scholarly journals Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease

2021 ◽  
Vol 10 (3) ◽  
pp. 475
Author(s):  
Alessandro Iannaccone ◽  
Emily Brabbit ◽  
Christiaan Lopez-Miro ◽  
Zoe Love ◽  
Victoria Griffiths ◽  
...  
Keyword(s):  
Disease Model ◽  
Recessive Mutation ◽  
Initial Increase ◽  
Imaging Features ◽  
Longitudinal Assessment ◽  
Prognostic Information ◽  
Related Disease ◽  
Cone Sensitivity ◽  
Human And Mouse ◽  
Sd Oct

NR2E3-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 (rd7) murine model, harboring a recessive mutation in the mouse ortholog of NR2E3, has been a well-studied disease model and recently evaluated as a therapeutic model for NR2E3-associated retinal degenerations. This study aims to draw parallels between human and mouse NR2E3-related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the rd7 mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of rd7 disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human NR2E3-related disease, was curated to identify further valuable correlates between human and mouse Nr2e3 disease. Results of this study validate the slow progression of NR2E3-associated disease in humans and the rd7 mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the rd7 mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between rd7 mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of NR2E3-associated retinopathies.

scholarly journals Immunoglobulin G4-related disease - diagnostic dilemma and importance of clinical judgement: a case report

2020 ◽  
Vol 8 (11) ◽  
pp. 4144
Author(s):  
Jagadeesh Chandrasekaran ◽  
Phani Krishna Machiraju
Keyword(s):  
Early Recognition ◽  
Elevated Serum ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Inflammatory Disorder ◽  
Imaging Features ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
The Right

Immunoglobulin G4 (IgG4)-related disease is a multi-organ, immune-mediated, fibro-inflammatory disorder characterized by tumefactive masses in the affected organs. Incidence and prevalence of IgG4-related disease (RD) are not clearly known and have slight male preponderance. It often involves multiple organs at the time of presentation or over the course of disease mimicking malignancy, Sjogren's syndrome, antineutrophil cytoplasmic antibodies associated vasculitis, infections. A thorough workup is needed to rule out these mimickers. A 33-year-old gentleman presented to us with history of progressive swelling in the right peri-orbital region for four years. On evaluation, abdominal imaging was notable for the sausage-shaped pancreas and hypoenchancing nodules in bilateral kidneys. Histological examination of right lacrimal gland revealed lymphoplasmacytic infiltrate and storiform fibrosis. Serum IgG4 levels were normal, and immunostaining was negative. A diagnosis of IgG4-RD was suggested because of multi-organ involvement, classical radiological and histopathological features. Awareness about IgG4-RD, an under-recognized entity is essential, as it is treatable, and early recognition may help in a favourable outcome. Appropriate use of clinicopathological, serological and imaging features in the right clinical context may help in accurate diagnosis. Elevated serum IgG4 levels and biopsy are not mandatory for the diagnosis.

scholarly journals Multimodal imaging of Hurler syndrome-related keratopathy treated with deep anterior lamellar keratoplasty

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Elodie Da Cunha ◽  
Cristina Georgeon ◽  
Nacim Bouheraoua ◽  
Marc Putterman ◽  
Françoise Brignole-Baudouin ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Multimodal Imaging ◽  
Lamellar Keratoplasty ◽  
Deep Anterior Lamellar Keratoplasty ◽  
Imaging Features ◽  
Hurler Syndrome ◽  
Hematopoietic Stem ◽  
First Choice ◽  
Anterior Lamellar Keratoplasty ◽  
Sd Oct

Abstract Background Hurler syndrome-associated keratopathy is an exceedingly rare corneal disorder that requires corneal transplantation in advanced stages. Precise assessment of the corneal condition is necessary for deciding which type of keratoplasty (i.e., deep anterior lamellar or penetrating) should be proposed. We aimed to confront the results of multimodal imaging with those of histology in a case of Hurler syndrome-associated keratopathy. Case presentation A 16-year-old patient with Hurler’s syndrome treated with hematopoietic stem cell transplantation was referred for decreased vision related to advanced keratopathy. The patient was treated with deep anterior lamellar keratoplasty (DALK) in both eyes with uncomplicated outcome. Visual acuity improved from 0.1 (20/200) preoperatively to 0.32 (20/63) and 0.63 (20/32) after transplantation. The corneal endothelial cell density was 2400 cells/mm2 in both eyes 3 years after transplantation. In vivo confocal microscopy (IVCM) and spectral domain optical coherence tomography (SD-OCT) were performed preoperatively. The corneal buttons retrieved during keratoplasty were processed for histology. In SD-OCT scans, corneal opacities appeared as diffuse stromal hyperreflectivity associated with increased corneal thickness. IVCM showed diffuse cytoplasmic granular hyperreflectivity and rounded/ellipsoid aspects of keratocytes, presence of small intracellular vacuoles, and hyperreflective epithelial intercellular spaces. Bowman’s layer was thin and irregular. The corneal endothelium was poorly visualized but no endothelial damage was observed. Histology showed irregular orientation and organization of stromal lamellae, with the presence of macrophages whose cytoplasm appeared clear and granular. A perinuclear clear halo was visible within the epithelial basal cells. Bowman’s layer featured breaks and irregularities. Conclusions The observed corneal multimodal imaging features in mucopolysaccharidosis-related keratopathy were concordant with histology. Compared with standard histology, multimodal imaging allowed additional keratocyte features to be observed. It revealed both morphological and structural changes of all corneal layers but the endothelium. This information is essential for therapeutic management which should include DALK as the first-choice treatment in case of impaired visual acuity.

