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Biomedical subjects

D M Albert

Publications and source records attributed to D M Albert.

At least 91 records · Page 5Linked to original sources

Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different lines of transgenic mice.

BACKGROUND: We compared the molecular phenotypes of central nervous system tumors arising in four different lines of transgenic mice (TGM) carrying the Simian virus 40 large T antigen driven by different promoters or enhancers. Two of the four lines developed primitive neuroectodermal tumors (PNETs) in the brain stem or pineal gland. A third TGM line developed retinoblastomas (a PNET-like tumor of the retina) as well as PNETs in the mesencephalon, while the fourth TGM developed retinoblastomas and adrenal pheochromocytomas. EXPERIMENTAL DESIGN: The expression of developmentally regulated polypeptides specific for the neuronal or glial lineage was examined in these PNETs using immunohistochemistry and Western blotting. RESULTS: Neoplastic cells in all of the PNETs exhibited neuronal, but no glial specific markers as evidenced by the invariable expression of synaptophysin, but no detectable glial fibrillary acidic protein or myelin basic protein. PNETs with a more differentiated neuronal phenotype expressed multiple neuronal polypeptides. The phenotypic properties of these PNETs closely resembled those found in human brain PNET biopsy samples and cell lines derived therefrom. CONCLUSIONS: We conclude that Simian virus 40 T antigen-induced PNETs in TGM exhibit the molecular phenotype of developing neurons or neuronal progenitor cells. Although many factors could influence the phenotype of these experimental PNETs (e.g., promoter, site of integration of the transgene) these PNETs appear to be suitable TGM models of human PNETs of the central nervous system.

Adrenal Gland Neoplasms↗

Adenovirus E1A expression controlled by the red pigment promoter in transgenic mice: a model for developmental abnormalities of the eye.

Four transgenic founder mice were produced that carry the adenovirus E1A gene under control of the human red pigment promoter. Two of the founder animals passed the transgene to progeny, and one line was bred to homozygosity. The line of mice homozygous for the transgene expressed E1A-specific RNA at a low level in their eyes; no expression could be detected in other tissues that were tested. Either the founder animals or their progeny exhibited developmental abnormalities of their eyes, including a small eye phenotype, retinal dysplasia, anterior cleavage syndrome, and retinal pigment epithelium dysplasia. Individuals from the same line of mice exhibited subsets of the abnormalities, e.g., many animals had one normal size eye and one small eye, even though both eyes contained E1A-specific RNA. No tumors resulted from E1A expression in animals monitored for 22 months.

Adenovirus E1A Proteins↗

Expression of retina-specific genes by mouse retinoblastoma cells.

PURPOSE: Two cell lines derived from ocular tumors of a transgenic mouse expressing the SV40 large T antigen have been established as models of human retinoblastoma. One line, TM, originated from a metastasis, and the other, TE, originated from the primary tumor. The authors compared these two lines with the normal adult mouse eye by analysis of the expression of five photoreceptor cell-specific proteins: IRBP, opsin, rod- and cone-specific transducins, and S-antigen. The authors sought to determine which of these proteins was expressed qualitatively and to examine semi-quantitatively for changes in the levels of expression in the cell lines. METHOD: Western blot analysis was used to detect photoreceptor-specific intracellular or secreted proteins. Total RNA was prepared from cultured cells or from mouse adult whole eye. Specific messenger levels in total RNA were determined either by northern hybridization analysis or by a semi-quantitative polymerase chain reaction (PCR), coupled to complementary DNA (cDNA) substrates prepared from total RNA. RESULTS: IRBP was present in the retinoblastoma cell lines and secreted into the medium. Neither S-antigen nor opsin were detectable by immunoblotting. IRBP and cone transducin mRNA were present in both cell lines. In contrast, opsin, rod transducin, and S-Antigen mRNAs were not detectable by PCR. beta-actin was present in the mRNA populations of whole eye and retinoblastoma. SV40 large T antigen mRNA was present only in retinoblastoma cells. CONCLUSIONS: IRBP and cone transducin expression in mouse retinoblastoma cells is independent of signaling provided directly or indirectly through large T antigen or Rb105 regulatory cascades. The pattern of photoreceptor-specific gene expression is similar to that seen in human retinoblastoma cell lines. These murine-derived cell lines may be useful as a tool to study IRBP and cone transducin expression in vitro and to determine early retinoblast expression patterns in the mouse.

Animals↗

Photoreceptor cell tumors in transgenic mice.

PURPOSE: To produce transgenic mice that express the SV40 T-antigen oncogene specifically in photoreceptor cells, giving rise to retinoblastoma tumors of photoreceptor cell origin; to characterize the mice with regard to transgene expression and pathology and to characterize the resulting tumors histologically. METHODS: Transgenic mice were generated that express T-antigen under the control of the murine interstitial retinol binding protein promoter. RESULTS: All mice produced developed either ocular or intracranial tumors, or both, at an early age. One line of mice was generated, and all mice of this line develop both retinal photoreceptor cell and pineal tumors by as early as 2 weeks of age. Cell lines have been established from both tumor types. CONCLUSIONS: These mice represent an animal model system for human trilateral retinoblastoma, in which retinoblastomas are accompanied by pineal tumors.

