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Chronic granulomatous disease (CGD) is an uncommon primary immune deficiency caused by phagocytes defective in oxygen metabolite production. It results in recurrent bacterial or fungal infections. Herein, we present a case of CGD with a large pulmonary granuloma in a neonate and review the imaging findings. The patient was a 24-day-old neonate admitted to the hospital with fever. A round opacified lesion was identified on the chest radiograph. Subsequent CT and MRI revealed a round mass with heterogeneous enhancement in the right lower lobe. There were foci of diffusion restriction in the mass. Surgical biopsy of the mass revealed chronic granuloma. Finally, the neonate was diagnosed with CGD caused by mutation of the gp91phox gene. Herein, we present the clinical and imaging findings of this unusual case of CGD. more...

Non-human primate models of Tuberculosis (TB) are one of the most commonly used within the experimental TB field because they closely mimic the whole spectrum of disease progression of human TB. However, the early cellular interactions of the pulmonary granuloma are still not well understood. The use of this model allows investigation into the early interactions of cells within pulmonary granulomas which cannot be undertaken in human samples. Pulmonary granulomas from rhesus and cynomolgus macaques from two timepoints post infection were categorised into categories 1 – 6 (early to late stage granulomas) and immunohistochemistry was used to identify CD68+ macrophages, CD3+ T cells and CD20+ B cells. Multinucleated giant cells and acid-fast bacilli were also quantified. At week four post infection, cynomolgus macaques were found to have more CD68+ cells than rhesus in all but category 1 granulomas. Cynomolgus also had a significantly higher percentage of CD20+ B cells in category 1 granulomas. At week twelve post infection, CD68+ cells were most abundant in category 4 and 5 granulomas in both species; however, there were no significant differences between them. CD3+ T cells and CD20+ B cells were significantly higher in the majority of granuloma categories in cynomolgus compared to rhesus. Multinucleated giant cells and acid-fast bacilli were most abundant in categories 5 and 6 at week 12 post challenge in both species. This study has identified the basic cellular composition and spatial distribution of immune cells within pulmonary granulomas in both rhesus and cynomolgus macaques over time. The data from this study will add to the knowledge already gained in this field and may inform future research on vaccines and therapeutics for TB. more...

Herein we present the pathological findings of different tuberculosis stages in Old and New World monkeys kept under human care in Rio de Janeiro, Brazil and naturally infected with Mycobacterium tuberculosis Complex. Fifteen nonhuman primates from five different colonies were incorporated into the study. There are 60% (9/15) Old World Monkeys and 40% (6/15) New World Monkeys. According to the gross and histopathologic findings, the lesions in nonhuman primates of this study are classified into the chronic-active, extrapulmonary, early-activation or latent-reactivation tuberculosis stage. Among the Old World Monkey, 66.7% (6/9) of nonhuman primates, all rhesus monkeys (Macaca mulatta), showed severe granulomatous pneumonia. In all Old World Monkeys cases, typical granulomas were seen in at least one organ regardless of the stage of the disease. In the New World Monkeys, the typical pulmonary granulomas were seen in 16.7% (1/6) of the cases, just in the latent-reactivation stage in Uta Hick’s Bearded Saki (Chiropotes utahickae). In this study, 66.7% (6/9) of Old World Monkeys (OWM) and 83.3% (5/6) of New World Monkeys (NWM) showed pulmonary changes at the histological evaluation. The tuberculosis diagnosis in the nonhuman primates in this study was based on pathological, immunohistochemical, molecular, and bacteriological culture. Although the typical presentation was observed in some cases, the absence of pulmonary granuloma did not exclude the tuberculosis occurrence in nonhuman primates of the Old and New World. Tuberculosis should be included as a cause of interstitial pneumonia with foamy macrophages infiltration in the New World nonhuman primates. Due to the high sensitivity of immunohistochemistry with Anti-Mycobacterium tuberculosis, we suggest the addition of this technique as a diagnostic tool of tuberculosis in the nonhuman primates even when the typical changes are not seen. more...

Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2022-06-27T13:55:57Z No. of bitstreams: 1 BRUNOMILENOMAGALHÃESDECARVALHO.pdf: 5323679 bytes, checksum: b6be357c8c4ef791384cedc4fe535f19 (MD5) Made available in DSpace on 2022-06-27T13:55:57Z (GMT). No. of bitstreams: 1 BRUNOMILENOMAGALHÃESDECARVALHO.pdf: 5323679 bytes, checksum: b6be357c8c4ef791384cedc4fe535f19 (MD5) Previous issue date: 2021-09-10 FAPEMA Schistosomiasis is a debilitating disease that can affect various tissues of the human body. The immune response starts with a predominance of Th1 cells and gradually changes to the Th2 profile from oviposition, for the formation and maturation of granulomas. While the lung is one of organs most susceptible organs, it is vulnerable to the parasite in both the acute and chronic phases. Within this context, the objective of this work is to describe the histopathological and histomorphometric alterations in the lung of mice infected with Schistosoma mansoni, as well as to investigate correlations with the presence of eosinophils in the blood, parasite eggs and hepatic granulomas. Initially, male Swiss mice were percutaneously infected with 50 cercariae of Schistosoma mansoni and euthanized after 60 (INF60) and 90 days after infection (INF90). At each time point, there was also euthanasia in a group composed of uninfected animals. Blood was obtained by puncture through the orbital plexus for evaluation of leukocytes. The rectum and liver were removed respectively to prove the infection and histomorphometric comparison. While the lungs were removed for histopathological and histomorphometric analysis. The data showed that within sixty days of infection, there was local and systemic eosinophilia (p more...

Crohn's disease (CD) is a chronic granulomatous disease that affects the gastrointestinal system. Additionally, CD has multiple extraintestinal manifestations, and bronchopulmonary manifestations are extremely rare. Pulmonary lesions can occur before the diagnosis of CD; thus, pulmonary manifestations are often overlooked, which leads to misdiagnoses. Herein, we present a case with pulmonary nodules being exhibited before the patient was diagnosed with CD. To the best of our knowledge, only a few cases concerning this phenomenon have been reported. We describe an 11-year-old boy with a two-year history of anemia and without any gastrointestinal symptoms. He did not receive any thorough inspection until arthralgia occurred. Multiple nodules were found in his bilateral lungs via computed tomography scan. Combined with the child's medical history, physical examinations, and all of the investigations, the final diagnosis was CD with pulmonary nodules and arthritis. After 2 months of treatment, the patient's symptoms had significantly improved. To summarize the clinical manifestations, auxiliary examination features, and treatments of CD in children with pulmonary involvement, we also review the relevant characteristics of pulmonary involvement in CD patients. This case indicates the importance of recognizing the pulmonary manifestations of CD. Clinicians should be aware of the possibility of CD when their patients have lung nodules, even in children with no typical manifestations of CD. more...

The involvement of the IL-23/IL23R pathway is well known in the disease pathogenesis of sarcoidosis and other inflammatory diseases. To date, the pathogenic mechanism of IL-23 is most notably described on CD4+ Th17 lymphocytes. However, the function of the IL23R on myeloid cells in sarcoidosis is poorly understood. Thus, the aim of the study is to investigate the role of the IL23R on myeloid cell in pulmonary granuloma formation. Methods: We generated IL23RLysMCre mice lacking the IL23R gene in myeloid cells. The importance of IL23R in myeloid cells for the development of sarcoidosis was studied in a mouse model of inflammatory lung granuloma formation through embolization of PPD from Mycobacterium bovis-coated Sepharose beads into previously PPD-immunized mice. In addition the function of IL23R on myeloid cells was studied in LPS or IFNγ stimulated BMDMs and BMDCs. The mRNA and protein expression levels of relevant cytokines were analyzed by RT-PCR (TaqMan) and ELISA. The composition of immune cells in BALF was quantified by flow cytometry and alteration in granuloma sizes were observed by H&E stained lung sections. Results: Mycobacterium Ag-elicted pulmonary granulomas tend to be smaller in IL23RLysMCre mice and NF-κB dependent Th1 cytokines in the murine lungs are reduced compared to wildtype mice. In line, we observed that IL23R-deficient bone marrow-derived macrophages show a reduced production of Th1 cytokines after LPS stimulation. Conclusion: We here for the first time demonstrate a role for IL23R on myeloid cells in pulmonary inflammation and granuloma formation. Our findings provide essential insights in the pathogenesis of inflammatory lung diseases like sarcoidosis, which might be useful for the development of novel therapeutics targeting distinct immunological pathways like IL-23/IL23R. more...

