity and HH and KK techniques were the least sensitive (0.8%). All techniques except qPCR-serum showed high accuracy (82­95.5%), differed significantly from COPT in positivity , and showed poor agreement with COPT. Medium agreement was seen with ELISA-IgG (Kappa = 0.377) and IFA (Kappa = 0.347). Parasitological techniques showed much lower positivity rates than those by other techniques. We suggest the possibility of using a combination of laboratory tools for the diagnosis of schistosomiasis in ALEs.

Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: A randomized double-blind study / Efeitos da suplementação de farinha de uva sobre marcadores inflamatórios e antioxidantes em pacientes em hemodiálise: Estudo duplo-cego randomizado

Introduction: Polyphenols contained in natural sources such as grapes, have been considered pharmacological agents to combat oxidative stress and inflammation, common features in Chronic Kidney Disease patients. Objective: To evaluate the effects of grape powder supplementation on inflammatory and antioxidant biomarkers in hemodialysis (HD) patients. Methods: The double-blind placebo-controlled randomized clinical trial evaluated non-diabetic HD patients that received grape powder (500 mg of polyphenols/day) (n = 16, 9 men, 53.0 ± 9.8 years of age, 111.6 ± 58.2 HD months) or placebo (n = 16, 9 men, 52.7 ± 13.7 years of age, 110.4 ± 93.1 HD months) for five weeks. The glutathione peroxidase (GSH-Px) activity and C-reactive protein (CRP) levels were evaluated by ELISA method. Results: After the intervention period, the patients receiving grape powder showed an increase in the GSH-Px activity (16.5 (41.0) to 42.0 (43.3) nmol/min/ml) (p < 0.05) and they did not have the CRP levels increased as seen in placebo group (2.6 (0.28) to 2.8 (0.23 mg/L) (p < 0.05). Conclusion: The use of grape powder as phenolic source could play an important role as an antioxidant and anti-inflammatory agent in non-diabetic HD patients. .

Introdução: Polifenóis contidos em fontes naturais, como as uvas, têm sido considerados agentes farmacológicos no combate ao estresse oxidativo e inflamação, condições comuns na Doença Renal Crônica. Objetivo: Avaliar os efeitos da suplementação de farinha de uva sobre marcadores inflamatórios e antioxidantes em pacientes submetidos à hemodiálise (HD). Métodos: Estudo randomizado, duplo-cego, placebocontrolado, no qual foram avaliados pacientes não diabéticos em HD que receberam farinha de uva (500 mg de polifenóis/dia) (n = 16, 9 homens, 53,0 ± 9,8 anos, 111,6 ± 58,2 meses em HD) ou placebo (n = 16, 9 homens, 52,7 ± 13,7 anos, 110,4 ± 93,1 meses em HD) por cinco semanas. A atividade da glutationa peroxidase (GSH-Px) e os níveis plasmáticos de proteína C-reativa (PCR) foram mensurados por meio do método ELISA. Resultados: Após o período de intervenção, os pacientes que receberam farinha de uva apresentaram elevação na atividade da GSH-Px (16,5 (41,0) para 42,0 (43,3) nmol/min/ml) (p < 0,05) e não foi observada elevação nos níveis de PCR, como visto no grupo placebo (2,6 (0,28) para 2,8 (0,23) mg/L) (p < 0,05). Conclusão: O uso da farinha de uva como fonte de polifenóis pode desempenhar um importante papel anti-inflamatório e antioxidante em pacientes não diabéticos submetidos à HD. .

Eclectic feeding behavior of Lutzomyia (Nyssomyia) intermedia (Diptera, Psychodidae, Phlebotominae) in the transmission area of American cutaneous leishmaniasis, state of Paraná, Brazil

Introduction The blood meal source of sandflies provides valuable information about the vector/host interaction and allows for an understanding of American cutaneous leishmaniasis (ACL) transmission mechanisms. The aim of this study was to identify the blood meal sources of Lutzomyia (Nyssomyia) intermedia in an endemic area of leishmaniasis in Brazil's State of Paraná using a precipitin test. Methods Sandflies were collected in the rural locality of Epitácio Pessoa within the City of Adrianópolis, State of Paraná, in southern Brazil. A total of 864 female sandflies were captured, and 862 (99.8%) were identified as L. intermedia species. However, two unidentified specimens were considered to be part of the genus Lutzomyia. Results Among the females examined, 396 specimens presented reactions to a certain type of tested antiserum, and most (67.9%) reacted to the simple type. These sandflies fed mainly on the blood of birds, opossums, and rodents, but specimens that fed on the blood of humans, dogs, horses, cattle, and cats were also found. Among the cross-reactions found (32.1%), bird/rodent, bird/opossum, bird/dog, bird/human, and horse/dog cross-reactions were the most common. Conclusions These results demonstrate a tendency in the eclectic feeding behavior of L. intermedia and support its potential role as a vector for ACL in the study area. .

Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis.

Detection of Aspergillus IgG antibodies is important in the diagnosis of chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Immunoprecipitation techniques to detect these antibodies appear to lack sensitivity and accurate quantitation compared with enzyme immunoassays (EIA). This study assessed the performance of two commercial EIAs compared with counterimmunoelectrophoresis (CIE). This was a prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies were detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG. Inter-assay reproducibility was determined for each method and 25 patients had two serum samples analysed within a 6-month interval. When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively) for detection of Aspergillus IgG antibodies. The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE titre. ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas Platelia IgG was 33%. Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL. The direction of CIE titre change over 6 months was mirrored by ImmunoCap IgG levels in 92% of patients, and by Platelia IgG in 72% of patients. Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to have better reproducibility and may be more suitable for monitoring patient disease.

Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account.

Análise da fonte alimentar de Panstrongylus megistus (Hemiptera, Reduviidae, Triatominae) e sua atual importância como vetor do Trypanosoma cruzi, no Estado de Minas Gerais / Analysis on the food source of Panstrongylus megistus (Hemiptera, Reduviidae, Triatominae) and its present importance as a vector for Trypanosoma cruzi, in the State of Minas Gerais

INTRODUÇÃO: A pesquisa da fonte alimentar dos triatomíneos auxilia no conhecimento sobre a biologia destes insetos, inclusive para inferir-se a importância dos mesmos como transmissores do Trypanosoma cruzi ao homem. MÉTODOS: O presente estudo objetivou registrar, através da reação de precipitina, a fonte alimentar de triatomíneos provenientes de 54 municípios da região centro-oeste de Minas Gerais, assim como a infecção natural destes para flagelados semelhantes ao Trypanosoma cruzi. RESULTADOS: De julho de 2003 até março de 2007, foram avaliados 416 insetos, todos da espécie Panstrongylus megistus. Somando-se as ocorrências, as aves (70 por cento) e os humanos (22,5 por cento) constituíram as principais fontes sanguíneas. Encontrou-se 16 (3,8 por cento) insetos positivos para flagelados semelhantes ao Trypanosoma cruzi sendo que oito realizaram hematofagia no homem. CONCLUSÕES: Os resultados demonstram necessidade de acentuar a vigilância entomológica na região, visto que foi detectada a possibilidade de ocorrência de novos casos da doença de Chagas através da transmissão vetorial.

INTRODUCTION: Investigation of the food source of triatomines helps in understanding the biology of these insects, and also helps to infer their importance in transmitting Trypanosoma cruzi to humans. METHODS: The present study aimed to use the precipitin reaction to record the food source of triatomines from 54 municipalities in the central-western region of the State of Minas Gerais, as well as their natural infection by flagellates similar to Trypanosoma cruzi. RESULTS: From July 2003 to March 2007, 416 insects were evaluated, all from the species Panstrongylus megistus. Among all these occurrences, birds (70 percent) and humans (22.5 percent) were the major blood sources. Sixteen (3.8 percent) of the insects were found to be positive for flagellates similar to Trypanosoma cruzi, and eight performed hematophagia on humans. CONCLUSIONS: The results show the need to increase the entomological surveillance in this region, given that the possibility of new cases of Chagas disease occurring through vector transmission was detected.

Hypersensitivity pneumonitis: evaluation and management.

Hypersensitivity pneumonitis consists of a group of diseases resulting from inhalation of organic particles causing an immunopathological reaction of the lungs in susceptible individuals. The diagnosis requires a detailed and careful history that would include social, environmental, and occupational status, pulmonary function tests, serum precipitins, bronchoalveolar lavage, imaging, and lung biopsy. Early recognition and avoidance of the causative agent is important although the use of corticosteroids hastens improvement of symptoms.

