Eosinophilic Intracytoplasmic Inclusion Bodies Research Articles

Ocorrência de raiva em ovinos no Rio Grande do Sul

Descreve-se a ocorrência de raiva em ovinos na região Central do Rio Grande do Sul em novembro de 2003. Foram afetados dois ovinos de raça mista, um macho de três meses e uma fêmea de 2,5 anos de idade que apresentaram sinais clínicos com evolução de cinco dias e caracterizados por dificuldade de locomoção, tremores musculares, decúbito lateral, convulsões, opistótono e febre. Histologicamente havia mielomeningoencefalite não-supurativa, associada a inclusões eosinofílicas intracitoplasmáticas (corpúsculos de Negri) em neurônios nos dois ovinos afetados. Em um ovino em que o gânglio de Gasser foi examinado, havia ganglionite não-supurativa. As lesões concentravam-se predominantemente na substância cinzenta da medula espinhal, no tronco encefálico e no cerebelo. Antígeno viral foi detectado em seções selecionadas de ponte e bulbo submetidas ao teste de imuno-histoquímica utilizando anticorpo policlonal anti-ribonucleoproteína do vírus da raiva. Os casos ocorreram em meio a um surto de raiva bovina transmitida por morcegos e foram considerados, com bases epidemiológicas, como transmitidos da mesma forma, como ocorre na raiva endêmica de bovinos no Rio Grande do Sul.

Outbreak of canine distemper in domestic ferrets (Mustela putorius furo)

In 2006 an outbreak of canine distemper affected 14 young domestic ferrets in Barcelona, Spain. Their clinical signs included a reduced appetite, lethargy, dyspnoea, coughing, sneezing, mucopurulent ocular and nasal...

A Range of Histologic Findings in Infantile Digital Fibromatosis

Infantile digital fibromatosis is a benign proliferation of myofibroblasts with characteristic eosinophilic intracytoplasmic inclusion bodies. Clinically, patients present in the first several years of life with asymptomatic, smooth, flesh-colored nodules located on the dorsal or lateral aspect of the fingers or toes. The lesions have a tendency for spontaneous regression and recur over 60% of the time following excision. Observation is often recommended, while surgery is reserved for cases of rapid growth or functional impairment. We report three patients, ranging in age from 8 months to 8 years, with infantile digital fibromatosis. All three patients presented with nodules on the hands or feet and all shared histologic findings of spindle cells with characteristic inclusion bodies. Pathologic features ranged from a haphazard arrangement of spindle cells with few inclusion bodies and numerous lymphocytes to a well-organized arrangement of spindle cells with abundant inclusion bodies and rare lymphocytes. All three patients underwent excision for diagnosis or treatment of their tumors with two of the patients experiencing a recurrence.

A severe outbreak of contagious ecthyma (orf) in a free-ranging musk ox ( Ovibos moschatus) population in Norway

During July–October 2004, 19 (18 calves, 1 yearling) free-ranging musk oxen ( Ovibos moschatus) at Dovre, Norway, were observed with contagious echtyma-like lesions, and 16 of them were euthanized. Six musk oxen were subjected to necropsy, histopathological and microbiological examinations. All euthanized animals had lesions consistent with contagious ecthyma presenting as wart-like, scabby lesions on the muzzle, lips, oral mucosa and limbs to a variable extent. The histopathological examination showed pustular dermatitis characterized by epidermal proliferation, reticular degeneration, degenerating keratinocytes with intracytoplasmic eosinophilic inclusion bodies, vesicopustules, microabscesses and multifocal ulcerations in the epidermis which was covered by a serocellular crust. Pathology and bacteriology showed evidence of secondary infections in the skin and draining lymph nodes. Electron microscopy (negative staining) of lesions from four animals detected parapoxvirus with the typical arrangement of the outer protein filaments. Parapoxvirus DNA was detected in tissue samples from two examined animals by polymerase chain reaction (PCR) with primers from the B2L-gene. A DNA sequence of 326 nucleotides from the amplicon was compared with similar DNA sequences from parapoxvirus isolated from sheep, reindeer, musk ox and cattle. The outbreak was caused by a virus similar to other circulating orf virus variants in Norway. Antibodies against parapoxvirus were detected with a virus neutralization test in 3 of 35 musk oxen (8.6%) sampled at Dovre between 2004 and 2006. This is the first report of a severe outbreak of contagious ecthyma in free-ranging musk oxen.