Animals↗

Nucleolar organizer regions in determining malignancy of pigmented conjunctival lesions.

We assessed the usefulness of silver staining of nucleolar organizer regions in the diagnosis of pigmented conjunctival tumors. Fifty-one biopsy specimens were silver stained to identify the nucleolar organizer regions. Nineteen nevi without atypia, three nevi with atypia, eight primary acquired melanosis lesions, and 14 melanomas were studied. In each specimen, silver staining of the nucleolar organizer regions was counted in 100 cells to yield an average of the silver staining of the nucleolar organizer region count. The mean silver staining of the nucleolar organizer region counts per cell was correlated with the degree of malignancy of pigmented conjunctival lesions as follows: nevi, 3.0; primary acquired melanosis, 3.2; nevi with atypia, 3.9; primary acquired melanosis with atypia, 5.0; and melanoma, 5.7 (Spearman correlation [rS] = .83, P = .0001; analysis of variance [ANOVA] F test = 20.9, P = .0001). A cutoff value of 4.0 (mean silver staining of nucleolar organizer regions per cell) will differentiate melanoma and primary acquired melanosis with atypia from other lesions (sensitivity, 100%; specificity, 96%). The silver staining of nucleolar organizer regions is a useful adjunct in determining the malignancy of pigmented conjunctival tumors.

Adolescent↗

Peripseudophakic membrane. Pathologic features.

A 70-yr-old woman underwent anterior segment reconstruction with repeated penetrating keratoplasty for visual rehabilitation. On removal of the failed keratoplasty button, the posterior chamber intraocular lens was found to be encased in a dense fibrous membrane that almost totally obliterated the anterior and posterior chambers of the eye. Anterior segment reconstruction included excision of the fibrous membrane, removal of the intraocular lens, iridoplasty, gonioplasty, anterior vitrectomy, and repeated penetrating keratoplasty. Recognition of fibrous tissue that extended through each of the four positioning holes of the optic of the lens implant and its transection was essential in avoiding complications during removal of the intraocular lens. Histopathologic and ultrastructural examination of the excised membrane revealed areas of metaplastic lens epithelium and fibrous scar tissue. This study, using immunofluorescence, is the first, to our knowledge, to characterize the specific collagenous components of a peripseudophakic membrane.

Aged↗

Cartilage graft epithelialization. A preliminary study using a goat model.

OBJECTIVE: To determine if the presence of a laryngeal stent adversely affects the epithelialization of an anterior costal cartilage graft. DESIGN: Twelve goats underwent laryngotracheoplasty using an anterior costal cartilage graft. No stent was used in six animals, and a modified endotracheal tube stent was used in the other six. The degree of epithelialization in each group was compared histologically, as well as other histologic criteria (epithelial metaplasia, cilia formation, and inflammatory cell infiltration). SETTING: Children's Hospital Medical Center of Cincinnati (Ohio) Medical Research Building. PATIENTS AND OTHER PARTICIPANTS: No human subjects were used in this study. MAIN OUTCOME MEASURES: Qualitative histologic analysis of cartilage graft epithelialization, epithelial metaplasia, cilia formation, and inflammatory cell infiltration was performed. The stent vs no-stent groups were compared histologically. RESULTS: In the stented group, one cartilage graft extruded, while five remained in place. All of the no-stent cartilage grafts remained in place. A trend was observed in the no-stent group toward increased cartilage graft epithelialization and cilia formation, while there was a decrease in epithelial metaplasia and infiltration by inflammatory cells. CONCLUSIONS: Although the study population was small, the presence of a laryngeal stent tended to predispose the graft to increased inflammation and epithelial metaplasia and may adversely affect cartilage graft epithelialization. The goat may be an adequate animal model for laryngotracheal reconstruction and, possibly, subglottic stenosis.

Animals↗

Primary adenocarcinoma of the lacrimal gland. A retrospective study.

BACKGROUND: Primary adenocarcinoma of the lacrimal gland is rare and usually appears in the literature as case reports. The authors retrospectively studied cases of primary adenocarcinoma of the lacrimal gland to determine which of the currently used methods was most effective in treating this tumor. METHODS: The authors requested cases of primary adenocarcinoma of the lacrimal gland from orbital surgeons and ocular pathologists worldwide. Of the cases referred, 13 examples of primary adenocarcinoma of the lacrimal gland could be confirmed and studied for clinical features, management, and outcome. RESULTS: The authors have follow-up data on all 13 patients. Six patients died of cancer, three are alive with recurrence, and four are alive and disease-free. CONCLUSION: Based on the results of this study, the authors ascertain that primary adenocarcinoma of the lacrimal gland is not inevitably fatal and should be treated with exenteration and adjuvant radiotherapy as soon as a histologic diagnosis is established. Shorter duration of symptoms before treatment appears to decrease the chance of metastases and increase the chance of long-term survival.

Adenocarcinoma↗

The time course of irradiation changes in proton beam-treated uveal melanomas.

BACKGROUND: Although histopathologic changes in uveal melanomas treated by irradiation have been well characterized, the timing of these effects after irradiation has not been previously evaluated. METHODS: The series consisted of a total of 92 eyes with uveal melanoma, enucleated at various intervals after proton irradiation (range, 1 month to 8 years) due to complications (n = 66) or tumor growth (n = 22), or at autopsy (n = 4). Study slides were read, using a standard protocol, by two pathologists masked to the timing of the enucleation after irradiation and the reason for the surgery. RESULTS: The prevalence of inflammation decreased whereas fibrosis increased with time from 15% of cases enucleated within 12 months (early cases) to 61% of those enucleated more than 30 months (late cases) after irradiation (P for trend = 0.0005). Tumor necrosis and blood vessel damage occurred early, and the prevalence of these changes was constant over time. Excluding tumors with evidence of growth after irradiation, mitotic figures became progressively less common as the interval between irradiation and enucleation increased (P for trend = 0.015); no mitotic figures were present in 40 high-power fields more than 30 months after irradiation. CONCLUSION: Histopathologic changes in irradiated melanomas vary according to the time elapsed since irradiation. Inflammation decreases with time whereas fibrosis becomes more prevalent with time after irradiation. Among controlled tumors, mitotic figures appear only in recently irradiated tumors.

Adult↗

Defects in an injection-molded intraocular lens.

Injection-molded intraocular lenses may undergo structural changes when exposed to solvents and fixatives during post-mortem examination. We report a case in which this phenomenon was seen in an injection-molded lens. We were able to duplicate these changes by immersing injection-molded lenses in 60% alcohol for 48 hours.

Aged↗

Melanotic neuroectodermal tumour of infancy.

The melanotic neuroectodermal tumour of infancy is a rare, pigmented neoplasm that most frequently arises from the anterior maxillary alveolar ridge. It presents in the first few months of life, and usually follows a benign course. A classical case is presented and the clinical, radiological and pathological characteristics are discussed. The importance of early conservative surgical excision is emphasized with, in general, a good prognosis. This tumour, which many otolaryngologists may not be familiar with, should be included in the differential diagnosis of head and neck neoplasms in infants and young children.

Humans↗

Nucleolar organizer regions in optic gliomas.

The biological nature of optic gliomas is controversial, with some considering them benign hamartomatous lesions, and others believing them to be true neoplasms. We evaluated the use of colloid silver impregnation of nucleolar organizer region-associated proteins (AgNORs) in making this distinction. Thirty-one optic gliomas, 14 optic nerve meningiomas, and a single case of giant cell glioblastoma multiforme (monstrocellular glioma) of the optic chiasm were stained for AgNORs and counted in a masked fashion. The optic gliomas contained 2.01 +/- 0.09 AgNORs per nucleus, similar to that of optic nerve meningiomas (2.15 +/- 0.15) and our previously reported counts for diffuse fibrillary astrocytoma (2.22 +/- 0.10), and significantly more than that of reactive astrocytosis (1.18 +/- 0.02). Six of the seven optic gliomas examined had compound AgNORs, a feature associated with malignancy in other tumour types. AgNOR counts did not correlate with clinical features, including those seen during the post-operation course. These data suggest that optic gliomas may be true neoplasms, and not benign hamartomas.

Adolescent↗

Uveal melanoma.

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Cytogenetics↗

Mast cells in human optic nerve.

PURPOSE: Mast cells are classically found in ocular tissues within the conjunctiva, choroid, and iris. The aim of this study was to examine their distribution in the optic nerve and its meninges. METHODS: Sixty-six human optic nerves were studied from normal subjects at autopsy, fetuses aborted for chromosomal abnormalities, and from enucleation specimens of patients with a variety of inflammatory, traumatic, neoplastic, and vascular disorders. Mast cells were identified using a stain for the enzyme chloroacetate esterase, and confirmed using toluidine blue, revealing metachromatic cytoplasmic granules. RESULTS: Mast cells were found scattered in the meninges of almost all optic nerves examined, frequently in perivascular locations, with densities up to 2325 mast cells/mm3 (mean 269.7 +/- 64.1 cells/mm3 in normal nerves). Mast cells were found in the optic nerve parenchyma in nerves from four eyes that had severe abnormality, often associated with neovascularization. Normal nerves, as well as nerves from fetuses aborted for congenital defects, had significantly fewer meningeal mast cells than those from eyes with inflammatory or vascular diseases. Degranulation of mast cells was observed more often in eyes with recent severe trauma. CONCLUSIONS: Based on their work and the work of others suggesting an association between mast cells and nervous system autoimmune disorders, the authors hypothesize a role for optic nerve mast cells in certain ocular inflammatory conditions.

Adult↗