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1.
Radiographics ; 44(5): e230134, 2024 May.
Article in English | MEDLINE | ID: mdl-38662588

ABSTRACT

Flow artifacts are commonly encountered at contrast-enhanced CT and can be difficult to discern from true pathologic conditions. Therefore, radiologists must be comfortable distinguishing flow artifacts from true pathologic conditions. This is of particular importance when evaluating the pulmonary arteries and aorta, as a flow artifact may be mistaken for a pulmonary embolism or dissection flap. Understanding the mechanics of flow artifacts and how these artifacts are created can help radiologists in several ways. First, this knowledge can help radiologists appreciate how the imaging characteristics of flow artifacts differ from true pathologic conditions. This information can also help radiologists better recognize the clinical conditions that predispose patients to flow artifacts, such as pneumonia, chronic lung damage, and altered cardiac output. By understanding when flow artifacts may be confounding the interpretation of an examination, radiologists can then know when to pursue other troubleshooting methods to assist with the diagnosis. In these circumstances, the radiologist can consider several troubleshooting methods, including adjusting the imaging protocols, recommending when additional imaging may be helpful, and suggesting which imaging study would be the most beneficial. Finally, flow artifacts can also be used as a diagnostic tool when evaluating the vascular anatomy, examples of which include the characterization of shunts, venous collaterals, intimomedial flaps, and alternative patterns of blood flow, as seen in extracorporeal membrane oxygenation circuits. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.


Subject(s)
Artifacts , Tomography, X-Ray Computed , Humans , Contrast Media , Pulmonary Artery/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/methods
2.
AIDS Res Hum Retroviruses ; 40(3): 158-170, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37548528

ABSTRACT

Human immunodeficiency virus (HIV) infection and the ensuing acquired immunodeficiency syndrome (AIDS) disproportionally affect young women, yet understanding of the factors promoting heterosexual transmission in the female genital tract is limited. Colonization with highly diverse, Lactobacillus-deficient communities (HDCs) increases a woman's risk of acquiring HIV-1 compared with colonization with Lactobacillus-dominated low diversity communities (LDCs). The polymicrobial nature of these communities has made it challenging to elucidate the microbial mechanisms responsible for modulating HIV susceptibility. Here, we analyzed conserved changes in small-molecule metabolites present in the cervicovaginal lavage fluid collected from women colonized with HDCs and LDCs with the goal of identifying possible chemicals influencing HIV infection. As in previous studies, we found that the catabolite of the branched-chain amino acid valine, 2-hydroxyisovalerate (2-HV), was a consistent component of dysbiotic HDC microbiota. Effects of 2-HV on HIV infection were assessed. In experimental infections with HIV, treatment with 2-HV increased infections of resting CD4+ T cells. To understand bacterial production of 2-HV in more detail, we cultured purified HDC and LDC bacteria and used mass spectrometry to identify two HDC bacteria that synthesize high levels of 2-HV. In contrast, protective vaginal Lactobacilli did not produce high levels of 2-HV. A genomic analysis of genes encoding 2-HV synthetic pathways showed a correlation between high-level production of 2-HV and pathways for synthesis of the immediate precursor 2-ketoisovalerate. Thus, 2-HV is a candidate mediator linking vaginal microbiome structure and heterosexual HIV transmission in women.


Subject(s)
HIV Infections , Vaginosis, Bacterial , Valerates , Female , Humans , HIV Infections/microbiology , T-Lymphocytes , Vagina , Bacteria
3.
AIDS Res Hum Retroviruses ; 40(2): 114-126, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37125442

