Search PubMed⌕ Search

Biomedical subjects

D M Albert

Publications and source records attributed to D M Albert.

At least 127 records · Page 7Linked to original sources
PubMed1991

Neuronal and glial properties of a murine transgenic retinoblastoma model.

Antigenic properties of a murine transgenic model for hereditary retinoblastoma, induced by a chimeric gene coding for Simian virus 40 large T antigen, an oncogene that inactivates the retinoblastoma susceptibility gene product, were studied by immunohistochemistry. All transgenic mice develop bilateral intraocular retinal tumors in the inner nuclear layer with Homer Wright-like rosettes, and one quarter develop midbrain tumors resembling trilateral retinoblastoma. Cell lines TE-1 and TM-1 were established from intraocular and metastatic tumors, respectively. Intraocular tumors reacted with antibodies to neuron-specific enolase and synaptophysin, while vimentin, glial fibrillary acidic, and S-100 proteins were detected only in reactive glia derived from adjacent retina. The midbrain tumors showed weak reactivity to synaptophysin, and they blended with reactive astrocytes positive for glial markers. The tumors were negative for cytokeratins. Finally both derived cell lines expressed synaptophysin and individual neurofilament triplet proteins in immunofluorescence and Western blotting, supporting their essentially neuronal nature. The antigenic profile resembles human retinoblastoma, but differences in morphology and antigen distribution suggest a more close relationship to neurons of the inner nuclear layer than to photoreceptor cells.

Animals↗
PubMed1991

Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma.

The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.

Animals↗
PubMed1991

Effect of butyrate and corticosteroids on retinoblastoma in vitro and in vivo.

The effect of sodium butyrate (NaB) alone and in combination with a glucocorticoid was studied on Y-79 retinoblastoma cells both in vitro and in vivo. Both NaB (0.5 and 4 mM) and hydrocortisone (1-100 microM) added separately to cells grown in suspension resulted in a small growth inhibition (less than 15%). A marked synergistic effect (75-77% growth inhibition) was observed in vitro when NaB and hydrocortisone were added in combination at all the concentrations tested. With in vivo experiments using the nude mouse model of retinoblastoma, the combination of NaB and methylprednisolone did not inhibit tumor growth.

Animals↗
PubMed1991

Morphologic and ultrastructural examination of I-A+ cells in the murine iris.

The surface membrane expression of major histocompatibility (MHC) class II antigens is an important prerequisite for presentation of foreign antigens to the immune system. Because particular antigens that are placed within the anterior chamber of the eye elicit a deviant form of immunity in which effector delayed-type hypersensitivity responses are suppressed, it has been proposed that novel MHC class II antigen-bearing cells exist in the tissues that line the anterior chamber. Class II MHC antigen expression has been identified within the iris, but the detailed morphologic description of these cells is incomplete. With the use of in situ immunoperoxidase and immunoelectron microscopic techniques, we examined the morphologic and ultrastructural characteristics of resident MHC-positive class II (I-A+) cells in murine irises. A significant number of these cells was found in the connective tissue of BALB/c irises. The majority showed extensive dendritic morphologic characteristics and formed a network throughout the iris that did not overlap. Ultrastructurally, I-A+ cells had an indented nucleus, some vacuoles, lysosomes, mitochondria, and an occasional phagosome within their cytoplasm and an absence of desmosomes or other intercellular junctions. Based on these features, it is unlikely that these cells are epithelial or endothelial in origin, but rather are similar to cells of the monocyte/macrophage/dendritic cell lineage. These results show the presence of an I-A+ dendritic cell population, within the murine iris, distributed in a pattern that is similar to that of Langerhans cells in the skin. Due to their compartmentalization within the eye, this cell population may represent a novel antigen-presenting cell that contributes to the immunologic privilege of the anterior chamber.

Animals↗
PubMed1990

The value of nucleolar organizer regions in uveal melanoma. The Collaborative Ocular Melanoma Study Group.