Generalized Fatal Cowpox virus Infection in a Cat with Transmission to a Human Contact Case

A 4-month-old female domestic shorthair cat was infected by a virus of the Poxvirus family. The animal developed a severe pneumonia and generalized ulcerating lesions of the skin. Histologically, typical eosinophilic intracytoplasmic inclusion bodies indicative of an Orthopoxvirus (OPV) infection were present. The lung showed grey-white to haemorrhagic nodular lesions with a central zone of complete necrosis of alveolar and bronchial tissue. Electron microscopy from skin and lung nodules revealed typical square-shaped OPV particles. Cultivation of the virus on chorio-allantoic membranes of embryonated chicken eggs resulted in haemorrhagic plaques. Restriction enzyme analysis, PCR and sequencing of the D8L gene identified the OPV isolate as a typical Cowpox virus. It was transmitted by the cat to a human contact person who developed a local nodular dermatitis at the inoculation site in association with signs of general infection and had an increase of OPV-specific neutralizing antibodies in paired serum samples.

Interferon-α Treatment of Molluscum Contagiosum in a Patient With Hyperimmunoglobulin E Syndrome

We report widely disseminated molluscum contagiosum that occurred in a 9-year-old boy secondary to hyperimmunoglobulin E syndrome, a primary immunodeficiency disorder. Cutaneous examination revealed numerous,widespread, skin-colored to translucent, firm, umbilicated papules of varying sizes. They were distributed throughout the perineal and gluteal areas and bilaterally over his lower limbs. A biopsy specimen from his skin lesion demonstrated lobulated epidermal growth that consisted of keratinocytes with large intracytoplasmic eosinophilic inclusion bodies and a central crater. These findings were consistent with the diagnosis of molluscum contagiosum. Many treatments for his skin lesions were ineffective, including physical destruction or manual extrusion of the lesions; cryotherapy; curettage; and topical therapies with phenol, trichloroacetic acid, and imiquimod. The patient was treated successfully with subcutaneous interferon-α for 6 months without any adverse effect.

Cutaneous Tumor-like Lesions Associated With Poxvirus Infection in Laughing Doves (Streptopelia senegalensis)

Cutaneous, tumor-like nodules were observed on the digits and distal wings in 6 of 52 laughing doves (Streptopelia senegalensis) kept in an aviary. The nodules were surgically removed, and the birds were treated postoperatively with tetracycline. Histopathologic examination of the resected tissue revealed eosinophilic intracytoplasmic inclusion bodies associated with a heavy infiltration of heterophils, lymphocytes, and fewer plasma cells. Electron microscopy revealed pox virions. No additional cases were reported after the birds were surgically treated and quarantined from the remainder of the aviary. The location of lesions on the digits and distal wing tips is unusual for poxvirus. To our knowledge, infection with poxvirus has not previously been diagnosed or reported in wild birds in the Sultanate of Oman.

Immunohistochemical detection of ubiquitin‐positive intracytoplasmic eosinophilic inclusion bodies in diffuse alveolar damage

To clarify the relationship between ubiquitin-positive pneumocytes and intracytoplasmic eosinophilic inclusion bodies (IB) in patients who died of diffuse alveolar damage (DAD). Eighteen patients with DAD were studied, in whom hyaline membranes were present in one or more out of five sections from each lobe of the lungs and 15 patients with no DAD. Light microscopy revealed hyaline membrane in over 25% of lobes from 18 patients with DAD. The cytoplasm of pneumocytes from six of 18 cases of DAD contained IB. Immunohistochemically, all IBs were characteristically positive for both ubiquitin (Ub) and cytokeratin KL-1. Cytoplasmic granules were also Ub+ in four cases of DAD without IB. IB+ or Ub+ pneumocytes were undetectable in non-DAD patients. We evaluated DAD severity based on hyaline membrane formation; the mean score in DAD with IB (3.60; n = 6) was significantly higher than that in Ub- (2.92; n = 8). Ub+ pneumocytes were found with or without IB among those cases with high DAD scores. These findings suggest that disordered proteolysis in the Ub-mediated proteasome system leads to the accumulation of abnormal ubiquitinated protein, which includes cytokeratin, in pneumocytes. This is the first report to suggest that Ub+ pneumocytes are associated with disease severity in patients with DAD.

