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Biomedical subjects

I Mikaelian

Publications and source records attributed to I Mikaelian.

At least 19 recordsLinked to original sources

Expression of terminal differentiation proteins defines stages of mouse mammary gland development.

Immunohistochemical analysis using paraffin-embedded specimens is the method of choice to evaluate protein expression at a cellular level while preserving tissue architecture in normal and neoplastic tissues. Current knowledge of the expression of terminal differentiation markers in the mouse mammary gland relies on the evaluation of frozen tissues by use of immunofluorescence. We assessed changes in patterns of expression of terminal differentiation markers throughout the development of the mouse mammary gland in paraffin-embedded tissues. The expression of alpha-smooth muscle actin (SMA) and keratins (K) 5, 8/18, and 14 was influenced by the development stage of the mammary gland. Expression of K5 and SMA was restricted to basal cells. Keratin 14 was consistently expressed by mammary basal cells, and was detected in scattered luminal cells from 13.5 days after conception through puberty. Labeling for K8/18 of luminal cells was heterogeneous at all times. Heterogeneous expression patterns in luminal cells suggest this layer has cells with a variety of biological functions. The absence of K6 expression at any stage of the development of the mammary gland was confirmed by use of reverse transcriptase-polymerase chain reaction analysis, which indicates that this intermediate filament is not a marker of the mammary gland stem cell. Finally, consistent with results of earlier studies, keratins 1, 10, 13, and 15, and filaggrin, involucrin, and loricrin were not detected at any stage of mammary gland development.

Actins↗

Follicular stem cell carcinoma: histologic, immunohistochemical, ultrastructural, and clinical characterization in 30 dogs.

Diagnostic records of 30 primary and one metastatic follicular stem cell carcinomas in 30 dogs were reviewed. Neoplastic cells had a clear cytoplasm and formed lobules and nests surrounded by a basement membrane. Trichoepitheliomatous and apocrine differentiations were noted in 22 of 30 (73%) and 21 of 30 (70%) primary tumors, respectively. Glycogen was present in 20 of 20 (100%) tumors tested, suggesting tricholemmal differentiation. Antibodies against AE1/AE3 cytokeratin, vimentin, and melanA/MART1 stained 29 of 30 (97%), 29 of 30 (97%), and 12 of 27 (44%) primary tumors, respectively. Small amounts of melanin were identified in 14 primary tumors, either on the hematoxylin and eosin-stained section (n = 6), or on the Fontana-stained section (n = 8 of 14). Ultrastructural features of neoplastic cells included cell junction complexes, swollen mitochondria, neuroendocrine-like granules, and intracytoplasmic non-membrane-bound accumulation of proteinaceous material. Features of this neoplasm are consistent with a follicular stem cell origin. Follow-up information was available for eight dogs. Metastases developed in the draining lymph node at the time of excision of the primary tumor (n = 1) or subsequently (n = 3).

Animals↗

Cutaneous smooth muscle tumors in the dog and cat.

Cutaneous smooth muscle tumors may arise from arrector pili muscles and from smooth muscles of the dermal vasculature. This report describes histologic and immunohistochemical features of eight arrector pili hamartomas in 8 dogs, 15 piloleiomyomas in 10 dogs and 3 cats, 10 piloleiomyosarcomas in 9 dogs and 1 cat, 1 angioleiomyoma in 1 cat, and 9 angioleiomyosarcomas in 6 dogs and 3 cats. Hamartomas and tumors arising from arrector pili muscles preferentially originated from the dorsal trunk. 5/5 (100%) arrector pili hamartomas, 10/12 (83%) piloleiomyomas, 4/5 (80%) piloleiomyosarcomas, 1/1 (100%) angioleiomyoma, and 6/7 (86%) angioleiomyosarcomas were positive for smooth muscle actin. 5/5 (100%) arrector pili hamartomas, 10/12 (83%) piloleiomyomas, 4/5 (80%) piloleiomyosarcomas, 1/1 (100%) angioleiomyoma, and 1/7 (14%) angioleiomyosarcomas were positive for desmin. Two incompletely excised canine angioleiomyosarcomas recurred locally. Metastases were not reported.

Animals↗

Adenomatous hyperplasia of the thyroid gland in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary and Hudson Bay, Quebec, Canada.