Preferência alimentar de Lutzomyia longipalpis (Lutz & Neiva, 1912) em área de transmissão de leishmaniose visceral em Mato Grosso / Feeding preference of Lutzomyia longipalpis (Lutz & Neiva, 1912) in transmission area of visceral leishmaniasis in Mato Grosso

O estudo dos hábitos alimentares e do conteúdo intestinal dos flebotomíneos permite a identificação dos hospedeiros, indicando os potenciais reservatórios das leishmanias. Este trabalho objetivou determinar a preferência alimentar de Lutzomyia longipalpis e sua relação com a transmissão da leishmaniose visceral. As capturas mensais foram realizadas em área de transmissão de leishmaniose visceral, município de Várzea Grande, Estado de Mato Grosso, no período de janeiro de 2004 a junho de 2006, utilizando-se armadilhas de luz CDC. Foram capturadas 2.376 fêmeas de Lutzomyia longipalpis, das quais 104 (4,4 por cento) estavam ingurgitadas, sendo 32 (30,8 por cento) capturadas no intradomicílio e 72 (69,2 por cento) no peridomicílio. Após reação de precipitina, observou-se que as fêmeas de Lutzomyia longipalpis alimentaram-se preferencialmente em aves (30,8 por cento) e roedores (21,2 por cento), mas também foram encontradas fêmeas alimentadas de sangue de humanos, gambás, bois, cavalos e cães, demonstrando o caráter oportunista da espécie.

Studies on the feeding habits and intestinal content of sandflies make it possible to identify hosts, thereby indicating potential reservoirs for Leishmania. The present study had the aim of determining the feeding preferences of Lutzomyia longipalpis and its relationship with the transmission of visceral leishmaniasis. Specimens were caught every month in a transmission area of visceral leishmaniasis, in the municipality of Várzea Grande, State of Mato Grosso, from January 2004 to June 2006, using CDC light traps. 2,376 females of Lutzomyia longipalpis were caught, of which 104 (4.4 percent) were engorged. Among these, 32 (30.8 percent) were caught inside homes and 72 (69.2 percent) in areas surrounding homes. From the precipitin reaction, it was observed that Lutzomyia longipalpis females fed preferentially on birds (30.8 percent) and rodents (21.2 percent), but they were also found to have fed on blood from humans, opossums, oxen, horses and dogs, thus demonstrating the opportunist nature of this species.

Fuentes de alimentación de panstrongylus herreri (hemiptera: Triatominae) capturados en utcubamba, amazonas - perú / Food sources of panstrongylus herreri (hemiptera: triatominae) collected in utcubamba, Amazonas - Peru

Objetivo. Identificar las fuentes de alimentación de Panstrongylus herreri, procedente del distrito de Cajaruro, provincia de Utcubamba, departamento de Amazonas. Materiales y métodos. El estudio se realizó en dos etapas: primera, se estandarizó la prueba de precipitina usando como antígenos sueros sanguíneos de: humano, perro, gato, cobayo y pollo, y anticuerpos específicos obtenidos por inoculaciónde los antígenos en conejos. Se alimentaron ninfas de Triatoma infestans del IV y V estadio criadas en laboratorio con sangre de perro,cobayo, pollo y humano para luego determinar la sensibilidad y especificidad de la prueba. Segunda, se aplicó la prueba de precipitina a 102ejemplares de P. herreri domiciliarios, procedentes de la zona de estudio. Resultados. Se obtuvo títulos de anticuerpos desde 1:10 000 a1:30 000. La especificidad de la prueba fue 100 por ciento para todos los intervalos de tiempo evaluados; mientras, que la sensibilidad varió de 70 a 100 por ciento. De los 102 P. herreri, en 93 ejemplares se detectó contenido intestinal y se encontró la fuente alimenticia en 77 de ellos, la sangre de cobayo (36,3 por ciento) fue la principal fuente de alimentación, seguido de humano (18,2 por ciento) y pollo (14,3 por ciento). El índice de infección tripano-triatomíno fue 62,4 por ciento. Conclusiones. La prueba de precipitina mostró mejor especificidad que sensibilidad. En las áreas de estudio, la fuente principal de alimentación de P. herreri es la sangre de cobayo, seguido del humano y pollo. El elevado índice de infección a Trypanosoma sp. relacionado con la fuente de alimentación por cobayo, nos indicaría que es el principal reservorio.