高齢者びまん性肺胞傷害におけるユビキチン陽性細胞についての研究

The ubiquitin proteasome system (UPS) is important because homeostasis through proteolysis and ubiquitin (Ub) has been observed to appear in diseases of the central nervous system. However, studies on UPS in relation to pulmonary diseases are few and no other investigators have described Ub-positive cells in the lung. Intracytoplasmic eosinophilic inclusion bodies in pneumocytes have been known to appear in cases of diffuse alveolar damage (DAD). We found that these inclusion bodies in DAD were positive for Ub. In this study, DAD cases in the elderly were studied to clarify the relationship between Ub-positive cells and cellular damage in the lungs. Representative lung fields from a total of 26 patients with DAD were studied immunohistochemically, using Ub staining. The severity of DAD was evaluated after each case was scored for hyaline membrane formation and lung injury, respectively. Non-DAD diseases from 19 autopsy cases were studied as controls. The mean age of both groups was 72.1. Variably sized and shaped eosinophilic inclusion bodies were found in 7 cases (26.9%) of the DAD cases (inclusion body group) and all inclusion bodies were positive for Ub and cytokeratin KL-1. Pneumocytes without inclusion bodies were occasionally positive for Ub, with an intracytoplasmic granular pattern, not only in the inclusion body group but also in the non-inclusion body group (4 of DAD cases). These Ub-positive cells (both Ub-positive inclusion bodies and the granular Ub-positive cells) were found to have high rate of hyaline membrane formation and lung injury in the DAD cases. Elderly DAD cases had Ub-positive inclusion bodies in pneumocytes and Ub-positive pneumocytes were found with or without the inclusion bodies in DAD. This means that accumulation of ubiquitinated protein including cytokeratin could be recognized as inclusion bodies in pneumocytes. The presence of these Ub-positive cells might be a morphological indicator for evaluation of cellular damage in the patients with DAD.

POXVIRUS INFECTION OF STELLER SEA LIONS (EUMETOPIAS JUBATUS) IN ALASKA

Lesions suggestive of poxvirus infection were observed in two Steller sea lions (Eumetopias jubatus) in Alaska during live capture-and-release studies during 2000 and 2001. Both of these animals, female pups in poor body condition, were from Prince William Sound; this population is part of the declining western stock. Umbilicated, typically ulcerated dermal nodules were present, primarily on the fore flippers in one case, and over most of the body in the second case. Histologically, there were discrete masses in the superficial dermis composed of epithelial cells, some of which contained eosinophilic intracytoplasmic inclusion bodies. Negative staining of skin biopsy homogenates demonstrated the presence of orthopoxvirus-like particles. Total DNA extracted from skin biopsies were analyzed by polymerase chain reaction (PCR) using primers that targeted the DNA polymerase and DNA topoisomerase genes. These primers directed the amplification of fragments 543 base pairs (bp) and 344 bp, respectively, whose deduced amino acid sequences indicated the presence of a novel poxvirus within the Chordopoxvirinae subfamily. Comparison of these amino acid sequences with homologous sequences from members of the Chordopoxvirinae indicated highest identity with orthopoxviruses.

Contagious Mucocutaneous Dermatitis of the Mountain Hare (Lepus timidus): Pathology and Cause

Contagious mucocutaneous dermatitis is a frequently encountered disease of mountain hares (Lepidus timidus) in Finland. We describe the histopathologic changes and propose an etiologic cause for this disorder. Fifty-three cases collected during 1982-2000 were examined histologically. Transmission electron microscopy was performed in one case. In fully developed lesions, keratinocytes in epidermis and follicular infundibula were swollen and contained large eosinophilic intracytoplasmic inclusion bodies with marked reticular and ballooning degeneration. In later stages, there was marked necrosis and ulceration with severe pyogranulomatous and suppurative inflammation. At this stage, no viral inclusions were detectable, but secondary Staphylococcus warnerii infection was present in most cases. In late lesions, there was dermal fibrosis with epidermal hyperplasia. No spiral-shaped bacteria suggesting treponematosis were detected at any stage. Ultrastructurally, swollen epidermal and follicle infundibular cells contained round intracytoplasmic inclusion bodies with a myriad of virions typical of poxvirus with a biconcave nucleocapsid core, two lateral bodies, and a clearly discernible outer lipoprotein capsule. The findings suggest that contagious mucocutaneous dermatitis in mountain hares is a viral disease caused by a poxvirus. The disease is often complicated by secondary bacterial infection, most commonly S. warneri.

