A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization.

The central pathogen-immune interface in tuberculosis is the granuloma, a complex host immune structure that dictates infection trajectory and physiology. Granuloma macrophages undergo a dramatic transition in which entire epithelial modules are induced and define granuloma architecture. In tuberculosis, relatively little is known about the host signals that trigger this transition. Using the zebrafish-Mycobacterium marinum model, we identify the basis of granuloma macrophage transformation. Single-cell RNA-sequencing analysis of zebrafish granulomas and analysis of Mycobacterium tuberculosis-infected macaques reveal that, even in the presence of robust type 1 immune responses, countervailing type 2 signals associate with macrophage epithelialization. We find that type 2 immune signaling, mediated via stat6, is absolutely required for epithelialization and granuloma formation. In mixed chimeras, stat6 acts cell autonomously within macrophages, where it is required for epithelioid transformation and incorporation into necrotic granulomas. These findings establish the signaling pathway that produces the hallmark structure of mycobacterial infection.

RNA Sequencing Analyses Reveal the Potential Mechanism of Pulmonary Injury Induced by Gallium Arsenide Particles in Human Bronchial Epithelioid Cells.

Extensive use of gallium arsenide (GaAs) has led to increased exposure to humans working in the semiconductor industry. This study employed physicochemical characterization of GaAs obtained from a workplace, cytotoxicity analysis of damage induced by GaAs in 16HBE cells, RNA-seq and related bioinformatic analysis, qRT-PCR verification and survival analysis to comprehensively understand the potential mechanism leading to lung toxicity induced by GaAs. We found that GaAs-induced abnormal gene expression was mainly related to the cellular response to chemical stimuli, the regulation of signalling, cell differentiation and the cell cycle, which are involved in transcriptional misregulation in cancer, the MAPK signalling pathway, the TGF-ß signalling pathway and pulmonary disease-related pathways. Ten upregulated genes (FOS, JUN, HSP90AA1, CDKN1A, ESR1, MYC, RAC1, CTNNB1, MAPK8 and FOXO1) and 7 downregulated genes (TP53, AKT1, NFKB1, SMAD3, CDK1, E2F1 and PLK1) related to GaAs-induced pulmonary toxicity were identified. High expression of HSP90AA1, RAC1 and CDKN1A was significantly associated with a lower rate of overall survival in lung cancers. The results of this study indicate that GaAs-associated toxicities affected the misregulation of oncogenes and tumour suppressing genes, activation of the TGF-ß/MAPK pathway, and regulation of cell differentiation and the cell cycle. These results help to elucidate the molecular mechanism underlying GaAs-induced pulmonary injury.

Hepatic hilar mass in an adolescent: a rare case of hepatobiliary tuberculosis.

BACKGROUND: Hepatobiliary tuberculosis is a rare manifestation of Mycobacterium tuberculosis infection, especially in younger patients. The non-specific symptoms and signs as well as the lack of definite imaging characteristics often impedes diagnosis. Definite diagnosis of tuberculosiscan be obtained through histopathological examination; conventional anti-tuberculosis drugs and surgery are the most commonly recommended treatments. CASE PRESENTATION: A previously healthy 15-year-old rural adolescent male presented with a 2-month history of weight loss and fatigue. We strongly suspected a Klatskin tumor; therefore, exploratory laparotomy was performed. However, the microscopical findings revealed a granuloma consisting of epithelioid cells, caseous necrosis, and lymphocytic infiltration, indicating caseating granulomatous inflammation and yielding a final diagnosis of hepatic hilar tuberculosis. CONCLUSION: Hepatic hilar tuberculosis is an extremely rare case; few physicians may have actually treated a case. This report therefore aims to improve the overall understanding of lymphatic tuberculosis of the hepatic hilum.

[Hepatic angiomyolipoma: a clinicopathologic features and prognosis analysis of 182 cases].

OBJECTIVE: To study the clinicopathological characteristics of hepatic angiomyolipoma (HAML) and to evaluate the correlation between clinicopathological parameters and tumor subtypes. METHODS: Retrospective analysis of clinicopathological features was conducted in 182 cases of HAML. RESULTS: HAML patients were predominantly female (M:F=1:4) and most commonly presented with non-specific symptoms. The median age at diagnosis was 46 years, ranged from 17 to 77 years. Tumor diameter was ranged from 0.3 to 32.0 cm with an average of 5.0 cm. Majority of the tumor was epithelioid type (112/165, 67.9%). Extramedullary hematopoiesis, multinucleated giant cells, intranuclear inclusions, nucleolus, cellular atypia, invasive growth pattern, multiple masses, hyperpigmentation and purpura-like changes mostly occurred in the epithelioid type (P<0.05). Extramedullary hematopoiesis was commonly seen in HAML, the significance of which was still uncertain. CONCLUSIONS: Most of HAML are epithelioid type, characterized by a proliferation of predominantly epithelioid cells, in which extramedullary hematopoiesis is commonly seen. Some morphologic features that may predict malignant such as necrosis, mitotic figures, and tumor emboli are only found in the epithelioid HAML. Mitotic activity, tumor necrosis, tumor thrombus, giant cells, periportal invasion, multiple lesions and tumors size over 10 cm are closely related with tumor recurrence and metastasis.