ABSTRACT

Decades of effort have yielded highly effective antiviral agents to treat HIV, but viral strains have evolved resistance to each inhibitor type, focusing attention on the importance of developing new inhibitor classes. A particularly promising new target is the HIV capsid, the function of which can be disrupted by highly potent inhibitors that persist long term in treated subjects. Studies with such inhibitors have contributed to an evolving picture of the role of capsid itself-the inhibitors, like certain capsid protein (CA) amino acid substitutions, can disrupt intracellular trafficking to alter the selection of target sites for HIV DNA integration in cellular chromosomes. In this study, we compare effects on HIV integration targeting for two potent inhibitors-a new molecule targeting CA, GSK878, and the previously studied lenacapavir (LEN, formerly known as GS-6207). We find that both inhibitors reduce integration in active transcription units and near epigenetic marks associated with active transcription. A careful study of integration near repeated sequences indicated frequencies were also altered for integration within multiple repeat classes. One notable finding was increased integration in centromeric satellite repeats in the presence of LEN and GSK878, which is of interest because proviruses integrated in centromeric repeats have been associated with transcriptional repression, inducibility, and latency. These data add to the picture that CA protein remains associated with preintegration complexes through the point in infection during which target sites for integration are selected, and specify new aspects of the consequences of disrupting this mechanism.


Subject(s)
HIV Infections , HIV-1 , Humans , Capsid/metabolism , Capsid Proteins/genetics , Capsid Proteins/metabolism , HIV Infections/genetics , DNA, Viral/genetics , Virus Integration
4.
Radiographics ; 43(7): e220176, 2023 07.
Article in English | MEDLINE | ID: mdl-37289644

ABSTRACT

Diffuse alveolar damage (DAD), which represents the pathologic changes seen after acute lung injury, is caused by damage to all three layers of the alveolar wall and can ultimately result in alveolar collapse with loss of the normal pulmonary architecture. DAD has an acute phase that predominantly manifests as airspace disease at CT owing to filling of the alveoli with cells, plasma fluids, and hyaline membranes. DAD then evolves into a heterogeneous organizing phase, with mixed airspace and interstitial disease characterized by volume loss, architectural distortion, fibrosis, and parenchymal loss. Patients with DAD have a severe clinical course and typically require prolonged mechanical ventilation, which may result in ventilator-induced lung injury. In those patients who survive DAD, the lungs will remodel over time, but most will have residual findings at chest CT. Organizing pneumonia (OP) is a descriptive term for a histologic pattern characterized by intra-alveolar fibroblast plugs. The significance and pathogenesis of OP are controversial. Some authors regard it as part of a spectrum of acute lung injury, while others consider it a marker of acute or subacute lung injury. At CT, OP manifests with various forms of airspace disease that are most commonly bilateral and relatively homogeneous in appearance at individual time points. Patients with OP most often have a mild clinical course, although some may have residual findings at CT. In patients with DAD and OP, imaging findings can be combined with clinical information to suggest the diagnosis in many cases, with biopsy reserved for difficult cases with atypical findings or clinical manifestations. To best participate in the multidisciplinary approach to patients with lung injury, radiologists must not only recognize these entities but also describe them with consistent and meaningful terminology, examples of which are emphasized in the article. © RSNA, 2023 See the invited commentary by Kligerman et al in this issue. Quiz questions for this article are available in the supplemental material.


Subject(s)
Acute Lung Injury , Pneumonia , Humans , Lung/diagnostic imaging , Pulmonary Alveoli/pathology , Disease Progression , Tomography, X-Ray Computed/methods , Acute Lung Injury/pathology
5.
Radiographics ; 43(7): e220138, 2023 07.
Article in English | MEDLINE | ID: mdl-37347699

