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Biomedical subjects

J M O'Brien

Publications and source records attributed to J M O'Brien.

123 records · Page 7Linked to original sources
PubMed1982

5'-deoxypyridoxal interaction with dexamethasone receptor: a new probe for structure and function of steroid receptors.

5'-Deoxypyridoxal, a vitamin B-6 analogue, increased the rate of dissociation of [3H]dexamethasone from HeLa S3 cytoplasmic glucocorticoid receptor complexes in vitro. This effect was achieved at millimolar concentrations of 5'-deoxypyridoxal, suggesting a low-affinity interaction of 5'-deoxypyridoxal with receptor. Loss of [3H]dexamethasone-receptor binding in the presence of 5'-deoxypyridoxal was pH dependent, and a plot of Kdiss vs. pH fit a simple sigmoidal titration curve with an inflection point at pH 7.8, suggesting that deprotonation of a single functional group on 5'-deoxypyridoxal increases Kdiss. Loss of [3H]dexamethasone binding in the presence or absence of unlabeled steroid also increased with pH, but no inflection point occurred over the range of pH tested. A titration of 5'-deoxypyridoxal indicated a pK of 7.94 for the pyridinium proton, suggesting deprotonation of the pyridinium nitrogen may account for the pH dependence of Kdiss of dexamethasone from receptor. 5'-Deoxypyridoxal also caused a decrease in nuclear [3H]-dexamethasone-receptor binding when incubated with whole HeLa S3 cells at 37 degrees C. Furthermore, 5'-deoxypyridoxal was effective in reducing nuclear binding of dexamethasone when added either simultaneously with [3H]dexamethasone or after achievement of equilibrium of steroid with receptor. The reduction in nuclear [3H]dexamethasone binding is highly specific for 5'-deoxypyridoxal. Several analogues of this compound, including 5'-deoxypyridoxamine, were ineffective. In addition, this effect was reversible following removal of extracellular 5'-deoxypyridoxal. Under these conditions, 5'-deoxypyridoxal was competitive with dexamethasone for binding to nuclear receptor, with KI = 8.1 X 10(-6) M. Scatchard plot analysis of dexamethasone-receptor binding in the presence or absence of 5'-deoxypyridoxal was consistent with an apparent reduced affinity of [3H]dexamethasone for receptor, which again suggests competitive interaction or allosteric interaction mediated dissociation. Glucocorticoids are known to stimulate alkaline phosphatase activity within HeLa S3 cells. In whole cell incubations, 5'-deoxypyridoxal was effective in reducing the dexamethasone-induced increase in alkaline phosphatase activity by 60% under conditions in which cell viability and cell growth were not affected.

Alkaline Phosphatase↗
PubMedDate not supplied

The genetics of retinoblastoma and current diagnostic testing.

We review the genetics of retinoblastoma and the most recent molecular detection methods. Retinoblastoma, the most common intraocular tumor in children, occurs in either a heritable or non-heritable form. The heritable form, which is highly penetrant and predisposes individuals to a considerably greater second tumor risk, can be distinguished most definitively through the use of genetic testing. Genetic testing for individuals and families suspected of carrying the heritable mutations can help ensure that more comprehensive treatment plans and accurate genetic counseling for affected individuals and their families are provided.

DNA, Neoplasm↗
PubMedDate not supplied

Combined hamartoma of the retina and retinal pigment epithelium as the presenting sign of neurofibromatosis-1.

The authors report a case of combined harmartoma of the retina and retinal pigment epithelium in a 6-year-old child as the presenting sign of neurofibromatosis-1. The patient was followed closely for three years but received no treatment. Observation over these years revealed no significant change in the patient's visual acuity. A referral to the University of California San Francisco (UCSF) Neurofibromatosis Clinic resulted in a diagnosis of neurofibromatosis (NF)-1, and she continues to be observed for further systemic manifestations of this disease. Combined hamartoma of the retina and retinal pigment epithelimicrom, a rare and benign tumor, can be easily mistaken for malignant processes such as retinoblastoma or choroidal melanoma. Ophthalmologists should also be aware of the association with neurofibromatosis and consider this diagnosis when such retinal findings are observed in a child.

Child↗
PubMedDate not supplied

Comparison of tape products on skin integrity.

A two-group, nonconcurrent design was used in this comparative study to assess the incidence of skin breakdown accompanying Durapore silk tape and Medipore soft cloth tape (both manufactured by 3M Health Care). A significantly higher number of skin tears were found with silk tape use (mean 2 = 7.69, p < 0.01). This type of skin damage caused patient discomfort and incurred additional treatment costs. Soft cloth tape is recommended to decrease skin tears in surgical patients.

Adhesives↗