Intralesional Fluorouracil Injection in Infantile Digital Fibromatosis

A 7-year-old Korean girl presented with an 8-month history of an erythematous hard plaque on her left hand. There was no history of trauma. On physical examination, a 1.4 0.8-cm firm plaque was observed on the ulnar surface of the left hand at the metacarpophalangeal level (Figure). Histopathologic examination showed moderately cellular fibroblasts throughout the dermis. Hematoxylineosin staining revealed eosinophilic intracytoplasmic inclusion bodies in fibroblasts. The inclusions stained bright red with Masson trichrome and deep purple with phosphotungstic acid–hematoxylin. They were negative for alcian blue and periodic acid–Schiff.

Extensive Lesions of Monkeypox in a Prairie Dog (Cynomys sp.)

Monkeypox with extensive lesions was diagnosed in a prairie dog that was involved in a recent human outbreak of monkeypox in the Midwestern United States. Gross lesions included oral ulcers, pulmonary consolidation, enlarged cervical and thoracic lymph nodes, and multifocal, small, white umbilicated plaques in the gastrointestinal wall. Microscopic lesions were extensive in the lungs and consisted of fibrinonecrotic bronchopneumonia with vasculitis and poorly defined eosinophilic intracytoplasmic inclusion bodies in cells thought to be alveolar epithelial cells, histiocytes, and fibroblasts. Multifocal necrotizing lesions, often accompanied by myxedema, were also present in most of the other examined organs. Aggregates of pox viral particles were observed within lesions by transmission electron microscopy. Monkeypox virus infection was confirmed by real-time polymerase chain reaction and virus culture at the Centers for Disease Control and Prevention. This report highlights the difficulties of rapid diagnosis of exotic or emerging diseases and further substantiates the prairie dog as an animal model of monkeypox.

Pulmonary Large Cell Carcinoma with Rhabdoid Phenotype

A 70-year-old woman presented with a coin lesion in her left lung. The tumor was well circumscribed and had a large area of central necrosis with a thin rim of viable tumor cells. It showed a solid growth pattern of polygonal cells with eosinophilic intracytoplasmic inclusion bodies. Immunohistochemically, the tumor cells were positive for vimentin, neural cell adhesion molecule, neuron-specific enolase, and vascular endothelial growth factor. Electron microscopy revealed intracytoplasmic inclusion bodies consisting of whorled intermediate filaments. Based on histological and immunohistochemical findings, the patient was diagnosed as having pulmonary large cell carcinoma with rhabdoid phenotype (LCCRP). The patient was in stage IA, and the histological findings may be the prototype of pure LCCRP. The tumor recurred after 6 years, and the second tumor had more apparent intracytoplasmic inclusion bodies. It is worthwhile detecting and recognizing the significance of these intracytoplasmic inclusions because of the poor prognosis of this tumor.

Histopathological Studies of Fowl Pox in Bantams

There was an outbreak of avian pox infection in a flock of bantams (Gallus domesticus) with gross lesions of erosions, crusts and nodules on the comb, eyelids, oral mucosa, legs and toes. In histopathological study eosinophilic intracytoplasmic inclusion bodies were visualized by light microscope in epithelial cells of the cutaneous nodules. Electron microscopy revealed numerous pox virions in the inclusion body.

Rapid purification and analysis of alpha-synuclein proteins: C-terminal truncation promotes the conversion of alpha-synuclein into a protease-sensitive form in Escherichia coli.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons and the formation of eosinophilic intracytoplasmic inclusion bodies known as Lewy bodies. Although alpha-synuclein is known to be a pivotal factor implicated in the pathogenesis of PD, its function remains to be elucidated. We used the pGEX expression system to develop a simple and rapid method for purifying alpha-synuclein proteins in suitable forms for biochemical studies of their functions. The wild-type alpha-synuclein protein was overexpressed in Escherichia coli and purified to approx. 80% purity with relatively high yields. We also used this expression system to investigate the expression pattern of the various domains of alpha-synuclein. With the exception of the alpha-synuclein protein that was truncated at amino acid residue 95, all domain constructs of alpha-synuclein were purified at similar levels with relatively high yields. Unexpectedly, removal of amino acid residues 96-140 in the C-terminal acidic region of alpha-synuclein promotes its conversion to a protease-sensitive form during expression and purification in E. coli. Our study suggests a method for generating useful reagents to investigate the molecular mechanism by which alpha-synuclein regulates the pathogenesis of PD.