ABSTRACT

Diffusion-weighted imaging (DWI) is a fundamental sequence not only in neuroimaging but also in oncologic imaging and has emerging applications for MRI evaluation of the chest. DWI can be used in clinical practice to enhance lesion conspicuity, tissue characterization, and treatment response. While the spatial resolution of DWI is in the order of millimeters, changes in diffusion can be measured on the micrometer scale. As such, DWI sequences can provide important functional information to MRI evaluation of the chest but require careful optimization of acquisition parameters, notably selection of b values, application of parallel imaging, fat saturation, and motion correction techniques. Along with assessment of morphologic and other functional features, evaluation of DWI signal attenuation and apparent diffusion coefficient maps can aid in tissue characterization. DWI is a noninvasive noncontrast acquisition with an inherent quantitative nature and excellent reproducibility. The outstanding contrast-to-noise ratio provided by DWI can be used to improve detection of pulmonary, mediastinal, and pleural lesions, to identify the benign nature of complex cysts, to characterize the solid portions of cystic lesions, and to classify chest lesions as benign or malignant. DWI has several advantages over fluorine 18 (18F)-fluorodeoxyglucose PET/CT in the assessment, TNM staging, and treatment monitoring of lung cancer and other thoracic neoplasms with conventional or more recently developed therapies. © RSNA, 2023 Quiz questions for this article are available in the supplemental material. Supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.


Subject(s)
Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Humans , Reproducibility of Results , Thorax , Diffusion Magnetic Resonance Imaging/methods , Radiologists
6.
3D Print Med ; 9(1): 13, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37103761

ABSTRACT

RATIONALE AND OBJECTIVES: The purpose of this study is to summarize a survey of radiology chief residents focused on 3D printing in radiology. MATERIALS AND METHODS: An online survey was distributed to chief residents in North American radiology residencies by subgroups of the Association of University Radiologists. The survey included a subset of questions focused on the clinical use of 3D printing and perceptions of the role of 3D printing and radiology. Respondents were asked to define the role of 3D printing at their institution and asked about the potential role of clinical 3D printing in radiology and radiology residencies. RESULTS: 152 individual responses from 90 programs were provided, with a 46% overall program response rate (n = 90/194 radiology residencies). Most programs had 3D printing at their institution (60%; n = 54/90 programs). Among the institutions that perform 3D printing, 33% (n = 18/54) have structured opportunities for resident contribution. Most residents (60%; n = 91/152 respondents) feel they would benefit from 3D printing exposure or educational material. 56% of residents (n = 84/151) believed clinical 3D printing should be centered in radiology departments. 22% of residents (n = 34/151) believed it would increase communication and improve relationships between radiology and surgery colleagues. A minority (5%; 7/151) believe 3D printing is too costly, time-consuming, or outside a radiologist's scope of practice. CONCLUSIONS: A majority of surveyed chief residents in accredited radiology residencies believe they would benefit from exposure to 3D printing in residency. 3D printing education and integration would be a valuable addition to current radiology residency program curricula.

7.
Clin Imaging ; 98: 67-73, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37023549

ABSTRACT

RATIONALE AND OBJECTIVES: An annual survey of chief residents in accredited North American radiology programs is conducted by the American Alliance of Academic Chief Residents in Radiology (A3CR2). The purpose of this study is to summarize the 2020 A3CR2 chief resident survey. MATERIALS AND METHODS: An online survey was distributed to chief residents from 194 Accreditation Council on Graduate Medical Education-accredited radiology residencies. Questions were designed to gather information about residency program practices, benefits, fellowship or advanced interventional radiology (IR) training choices, and the integration of IR training. Subsets of questions focused on the perception of corporatization, non-physician providers (NPPs), and artificial intelligence (AI) in radiology and their relationship to the radiology job market. RESULTS: 174 individual responses from 94 programs were provided, yielding a 48 % program response rate. Extended emergency department coverage has steadily decreased over the last 5 years (2016-2020), however only 52 % of programs have independent overnight call (without attending coverage). Regarding the impact of new integrated IR residencies on training, 42 % indicated there was no appreciable impact on their DR or IR training, while 20 % indicated DR training for IR residents suffered and 19 % indicated IR training for DR residents suffered. Corporatization in radiology was perceived as the biggest potential threat to the future job market. CONCLUSIONS: Integration of IR residency did not detrimentally affect DR or IR training in most programs. Radiology resident perception of corporatization, NPPs, and AI may help residency programs shape educational content.


