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Biomedical subjects

D Fader

Publications and source records attributed to D Fader.

6 recordsLinked to original sources

Isolated extragenital bowenoid papulosis of the neck.

We report a case of extragenital bowenoid papulosis (BP) in a healthy immunocompetent 42-year-old man. The lesions occurred on the anterolateral aspects of the neck and were not associated with genital, oral, or periungual lesions. Lesional skin tested positive with the Digene hybrid capture system cocktail assay that identifies infection with a mixture of high to intermediate oncogenic human papillomavirus (HPV) types, including types 16, 18, 31, 33, 35, 45, 51, 52, and 56. This cocktail assay identifies infection with HPV types typically associated with high-grade squamous intraepithelial lesions and invasive carcinoma. This case represents the sixth case of isolated cutaneous BP occurring a significant distance from the genital region.

Adult↗

Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children.

BACKGROUND: Tacrolimus is a potent immunosuppressant used in organ transplant recipients; an ointment formulation is being developed as a therapeutic agent for atopic dermatitis. OBJECTIVE: Our purpose was to define the pharmacokinetics and evaluate tacrolimus 0.3% ointment as therapy for moderate to severe atopic dermatitis. METHODS: Thirty-nine patients, 5 to 75 years of age, received 14 applications over 8 days. Serial blood samples were collected on days 1 and 8, with predose samples collected on days 2 through 7. Overall response and signs/symptoms were rated daily on days 1 through 11. Incidence of adverse events and laboratory profile were determined. RESULTS: Mean area under the curve (0.9 to 42.5 ng x hr/ml) was highly variable and appeared to be related to size of application area. No systemic accumulation of tacrolimus was observed. Comparison to historical intravenous data indicates that absolute bioavailability of topical tacrolimus was less than 0.5%. Ninety-five percent of patients showed at least good improvement. All adverse events were transient. Burning was the most common application site adverse event and vasodilatation ("flushing/warmth") was the most common nonapplication site adverse event. No drug-related changes in laboratory profile were observed. CONCLUSION: The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.

Administration, Cutaneous↗

Bovine dopamine beta-hydroxylase cDNA. Complete coding sequence and expression in mammalian cells with vaccinia virus vector.

We have isolated cDNA clones for bovine dopamine beta-hydroxylase from an adrenal medulla cDNA library and have determined the complete coding sequence. The largest cDNA clone isolated from the library is 2.4 kilobase pairs (kb) and contains an open reading frame of 1788 bases, coding for a protein of 597 amino acids and Mr = 66,803. The predicted amino acid sequence of the bovine cDNA contains 85% identity with human dopamine beta-hydroxylase (Lamouroux, A., Vingny, A., Faucon Biquet, N., Darmon, M. C., Franck, R., Henry, J.P., and Mallet, J. (1987) EMBO J. 6, 3931-3937; Kobayashi, K., Kurosawa, Y., Fujita, K., and Nagatsu, T. (1989) Nucleic Acids Res. 17, 1089-1102). Northern blot analysis reveals that the cDNA hybridizes to an mRNA of 2.4 kb present in bovine adrenal medulla, but not in kidney, heart, or liver. In addition, the cDNA hybridizes to a second RNA species of 5.5 kb, which is 4-fold less abundant than the 2.4-kb RNA. In vitro translation of a synthetic RNA transcribed from the 2.4-kb cDNA produces a 68-kDa protein, which is specifically immunoprecipitated by antiserum to bovine dopamine beta-hydroxylase. The 2.4-kb cDNA was cloned into a vaccinia virus vector, and the recombinant virus was used to infect the rat pheochromocytoma PC12 and monkey BSC-40 fibroblast cell lines. In both cell lines, infection with recombinant virus produces a protein of Mr = 75,000, which reacts with antiserum to bovine dopamine beta-hydroxylase. These results indicate that the 2.4-kb cDNA contains the genetic information necessary to code for the bovine dopamine beta-hydroxylase subunit.

Amino Acid Sequence↗

Interaction of cyclic AMP and cell-cell contact in the control of tyrosine hydroxylase RNA.

The interaction between cell-cell contact and cyclic AMP-mediated control of the rat tyrosine hydroxylase (TH) gene was investigated in subclones of the PC12 rat pheochromocytoma cell line. Increasing cell culture density and elevation of intracellular cyclic AMP levels with forskolin both cause augmentation of TH RNA levels. However, the extent of increase in TH RNA following forskolin treatment is less in cultures grown at high density than those at low density, suggesting that there may be an interaction in the mechanism by which these two treatments modulate TH RNA levels. The role of cis-acting sequences in the TH gene in the induction of TH RNA by cyclic AMP and cell density was determined by the use of plasmid constructs containing the 5'-flanking sequences of the TH gene directing the transcription of the reporter gene, chloramphenicol acetyltransferase (CAT). Using transient transfection assays in PC12 cells, we have mapped the site of cyclic AMP regulation of the TH gene to a region between -60 and -41. Stable transformants of PC12 cells which express p5'TH CAT (-773/+27) were isolated and the activity of CAT following treatment of cells with forskolin and growth at different cell densities was evaluated. CAT activity does not differ between cells grown at low or high density. Forskolin induces CAT activity 2-4 fold, but the extent of induction does not vary with changes in cell culture density. We conclude from these experiments that the intracellular mechanism by which increased cell-cell contact modulates TH RNA levels is not through interaction with the same genomic elements as those which regulate gene expression by cyclic AMP.

Animals↗

The respiratory sinus arrhythmia: a measure of cardiac age.

A method developed for quantifying respiratory sinus arrhythmia (RSA) during voluntary cardiorespiratory synchronization relies on computer-assisted rhythmometric cosinor analysis of instantaneous heart rate data. The RSA was present in all subjects tested, even those at advanced ages. The amplitude of the RSA falls approximately 10 percent per decade. An individual with a transplanted heart and one with severe diabetic neuropathy each had resting RSA values that were normal for their ages. The shape and amplitude of the RSA during voluntary cardiorespiratory synchronization may reflect the suppleness of the heart and its response to rhythmically changing intrathoracic pressure and the subsequent ebb-and-flow of venous return. Our technology allows objective quantitative assessment of the biologic age of the heart and also the effect of any drug, disease, or behavior that affects the RSA.

Adult↗