- Carcinoma Erysipeloides From Metastatic Cutaneous Squamous Cell Carcinoma Initially Mistaken for Intralymphatic Histiocytosis. [Journal Article]
- AJAm J Dermatopathol 2019; 41(7):522-525
- Intralymphatic histiocytosis is a rare dermatologic disorder, commonly associated with inflammatory disorders and rarely malignancy. Carcinoma erysipeloides (CE) is a rare pseudoinflammatory cutaneou…
Intralymphatic histiocytosis is a rare dermatologic disorder, commonly associated with inflammatory disorders and rarely malignancy. Carcinoma erysipeloides (CE) is a rare pseudoinflammatory cutaneous eruption that resembles soft -tissue infections as result of intralymphatic metastasis and subsequent lymphatic obstruction. Breast carcinoma represents most of the CE cases, but rarely other malignancies are involved. This report discusses a patient with a history of cutaneous squamous cell carcinoma (SCC) of the temple, who was initially diagnosed with intralymphatic histiocytosis located on his upper extremity, resistant to treatment. Further dermatologic and pathologic review later revealed metastatic SCC restricted to the dermal lymphatics, creating a CE reaction, initially obscured by intralymphatic histiocytes. This case highlights the difficulty in diagnosing metastatic carcinoma when the malignant cells are accompanied by a dense histiocytic infiltrate. The case demonstrates a rare presentation of CE due to metastatic cutaneous SCC and highlights the need for persistent investigation when confronted with nonconforming pathology.
- Fibrocytes in Chronic Periaortitis. [Journal Article]
- ARArthritis Rheumatol 2019 Jun 24
- CONCLUSIONS: Fibrocytes are enriched in the peripheral blood of CP patients and infiltrate target lesions; their accumulation in the pathologic tissue might be driven by CXCL12, and Th2-skewed immune responses are likely to facilitate their differentiation. This article is protected by copyright. All rights reserved.
- The role of CXCR3 and its ligands CXCL10 and CXCL11 in the pathogenesis of celiac disease. [Journal Article]
- MMedicine (Baltimore) 2019; 98(25):e15949
- The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissu…
The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissues and be activated in different inflammatory disorders, such as celiac disease (CD).The aim of this study was to investigate the expression level of CXCR3, CXCL10, and CXCL11 genes in celiac patients compared to healthy controls. Both cohorts have been recruited from the Iranian population.In this case-control study, biopsy specimens were collected from 71 celiac patients (60.5% female) and 90 control subjects (57% female) during 2016. Total RNA was extracted and mRNA expression levels of CXCR3, CXCL10, and CXCL11 genes were investigated by SYBR green qPCR.Based on qPCR and relative quantification method, the mRNA expression levels of CXCR3, CXCL10, and CXCL11 were significantly higher in duodenal biopsies of celiac patients compared to healthy controls in the study population (P = .038, P = .021, and P = .012 respectively).The result of this study showed that CXCR3/CXCL10/CXCL11 signaling axis is overexpressed in the small intestinal mucosa of CD patients compared to controls. This finding might explain the specific enrollment of the main cell populations that infiltrate the epithelium.
- MIC-1/GDF15 overexpression is associated with increased functional recovery in traumatic spinal cord injury. [Journal Article]
- JNJ Neurotrauma 2019 Jun 22
- Spinal cord injury (SCI) has devastating consequences, with limited therapeutic options, thus improving its functional outcome is a major goal. The outcome of SCI is contributed to by neuroinflammati…
Spinal cord injury (SCI) has devastating consequences, with limited therapeutic options, thus improving its functional outcome is a major goal. The outcome of SCI is contributed to by neuroinflammation, which may be a target for improved recovery and quality of life after injury. MIC-1/GDF15 has been identified as a potential novel therapy for CNS injury because it is an immune regulatory cytokine with neurotrophic properties. Here we used MIC-1/GDF15 knockout (KO) and overexpressing/transgenic (Tg) and WT animals to explore its putative therapeutic benefits in a mouse model of contusive SCI. MIC-1/GDF15 Tg mice had superior locomotor recovery and reduced secondary tissue loss at 28 days compared to their KO and WT counterparts. Overexpression of MIC-1/GDF15 coincided with increased expression of MCP-1/CCL2 at the lesion site (28 days post SCI) and enhanced recruitment of inflammatory cells to the injured spinal cord. This inflammatory cellular infiltrate included an increased frequency of macrophages and DCs that mostly preceded recruitment of CD4+ and CD8+ T cells. Collectively, our findings suggest MIC-1/GDF15 is associated with beneficial changes in the clinical course of SCI that are characterised by altered post injury inflammation and improved functional outcome. Further investigation of MIC-1/GDF15 as a novel therapeutic target for traumatic SCI appears warranted.