Imaging features of immunoglobulin G4-related disease

2016 ◽  
Vol 60 (6) ◽  
pp. 707-713 ◽  
Author(s):  
Jonathan Dillon ◽  
Andrea Dart ◽  
Tom Sutherland
Keyword(s):  
Imaging Features ◽  
Immunoglobulin G4 ◽  
Related Disease

Failure of Erythropoiesis and Megakaryocytopoiesis in RASA3 Mutant Scat Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 680-680
Author(s):  
Lionel Blanc ◽  
Babette Gwynn ◽  
Steven L. Ciciotte ◽  
Luanne L. Peters
Keyword(s):  
Bone Marrow ◽  
Positional Cloning ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Inbred Mouse Strain ◽  
Recessive Mutation ◽  
Initial Increase ◽  
Severe Anemia ◽  
Wild Type ◽  
Hematopoietic Stem

Abstract Abstract 680 Scat (severe combined anemia and thrombocytopenia) is a spontaneous, autosomal recessive mutation coisogenic with the BALB/cBy inbred mouse strain. Homozygous scat mice present a cyclic phenotype with alternating episodes of crisis and remission. As its name implies, crisis episodes are characterized by severe anemia and thrombocytopenia, but significant lymphocyte depletion occurs as well. The first crisis episode begins in utero, lasts until postnatal day (P) 9 on average, and is associated with 10–15% mortality. Remarkably, in homozygotes that survive the first crisis, a remission phase occurs wherein the disease phenotype reverts to normal. This remission is transient, however, and is followed by a second crisis episode during which 94% of scat/scat mice die by P30. Previously we showed that the scat phenotype is transferrable via the hematopoietic stem cells and is also recapitulated in scat/scat, Hox11−/− double homozygotes in which a spleen does not develop, indicating that the splenic micro-environment plays little or no role in disease appearance or progression. Positional cloning of scat revealed a missense mutation in Rasa3 encoding a GTPase activating protein (GAP) that negatively regulates Ras function by accelerating GTP hydrolysis and converting Ras to the inactive GDP bound form. We further showed that Rasa3 is a conserved gene critical to vertebrate erythropoiesis via morpholino knockdowns in zebrafish which resulted in profound anemia. Here we report data that shed further light on RASA3 function during hematopoiesis. Overall, the data indicate that defects in RASA3 profoundly and negatively impact erythropoiesis and megakaryocytopoieis through, at least in part, a Ras-mediated mechanism. FACS analyses of scat spleen and bone marrow erythroid populations reveal a severe block in erythropoiesis during crisis periods. In the spleen, despite an initial increase in size due to expansion of Ter-119+ cells, there is ultimately a loss of compensatory erythropoiesis resulting in a return to normal cellularity and a striking loss of hemoglobinized cells as the crisis phenotype deepens. In addition, the bone marrow shows loss of Ter-119+ cells and overall cell depletion during crisis. Megakaryocyte numbers are increased in scat crisis BM and spleen. By transmission electron microscopy, scat crisis megakaryocytes display features characteristic of a significant developmental delay: a disorganized demarcation membrane system with no platelet forming areas and few granules with hypersegmented nuclei and excess rough endoplasmic reticulum. In addition to the severe anemia and thrombocytopenia, a significant lymphopenia occurs in scat crisis mice. However, the scat phenotype is not lymphocyte mediated, as the scat phenotype is completely recapitulated in mice doubly homozygous for scat and the immunodeficient mutations, scid and Rag1tm1Mom, in which B- and T-lymphocytes are completely depleted. Together these results suggest that lymphopenia is a secondary phenomenon in scat, and the severe anemia and thrombocytopenia aspect of the phenotype neither follows from nor is dependent upon loss of lymphocytes. Despite the delay observed in erythroid differentiation, some mature red cells are produced although ∼50% of these are reticulocytes. By confocal microscopy, we show that RASA3 protein localizes to the plasma membrane as well as internal membrane compartments in wild type reticulocytes, where it partially colocalizes with CD71. Western blot analyses of reticulocytes after Percoll gradient purification show that RASA3 is lost during the maturation step, both in vivo and in vitro. Interestingly, in scat, RASA3 is present in reticulocytes, but appears to be mislocalized, the protein being found in the cytosol. Preparation of ghosts from wild type and scat reticulocytes confirms that RASA3 is not attached to the membrane in scat animals during crisis. In pull-down assays active GTP-bound Ras is increased in scat crisis reticulocytes when compared to wild type, suggesting that scat is a RASA3 loss of function mutation due to its mislocalization and demonstrating a critical role for the RASA3-Ras axis during mammalian erythropoiesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Radiogenomics and Radiomics in Liver Cancers

