An Adult Case of Adenovirus-Associated Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is an autoimmune neurological disease that predominately affects pediatric population. Only a single fatal adult case of adenovirus-associated ADEM has previously been published by Qamar et al. in 2021. Here, we present an adult case of adenovirus-associated ADEM, which was diagnosed early in her clinical course. The patient was treated with the prompt initiation of steroids, intravenous immune globulin (IVIG), and plasmapheresis (PLEX), and the patient recovered fully. This case highlights the importance of early accurate diagnosis for other clinicians to treat adenovirus-associated ADEM in a timely fashion to prevent a potentially fatal outcome.

Protein kinase D3 promotes neutrophil migration during viral infection.

Protein kinase D (PKD) is a serine/threonine kinase family with three isoforms (PKD1-3) that are expressed in most cells and implicated in a wide array of signaling pathways, including cell growth, differentiation, transcription, secretion, polarization and actin turnover. Despite growing interest in PKD, relatively little is known about the role of PKD in immune responses. We recently published that inhibiting PKD limits proinflammatory cytokine secretion and leukocyte accumulation in mouse models of viral infection, and that PKD3 is highly expressed in the murine lung and immune cell populations. Here we focus on the immune-related phenotypes of PKD3 knockout mice. We report that PKD3 is necessary for maximal neutrophil accumulation in the lung following challenge with inhaled polyinosinic:polycytidylic acid, a double-stranded RNA, as well as following influenza A virus infection. Using reciprocal bone marrow chimeras, we found that PKD3 is required in the hematopoietic compartment for optimal neutrophil migration to the lung. Ex vivo transwell and chemokinesis assays confirmed that PKD3-/- neutrophils possess an intrinsic motility defect, partly because of reduced surface expression of CD18, which is critical for leukocyte migration. Finally, the peak of neutrophilia was significantly reduced in PKD3-/- mice after lethal influenza A virus infection. Together, these results demonstrate that PKD3 has an essential, and nonredundant, role in promoting neutrophil recruitment to the lung. A better understanding of the isoform-specific and cell type-specific activities of PKD has the potential to lead to novel therapeutics for respiratory illnesses.

Imaging and Clinical Findings in a Series of Six Cases of Rare Primary Mediastinal Liposarcoma.

Primary mediastinal liposarcoma is a rare, fat-containing malignant lesion that can manifest incidentally with varied imaging appearances. The size and location within the mediastinum can vary among patients. Here, the authors describe the clinical presentation, radiographic characteristics, management, and prognosis in a series of six patients with primary mediastinal liposarcoma. The following case series suggests that even simple-appearing fatty intrathoracic lesions may lead to the development of malignant imaging features. Keywords: Conventional Radiography, CT, MR Imaging, PET/CT, Soft Tissues/Skin, Thorax, Mediastinum ©RSNA, 2022.

A 73-Year-Old Woman With Progressive Shortness of Breath and Right-Sided Hemithorax Opacity.

CASE PRESENTATION: A 73-year-old frail woman presented with 3 months of progressively worsening exertional dyspnea, mild cough with white mucus, voice changes, and few episodes of dysphagia. She denied weight loss, night sweats, chest pain, or hemoptysis. Medical history was significant for hypertension, remote 30 years of tobacco use, and regular alcohol use. She had neither asbestos nor occupational exposure. She had no family history of malignancy.

Laparoscopic Right Hemicolectomy to Curatively Treat Primary Leiomyosarcoma at the Ileocecal Valve.

Primary leiomyosarcomas of the colon (PLC) are rare tumors, representing 0.12% of all colon malignancies. We report a 59-year-old man with weight loss, mild anemia, and rectal bleeding. Colonoscopy revealed a 3.2 × 2.6-cm mass at the ileocecal valve. Histopathological examination of the biopsy showed a spindle cell neoplasm that stained positive for smooth muscle actin, caldesmon, and desmin. A diagnosis of PLC was made. Subsequently, a laparoscopic right hemicolectomy was performed, and no local recurrence was noted 6 months after the resection. Given the rarity of PLC, more studies on the clinical features and treatments of this tumor are warranted.

RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis.

BACKGROUND: Allergens elicit host production of mediators acting on G-protein-coupled receptors to regulate airway tone. Among these is prostaglandin E2 (PGE2), which, in addition to its role as a bronchodilator, has anti-inflammatory actions. Some patients with asthma develop bronchospasm after the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs, a disorder termed aspirin-exacerbated respiratory disease. This condition may result in part from abnormal dependence on the bronchoprotective actions of PGE2. OBJECTIVE: We sought to understand the functions of regulator of G protein signaling 4 (RGS4), a cytoplasmic protein expressed in airway smooth muscle and bronchial epithelium that regulates the activity of G-protein-coupled receptors, in asthma. METHODS: We examined RGS4 expression in human lung biopsies by immunohistochemistry. We assessed airways hyperresponsiveness (AHR) and lung inflammation in germline and airway smooth muscle-specific Rgs4-/- mice and in mice treated with an RGS4 antagonist after challenge with Aspergillus fumigatus. We examined the role of RGS4 in nonsteroidal anti-inflammatory drug-associated bronchoconstriction by challenging aspirin-exacerbated respiratory disease-like (ptges1-/-) mice with aspirin. RESULTS: RGS4 expression in respiratory epithelium is increased in subjects with severe asthma. Allergen-induced AHR was unexpectedly diminished in Rgs4-/- mice, a finding associated with increased airway PGE2 levels. RGS4 modulated allergen-induced PGE2 secretion in human bronchial epithelial cells and prostanoid-dependent bronchodilation. The RGS4 antagonist CCG203769 attenuated AHR induced by allergen or aspirin challenge of wild-type or ptges1-/- mice, respectively, in association with increased airway PGE2 levels. CONCLUSIONS: RGS4 may contribute to the development of AHR by reducing airway PGE2 biosynthesis in allergen- and aspirin-induced asthma.

RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice.

A cardinal feature of asthma is airway hyperresponsiveness (AHR) to spasmogens, many of which activate G protein-coupled receptors (GPCRs) on airway smooth muscle (ASM) cells. Asthma subtypes associated with allergy are characterized by eosinophilic inflammation in the lung due to the type 2 immune response to allergens and proinflammatory mediators that promote AHR. The degree to which intrinsic abnormalities of ASM contribute to this phenotype remains unknown. The regulators of G protein signaling (RGS) proteins are a large group of intracellular proteins that inhibit GPCR signaling pathways. RGS2- and RGS5-deficient mice develop AHR spontaneously. Although RGS4 is upregulated in ASM from patients with severe asthma, the effects of increased RGS4 expression on AHR in vivo are unknown. Here, we examined the impact of forced RGS4 overexpression in lung on AHR using transgenic (Tg) mice. Tg RGS4 was expressed in bronchial epithelium and ASM in vivo, and protein expression in lung was increased at least 4-fold in Tg mice compared with wild-type (WT) mice. Lung slices from Tg mice contracted less in response to the m3 muscarinic receptor agonist methacholine compared with the WT, although airway resistance in live, unchallenged mice of both strains was similar. Tg mice were partially protected against AHR induced by fungal allergen challenge due to weakened contraction signaling in ASM and reduced type 2 cytokine (IL-5 and IL-13) levels in Tg mice compared with the WT. These results provide support for the hypothesis that increasing RGS4 expression and/or function could be a viable therapeutic strategy for asthma.

Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents.

The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 +/- 0.27 and 3.4 +/- 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.