Subject(s)
Internship and Residency , Radiologists , Radiology , Surveys and Questionnaires , Radiologists/statistics & numerical data , Internship and Residency/statistics & numerical data , Radiology, Interventional , Professional Corporations , Artificial Intelligence , Radiology/education , Radiology/organization & administration , Radiology/trends , United States , Humans , Male , Female
8.
Acad Radiol ; 30(9): 2050-2058, 2023 09.
Article in English | MEDLINE | ID: mdl-36813667

ABSTRACT

RATIONALE AND OBJECTIVES: An annual survey of chief residents in accredited North American radiology programs is conducted by the American Alliance of Academic Chief Residents in Radiology (A3CR2). Special topics surveyed for the 2021-2022 academic year were procedural competency and virtual radiology education in the COVID-19 pandemic. The purpose of this study is to summarize the 2021-2022 A3CR2 chief resident survey. MATERIALS AND METHODS: An online survey was distributed to chief residents from 197 Accreditation Council on Graduate Medical Education-accredited radiology residency programs. Chief residents responded to questions regarding their individual procedural readiness and attitudes on virtual radiology education. A single chief resident from each residency answered programmatic questions including the use of virtual education, faculty coverage, and fellowship choices among their graduating classes. RESULTS: We received 110 individual responses from 61 programs, yielding a 31% program response rate. Although the majority (80%) of programs maintained purely in-person attending readout throughout the COVID 19 pandemic, only 13% of programs reported purely in-person didactics and 26% converted to all virtual didactics. The majority (53%-74%) of chief residents perceived virtual learning (in read-out, case conference, and didactic formats) to be less effective than in-person learning. One third of chief residents reported decreased procedural exposure during the pandemic, and 7%-9% of chief residents felt uncomfortable with basic procedures (basic fluoroscopy examinations, basic aspiration/drainage procedures, and superficial biopsy procedures). The number of programs with 24/7 attending coverage increased from 35% in 2019 to 49% in 2022. Body, neuroradiology, and interventional radiology were the most popular advanced training options among graduating radiology residents. CONCLUSION: The COVID-19 pandemic had a profound impact on radiology training, particularly in terms of virtual learning. These survey results suggest that although digital learning offers increased flexibility, most residents still prefer in-person readout and didactics. Despite this, virtual learning will likely remain a viable option as programs continue to evolve following the pandemic.


Subject(s)
COVID-19 , Internship and Residency , United States , Humans , Pandemics , COVID-19/epidemiology , Surveys and Questionnaires , Radiography , Radiology, Interventional
9.
Radiographics ; 42(5): 1283-1302, 2022.
Article in English | MEDLINE | ID: mdl-35960664

ABSTRACT

Aortopathy is a term most commonly used to describe a group of genetic diseases that predispose patients to an elevated risk of aortic events including aneurysm and acute aortic syndrome. Types of genetic aortopathy are classified as either heritable or congenital, with heritable thoracic aortic disease (HTAD) further subclassified into syndromic HTAD or nonsyndromic HTAD, the former of which is associated with specific phenotypic features. Radiologists may be the first physicians to encounter features of genetic aortopathy, either incidentally or at the time of an acute aortic event. Identifying patients with genetic aortopathy is of substantial importance to clinicians who manage thoracic aortic disease, because aortic diameter thresholds for surgical intervention are often lower than those for nongenetic aortopathy related to aging and hypertension. In addition, when reparative surgery is performed, the approach and extent of the repair may differ in patients with genetic aortopathy. The radiologist should also be familiar with competing diagnoses that can result in acute aortic events, mainly acquired inflammatory and noninflammatory thoracic aortic disease, because these conditions may be associated with increased risks of similar pathologic endpoints. Because many imaging and phenotypic features of various types of genetic aortopathy overlap, diagnosis and determination of appropriate follow-up recommendations can be challenging. A multidisciplinary approach with the use of imaging is often required and, once the diagnosis is made, imaging has additional importance because of the need for lifelong follow-up. ©RSNA, 2022.


