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Biomedical subjects

D P Lee

Publications and source records attributed to D P Lee.

9 recordsLinked to original sources

Intracoronary radiation with a 32P source wire.

The Proliferation REduction with Vascular ENergy Trial (PREVENT) is a prospective randomized study of the safety and efficacy of intracoronary brachytherapy to reduce restenosis. A beta-emitter, 32P, is embedded on a wire tip and delivered to the target site through a centering catheter immediately following a coronary intervention. The radiation doses are 16, 20, and 24 Gy measured at 1 mm within the vessel wall. Follow-up includes an angiogram and IVUS at 6 months. Phase I of this trial has been completed with results expected in early 1999.

Angioplasty, Balloon, Coronary

Equivalent reduction of proteinuria in hypertensives by either nifedipine GITS or enalapril: disparate effects on neurohormones and ambulatory blood pressure and the influence of salt.

OBJECTIVE: We compared the efficacy of two classes of antihypertensive therapy on ambulatory blood pressure control and proteinuria in patients with hypertension. Furthermore, we determined the effects of the interaction of these therapies on neurohormonal activation and of the patients' ambient sodium intake on the outcomes. METHODS: Sustained-release nifedipine (nifedipine gastrointestinal therapeutic system, GITS) 30-120 mg/day was compared in a double-blind sequential randomized placebo-controlled trial with enalapril 5-30 mg/day regarding office and 24-hour blood pressure control, plasma renin activity, noradrenaline and adrenaline levels and 24-hour urinary protein and sodium in 46 elderly nondiabetic hypertensive patients in a 16- to 18-week trial. RESULTS: Both nifedipine GITS and enalapril controlled ambulatory blood pressure during the day and at peak effect. Nifedipine GITS controlled ambulatory blood pressure during the early morning surge and at night time as well. Nifedipine GITS increased plasma renin activity and noradrenaline by 50 and 20%, respectively, compared to the 150 and 0% change produced by enalapril. Both nifedipine GITS and enalapril reduced proteinuria by 37%. Patients had increasing levels or proteinuria proportional to higher ambient sodium intake (r = 0.48; p < 0.01). This effect was accentuated during nifedipine GITS therapy as compared to enalapril. CONCLUSION: Nifedipine GITS was superior to enalapril in controlling ambulatory blood pressure, but they were equivalent in reducing proteinuria (37%). They had disparate effects on neural activation and the duration of action. Raised protein excretion appears to be associated with raised sodium intake. This was apparent especially during nifedipine XL therapy.

Aged

An erythroid-specific, developmental-stage-independent enhancer far upstream of the human "beta-like globin" genes.

We have identified an erythroid-specific enhancer element far upstream of the human "beta-like globin" genes, at 10.2-11.0 kilobases 5' of the embryonic epsilon-globin gene, and thus at 53-54 kilobases 5' of the adult beta-globin gene. It is capable of enhancing the expression of a cis-linked test gene by up to 300-fold. This enhancer element is apparently developmental-stage-independent, as it is functional at the embryonic and the adult developmental stages in erythroid cells that are expressing the respective beta-like globin genes. The enhancer and globin promoter sequences work in synergy and are capable of conferring on a cis-linked gene the high transcriptional efficiency (enhancer function), erythroid specificity (enhancer and promoter functions), and developmental-stage specificity (promoter function) that are characteristic of the in vivo transcription of the beta-like globin genes in erythroid cells.

Age Factors

Chromatographic evaluation of large-pore and non-porous polymeric reversed phases.

The polymeric reversed-phase packing material, PRP-1, a macroporous copolymer of styrene and divinylbenzene has been used for the liquid chromatographic analysis of proteins, peptides, oligonucleotides, pharmaceuticals and other biologically active materials. The PRP-1 phase has an average pore diameter of 75 A which may limit its applicability to smaller molecules. Hence a complementary series of larger pore poly(styrene-divinylbenzene) packing materials has been prepared. Chromatographic evaluation of 100-, 200- and 300-A polymeric stationary phases showed identical small molecule selectivity through the series and similar sample load capacities. The 300-A material showed the best resolution of protein samples during gradient elution. Its performance is compared to that of a non-porous PRP whose pore diameter may be considered infinite. Ghosting, recovery and column efficiency were also evaluated. The chief benefit of the PRP packing is its hydrolytic stability from pH 1 to 13. Hydrolytic removal of protein contaminants from analytical PRP columns and packings was demonstrated.

Chromatography

Evidence that forskolin binds to the glucose transporter of human erythrocytes.

Binding of [4-3H]cytochalasin B and [12-3H]forskolin to human erythrocyte membranes was measured by a centrifugation method. Glucose-displaceable binding of cytochalasin B was saturable, with KD = 0.11 microM, and maximum binding approximately 550 pmol/mg of protein. Forskolin inhibited the glucose-displaceable binding of cytochalasin B in an apparently competitive manner, with K1 = 3 microM. Glucose-displaceable binding of [12-3H]forskolin was also saturable, with KD = 2.6 microM and maximum binding approximately equal to 400 pmol/mg of protein. The following compounds inhibited binding of [12-3H]forskolin and [4-3H]cytochalasin B equivalently, with relative potencies parallel to their reported affinities for the glucose transport system: cytochalasins A and D, dihydrocytochalasin B, L-rhamnose, L-glucose, D-galactose, D-mannose, D-glucose, 2-deoxy-D-glucose, 3-O-methyl-D-glucose, phloretin, and phlorizin. A water-soluble derivative of forskolin, 7-hemisuccinyl-7-desacetylforskolin, displaced equivalent amounts of [4-3H]cytochalasin B or [12-3H]forskolin. Rabbit erythrocyte membranes, which are deficient in glucose transporter, did not bind either [4-3H]cytochalasin B or [12-3H]forskolin in a glucose-displaceable manner. These results indicate that forskolin, in concentrations routinely employed for stimulation of adenylate cyclase, binds to the glucose transporter. Endogenous ligands with similar specificities could be important modulators of cellular metabolism.

Adenylyl Cyclases