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Jacinto JGP, Wohlsein P, Häfliger IM, Karl M, Pohlers M, Plobner L, Grünberg W, Drögemüller C. A missense variant in DGKG as a recessive functional variant for hepatic fibrinogen storage disease in Wagyu cattle. J Vet Intern Med 2023; 37:2631-2637. [PMID: 37681469 PMCID: PMC10658517 DOI: 10.1111/jvim.16865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 08/24/2023] [Indexed: 09/09/2023] Open
Abstract
Hepatic fibrinogen storage disease (HFSD) was diagnosed in a 5-month-old Wagyu calf with a history of recurrent respiratory disease. It was characterized by lethargy, dehydration, acidemia, and increased liver enzyme activities. Histologically, disseminated hepatocytes were swollen and showed a single, sharply demarcated, faintly eosinophilic cytoplasmic inclusion with a ground-glass appearance, with the nucleus in an eccentric position. Cytoplasmic inclusions did not stain with the periodic acid-Schiff (PAS) reaction. Using a rabbit polyclonal antibody against fibrinogen, the cytoplasmic vacuoles in the hepatocytes stained intensely. Electron microscopy disclosed hepatocytes with membrane-bound cytoplasmic inclusions filled with fine granular material interspersed with a few coarse-grained electron-dense granules. A trio whole-genome sequencing approach identified a deleterious homozygous missense variant in DGKG (p.Thr721Ile). The allele frequency in 209 genotyped Wagyu was 7.2%. This is a report of a DGKG-related recessive inherited disorder in cattle and adds DGKG to the list of candidate genes for HFSD in other species.
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Affiliation(s)
- Joana G. P. Jacinto
- Department of Veterinary Medical SciencesUniversity of BolognaBolognaSwitzerland
- Institute of Genetics, Vetsuisse FacultyUniversity of BernBernSwitzerland
| | - Peter Wohlsein
- Department of PathologyUniversity of Veterinary Medicine HannoverHannoverGermany
| | - Irene M. Häfliger
- Institute of Genetics, Vetsuisse FacultyUniversity of BernBernSwitzerland
| | | | | | | | - Walter Grünberg
- Clinic for Cattle, University of Veterinary Medicine HannoverHannoverGermany
- Clinic for Ruminants and Herd Health Management, Justus‐Liebig University GiessenGießenGermany
| | - Cord Drögemüller
- Institute of Genetics, Vetsuisse FacultyUniversity of BernBernSwitzerland
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Fernández A, Câmara N, Sierra E, Arbelo M, Bernaldo de Quirós Y, Jepson PD, Deaville R, Díaz-Delgado J, Suárez-Santana C, Castro A, Hernández JN, Godinho A. Cetacean Intracytoplasmic Eosinophilic Globules: A Cytomorphological, Histological, Histochemical, Immunohistochemical, and Proteomic Characterization. Animals (Basel) 2023; 13:2130. [PMID: 37443929 DOI: 10.3390/ani13132130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
The nature, etiopathogenesis, and clinicopathologic relevance of the prevalent intracytoplasmic eosinophilic globules (IEGs) within hepatocytes of cetaceans are unknown. This study aims to evaluate the presence and characterize the IEGs in the hepatocytes of cetaceans using histochemical and immunohistochemical electron microscopy, Western blot, lectin histochemistry, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry techniques. A total of 95/115 (83%) animals (16 species) exhibited histologically evident intracytoplasmic round to oval, single to multiple, hyaline eosinophilic globules within the hepatocytes. These globules were largely PAS-positive, diastase resistant, and were immunopositive for fibrinogen (FB, 97%), albumin (Alb, 85%), and α1-antitrypsine (A1AT, 53%). The IEG positivity for FB and A1AT were correlated with live-stranding, hepatic congestion and a good nutritional status. The cetaceans lacking IEGs were consistently dead stranded and had poor body conditions. The IEGs in 36 bycaught cetaceans were, all except one, FB-positive and A1AT-negative. The IEGs exhibited morphologic and compositional variations at the ultrastructural level, suggesting various stages of development and/or etiopathogenesis(es). The glycocalyx analysis suggested an FB- and A1AT-glycosylation pattern variability between cetaceans and other animals. The proteomic analyses confirmed an association between the IEGs and acute phase proteins, suggesting a relationship between acute stress (i.e., bycatch), disease, and cellular protective mechanisms, allowing pathologists to correlate this morphological change using the acute hepatocytic cell response under certain stress conditions.
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Affiliation(s)
- Antonio Fernández
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Nakita Câmara
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
- The Oceanic Platform of the Canary Islands (PLOCAN), Carretera de Taliarte, s/n, 35200 Telde, Canary Islands, Spain
- Loro Parque Foundation, Avenida Loro Parque, s/n, 38400 Puerto de la Cruz, Canary Islands, Spain
| | - Eva Sierra
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Manuel Arbelo
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Yara Bernaldo de Quirós
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Paul D Jepson
- Zoological Society of London, Institute of Zoology, Regent's Park, London NW1 4RY, UK
| | - Rob Deaville
- Zoological Society of London, Institute of Zoology, Regent's Park, London NW1 4RY, UK
| | - Josué Díaz-Delgado
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Cristian Suárez-Santana
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Ayoze Castro
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
- The Oceanic Platform of the Canary Islands (PLOCAN), Carretera de Taliarte, s/n, 35200 Telde, Canary Islands, Spain
| | - Julia N Hernández
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
| | - Ana Godinho
- Veterinary Histology and Pathology, Atlantic Center for Cetacean Research, University Institute of Animal Health and Food Safety (IUSA), Veterinary School, University of Las Palmas de Gran Canaria, Calle Transmontaña, s/n, 35416 Arucas, Canary Islands, Spain
- Rua Central de Gandra, University Institute of Health Sciences (IUCS)-CESPU, 4585-116 Gandra, Portugal
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Ye F, Yue Y, Li S, Chen T, Bai G, Liu M, Zhang S. Presence of HBsAg, HBcAg, and HBVDNA in ovary and ovum of the patients with chronic hepatitis B virus infection. Am J Obstet Gynecol 2006; 194:387-92. [PMID: 16458634 DOI: 10.1016/j.ajog.2005.07.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2005] [Revised: 06/12/2005] [Accepted: 07/05/2005] [Indexed: 12/09/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the presence and distribution of Hepatitis B virus antigen (HBVAg) and Hepatitis B virus deoxyribonucleic acid (HBVDNA) in ovary with chronic hepatitis B virus. STUDY DESIGN The immunohistochemistry method and in situ hybridization method were used to detect the hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAg), and HBVDNA in ovary of patients with chronic hepatitis B infection. RESULTS HBsAg presented in the ovum-granular cell and interstitial cell of ovary. HBsAg located in the cytomembrane and cytoplasm. HBcAg presented in the ovum-granular cell-interstitial cell and endothelium cell of interstitial blood vessel of ovary, and the HBcAg may present in the ovum at different stage. HBcAg was situated at the cytomembrane, cytoplasm, and nucleus. HBVDNA was detected in the ovum at different stage as HBcAg and in granular cell, interstitial cell of ovary. In the same ovary tissue, HBVDNA was positive in some ova, but it was weakly positive or negative in other ova. HBVDNA distributed mainly in nucleus, but also can be detected in the cytoplasm. CONCLUSION HBV could infect the ovum at different stage and replicate in it. This may be an important mechanism of HBV vertical transmission.
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Affiliation(s)
- Feng Ye
- Department of Infectious Disease, The First Hospital of Xi'an Jiaotong University, Xi'an, China.
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