Arthritis is a persistent autoimmune ailment occurs more in females than in male above the age of 40. Itinitially affects the lining of synovial joint and the secretion of low synovial fluid also can lead to rheumatoidarthritis. It primarily affects the patient’s health swelling in joint, redness and level decreases eventually.Diagnosis at an early stage of rheumatoid arthritis is the key to prevent from severe injuries in joint andother bone related diseases. There is also several plant based anti-inflammatory compound which involvesin decreasing the pathogenesis of the ailment. There are several diseases related to rheumatoid arthritis,it includes pulmonary granuloma, vesicle damages and other symptoms are expected to occur early ifunnoticed. This article discusses the risk factors, damages to joint and pharmacological therapies availablefor the diseases. more...

Sarcoidosis is characterized by noncaseating granulomas with an unknown cause that present primarily in the lung. Propionibacterium acnes, an immunogenic commensal skin bacterium involved in acne vulgaris, has been implicated as a possible causative agent of sarcoidosis. Here, we demonstrate that a viable strain of P. acnes isolated from a patient with sarcoidosis and instilled intratracheally into wild-type mice can generate pulmonary granulomas similar to those observed in patients with sarcoidosis. The formation of these granulomas is dependent on the administration of viable P. acnes. We also found that mice deficient in the innate immunity adapter protein MyD88 had a greater number and a larger area of granuloma lesions compared with wild-type mice administered P. acnes. Early after P. acnes administration, wild-type mice produced proinflammatory mediators and recruited neutrophils into the lung, a response that is dependent on MyD88. In addition, there was an increase in granuloma number and size after instillation with P. acnes in mice deficient in CybB, a critical component of nicotinamide adenine dinucleotide phosphate oxidase required for the production of reactive oxygen species in the phagosome. Myd88−/− or Cybb−/− mice both had increased persistence of P. acnes in the lung, together with enhanced granuloma formation. In conclusion, we have generated a mouse model of early granuloma formation induced by a clinically relevant strain of P. acnes isolated from a patient with sarcoidosis, and, using this model, we have shown that a deficiency in MyD88 or CybB is associated with impaired bacterial clearance and increased granuloma formation in the lung. more...

Objective: The aim of this report is to describe a case with Aspergillus vertebral osteomyelitis complicating pulmonary granuloma in an immunocompetent adult. Clinical Presentation and Intervention: A 53-year-old male patient was found to have lesions on lumbar vertebra 5 months after thoracoscopic resection of pulmonary granuloma that lacked a definite etiology. Three operations on the lumbar lesions were performed successively; however, an Aspergillus infection was not confirmed until hyphae were clearly detected at the last surgery. The patient was treated with voriconazole and recovered well. Conclusion: This case shows that simultaneous occurrence of granulomatous nodules in the lung and vertebral lesions should raise suspicion of aspergillosis, even in immunocompetent patients. more...

Background and objective Previous studies have demonstrated increases of inflammatory mediators in sarcoidosis while epidemiological studies have also demonstrated an association with increased fungi exposure. This study measured the level of β-glucan in the lungs and of inflammatory mediators in serum, and correlated both with the extent of pulmonary granuloma infiltration. Methods This is a cross-sectional study of 98 patients with sarcoidosis and 26 controls. β-glucan, a cell wall constituent of fungi, was measured in bronchoalveolar lavage. Inflammatory mediator levels were determined in serum. The extent of granuloma infiltration was estimated on the chest X-ray. Exposure to fungi at home was determined by taking air samples in bedrooms and analysing for the presence of β-N-acetylhexosaminidase. Results Significantly, higher levels of β-glucan were found in broncho-alveolar lavage in subjects with sarcoidosis as compared with controls. There were significant positive relationships between the extent of granuloma infiltration and the levels of the different inflammatory mediators, except for interleukin-10. Domestic fungal exposure was higher among subjects with sarcoidosis. Conclusions This is the first time that a specific agent, previously suspected to be related to the risk of sarcoidosis, has been detected in the lung of subjects with sarcoidosis and related to the levels of inflammatory mediators and the degree of home exposure to fungi. The results suggest that exposure to fungi should be explored when investigating patients with sarcoidosis. more...

Stenotrophomonas maltophilia is a gram negative bacterium that primarily affects immunocompromised and clinically debilitated patients. It is known to affect many tissues and organ systems of the body, but it rarely causes otitis externa. We reported a case of otitis externa due to S. maltophilia in a 22-year-old immunocompromised male who had bilateral otalgia and ear discharge, as well as left facial nerve palsy in combination with hearing loss. Further investigations revealed S. maltophilia in ear drainage cultures, including a deep swab taken during surgical debridement. Systemic antibiotics in combination with local treatment were effective in controlling the infection and resulted in the resolution of his signs and symptoms, except for the hearing loss. We believe that early identification of the pathogen and treatment of the infection might lead to a favorable outcome. Key words: Stenotrophomonas maltophilia, opportunistic infection, otitis externa. more...