Silver staining of nucleolar organizer regions is an objective method for evaluating the malignancy of a variety of tumors. We studied 126 ciliochoroidal melanomas, three coincidental nevi that occurred in eyes with melanomas, and one magnocellular nevus collected from the Collaborative Ocular Melanoma Study to determine the effectiveness of the silver-stained nucleolar organizer region technique in assessing the malignant potential of these tumors. Malignant lesions demonstrated higher mean silver-stained nucleolar organizer region counts (4.347) than benign nevi (1.855) (P less than or equal to .0001). Among malignant melanomas, mixed-cell melanomas had slightly higher counts than spindle-cell melanomas (P less than or equal to .0001), but this difference was not important clinically. Results were also compared to other histopathologic variables, which disclosed correlation of silver-stained nucleolar organizer regions with mitoses and tumor size. Comparison with computerized cytomorphometric analyses of prognosis also disclosed significant correlation. This technique may prove to be a useful adjunct in the assessment of malignancy and treatment response of uveal melanomas.

Cell Count↗
PubMed1990

Aqueous humor contains transforming growth factor-beta and a small (less than 3500 daltons) inhibitor of thymocyte proliferation.

The anterior chamber of the eye is an immunologically privileged site in which allografts survive longer than at other body sites. In this regard, it is relevant that aqueous humor (AH) inhibits lymphocyte proliferation. In order to analyze AH for specific substances that inhibit thymocyte proliferation, samples of human AH, murine AH, and rhesus monkey AH were added to cultures of thymocytes stimulated by IL-1 or IL-2 in the presence of PHA. All samples of AH tested had potent inhibitory activity on thymocyte proliferation in this system. Inhibitory activity was lost by heating AH to 80 degrees C for 1 h. Dialysis of murine AH indicated that species smaller than 3500 Da were capable of mediating this activity; we have termed the factor(s) responsible for this "small inhibitory factor(s) of AH." Retentate, containing species larger than 3500 Da, retained inhibitory activity, but less than nondialyzed AH. Assays for PGE2 demonstrated that murine and human AH contained small quantities of PGE2. These quantities were insufficient to inhibit thymocyte proliferation in our assay system. Furthermore, AH from mice treatend with indomethacin had full inhibitory activity. Assays for transforming growth factor beta (TGF-beta) after acid activation demonstrated significant quantities of latent TGF-beta within human and murine AH which could be largely neutralized by antisera to TGF-beta. Active TGF-beta "activity" was also present without acid activation in samples of AH at a level approximately 20% that of latent TGF-beta. However, most of this "activity" could not be neutralized by antisera to TGF-beta. AH contains factors capable of limiting thymocyte proliferation.

Animals↗
PubMed1990

Recurrence of posterior polymorphous corneal dystrophy after penetrating keratoplasty.

Recurrence of a corneal dystrophy after keratoplasty can occur in multiple dystrophies, including macular, granular, and lattice dystrophies. We treated two unrelated patients who had documented posterior polymorphous dystrophy and who, in previously clear grafts, developed haziness in the zone of Descemet's membrane, which led to graft failure. Histologic examination of the keratoplasty specimen showed changes typical of posterior polymorphous dystrophy.

Corneal Dystrophies, Hereditary↗
PubMed1990

Harderian gland pathology in transgenic mice carrying the MMTV/v-Ha-ras gene.

Twenty-four Harderian glands from 16 transgenic mice carrying a v-Ha-ras gene under the control of the mouse mammary tumor virus promoter were examined histologically upon death of the animals. Eight glands were histologically normal and eleven were hyperplastic. Four additional glands showed predominantly hyperplasia, but also contained foci of dysplasia and in situ carcinoma. One gland contained an adenocarcinoma. The range of pathology observed in the Harderian glands of these transgenic mice was similar to that which arises spontaneously, although hyperplasia, and not adenoma, occurred in these mice as the benign tumor.

Adenocarcinoma↗
PubMed1990

Retinoblastoma in transgenic mice.

Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, p105Rb (refs 1 and 2). Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohistochemical features identical to those of human retinoblastoma. Furthermore, we demonstrate a specific association between p105Rb and T antigen in mouse retinoblastoma tumour cells. Thus, the occurrence of these tumours is in vivo evidence for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. As an animal model for heritable retinoblastoma, these mice should allow the study of the ontogeny, pathogenesis and treatment of this malignant disease.