Subject(s)
Aortic Diseases , Aorta , Aorta, Thoracic/diagnostic imaging , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Aortic Diseases/genetics , Aortic Valve/abnormalities , Aortic Valve/pathology , Aortic Valve/surgery , Diagnostic Imaging , Humans , Syndrome
12.
Radiographics ; 42(1): 69-86, 2022.
Article in English | MEDLINE | ID: mdl-34951836

ABSTRACT

Acute aortic syndrome (AAS) is classically attributed to three underlying pathologic conditions-aortic dissection (AD), intramural hematoma (IMH), and penetrating atherosclerotic ulcer (PAU). In the majority of cases, the basics of image interpretation are not difficult and have been extensively reviewed in the literature. In this article, the authors extend existing imaging overviews of AAS by highlighting additional factors related to the diagnosis, classification, and characterization of difficult AAS cases. It has been well documented that AAS is caused not only by an AD but by a spectrum of lesions that often have overlap in imaging features and are not clearly distinguishable. Specifically, phase of contrast enhancement, flow artifacts, and flapless AD equivalents can complicate diagnosis and are discussed. While the A/B dichotomy of the Stanford system is still used, the authors subsequently emphasize the Society for Vascular Surgery's new guidelines for the description of acute aortic pathologic conditions given the expanded use of endovascular techniques used in aortic repair. In the final section, atypical aortic rupture and pitfalls are described. As examples of pericardial and shared sheath rupture become more prevalent in the literature, it is important to recognize contrast material third-spacing and mediastinal blood as potential mimics. By understanding these factors related to difficult cases of AAS, the diagnostic radiologist will be able to accurately refine CT interpretation and thus provide information that is best suited to directing management. Online supplemental material is available for this article. ©RSNA, 2021.


Subject(s)
Aortic Diseases , Aortic Dissection , Aortic Dissection/diagnostic imaging , Aorta , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Hematoma/complications , Hematoma/diagnostic imaging , Humans , Tomography, X-Ray Computed/adverse effects , Ulcer/complications , Ulcer/diagnostic imaging
13.
Radiographics ; 41(5): 1300-1320, 2021.
Article in English | MEDLINE | ID: mdl-34415808

ABSTRACT

While many of the classic open surgical repairs are still used to repair the ascending aorta, management of the aortic arch has become more complex via implementation of newer open surgical and endovascular techniques. Furthermore, techniques are often combined in novel repairs or to allow extended anatomic coverage. As such, a framework that rests on understanding the expected postoperative appearance is necessary for the diagnostic radiologist to best interpret CT studies in these patients. After reviewing the imaging appearances of the common components used in proximal aortic repair, the authors present a structured approach that focuses on the key relevant questions that diagnostic radiologists should consider when interpreting CT studies in these patients. For repair of the ascending aorta, this includes determining whether the aortic valve has been repaired, whether the sinuses of Valsalva have been repaired, and how the coronary arteries were managed, when necessary. In repairs that involve the aortic arch, the relevant considerations relate to management of the arch vessels and the distal extent of the repair. In focusing on these questions, the diagnostic radiologist will be able to identify and describe the vast majority of repairs. Understanding these questions will also facilitate improved understanding of novel repairs, which often use these basic building blocks. Finally, complications-which typically involve infection, noninfectious repair breakdown, hemorrhage, problems with endografts, or disease of the remaining adjacent aorta-will be identifiable as deviations from the expected postoperative appearance. Online supplemental material is available for this article. ©RSNA, 2021.