We evaluated thyroid gland lesions in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary (n = 16) and Hudson Bay (n = 14). Follicular cysts and nodules of adenomatous hyperplasia of the thyroid gland were found in eight and nine adults from the St. Lawrence Estuary (n = 10), respectively, and in four and six adults from Hudson Bay (n = 14), respectively. The total volume of the lesions of thyroid adenomatous hyperplasia was positively correlated with age in both populations. Comparison between populations could not be performed because of differences in age structures of sample groups. Beluga whales from both populations have unique thyroid lesions among marine mammals.

Age Factors↗

Cutaneous fibropapilloma in a mountain lion (Felis concolor).

A 12-yr-old mountain lion (Felis concolor) developed a 0.5-cm3 raised nonpigmented and nonulcerated mass between the lip and the nasal planum. The tumor was surgically removed and diagnosed histologically as a fibropapilloma. The tumor recurred 1 yr later, at which time it was again excised, and the diagnosis was reconfirmed by biopsy. Frozen tissue from the second excision was submitted for polymerase chain reaction testing for papillomavirus. The 176-base pair polymerase chain reaction product recovered from the tumor was cloned and sequenced. The papillomavirus had 96% homology with a papillomavirus previously retrieved from a fibropapilloma in a domestic cat and is the next most closely related to bovine papillomavirus type 1. This is the first report of a virus-associated fibropapilloma in a mountain lion.

Animals↗

Keloidal fibromas and fibrosarcomas in the dog.

Sixteen dogs (2-12 years of age) presented with one (n = 15) or two (n = 1) cutaneous nodules (n = 16) or a dermal plaque (n = 1). Intact males (n = 9) and neutered males (n = 4) were more affected than were females (n = 3). Histologically, these lesions were characterized by focal dermal and subcutaneous deposition of thick hyalinized collagen fibers intermingled with fibroblasts, and in 13 of 17 lesions, a variable number of CD18-positive cells were interpreted as reactive macrophages. Fibroblasts in three dogs formed intersecting fascicles, interpreted as evidence of malignant transformation. The terms keloidal fibroma and keloidal fibrosarcoma can be applied to these lesions. Excision was curative in five dogs with keloidal fibroma for which follow-up was available. However, because malignant transformation may occur, wide excision of canine keloidal lesions is warranted.

Animals↗

Organotins in zebra mussels (Dreissena polymorpha) and sediments of the Quebec City Harbour area of the St. Lawrence River.

Toxic antifouling agents such as tributyltin (TBT) and triphenyltin (TPT) have been released in aquatic ecosystems through the use of antifouling paint applied to ship hulls, pleasure crafts and fish nets and these compounds can bioaccumulate in aquatic organisms. The purpose of this study was 1) to assess the extent of the distribution of organotins from a contaminated marina to the St. Lawrence River system by measuring organotin concentrations in zebra mussels (Dreissena polymorpha) and in sediments collected from 9 sites along the St. Lawrence River near Quebec City in July 1998, and 2) to examine the histopathological condition of zebra mussel tissues from these sites. TBT concentrations in zebra mussels were between 37 and 1078 ng Sn g(-1) wet weight, with the highest value found in the Bassin Louise marina. Elevated concentrations were also found in two other marinas. The concentrations decreased sharply to background levels just outside the marinas. All butyltins were detected in all sediments analysed, with highest values found in the Bassin Louise marina. Phenyltins were detected in three of the nine sites in low concentrations (<55 ng Sn g(-1)) in zebra mussels. There was a significant correlation between TBT in sediments and mussels. Gonadal development of zebra mussels varied largely between sites, and was negatively associated to TBT levels in mussel tissue. This study shows that TBT contamination remains a problem in localised freshwater sectors of the St. Lawrence River.

Animals↗

Dermatophilus-like infection in beluga whales, Delphinapterus leucas, from the St. Lawrence estuary.

Six beluga whales (Delphinapterus leucas) found dead on the shores of the St. Lawrence estuary had multiple slightly depressed greyish round areas randomly distributed over the whole body. Histologically, the surface of these areas was covered with a thick layer of Dermatophilus-like organisms which invaded the stratum corneum. The underlying stratum spinosum had marked spongiosis and vacuolar degeneration. Minimal neutrophilic infiltration was present within the underlying dermal papillae. To the authors' knowledge, dermatophilosis in cetaceans has not been reported previously.

Animals↗

Seroprevalence of antibodies to Toxoplasma gondii in lynx (Lynx canadensis) and bobcats (Lynx rufus) from Québec, Canada.