- New toxicity testing of PQ grass allergy immunotherapy to support product development. [Journal Article]
- JAJ Appl Toxicol 2019 Jun 23
- PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthm…
PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l-tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL®). Previous non-clinical safety testing, including rat repeat dose toxicity in adult and juvenile animals, rat reproductive toxicity and rabbit local tolerance studies showed no safety findings of concern. A new Good Laboratory Practice compliant rat subcutaneous repeat dose toxicity study to evaluate a higher clinical dose and modified posology (once every 2 weeks for 13 weeks) showed no signs of toxicity. As seen in previous studies, relatively minor, immunostimulatory effects were seen such as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased A/G ratio) and increased fibrinogen as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL and/or the presence of l-tyrosine within the adjuvanted vaccine. This new toxicity study with PQ Grass therefore supports longer posology with higher dose levels.
- Gal-3 Deficiency Suppresses Novosphyngobium aromaticivorans Inflammasome Activation and IL-17 Driven Autoimmune Cholangitis in Mice. [Journal Article]
- FIFront Immunol 2019; 10:1309
- Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of …
Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3-/- mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3-/- and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1β (IL-1β) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1β production compared with Lgals3-/- cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1β and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC.
- Harnessing Microglia and Macrophages for the Treatment of Glioblastoma. [Review]
- FPFront Pharmacol 2019; 10:506
- Glioblastoma multiforme (GBM) is the most malignant form of brain tumors, with a dismal prognosis. During the course of the disease, microglia and macrophages both infiltrate the tumor microenvironme…
Glioblastoma multiforme (GBM) is the most malignant form of brain tumors, with a dismal prognosis. During the course of the disease, microglia and macrophages both infiltrate the tumor microenvironment and contribute considerably in glioma development. Thus, tumor-associated microglia and macrophages have recently emerged as potentially key therapeutic targets. Here, we review the physiology of microglia and their responses in brain cancer. We further discuss current treatment options for GBM using radiotherapy, and novel advances in our knowledge of microglia physiology, with emphasis on the recently discovered pathway that controls the baseline motility of microglia processes. We argue that the latter pathway is an interesting therapeutic avenue to pursue for the treatment of glioblastoma.
- [Erythroderma revealing IPEX syndrome]. [Journal Article]
- ADAnn Dermatol Venereol 2019 Jun 21
- CONCLUSIONS: IPEX syndrome is characterized by early secretory enteropathy with profuse diarrhea, dermatitis and diabetes mellitus. Onset usually occurs within the first weeks or months of life, and the natural course of the disease is often lethal. Cutaneous manifestations appear to be mostly eczematiform, psoriasiform or ichthyosiform. These may be the first sign of the disease and a common inflammatory skin disorder may be wrongly diagnosed. The severity of the lesions and their limited response to topical steroids should alert the clinician.The early onset of severe cutaneous manifestations with persistent lesions and poor response to topical steroids should lead to an early skin biopsy. If histopathological changes show a cytotoxic lymphocytic infiltrate with keratinocyte necrosis, a diagnosis of primary immunodeficiency must be considered enabling rapid intitation of specific management.
- Rare Kodamaea ohmeri keratitis following a trivial vegetative trauma. [Journal Article]
- BCBMJ Case Rep 2019 Jun 22; 12(6)
- Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in…
Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in mortality. To the best of our knowledge, we identified the first case of K. ohmeri keratitis following an injury with vegetative material. A 57-year-old woman with underlying, poorly controlled diabetes mellitus was gardening when a tree leaf accidentally poked her in the eye. Two weeks later, the patient presented with right eye pain, redness and progressive blurring of vision due to a traumatised right cornea. Slit-lamp examination showed a small inferior paracentral corneal stromal infiltrate with overlying epithelial defect. A corneal scraping sample yielded K. ohmeri from Analytical Profile Index (API) 20C yeast identification system. She was treated with intensive topical amphotericin B and fluconazole. After 6 weeks of treatment, the keratitis resolved with faint scar tissue, and her visual acuity improved.
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- Imbalance of Genes Encoding Natural Killer Immunoglobulin-like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer. [Journal Article]
- GGastroenterology 2019 Jun 20
- CONCLUSIONS: In a multi-dimensional analysis of DNA from blood samples of patients with BDC in Europe, we found patients to have multiple alterations at the KIR and HLA gene loci compared with controls. These alterations might affect NK cell tumor surveillance. NK cells from bile duct tumors expressed KIRs and were found in tumors that expressed cognate ligands. This should be considered in development of immune-based therapies for BDC.