Objective. To identify the food sources of Panstrongylus herreri from district of Cajaruro, province of Utcubamba, department of Amazonas. Material and methods. The study was performed in two steps: in the first, a precipitin test was standardized using as antigen, blood sera from human being, dog, cat, guinea pig and chicken and the specific antibodies obtained by inoculation of the antigens in rabbits. Nymphs of Triatoma infestans (IV and V instars)maintained in the laboratory were fed on dog, cat, guinea pig, and human being to determine the sensitivity and the specificity of the precipitin test. In the second step, 102 P. herreri specimens collected from houses of the two villageswere submitted to the standardized precipitin test. Results. The developed test permitted good titles of antibodies in the range from 1:10 000 to 1:30 000. The specificity was 100 per cent and the sensitivity was 70 per cent to 100 per cent. Of the 102 P. herreri specimens were detected intestinal content in 93 and found the food source in 77 of them, the blood of guinea pig (36.3 per cent) was the main source of food, followed by human (18.2 per cent) and chicken (14.3 per cent).The Trypano-triatomine index was 62.4 per cent. Conclusions. The precipitin test showed better specificity than sensitivity. In this study sites, the main food source of P. herreri was guinea pig follow by the human being and chicken. The high rate of insects carrying Trypanosoma sp. was related to the insects fed on guinea pig pointing it out as reservoir of the parasite.

Molecular basis for the unique deubiquitinating activity of the NF-kappaB inhibitor A20.

Nuclear factor kappaB (NF-kappaB) activation in tumor necrosis factor, interleukin-1, and Toll-like receptor pathways requires Lys63-linked nondegradative polyubiquitination. A20 is a specific feedback inhibitor of NF-kappaB activation in these pathways that possesses dual ubiquitin-editing functions. While the N-terminal domain of A20 is a deubiquitinating enzyme (DUB) for Lys63-linked polyubiquitinated signaling mediators such as TRAF6 and RIP, its C-terminal domain is a ubiquitin ligase (E3) for Lys48-linked degradative polyubiquitination of the same substrates. To elucidate the molecular basis for the DUB activity of A20, we determined its crystal structure and performed a series of biochemical and cell biological studies. The structure reveals the potential catalytic mechanism of A20, which may be significantly different from papain-like cysteine proteases. Ubiquitin can be docked onto a conserved A20 surface; this interaction exhibits charge complementarity and no steric clash. Surprisingly, A20 does not have specificity for Lys63-linked polyubiquitin chains. Instead, it effectively removes Lys63-linked polyubiquitin chains from TRAF6 without dissembling the chains themselves. Our studies suggest that A20 does not act as a general DUB but has the specificity for particular polyubiquitinated substrates to assure its fidelity in regulating NF-kappaB activation in the tumor necrosis factor, interleukin-1, and Toll-like receptor pathways.

Contribution of annexin 2 to the architecture of mature endothelial adherens junctions.

The vascular endothelial cadherin (VE-cad)-based complex is involved in the maintenance of vascular endothelium integrity. Using immunoprecipitation experiments, we have demonstrated that, in confluent human umbilical vein endothelial cells, the VE-cad-based complex interacts with annexin 2 and that annexin 2 translocates from the cytoplasm to the cell-cell contact sites as cell confluence is established. Annexin 2, located in cholesterol rafts, binds to both the actin cytoskeleton and the VE-cad-based complex so the complex is docked to cholesterol rafts. These multiple connections prevent the lateral diffusion of the VE-cad-based complex, thus strengthening adherens junctions in the ultimate steps of maturation. Moreover, we observed that the down-regulation of annexin 2 by small interfering RNA induces a delocalization of VE-cad from adherens junctions and consequently a destabilization of these junctions. Furthermore, our data indicate that the decoupling of the annexin 2/p11 complex from the VE-cad-based junction, triggered by vascular endothelial growth factor treatment, facilitates the switch from a quiescent to an immature state.

ATP binding by monarch-1/NLRP12 is critical for its inhibitory function.

The recently discovered nucleotide binding domain-leucine rich repeat (NLR) gene family is conserved from plants to mammals, and several members are associated with human autoinflammatory or immunodeficiency disorders. This family is defined by a central nucleotide binding domain that contains the highly conserved Walker A and Walker B motifs. Although the nucleotide binding domain is a defining feature of this family, it has not been extensively studied in its purified form. In this report, we show that purified Monarch-1/NLRP12, an NLR protein that negatively regulates NF-kappaB signaling, specifically binds ATP and exhibits ATP hydrolysis activity. Intact Walker A/B motifs are required for this activity. These motifs are also required for Monarch-1 to undergo self-oligomerization, Toll-like receptor- or CD40L-activated association with NF-kappaB-inducing kinase (NIK) and interleukin-1 receptor-associated kinase 1 (IRAK-1), degradation of NIK, and inhibition of IRAK-1 phosphorylation. The stable expression of a Walker A/B mutant in THP-1 monocytes results in increased production of proinflammatory cytokines and chemokines to an extent comparable to that in cells in which Monarch-1 is silenced via short hairpin RNA. The results of this study are consistent with a model wherein ATP binding regulates the anti-inflammatory activity of Monarch-1.