[Effects of Mechanical Stretch on Expression of Airway Remodeling Associated Factors in Human Bronchial Epithelioid Cells].

This study is aimed to investigate the effects of mechanical stretch on the expression of transforming growth factor-ß1（TGF-ß1）and fibroblast growth factor-2（FGF-2）,and the signaling pathway in human bronchial epithelioid（16HBE）cells under mechanical stretch.Using loading device with flexible substrate（FX-4000T）to stretch 16 HBE cells,we found that the stretching elongation was 15%,at frequency of 1Hz,stretching for 0.5h,1h,1.5hand 2h.Choosing the higher expression of TGF-ß1,FGF-2and Ca2+group to carry out intervention experiments,we used the cells pretreated with canonical transient receptor potential 1（TRPC1）channel antagonist SKF96365,protein kinase C（PKC）inhibitor HA-100,and thereafter mechanical stretch to interpose.Compared with those in the blank control group,TGF-ß1and FGF-2'protein and mRNA,intracellular Ca2+fluorescence intensity were higher,and the differences were statistically significant（P<0.05）at the 4time points,0.5h,1h,1.5h and 2h.At 0.5h,the increasing rate was the highest.TGF-ß1protein and mRNA,FGF-2protein and mRNA,intracellular Ca2+luorescence intensity in the stretch+SKF96365and stretch+ HA-100 intervented group were decreased,the differences were statistically significant than those in 0.5hstretch group（P<0.05）without intervention.The expression of TGF-ß1,FGF-2 was up-regulated in 16 HBE cells under mechanical stretch,PKC,TRPC1,and Ca2+may participate in the signal path.

Minute perivascular epithelioid cell (PEC) nests in the abdominal lymph nodes--a putative precursor of PEComa.

A perivascular epithelioid cell tumor (PEComa) is a peculiar growth defined as a mesenchymal tumor composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Because neither normal counterparts nor precursor lesions of PEComa have been identified, we examined minute PEC nests, ranged from 0.8 mm to 10 mm, to investigate the possible origin of the PEComa. We examined a total of 80 677 para-aortic and pelvic lymph nodes that were systematically dissected from 1656 patients for gynecological malignancies. The identified lesions were confirmed immunohistochemically with multiple PEC markers, including smooth muscle actin, HMB45, melan-A, MiTF, ER and PgR. A total of 66 minute PEC nests were found in 21 patients (1.3% of the total population) with an average frequency of 3.1 lesions per patient. In cases of multiple involvement, 11 of 13 nests were located at the same level of multiple lymph node or on continuous levels. The lesions were preferentially distributed at the level of para-aortic and high pelvic lymph nodes. All nests were positive for actin and HMB45, whereas the other markers were positive with varying frequencies. The minute PEC nests may be associated with the possible normal counterpart of PEComas.

A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials.

BACKGROUND: The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. RESULTS: Carbon black particles (Printex 90) and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs). Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 µg/ml (0.38 µg/cm2) of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1) as well as profibrotic (M2) phenotypic markers. CONCLUSIONS: Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model offers a time- and cost-effective platform to evaluate the potential of engineered high aspect ratio nanomaterials, including carbon nanotubes, nanofibers, nanorods and metallic nanowires, to induce granulomas following inhalation.

Tuberculosis of the thyroid gland: magnetic resonance imaging appearances.

Tuberculosis involving the thyroid gland is a rare occurrence. We report a case of cytologically-diagnosed thyroid gland tuberculosis in a 21-year-old man who presented with thyroid swelling of short duration, and describe the magnetic resonance (MR) imaging appearances of the lesion, which to our knowledge, has not been previously described. We also report a rare complication of abscess formation in the track of the fine needle aspiration. The intermediate signal intensity of the lesions on both T1- and T2-weighted MR images may provide a clue about tuberculosis, as clinical suspicion is low due to the rarity of the disease.

Malignant perivascular epithelioid cell tumour of the round ligament mimics leiomyoma on computed tomography.

We report a case of a 45-year-old woman who had a palpable mass in the left lower quadrant of the abdomen. Computed tomography (CT) showed a circumscribed mass in the left round ligament of the uterus. The mass had heterogeneous density and enhancement accompanied by mottled calcification, which was initially identified as a leiomyoma. A histopathological examination revealed a malignant perivascular epithelioid cell tumour (PEComa), which is a rare soft tissue tumour. This case demonstrates that the appearance of malignant PEComa on the CT can mimic leiomyoma, which is the most common tumour of the round ligament. To the best of our knowledge, this is the first report of a CT appearance of this round ligament tumour. The radiological features and differential diagnosis are discussed.