Diagnostics ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Aman Saini ◽  
Ilana Breen ◽  
Yash Pershad ◽  
Sailendra Naidu ◽  
M. Knuttinen ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Information ◽  
Clinical Decision ◽  
Molecular Profile ◽  
Imaging Features ◽  
Imaging Data ◽  
Prognostic Information ◽  
Cross Sectional ◽  
Related Field ◽  
Liver Cancers

Radiogenomics is a computational discipline that identifies correlations between cross-sectional imaging features and tissue-based molecular data. These imaging phenotypic correlations can then potentially be used to longitudinally and non-invasively predict a tumor’s molecular profile. A different, but related field termed radiomics examines the extraction of quantitative data from imaging data and the subsequent combination of these data with clinical information in an attempt to provide prognostic information and guide clinical decision making. Together, these fields represent the evolution of biomedical imaging from a descriptive, qualitative specialty to a predictive, quantitative discipline. It is anticipated that radiomics and radiogenomics will not only identify pathologic processes, but also unveil their underlying pathophysiological mechanisms through clinical imaging alone. Here, we review recent studies on radiogenomics and radiomics in liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastases to the liver.

scholarly journals Neurological involvement of IgG4-related disease: description of a case and review of the literature

2017 ◽  
Vol 31 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Marco Varrassi ◽  
Camilla Gianneramo ◽  
Francesco Arrigoni ◽  
Paolo Cerrone ◽  
Patrizia Sucapane ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lower Limbs ◽  
Neurological Involvement ◽  
Imaging Features ◽  
Spinal Root ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Clinical Presentations ◽  
The Central Nervous System

IgG4-related disease is a recently discovered pathological entity, histologically characterised by fibrosis and IgG4-positive plasma cell infiltration. This condition may virtually involve every site of the organism, with a various range of clinical presentations. The most commonly affected organ is the pancreatic gland, but it can also involve the biliary tract, salivary and lacrimal glands, kidneys, orbital tissues, lymph nodes, lungs and many others. More recently, IgG4-related disease has been demonstrated to involve, in rare cases, also the central nervous system, with a pattern mainly characterised by hypertrophic pachymeningitis. In this paper we evaluated the clinical and magnetic resonance imaging features of the IgG4-related disease in the central nervous system, reporting a case of brain and spinal cord involvement. In our case, in fact, a 62-year-old man complaining of paresthesia, burning dysesthesia and severe hyposthenia in the lower limbs presented with inflammatory pseudotumour with orbital involvement and focal dural and spinal root thickening.

scholarly journals Magnetic resonance imaging features of large endolymphatic sac compartments: audiological and clinical correlates

2012 ◽  
Vol 126 (6) ◽  
pp. 586-593 ◽  
Author(s):  
S E J Connor ◽  
A Siddiqui ◽  
R O'Gorman ◽  
J R Tysome ◽  
A Lee ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hearing Loss ◽  
Magnetic Resonance ◽  
Endolymphatic Sac ◽  
Fluid Loss ◽  
Imaging Features ◽  
Resonance Imaging ◽  
Clear Fluid ◽  
Prognostic Information ◽  
Imaging Characteristics