Animals↗
PubMed1990

Anophthalmia in the focal dermal hypoplasia syndrome.

We examined an orbital exenteration specimen from an anophthalmic patient with focal dermal hypoplasia. Eyelid angiofibromas were evident and immunoperoxidase studies for human papilloma virus were negative. Orbital tissue contained a ductal cyst, chronic inflammation of the lacrimal duct and sac, rudimentary conjunctival fornices, lacrimal gland, striated muscle, and adipose tissue. Microscopic examination revealed a posteriorly located cystic structure with uveal and lens remnants. Neuroectodermal structures consistent with retina, optic nerve, or meninges were not observed, thus representing true anophthalmia. These findings remain as the only histopathologic description of ocular tissues in patients with focal dermal hypoplasia.

Adult↗
PubMed1990

Ligneous conjunctivitis with ear involvement.

We report the association of ligneous conjunctivitis with middle-ear and tympanic membrane involvement in two children. Eye and ear specimens revealed histopathologic and ultrastructural findings consistent with ligneous conjunctivitis, characterized by an amorphous, eosinophilic material with acute and chronic nongranulomatous inflammation. Ear specimens demonstrated granulation tissue along with the above features. Conjunctival and ear lesions from these patients were studied histochemically, immunohistochemically, and ultrastructurally. Our studies demonstrate fibrin and albumin deposition as a common feature in all lesions. Deposition of other components, such as mucopolysaccharides, amyloid, immunoglobulins, and mast cells, were, however, variable. The diversified nature of these lesions, together with the association of eye and ear disease, substantiates the existence of an underlying systemic disorder of unknown cause.

Amyloid↗
PubMed1990

Ocular and associated systemic findings in suspected child abuse. A necropsy study.

We reviewed complete ocular and systemic necropsy findings of 10 consecutive children who died of suspected child abuse. All 10 children had evidence at necropsy of blunt head trauma, although external signs of blunt trauma occasionally were covert. Ocular injuries were observed in 7 of the 10 cases and when present always included retinal, vitreous, and subdural optic nerve hemorrhages. In 5 cases, intrascleral hemorrhage from the circle of Zinn occurred at the sclera-optic nerve junction. In 4 cases, traumatic retinoschisis or tractional retinal folds were present. Anterior segment findings were uniformly consistent with blunt trauma. Hemosiderin, indicating old hemorrhage, was present in 3 cases. Intracranial hemorrhage, present in all cases with abnormal ocular findings, was always accompanied by signs of direct head trauma, such as subgaleal hemorrhage, skull fracture, cerebral contusion, or external contusions, which are sometimes subtle or hidden beneath the hair.

Child Abuse↗
PubMed1990

A transgenic mouse model for trilateral retinoblastoma.

We present a murine model of trilateral retinoblastoma. Ocular retinoblastoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically expressed within retinal cells in this model. All animals that carry this genetic alteration develop multifocal retinal tumors. Midbrain tumors are observed in 15% of ocular tumor-bearing animals, and these arise ventral to the cerebral aqueduct at the level of the pineal gland. Both ocular and central nervous system neoplasms are heritable in heterozygous offspring through 10 sequential generations of breeding. Retinal tumors display the gross appearance, invasive properties, light and electron microscopic features, and immunohistochemical staining characteristics of human retinoblastoma. The light and electron microscopic characteristics as well as immunocytochemical features of undifferentiated midline central nervous system neoplasms further correlate with human trilateral retinoblastoma. We postulate an alternative mechanism of retinoblastoma tumorigenesis that involves functional inactivation of retinoblastoma protein locally in the face of an intact retinoblastoma gene locus.

Animals↗
PubMed1990

Host factors, UV radiation, and risk of uveal melanoma. A case-control study.