Epithelioid cells in mediastinal lymph nodes of cattle without cancer.

Epithelioid cells are found in lymph nodes in cases of metastatic carcinoma; however, epithelioid cells with benign features have also been discovered incidentally in lymph nodes. Epithelioid cells were observed in mediastinal lymph nodes of cattle without cancer during routine diagnostic necropsy. To explain this finding, the authors evaluated the prevalence and histopathologic, immunohistochemical, and ultrastructural features retrospectively using mediastinal lymph nodes from 110 cattle and found that 66 of the lymph nodes contained epithelioid cells. In all 66 nodes, most of the epithelioid cells were individual or aggregated in nodal sinuses; in 21 nodes, some epithelioid cells formed tubular structures. The individual and aggregated epithelioid cells were mostly considered to be mesothelial in origin by immunohistochemical and ultrastructural examination; presumably, they entered the lymph nodes via lymphatic vessels, because they were found in afferent lymphatic vessels and nodal sinuses. Although the presence of epithelioid cells in lymph nodes prompts suspicion of metastatic carcinoma, the epithelioid cells in these bovine lymph nodes did not disrupt nodal architecture, lacked atypia or mitotic figures, and did not invade nodal parenchyma.

[Endometrial decidualization as a factor that regulates cytothrophoblastic invasion during the first trimester of pregnancy].

Endometrial stromal cell decidualization is a multistage process that starts with the late secretory phase of a menstrual cycle and then continues in the first months of pregnancy. Under the influence of the hormone progesterone, precursor cells undergo a unique structural and functional transformation from the adventitional cells of spiral arteries containing a marker of smooth muscles (desmin) through pre-decidual cells to the decidual intermediate cells expressing a marker of the extraembryonic mesoderm (vimentin), and IGFBR-1 and then to the typical epithelioid decidual cells.

[Cytogenetic impacts of air-argon environment on epitheliocytes of the mice cornea].

The purpose was to look into the effects of 24-hr. exposure in a normoxic air-argon environment (AAE) on the epitheliocyte proliferative system, i.e. chromosomal aberrations dynamics and cornea proliferative activity, in laboratory mice. Argon was found to significantly decrease the percentage of spontaneous mutations in cells and, probably, to induce reversible inhibition of cell division. Subsequent experiments may not only disclose the still unknown properties and advantages of argon but also shed light on cell mechanisms triggered by the noble gases in general.

Endometritis xantogranulomatosa. Presentación de un caso / Xanthogranulomatous endometritis. A report of a case

Se presenta una caso de endometritis xantogranulomatosa, en una mujer de 74 años, que se presenta clínicamente como un piometra. Histológicamente se observan abundantes detritus celulares y reemplazamiento del endometrio por sábanas de histiocitos espumosos, algunos con hemosiderina, entremezclados con linfocitos, células plasmáticas, ocasionales leucocitos polimorfonucleares, células gigantes multinucleadas de tipo cuerpo extraño en relación con agujas de colesterol y numerosos granulomas sin evidencia de necrosis. La mayoría de los casos de endometritis xantogranulomatosa publicados se han presentado clínicamente como un hematometra o piometra senil benigno, en mujeres postmenopaúsicas. Puede estar asociada a un carcinoma de endometrio. La inflamación xantogranulomatosa es probablemente una respuesta macrofágica a los detritus necróticos y hemorrágicos retenidos

This is the report of a case of xanthogranulomatous endometritis in a 74-year-old woman, that has presented clinically as pyometra. Histologically there are large amounts of cell detritus and effacement of the endometrium by sheets of foamy histiocytes, some with hemosiderin pigment, amongst which are lymphocytes, plasma cells, occasional polymorphonuclear leukocytes, foreign-body giant multinucleated cells around cholesterol clefts and numerous granulomas without necrosis. The majority of the published cases of xanthogranulomatous endometritis have been presented clinically as haematometra or benign senile pyometra, in postmenopausal women. It may be associated with endometrial carcinoma. The xanthogranulomatous inflammation is probably a macrophage response to retained hemorrhagic and necrotic debris

Cambios fenotípicos del epitelio mamario inducidos por su entorno celular / Phenotypical changes of mammary epithelium induce by its celullar surroundings

Se presenta una revisión bibliográfica relacionada con la funcionalidad de la matriz extracelular y sus distintos componentes en el sentido de gatillar y modular el proceso biológico de la diferenciación celular, con especial énfasis en los diferentes fenotipos adquiridos por las células pertenecientes al epitelio mamario de ratas mantenido en cultivo, como resultado de la inducción al proceso de diferenciación tanto en ausencia como en presencia de constituyentes de dicha matriz.