AbstractObjectives:(1) To study the prevalence and characteristics of large endolymphatic sac internal compartments on thin-section T2- and T2*-weighted magnetic resonance imaging, and to relate these to other large endolymphatic sac magnetic resonance imaging features, and (2) to correlate the compartment imaging features, endolymphatic sac size and labyrinthine anomalies with the patients' clinical and audiological data.Method:Magnetic resonance imaging studies for 38 patients with large endolymphatic sac anomalies were retrospectively reviewed in a tertiary referral centre. Endolymphatic sac compartment presence, morphology and imaging signal were assessed. Endolymphatic sac size and labyrinthine anomalies were also recorded. Endolymphatic sac compartments and other imaging features were correlated with clinical and audiological data.Results:Compartments were present in 57 per cent of the imaged endolymphatic sacs, but their presence alone did not correlate with other imaging features or clinical data. The endolymphatic sac : internal auditory meatus signal ratio was associated with a history of sudden or fluctuating hearing loss. Hearing loss correlated with opercular and extraosseous endolymphatic sac size measurements. A larger midpoint intraosseous endolymphatic sac size was associated with clear fluid loss at cochlear implantation.Conclusion:The magnetic resonance imaging characteristics of large endolymphatic sac compartments have been defined. The endolymphatic sac size and distal compartment signal should be recorded, as these provide prognostic information and assist the planning of appropriate interventions.

scholarly journals POS1384 DIFFERENT CLINICAL CHARACTERISTICS OF IGG4-RRD PATIENTS AND NON-IGG4-RRD PATIENTS: A LARGE CHINESE COHORT STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 975.1-975
Author(s):  
Z. Wang ◽  
L. Jiaxi ◽  
Y. Liu
Keyword(s):  
Internal Medicine ◽  
Salivary Gland ◽  
Retrospective Study ◽  
Respiratory Disease ◽  
Clinical Characteristics ◽  
Imaging Features ◽  
Immunoglobulin G4 ◽  
Related Disease ◽  
Respiratory Involvement ◽  
Igg4 Related Disease

Background:IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involve multiple organs. The respiratory tract is one of the most frequently involved sites.Objectives:This study aimed to compare the demographic and clinical characteristics of IgG4-related respiratory disease (IgG4-RRD) and non-IgG4-RRD patients in a large cohort.Methods:We carried out a retrospective study of 452 cases of IgG4-RD (104 IgG4-RRD patients and 348 non-IgG4-RRD patients) diagnosed at Peking University People’s Hospital between 2003 and 2020.Results:IgG4-RRD patients had an elder age of disease onset and diagnosis. Multiorgan involvement and hypocomplementemia were more common in IgG4-RRD. Besides, the level of ESR, eosinophilia, IgG and IgG4 were higher in IgG4-RRD patients. In IgG4-RRD group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the non-IgG4-RRD group. Also, more numbers of organ involvement and biliary involvement were independent risk factors for the development of respiratory involvement in IgG4-RD patients.Conclusion:Our study revealed demographic, clinical, laboratory and imaging features of IgG4-RRD patients and the underlying differences in pathogenesis between the two phenotypes, which have important implications for the diagnosis and treatment of the disease.References:[1]Morales AT, Cignarella AG, Jabeen IS, Barkin JS, Mirsaeidi M. An update on IgG4-related lung disease. European journal of internal medicine. 2019;66:18-24.[2]Stone JH, Zen Y, Deshpande V. IgG4-related disease. The New England journal of medicine. 2012;366(6):539-51.[3]Vasaitis L. IgG4-related disease: A relatively new concept for clinicians. European journal of internal medicine. 2016;27:1-9.[4]Matsui S, Yamamoto H, Minamoto S, Waseda Y, Mishima M, Kubo K. Proposed diagnostic criteria for IgG4-related respiratory disease. Respiratory investigation. 2016;54(2):130-2.[5]Cao L, Chen YB, Zhao DH, Shi WF, Meng S, Xie LX. Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease. Journal of thoracic disease. 2017;9(3):547-54.[6]Wallace ZS, Perugino C, Matza M, Deshpande V, Sharma A, Stone JH. Immunoglobulin G4-related Disease. Clinics in chest medicine. 2019;40(3):583-97.[7]Matsui S. IgG4-related respiratory disease. Modern rheumatology. 2019;29(2):251-6.[8]Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56(9):813-24.[9]Fei Y, Shi J, Lin W, Chen Y, Feng R, Wu Q, et al. Intrathoracic Involvements of Immunoglobulin G4-Related Sclerosing Disease. Medicine. 2015;94(50):e2150.[10]Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis & rheumatology (Hoboken, NJ). 2015;67(9):2466-75.[11]Yamada K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, et al. New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. Arthritis research & therapy. 2017;19(1):262.[12]Borges T, Silva S. IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? Modern rheumatology. 2020;30(4):609-16.[13]Liu Y, Xue M, Wang Z, Zeng Q, Ren L, Zhang Y, et al. Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients. Rheumatology (Oxford, England). 2020;59(3):634-40.[14]Matsui S, Taki H, Shinoda K, Suzuki K, Hayashi R, Tobe K, et al. Respiratory involvement in IgG4-related Mikulicz’s disease. Modern rheumatology. 2012;22(1):31-9.Disclosure of Interests:None declared

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