Subject(s)
Aorta, Thoracic , Endovascular Procedures , Aorta , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Humans , Postoperative Complications/diagnostic imaging , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
15.
Radiographics ; 41(3): 742-761, 2021.
Article in English | MEDLINE | ID: mdl-33939537

ABSTRACT

Hemoptysis, which is defined as expectoration of blood from the alveoli or airways of the lower respiratory tract, is an alarming clinical symptom with an extensive differential diagnosis. CT has emerged as an important noninvasive tool in the evaluation of patients with hemoptysis, and the authors present a systematic but flexible approach to CT interpretation. The first step in this approach involves identifying findings of parenchymal and airway hemorrhage. The second step is aimed at determining the mechanism of hemoptysis and whether a specific vascular supply can be implicated. Hemoptysis can have primary vascular and secondary vascular causes. Primary vascular mechanisms include chronic systemic vascular hypertrophy, focally damaged vessels, a dysplastic lung parenchyma with systemic arterial supply, arteriovenous malformations and fistulas, and bleeding at the capillary level. Evaluating vascular mechanisms of hemoptysis at CT also entails determining if a specific vascular source can be implicated. Although the bronchial arteries are responsible for most cases of hemoptysis, nonbronchial systemic arteries and the pulmonary arteries are important potential sources of hemoptysis that must be recognized. Secondary vascular mechanisms of hemoptysis include processes that directly destroy the lung parenchyma and processes that directly invade the airway. Understanding and employing this approach allow the diagnostic radiologist to interpret CT examinations accurately in patients with hemoptysis and provide information that is best suited to directing subsequent treatment. ©RSNA, 2021.


Subject(s)
Embolization, Therapeutic , Hemoptysis , Bronchial Arteries , Hemoptysis/diagnostic imaging , Hemoptysis/etiology , Hemoptysis/therapy , Humans , Lung , Pulmonary Artery , Tomography, X-Ray Computed
16.
Chest ; 160(4): 1492-1511, 2021 10.
Article in English | MEDLINE | ID: mdl-33957099

ABSTRACT

BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown. RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior? STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ2 test, and multivariable analyses were used for statistical analysis. RESULTS: A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC. INTERPRETATION: EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding.


Subject(s)
Acute Lung Injury/diagnostic imaging , Hemorrhage/diagnostic imaging , Lymphadenopathy/diagnostic imaging , Vaping/adverse effects , Acute Lung Injury/etiology , Adolescent , Adult , Aged , Dronabinol/administration & dosage , Electronic Nicotine Delivery Systems , Female , Hemorrhage/etiology , Humans , Lung Injury/diagnostic imaging , Lung Injury/etiology , Lymphadenopathy/etiology , Male , Middle Aged , Nicotine/administration & dosage , Nicotinic Agonists/administration & dosage , Psychotropic Drugs/administration & dosage , Tomography, X-Ray Computed , Young Adult
17.
Virology ; 548: 117-123, 2020 09.
Article in English | MEDLINE | ID: mdl-32838932

ABSTRACT

The matrix (M) protein of vesicular stomatitis virus (VSV) plays a key role in immune evasion. While VSV has been thought to suppress the interferon (IFN) response primarily by inhibiting host cell transcription and translation, our recent findings indicate that the M protein also targets NF-κB activation. Therefore, the M protein may utilize two distinct mechanisms to limit expression of antiviral genes, inhibiting both host gene expression and NF-κB activation. Here we characterize a recently reported mutation in the M protein [M(D52G)] of VSV isolate 22-20, which suppressed IFN mRNA and protein production despite activating NF-κB. 22-20 inhibited reporter gene expression from multiple promoters, suggesting that 22-20 suppressed the IFN response via M-mediated inhibition of host cell transcription. We propose that suppression of the IFN response and regulation of NF-κB are independent, genetically separable functions of the VSV M protein.


Subject(s)
Interferon-beta/immunology , NF-kappa B/immunology , Vesicular Stomatitis/immunology , Vesicular stomatitis Indiana virus/immunology , Viral Matrix Proteins/immunology , Animals , Cell Line , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Interferon-beta/genetics , Mice , NF-kappa B/genetics , Vesicular Stomatitis/genetics , Vesicular Stomatitis/virology , Vesicular stomatitis Indiana virus/genetics , Vesicular stomatitis Indiana virus/physiology , Viral Matrix Proteins/genetics
18.
J Assist Reprod Genet ; 35(6): 993-1003, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29536385