Oroesophageal Adenovirus-like Infection in a Palm Viper, Bothriechis marchi, with Inclusion Body-like Disease

ABSTRACT An adult, captive-born palm viper, Bothriechis marchi, was found dead in its enclosure. Histologically, there were eosinophilic intracytoplasmic inclusion bodies within epithelial cells in the stomach, intestine, lung, trachea, and esophagus. In addition, there were basophilic intranuclear inclusion bodies in mucosal epithelial cells lining the oral cavity and esophagus with multifocal subacute esophagitis and stomatitis. Electron microscopy of the intranuclear inclusion bodies revealed crystalline arrays of hexagonal, 65 - 68 nm, particles morphologically consistent with Adenovirus. This palm viper was diagnosed with inclusion body-like disease, as previously reported in palm vipers, with concurrent esophagitis and stomatitis due to infection with adenovirus-like particles.

Morbilliviral Dermatitis in Seals

A juvenile female hooded seal (Cystophora cristata) and a juvenile male harp seal (Phoca groenlandica) stranded separately on the New Jersey (USA) coast and were taken to a marine mammal rehabilitation center. Both were lethargic and emaciated, had dermatitis, and died. Histologic skin lesions in the seals were similar and consisted of epidermal and follicular epithelial hyperplasia, hyperkeratosis, degeneration, and necrosis. The most distinctive finding was extensive syncytial zones bounded superficially by hyperkeratosis and deeply by hyperplastic basal cells. Eosinophilic intracytoplasmic inclusion bodies were present in epithelial cells. Morbilliviral antigen was demonstrated in the skin lesions by immunohistochemistry. Phocine distemper virus was detected in the skin by reverse transcription polymerase chain reaction and a phocine distemper virus-specific probe using the Southern blot technique. This is the first report of morbilliviral dermatitis in marine mammals.

Concurrent Coccidiosis and Bovine Papular Stomatitis Infection in Calves

Seifi, H.A., Movassaghi, A.R., Mohri, M., Rad, M., Aslani, M.R., Parand, A. and Razmi, Gh. 2000. Concurrent coccidiosis and bovine papular stomatitis infection in calves. J. Appl. Anim. Res., 18: 103–108. A group of 23 calves (2–3 months) showed diarrhoea after weaning and short distance transportation. Buccal cavity lesions of papular nature on the muzzle, gingivae, buccal papillae, inner surface of the lips and hard palate were observed. Buccal cavity lesions showed hyperplastic epithelium which consisted of focal areas of ballooning degeneration. Eosinophilic intracytoplasmic inclusion bodies, characteristic of bovine papular stomatitis were seen in the affected cells. At necropsy, sexual and asexual forms of coccidia were determined on the epithelium of the caecal and colonic crypts. Large number of oocysts were detected on the faecal examination. All the affected calves were treated by intramuscular injection of sulphadimidine. Newly weaned calves were fed lasolosid as prophylaxis. One month after the onset of outbreak, the syndroṁe subsided.

Listeriosis in a raccoon dog (Nyctereutes procyonoides) associated with canine distemper.

A wild raccoon dog (Nyctereutes procyonoides) that manifested severe illness and died was examined. Necropsy revealed severe emaciation, systemic icterus and petechial hemorrhages on the mucous membranes. Histopathologically, necroses were seen in the liver and brain stem associated with meningitis. Eosinophilic intranuclear inclusion bodies were observed in the spleen and intestinal mucosa, and eosinophilic intracytoplasmic inclusion bodies were seen in transitional epithelium in the bladder. Listeria monocytogenes 4b was isolated from the liver, spleen, kidneys and lungs, and the pathogen was also detected in the liver and brain stem immunohistopathologically. The disease was diagnosed as listeriosis associated with canine distemper virus infection in a raccoon dog.