患者は57歳女性．2000年12月に肺癌に対し，胸腔鏡補助下右S3区域切除施行．病理診断は高分化型腺癌，Stage IAであった．術後4年目の胸部X線，CTにて右上葉に5×5cmの腫瘤陰影を認めた．右肺癌再発を疑い胸腔鏡下手術を行った．右上葉に臓側胸膜の引きつれを伴う弾性硬の腫瘤を認めた．術中迅速病理検査では悪性所見は得られなかったが，肉眼所見では悪性が強く疑われたため，右上中葉切除を行った．切除標本肉眼的所見では腫瘤は5.5×5.0cm，割面は白色，周囲との境界は明瞭で，内部に黄緑色の膿汁の貯留を認めた．切除標本の軟X線写真にて，病変部の辺縁にほぼ一致して前回手術時のステープルラインを認めた．病理組織学的検査では肉芽腫形成を認めた．膿汁の培養からMycobacterium aviumが検出された．以上から自験例を肺癌術後のステープルラインに発生した非定型抗酸菌症を伴う肺肉芽腫と判断した． more...

Macrophages and α-smooth muscle actin immunopositive myofibroblasts are thought to be crucial cells in granuloma formation. In this study, the reactive cell kinetics was investigated in Sephadex bead-induced rat pulmonary granulomas (1mg/ml saline/head; intravenously) from l hour to 90 days after the injection. Intravenously administered Sephadex beads occluded pulmonary arteries and caused granulomatous pulmonary arteritis. The inflammatory cells appeared first around the trapped beads and then granuloma lesions developed within 24 hours. Three days later, the granulomas mainly consisted of neutrophils, macrophages, eosinophils, and giant cells. Immunohistochemically, the number of ED1-positive macrophages quickly increased 24 hours after the injection, and a large number of macrophages were still found 3 days after the injection. Alpha-smooth muscle actin immunopositive myofibroblasts increased in numbers from 3 to 7 days after theinjection. These results indicate that the appearance of myofibroblasts in pulmonary granulomas might be mediated by macro-phages, which were the most predominant inflammatory cells in the present pulmonary granuloma. more...

In patients with suspicion of lung malignancy, FDG PET/CT is frequently used as a diagnostic and staging imaging modality. However, false positive findings are not uncommon. We demonstrate a case with FDG-avid pulmonary nodules, mimicking lung cancer. After histopathological examination they appeared to be the result of persistent inflamed tissue, due to talcage pleurodesis, which occurred 48 years ago. We concluded that, nearly five decades after talcage pleurodesis, there can still be an ongoing inflammation reaction in the pleurae, which can be detected by FDG PET/CT. more...

Natural bactericidal resistance of Mycobacterium bovis BCG is under the control of a single gene, Bcg. The development of lung granulomas in susceptible (Bcgs) and resistant (Bcgr) mice was studied in two sets of Bcg-congenic systems, the BALB/c (Bcgs) -C.D2 (BALB/c.Bcgr) pair and the B10. A (Bcgs) -B10. Ar (Bcgr) pair, by using BCG as well as foregin-body granuloma-inducing agents, dextran beads. Large lung granulomas induced by the intratracheal challenge of either BCG or dextran beads developed in Bcgs mice. By contrast, minimal lesions were produced in Bcgr mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced in Bcgs mice by either BCG or dextran beads contained a large amount of interleukin 1 (IL-1) activity but not IL-2 or IL-4 activity. Very low IL-1 activity was detectable in extracts from Bcgr mice challenged with BCG and dextran beads. The activity of IL-1 was correlated with activity/size of the granulomatous inflammation in mice.These results incucate that the Bcg gene has pleiotropic effects on the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that macrophage-derived cytokines participate in granuloma formation. more...

In order to evaluate the role of the T cell function and T cell subsets on murine pulmonary granuloma reconstruction, histological and immunohistological analyses were done during serial studies on murine pulmonary granuloma formation induced by intratracheal administration of antigen binding Cepharose 4B beads. This granuloma formation showed antigen specific pattern and the most vigorous responce showed on the time at 72 hour after challenge.In the induction phase, Thy-1 positive and Lyt 1 positive T cells seemed dominant around beads. However, in the effector phase, i.e., 72-168 hour after beads challenge, Thy-1 positive and Lyt 2 positive T cells were dominant in peripheral protions of granuloma. This result showed that cytototoxic T cell would play an important role on the reconstruction of granulomatous lesions. more...