ABSTRACT

PURPOSE: To assess expression of the histone demethylases KDM4A and KDM4B in granulosa collected from women undergoing oocyte retrieval and to determine if expression was related to pregnancy outcome. METHODS: Cumulus and mural granulosa cells were obtained from women undergoing oocyte retrieval. KDM4A and KDM4B mRNA expression was determined by qRT-PCR. KDM4A and KDM4B proteins were immunohistochemically localized in ovarian tissue sections obtained from archival specimens. RESULTS: KDM4A and KDM4B protein was localized to oocytes, granulosa cells, and theca and luteal cells in ovaries from reproductive-aged women. KDM4A and KDM4B mRNA expression was overall higher in cumulus compared to mural granulosa. When comparing granulosa demethylase gene expression, KDM4A and KDM4B mRNA expression was higher in both cumulus and mural granulosa from not pregnant patients compared to patients in the pregnant-live birth group. CONCLUSIONS: Histone demethylases KDM4A and KDM4B mRNA are differentially expressed in cumulus and mural granulosa. Expression of both KDM4A and KDM4B mRNA was lower in cumulus granulosa and mural granulosa from pregnant compared to not pregnant patients. These findings suggest that altered expression of histone demethylases may impact epigenetic changes in granulosa cells associated with pregnancy.


Subject(s)
Fertilization in Vitro , Granulosa Cells/metabolism , Histones/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Ovarian Follicle/metabolism , Adult , Female , Granulosa Cells/cytology , Humans , Oocyte Retrieval , Ovarian Follicle/cytology , Pregnancy , Pregnancy Outcome , Young Adult
19.
Pediatr Dermatol ; 34(4): e210-e211, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28425139

ABSTRACT

An 18-year-old man presented for evaluation of a 1-year history of painful nodules on the scalp with associated hair loss. Physical examination revealed multiple confluent, fluctuant, boggy nodules on the scalp with overlying alopecic patches. Based on these findings, a diagnosis of dissecting cellulitis of the scalp was made and the patient was successfully treated with oral isotretinoin therapy.


Subject(s)
Alopecia/etiology , Cellulitis/diagnosis , Isotretinoin/therapeutic use , Scalp Dermatoses/diagnosis , Skin Diseases, Genetic/diagnosis , Adolescent , Cellulitis/drug therapy , Humans , Male , Scalp/pathology , Scalp Dermatoses/drug therapy , Skin Diseases, Genetic/drug therapy
20.
Virology ; 499: 99-104, 2016 12.
Article in English | MEDLINE | ID: mdl-27643886

ABSTRACT

A previous study found that NF-κB activation is delayed in L929 cells infected with wild-type (wt) strains of VSV, while activation occurred earlier in cells infected with mutant strain T1026R1 (R1) that encodes a mutation in the cytotoxic matrix (M) protein. The integrity of the other R1 proteins is unknown; therefore our goal was to identify the viral component responsible for preventing NF-κB activation in L929 cells. We found that the M protein inhibits viral-mediated activation of NF-κB in the context of viral infection and when expressed alone via transfection, and that the M51R mutation in M abrogates this function. Addition of an IκB kinase (IKK) inhibitor blocked NF-κB activation and interferon-ß mRNA expression in cells infected with viruses encoding the M51R mutation in M. These results indicate that the VSV M protein inhibits activation of NF-κB by targeting an event upstream of IKK in the canonical pathway.


Subject(s)
NF-kappa B/metabolism , Vesicular stomatitis Indiana virus/physiology , Viral Matrix Proteins/metabolism , Animals , Cell Line , Cells, Cultured , Enzyme Activation , Gene Expression , I-kappa B Kinase/metabolism , Interferon-beta/genetics , Interferon-beta/metabolism , Mice , NF-kappa B/antagonists & inhibitors , Protein Binding , Vesicular Stomatitis/genetics , Vesicular Stomatitis/metabolism , Vesicular Stomatitis/virology , Viral Matrix Proteins/genetics
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