Uveal melanoma threatens life, as well as sight. To evaluate the effect of constitutional factors and UV radiation on the risk of uveal melanoma, 197 cases in New England were compared with 385 matched population controls, identified by random-digit dialing, and 337 cases residing within the United States were compared with 800 sibling controls. In the population-based comparison, estimated relative risks (RRs) of uveal melanoma, after adjustment for other factors, were elevated for the following: ancestry from more northern latitudes with a substantially elevated risk for Northern European ancestry (RR, 6.5; 95% confidence interval [CI], 1.9 to 22.4) and more than a twofold risk for British ancestry (RR, 2.4; 95% CI, 1.1 to 5.1), as compared with Southern European or other Mediterranean heritage; light skin color as compared with dark (RR, 3.8; 95% CI, 1.1 to 12.6); and 10 or more cutaneous nevi as compared with none (RR, 2.7; 95% CI, 1.5 to 4.9). There was a statistically significant trend for increasing risk with more northern heritage and more moles. Southern residence (below latitude 40 degrees N) for more than 5 years also increased risk (RR, 2.8; 95% CI, 1.1 to 6.9), as compared with none. In both comparisons, use of sunlamps was a risk determinant (RR, 3.4; 95% CI, 1.1 to 10.3 with random-digit dialed controls and RR, 2.3; 95% CI, 1.2 to 4.3 with sibling controls, comparing occasional or frequent use to never use), as was intense sun exposure (RR, 1.7; 95% CI, 0.9 to 3.0 and RR, 2.1; 95% CI, 1.4 to 3.2, respectively). However, birthplace below latitude 40 degrees N and outdoor work were associated with a lower risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Endoscopic examination of the neonatal larynx at extubation: a prospective study of variables associated with laryngeal damage.

Despite postmortem and clinical studies, the etiological factors that determine why only a proportion of intubated neonates develop subglottic stenosis remain unclear. This prospective study was initiated to identify factors that were associated with laryngeal abnormalities secondary to intubation. Thirty neonates were examined at extubation by two independent observers blinded to the neonate's ventilatory history. Thirty-six possible prognostic indicators were recorded for each neonate. After screening by univariate (chi 2) analysis, 10 indicators were selected for further analysis. Of these 10 selected only two indicators showed an association with the laryngeal appearance. Active neonates had significantly more abnormalities in the supraglottis (P = 0.004) than those who were quiescent. Younger neonates had more abnormalities in the glottis though the significance level was marginal (P = 0.056). Other prognostic indicators, including birthweight, gestational age, duration of intubation and frequency of intubation, were not significantly related to laryngeal appearance. This study supports the hypothesis that the etiology of laryngotracheal stenosis is multifactorial, and has identified two possible etiological factors: age and neonatal activity. Neonatal activity has not been identified previously as an etiological factor. The contribution of individual factors may vary from one neonatal unit to another, as a result of variation in intubation, ventilation and extubation policy. This could explain the inconsistency in etiological factors identified by previous studies. It is therefore not yet possible to recommend a standard technique for the ventilation of premature neonates that would further reduce the incidence of laryngotracheal stenosis.

Erythema↗
PubMed1990

Hidradenoma papilliferum of the upper eyelid arising from the apocrine gland of Moll.

Hidradenoma papilliferum is derived from apocrine sweat glands and was originally described as a tumor located in the anogenital area. The authors recently examined a 78-year-old man with a hidradenoma papilliferum at the margin of the upper eyelid. While the tumor was located in the dermis, serial sections showed a connection to the epidermis and neoplastic cells partially replacing a gland of Moll. There were glandular structures with luminal cells that showed apical decapitation-type secretion, indicating the apocrine origin of the tumor. The luminal cells also contained granules that stained with periodic acid-Schiff (PAS) stain and were diastase resistant. Results of examination of the duct-forming cells by transmission electron microscopy showed adluminal villi, focal decapitation secretion, luminal cytoplasmic debris, and electron-dense cytoplasmic secretory granules. Because the apocrine glands of Moll are localized adjacent to the eyelid cilia, hidradenoma papilliferum and other tumors of apocrine origin should be considered in the clinical setting of a mass at the eyelid margin.

Adenoma, Sweat Gland↗