Meis family proteins are required for hindbrain development in the zebrafish.

Meis homeodomain proteins function as Hox-cofactors by binding Pbx and Hox proteins to form multimeric complexes that control transcription of genes involved in development and differentiation. It is not known what role Meis proteins play in these complexes, nor is it clear which Hox functions require Meis proteins in vivo. We now show that a divergent Meis family member, Prep1, acts as a Hox co-factor in zebrafish.

Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish.

Many Hox proteins are thought to require Pbx and Meis co-factors to specify cell identity during embryogenesis. Here we demonstrate that Meis3 synergizes with Pbx4 and Hoxb1b in promoting hindbrain fates in the zebrafish. We find that Hoxb1b and Pbx4 act together to induce ectopic hoxb1a expression in rhombomere 2 of the hindbrain.

A novel pbx family member expressed during early zebrafish embryogenesis forms trimeric complexes with Meis3 and Hoxb1b.

pbx genes encode homeodomain-containing transcriptional regulators that interact with other proteins to control embryogenesis and tumorigenesis. We present the characterization of a zebrafish pbx CDNA that appears to encode a novel family member, pbx4. pbx4 RNA is maternally deposited and is detected throughout the zebrafish embryo during blastula stages.

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.

Background: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide.

Methods: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.

Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension.

The 24-h blood pressure control of bisoprolol, a new beta-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg.