Biomedical subjects

M A Brantley

Publications and source records attributed to M A Brantley.

8 recordsLinked to original sources

PubMed2004

Juvenile neuronal ceroid lipofuscinosis (Batten disease) CLN3 mutation (Chrom 16p11.2) with different phenotypes in a sibling pair and low intensity in vivo autofluorescence.

BACKGROUND: The neuronal ceroid lipofuscinoses (Batten disease) are a heterogeneous group of autosomal recessively inherited disorders causing progressive neurological failure, mental deterioration, seizures and visual loss secondary to retinal dystrophy. The juvenile type is of special interest to the ophthalmologist as visual loss is the earliest symptom of the disorder. HISTORY AND SIGNS: We present two siblings with severe retinal dystrophy due to juvenile Batten disease. Sibling A (age 10) presented with visual loss, photophobia and night blindness, starting at age 4. His vision was perception of light by the age of 10.5 years. Fundus examination revealed severe pigmentary retinopathy. Sibling B (age 7) presented with night vision difficulties. Fundus examination revealed a bull's eye maculopathy with minimal peripheral atrophic changes. In vivo autofluorescence level was found to be very low. Electroretinography (ERG) showed generalized retinal dysfunction involving both cone and rod systems, with an electronegative maximal response. In both siblings vacuolated lymphocytes were found on a peripheral blood film and on molecular genetic testing both were homozygous for the commonly reported 1.02-kb deletion of the CLN3 gene. THERAPY AND OUTCOME: Although there is no effective treatment, the early diagnosis allowed accurate genetic and social counseling. CONCLUSIONS: Juvenile Batten disease should be considered in children with a retinal dystrophy, especially where there is a bull's eye maculopathy and an abnormal full field ERG. The novel finding of very low in vivo autofluorescence is consistent with histopathological studies and may be secondary to photoreceptor cell loss.

Blindness↗

PubMed2004

Association between posterior uveal melanoma and iris freckles, iris naevi, and choroidal naevi.

AIM: To investigate the association between posterior uveal melanoma and iris freckles, iris naevi, and choroidal naevi. METHODS: Cross sectional study of 65 patients with posterior uveal melanoma and 218 controls. Iris colour, iris freckles, iris naevi, and choroidal naevi were recorded for each eye of each patient. RESULTS: Iris freckles were present in 40 (61.5%) patients with melanoma and 135 (61.9%) controls (p = 0.494). Iris naevi were present in four (6.2%) patients with melanoma and nine (4.1%) controls (p = 0.955). Choroidal naevi were present in 12 (18.5%) patients with melanoma and 38 (17.4%) controls (p = 0.815). CONCLUSION: This study did not detect an association between posterior uveal melanoma and iris freckles, iris naevi, or choroidal naevi.

Adult↗

PubMed2004

Association between choroidal pigmentation and posterior uveal melanoma in a white population.

BACKGROUND/AIMS: It is well known that light skin pigmentation is a risk factor for cutaneous melanoma. The aim of this study was to investigate the analogous association between choroidal pigmentation and posterior uveal melanoma. METHODS: Cross sectional study of 65 consecutive patients diagnosed with posterior uveal melanoma (melanoma group) and 218 consecutive patients referred for general retinal evaluation (control group). All patients were white. A clinical grading system for estimating choroidal pigmentation was developed and histologically validated in seven patients. RESULTS: Melanoma patients with light iris colour were significantly more likely to have darker choroidal pigmentation than controls (p = 0.005). Darker choroidal pigmentation was associated histologically with increased density of choroidal melanocytes (p = 0.005). CONCLUSIONS: Increased choroidal pigmentation, as a result of an increase in the density of pigmented choroidal melanocytes, is not protective but may actually be a risk factor for the development of posterior uveal melanoma in white patients. This finding may have implications for understanding the pathogenesis of uveal melanoma.

Adult↗

PubMed2001

The molecular biology of retinoblastoma.

Retinoblastoma, a rare pediatric eye tumor, has served as an important model for the heritable predisposition to cancer. The retinoblastoma protein, Rb, functions as a tumor suppressor by controlling progression through the cell cycle. Rb function is regulated primarily by its phosphorylation state, which is determined by the complex interaction of multiple kinases and their inhibitors that together form the 'Rb pathway'. This pathway has been found to be functionally inactivated in almost all types of cancer. Despite recent advances in our understanding of Rb function, the precise role of Rb loss in the development of retinoblastoma remains unclear. Recent work in genetically altered mice has suggested that an additional mutation in another gene is required for retinal tumor formation. An alternative model presented here is based on the noncell-autonomous functions of Rb contributing to tumorigenesis.

Genes, Retinoblastoma↗

PubMed2000

Inactivation of retinoblastoma protein in uveal melanoma by phosphorylation of sites in the COOH-terminal region.

Uveal melanoma is the most common malignancy of the eye, but little is known about its underlying genetic defects. Melanomas of uveal origin, unlike those of the skin, are rarely familial and have not been linked consistently to mutations in tumor suppressor genes. Here, we investigated the Rb pathway in uveal melanoma. Most tumors displayed strong immunostaining for Rb and p16, suggesting that they were not mutationally inactivated. However, Rb was frequently phosphorylated at serine-807 and serine-811, and cyclin D1 was expressed in many of the tumors. Mutation of these serine residues prevented cyclin D-dependent phosphorylation from inactivating Rb in cultured cells. We conclude that Rb is frequently inactivated in uveal melanoma by phosphorylation of residues in the COOH-terminal region that regulate its activity, and one mechanism for this phosphorylation is overexpression of cyclin D.

Cyclin D↗

PubMed2000

Deregulation of the Rb and p53 pathways in uveal melanoma.

Uveal melanoma is the most common primary eye cancer, yet its molecular pathogenesis is poorly understood. In this study, we investigated the immunohistochemical expression of proteins in the Rb and p53 tumor suppressor pathways in 33 uveal melanomas from enucleated eyes. Strong nuclear staining for Rb was present in most tumors. However, a few cases displayed weak nuclear staining and strong cytoplasmic staining (possibly indicating Rb mutation), and this aberrant staining correlated strongly with failed radiotherapy or thermotherapy before enucleation. Staining for cyclin D1 was positive in most tumors and was associated with advanced age and larger tumor size, which are both poor prognostic factors. Generally, immunostaining for p53 was weak (suggesting a lack of p53 mutations), although p53 positivity correlated strongly with staining for phosphorylated Rb, supporting the notion that inappropriate phosphorylation of Rb can induce p53. Strong immunostaining for MDM2, which can functionally block p53 activity, was observed in most tumors and correlated significantly with female sex. Strong cytoplasmic staining was observed for Bcl2, which can inhibit both p53-dependent and -independent apoptosis. We conclude that Rb and p53 are mutated infrequently in uveal melanoma, but their respective pathways may be functionally inactivated.

Adult↗

PubMed1991

Evaluation of simple models of auditory profile analysis using random reference spectra.

This article describes further study of the finding reported by Green et al. [J. Acoust. Soc. Am. 73, 639-643 (1983)] and others that, in certain conditions, the threshold of detectability for an intensity increment to the center tone of a multitone reference spectrum decreased as the number of nonsignal tones increased. That result was considered remarkable since critical-band theory would predict that these nonsignal tones, spaced outside the "critical band" containing the signal, would have no effect on or, at most, slightly decrease within-band detectability--and certainly could not account for the result of improved detectability found in the study cited above. Recently, Henn and Turner [J. Acoust. Soc. Am. 88, 126-131 (1990)] were unable to replicate the result described above, concluding that the phenomenon exists only in "limited conditions" and that is "highly individual" in nature. Further, they speculated that the most likely reason for the discrepancy between their study and previous studies was the selection and/or training of the observers. The present study addressed the effects of the amount of subject training on the finding of Green et al. while controlling the potential effects of stimulus order. Specifically, for a group of three "naive" listeners, thresholds were measured for 3-, 7-, and 21-tone inharmonic complexes as a function of the amount of practice in a mixed-block design. In all cases the group mean thresholds decreased as the number of nonsignal tones increased both initially and after extensive practice for both fixed- and roving-level conditions. Thus the effect does not appear to be an artifact of the amount or order of training subjects receive. The possible role of subject sample size and the magnitude of individual differences in obtaining the effect remains an open question. Two hypotheses suggested to account for the improvement in threshold with increasing number of nonsignal tones were evaluated. The hypotheses were represented by simple mathematical models, referred to as the "multiple-comparison" and "pitch-cue" models. The predictions of both models were compared with the results of a series of detection experiments in which the independent variables were the number of nonsignal tones and amount of random, within-trial "amplitude perturbation" [cf. Kidd et al., J. Acoust. Soc. Am. 79, 1045-1053 (1986)] of the nonsignal tones. Neither model, as applied, provided a satisfactory account of the effects of the main variables of number of tones and amount of perturbation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Roving-level tone-in-noise detection.

The detectability of tones, or of intensity increments to tones, in bands of random noise was measured for conditions in which the overall level was fixed or was randomly roved from interval to interval of every experimental trial. The purpose of the within-trial rove was to limit the usefulness of a detection strategy based on overall level or level within a single "critical band." At "supracritical" bandwidths, the functions relating masked threshold to noise bandwidth for the roved conditions were similar to those obtained when no rove was employed. At "subcritical" bandwidths, thresholds were higher in some roved conditions, but, for the largest rove, were still lower than would be predicted from arguments based purely on level detection--with one exception. A comparison of observer performance relative to the statistical limits imposed by the roving-level procedure indicated that the traditional critical-band energy-detector model could not account for the results, which are attributed to discrimination based on spectral shape or on waveshape.

Adult↗