The seroprevalence of antibodies to Toxoplasma gondii was investigated in trapped lynx (Lynx canadensis) and bobcats (Lynx rufus) from Québec, Canada. Forty-seven of 106 (44%) lynx and 4 of 10 (40%) bobcats had positive titers for T. gondii (> or = 25) by means of the modified agglutination test incorporating mercaptoethanol and formalin-fixed tachyzoites. Seroprevalence was significantly higher (P < 0.0001) in adult lynx than in juvenile lynx. The presence of antibodies to T. gondii in lynx and bobcats suggests that this organism is widespread in the wild and that exposure to wild felids and game animals from Québec may represent a potential source of infection for humans.

Age Factors↗

Adenocarcinoma of the small intestine in a ringed seal from Hudson Bay.

Nineteen wild ringed seals (Phoca hispida) were killed in winter 1999 to assess the health status of seals harvested in eastern Hudson Bay (Quebec, Canada). One of these seals, an 11-yr-old male, had a poorly differentiated adenocarcinoma that severely constricted the lumen of the distal small intestine. The tumor was characterized by proliferation of polygonal epithelial cells that formed closely packed acini and cords. This appears to be the first reported case of adenocarcinoma of the small intestine in Pinnipedia.

Adenocarcinoma↗

Mycoplasmosis in evening and pine grosbeaks with conjunctivitis in Quebec.

An outbreak of conjunctivitis affected evening grosbeaks (Coccothraustes vespertinus) and pine grosbeaks (Pinicola enucleator) in Quebec (Canada) during the winter 1998-99. One to 30% of the individuals from these two species were sick at 13 feeding stations. Sick birds were thin and had unilateral or bilateral catarrhal and lymphoplasmacytic conjunctivitis and rhinitis, and mucopurulent infra-orbital sinusitis. Mycoplasmal organisms were isolated in cultures in an affected evening grosbeak and identified as Mycoplasma gallisepticum by direct immunofluorescence. Random amplified polymorphic DNA (RAPD) fingerprinting of this isolate resulted in a banding pattern that was identical to patterns of M. gallisepticum isolates made from similar lesions in house finches (Carpodacus mexicanus) and American gold finches (Carduelis tristis) throughout eastern North America. Mycoplasma gallisepticum was identified by polymerase chain reaction in another evening grosbeak and a pine grosbeak. These observations suggest that the same strain of M. gallisepticum is the likely etiology for the observed disease in evening and pine grosbeaks in Canada and represent an extension of the host-species range for the ongoing epidemic of M. gallisepticum conjunctivitis in eastern North America.

Animals↗

Ichthyophonus-like infection in wild amphibians from Québec, Canada.

Myositis associated with infection by Ichthyophonus-like organisms was diagnosed in 35 of 260 (13%) wild amphibians collected in Quebec, Canada, from 1959 to 1964 (n = 30), and 1992 to 1999 (n = 230). Infection was diagnosed in 17 green frogs Rana clamitans, 9 wood frogs R. sylvatica, 4 red-spotted newts Notophthalmus viridescens, 3 bullfrogs R. catesbeiana, 1 spring peeper Pseudacris crucifer, and 1 pickerel frog R. palustris. The spring peeper and one of the bullfrogs were collected in 1964 from the Mont Saint-Hilaire Biosphere Reserve, indicating long-term presence of the organism. Spores of the organisms invaded striated muscle fibers and were associated with variable degrees of granulomatous and eosinophilic inflammation. Infection was considered fatal in 2 green frogs, 1 wood frog, and 1 red-spotted newt. It was considered potentially significant in 3 additional green frogs in which up to 100% of the fibers of some muscles were replaced by spores associated with a severe granulomatous reaction. Ultrastructural features of Ichthyophonus-like spores included a thick trilaminated wall, a paramural cytoplasm, multiple nuclei, oval mitochondria with short tubulo-vesicular cristae and numerous ribosomes. This report represents 4 new host records and shows that ichthyophonosis is enzootic in amphibians from Quebec.

Amphibians↗

Suprasellar germinoma in three lake whitefish (Coregonus clupeaformis).

Suprasellar germinomas were identified in three wild-caught lake whitefish (Coregonus clupeaformis) from the St. Lawrence River, Quebec, Canada. Histologically, the three tumors expanded the subarachnoid space of the ventral surface of the brain immediately adjacent to the pituitary gland and, in one case, infiltrated the adjacent neuropil. These tumors were characterized by nests and sheets of round cells with a high mitotic rate, separated by a scant amount of loose fibrovascular stroma. The stroma was infiltrated by a moderate number of small mononuclear cells, including rare CD3-immunoreactive lymphocytes. This is the first report of intracranial germinoma in a fish species.

Animal Diseases↗

Toxoplasmosis in beluga whales (Delphinapterus leucas) from the St Lawrence estuary: two case reports and a serological survey.

Toxoplasmosis was diagnosed in two free-ranging beluga whales from the St Lawrence estuary, Quebec, Canada, in 1988 and 1998. Histologically, tachyzoites and bradyzoites were present in the brain, spleen, lymph nodes, adrenals and lungs of both animals, and in the thymus of one. These organisms were readily labelled by an indirect immunohistochemical method for Toxoplasma gondii antigens. In the lymph nodes, spleen and lungs the organisms were associated with histiocytic infiltration. In the brain of one animal they were associated with mild multifocal gliosis and haemorrhages. There was no evidence of concomitant morbillivirus infection. Serum samples were collected from 22 beluga whales stranded between 1995 and 1998 on the shores of the St Lawrence Estuary and examined for antibodies to T. gondii by the modified agglutination test. Antibody titres of s25 were found in six (27%) of the animals. This is the first confirmed report of toxoplasmosis in beluga whales.

Animals↗

Epstein-Barr virus EB2 protein exports unspliced RNA via a Crm-1-independent pathway.

Human herpesviruses encode posttranscriptional activators that are believed to up-regulate viral replication by facilitating early and late gene expression. We have reported previously that the Epstein-Barr virus protein EB2 (also called M or SM) promotes nuclear export of RNAs that are poor substrates for spliceosome assembly, an effect that closely resembles the human immunodeficiency virus type 1 Rev-dependent nuclear export of unspliced viral RNA. Here we present experimental data showing that EB2 efficiently promotes the nuclear export of unspliced RNA expressed from a Rev reporter construct. Site-directed mutagenesis as well as domain swapping experiments indicate that a leucine-rich region found in the EB2 protein, which matches the consensus sequence for the leucine-rich nuclear export signal, is not a nuclear export signal per se. Accordingly, leptomycin B (LMB), a specific Crm-1 inhibitor, impairs Rev- but not EB2-dependent nuclear export of unspliced RNA. Moreover, EB2 nucleocytoplasmic shuttling visualized by a heterokaryon assay is, unlike Rev shuttling, not affected by LMB. We also show that overexpression of an N-terminal deletion mutant of Nup214/can, a major nucleoporin of the nuclear pore complex involved in several aspects of nuclear transport, blocks both Rev- and EB2-dependent nuclear export of RNA. These results strongly suggest that EB2 nuclear export of unspliced RNA is mediated by a Crm-1-independent pathway.

3T3 Cells↗

Fibroleiomyomas of the tubular genitalia in female beluga whales.

Fibroleiomyomas of the tubular genitalia were diagnosed in 6 of 9 adult female beluga whales from the St. Lawrence estuary, Quebec, Canada. These tumors were located in the vagina (6 of 6), the cervix (2 of 6), and the uterus (1 of 6). Endogenous hormones or xeno-estrogens may be implicated in the occurrence of these tumors.

Animals↗

Feline papillomas and papillomaviruses.

Papillomaviruses (PVs) are highly species- and site-specific pathogens of stratified squamous epithelium. Although PV infections in the various Felidae are rarely reported, we identified productive infections in six cat species. PV-induced proliferative skin or mucous membrane lesions were confirmed by immunohistochemical screening for papillomavirus-specific capsid antigens. Seven monoclonal antibodies, each of which reacts with an immunodominant antigenic determinant of the bovine papillomavirus L1 gene product, revealed that feline PV capsid epitopes were conserved to various degrees. This battery of monoclonal antibodies established differential expression patterns among cutaneous and oral PVs of snow leopards and domestic cats, suggesting that they represent distinct viruses. Clinically, the lesions in all species and anatomic sites were locally extensive and frequently multiple. Histologically, the areas of epidermal hyperplasia were flat with a similarity to benign tumors induced by cutaneotropic, carcinogenic PVs in immunosuppressed human patients. Limited restriction endonuclease analyses of viral genomic DNA confirmed the variability among three viral genomes recovered from available frozen tissue. Because most previous PV isolates have been species specific, these studies suggest that at least eight different cat papillomaviruses infect the oral cavity (tentative designations: Asian lion, Panthera leo, P1PV; snow leopard, Panthera uncia, PuPV-1; bobcat, Felis rufus, FrPV; Florida panther, Felis concolor, FcPV; clouded leopard, Neofelis nebulosa, NnPV; and domestic cat, Felis domesticus, FdPV-2) or skin (domestic cat, F. domesticus, FdPV-1; and snow leopard, P. uncia, PuPV-2).

Animals↗