On the bulky appliances and artero-venous anastomoses in the vascular district of the base of the brain.

It has been studied the vascular territory of the base of the brain and it has been pointed out the presence of characteristical structural arrangements of the vasal wall and artero-venous anastomoses. The just mentioned characteristical structures are placed in points where a vessel divides itself or creates a collateral branch and their functional engagement is target-oriented to control the blood flux.

Microscopic analysis of three different spinal needle tips after experimental subarachnoid puncture.

BACKGROUND AND OBJECTIVES: Previous studies have shown the vulnerability of the tips of cutting type thin spinal needles and the possibility of foreign material passing into the subarachnoid space during the lumbar puncture. We made a microscopic analysis to compare two commonly used noncutting pencil-point spinal needles with different tip designs. Needles with a cutting tip design were included as reference. METHODS: Four fresh cadavers were placed in the lateral position and their backs were scrubbed with disinfectant solution containing 0.1% fluorescein. Thirty-two spinal needles (27 gauge) of each type (modified Quincke, modified Sprotte, and modified Whitacre) were inserted through an introducer at interspaces L2-5 into the subarachnoid space. Under visual control (spinal canal opened ventrally) all the needle tips were cut after successful subarachnoid puncture; 16 needles of each tip design were investigated under a fluorescence microscope, and another 16 needle tips were collected into test tubes and cytocentrifuged smears were prepared. The tips and smears with the most obvious findings were photographed under a microscope. RESULTS: On microscopy, only 2 needle tips were damaged (1 modified Quincke and 1 modified Whitacre). Visible fluorescent tissue particles were more frequently seen on modified Quincke needles (56%) compared with modified Sprotte (37%) and Whitacre (37%) needles (NS). In the cytocentrifugation smears, the largest clusters of epithelioid cells and muscle fibers were observed in the Quincke group. In the Whitacre group many fewer and smaller cell clusters including small muscle particles were seen, and only minor epithelioid cells were found in the Sprotte group. CONCLUSIONS: Tissue coring seems to be a common phenomenon during lumbar puncture. The most prominent attachments appeared with a cutting Quincke-type spinal needle.

Establishment and characterization of a new continuous cell line from Lutzomyia longipalpis (Diptera: psychodidae) and its susceptibility to infections with arboviruses and Leishmania chagasi.

Embryonic tissue explants of the sand fly Lutzomyia longipalpis (Lutz & Neiva 1912) the main vector of Leishmania chagasi (Cunha and Chagas), were used to obtain a continuous cell line (Lulo). The tissues were seeded in MM/VP12 medium and these were incubated at 28 masculineC. The first subculture was obtained 45 days after explanting and 96 passages have been made to date. Lulo is composed of epithelioid cells, showed a 0.04 generations/hour exponential growth rate and population doubling time at 24.7 h. The cell line isoenzymatic profiles were determined by using PGI, PGM, MPI and 6-PGDH systems, coinciding with patterns obtained from the same species and colony's pupae and adults. The species karyotype characteristics were recognized (2n = 8), in which pair 1 is subtelocentric and pairs 2, 3 and 4 are metacentric. Lulo was free from bacterial, fungal, mycoplasmic and viral infection. Susceptibility to five arbovirus was determined, the same as Lulo interaction with Leishmania promastigotes.

Growth inhibition of Candida albicans by vaginal cells from naïve mice.

Recurrent vulvovaginal candidiasis (RVVC) is a common idiopathic mucosal infection caused by Candida albicans. Current data suggests that local immunity is more important than that in the peripheral circulation for protection against infection. In the present study, anti-Candida innate resistance at the vaginal mucosa was investigated using a murine model. For this, splenic and vaginal cells were assessed for in vitro growth inhibition (GI) of C. albicans and cytotoxicity of natural killer (NK) cell-sensitive tumour targets (YAC-1). As expected, significant GI of C. albicans by splenic cells was mediated predominantly by polymorphonuclear leucocytes (PMNL) at effector to target (E:T) ratios of 100 and 50:1. From the vaginal mucosa, naïve unfractionated, but not nylon wool non-adherent (NWN), cells extracted from whole vaginal tissue showed significant GI of C. albicans at E:T ratios as low as 1:1, but only modest killing of YAC-1 targets at all E:T ratios. Subsequent experiments showed significant GI of C. albicans by vaginal epithelioid-enriched cells and with several epithelial cell lines, but not in supernatants collected from the co-cultures. In contrast, lymphoid cell lines had no anti-Candida activity. These results suggest that anti-Candida activity is present at the vaginal mucosa, but unlike that from the spleen, the vaginal activity appears to be predominantly mediated by epithelial cells.