Pulmonary granulomas were induced in rabbits with Freund’s complete adjuvant. Histologic alterations, the mitotic index and Feulgen-DNA amounts determined by a cytophotometric method were studied. The mitotic index and DNA amounts increased significantly within the first hours and reached peak values on the 3rd day, then showed a tendency to decrease after the 7th day. After the 3rd day, a certain dissociation was noted between the mitotic index and Feulgen-DNA amount. The change in Feulgen-DNA content reflects the functional alterations that characterize pulmonary granuloma. more...

Anti-rabbit alveolar macrophage goat serum (AMS), adsorbed of hemolysins and hemagglutinins, exhibited complement-dependent cytotoxicity for the following rabbit target cells: alveolar macrophages, thymocytes, and kidney (RK-13) cells. The intravenous injection of AMS, sufficient to reduce markedly the dermal tuberculin reaction in BCG-sensitized rabbits, did not suppress the development of BCG-induced chronic and accelerated pulmonary granulomas. These observations are discussed in relation to delayed sensitivity, allergic granuloma formation, and cell-associated immunity. more...

Two patients with co-existing meningeal and pulmonary cryptococcosis were successfully treated by pulmonary resection and chemotherapy. Under cover of miconazole and 5-fluorocytosine, pulmonary mass lesions were successfully removed despite the fact that the patients had meningitis. The patients recovered from meningitis immediately after the surgical procedures and show no recurrence of meningeal symptoms more than 2 years after the operation. It appears that early removal of a pulmonary cryptococcal focus combined with antifungal agents may give a quite favourable outcome for meningitis. more...

This is the second report of Mycobacterium thermoresistibile as the etiological agent of a pulmonary granuloma and the first occurrence of this organism in a patient who has not been outside the continental United States. The organism is susceptible to rifampin, ethambutol, and streptomycin but resistant to isoniazid and p-aminosalicylic acid. more...

The relationship between dermal delayed hypersensitivity (DH) and granulomatous hypersensitivity was studied in rabbits sensitized with killed mycobacteria. Specific antigen challenge of sensitized animals resulted in extensive pulmonary granulomatous inflammation and induced suppression of both dermal DH and dermal granuloma formation. Whereas suppression of DH was concomitant with pulmonary granuloma formation, as is the case in a number of granulomatous diseases, a causal relationship between the two did not exist. Both DH and dermal granulomatous hypersensitivity were significantly suppressed whether or not the antigen challenge was of a granulomagenic (particulate) or nongranulomagenic (soluble) form. The data presented indicate that granulomatous hypersensitivity and DH are selectively suppressed with regard to different anatomical sites. more...

An infarcted pulmonary granuloma meeting the criteria of a “coin lesion” in a 44-year-old man is attributed to the presence of a horse bot, Gasterophilus sp. (probably a second-stage larva of Gasterophilus intestinalis ), on the basis of identifiable remains in sections of the lesion. This appears to be a unique and exceptional case of a horse bot causing myiasis as an adventitious and unsuccessful parasite in the human lung. While the occurrence can be rationalized biologically and pathologically, confirmatory evidence of the suggested course of events leading to the formation of the lesion was not obtained. more...

PAREGORIC, which contains 130 mg of opium per ounce, is now the major narcotic used in Detroit. Its use as an illegal opium source has developed within the last four years (Table 1). Paregoric is ahydroalcoholic solution containing not more than 129.6 mg of powdered opium per 29.573 ml ( 1 fluid oz) or per 283 gm with anise oil, benzoic acid, and camphor. Until April 20, 1964, paregoric was an exempt narcotic in Michigan, and could be purchased at pharmacies without prescription. The drug is usually concentrated by boiling before intravenous instillation. Users often mix paregoric with the amphetamines, secobarbital, glutethimide, other barbiturates, or tripelennamine. The talcum filler of tripelennamine has been associated with diffuse pulmonary granuloma and subsequent pulmonary hypertension. 1 The benzoic acid, camphor, and anise of paregoric are irritants and lead to occlusive sclerosis after intravenous instillation. Therefore, the median cubital vein (most often used by more...