Biomedical subjects

Donald W Buck

Publications and source records attributed to Donald W Buck.

3 recordsLinked to original sources

PubMed2006

Adjustable vs set-pressure valves decrease the risk of proximal shunt obstruction in the treatment of pediatric hydrocephalus.

INTRODUCTION: The use of programmable shunt valves has increased dramatically in the practice of pediatric hydrocephalus. Despite theoretical advantages, it remains unclear if the use of programmable vs set-pressure valves affects shunt outcome. MATERIALS AND METHODS: The clinical and radiological records of all pediatric patients undergoing ventriculoperitoneal (VP), ventriculopleural (VPl), and ventriculoatrial (VA) shunt surgery from 2001 to 2004 at an academic institution were reviewed. The association of programmable vs set-pressure valves with subsequent shunt revision was assessed by Kaplan-Meier shunt survival plots and log-rank analysis. RESULTS: A total of 279 VP, VPl, and VA shunt surgeries were performed on patients with median (interquartile range) age of 4 (1-14) years (161 male, 118 female; 158 communicating, 122 obstructive hydrocephalus). Programmable valves were used in 76 (27%) cases and set-pressure valves in 203 (73%). At mean+/-SD follow-up of 17 +/- 13 months, programmable vs set-pressure valves were associated with reduced risk of both overall shunt revision [26 (35%) vs 109 (54%); relative risk (RR) (95% CI); 0.61 (0.41-0.91), p = 0.016] and proximal obstruction [9 (12%) vs 58 (28%); RR (95% CI); 0.39 (0.27-0.80), p = 0.006]. There was no difference in distal obstruction [3 (4%) vs 11 (5%) cases], infection [6 (8%) vs 12 (6%) cases], valve obstruction [0 (0%) vs 4 (2%)], or shunt disconnection [2 (3%) vs 1 (1%)] between adjustable and set-pressure valves, respectively. CONCLUSION: In our experience, the use of programmable vales was associated with a decreased risk of proximal shunt obstruction and shunt revision. Programmable valves may be preferred in patients frequently experiencing proximal shunt failure. A prospective, controlled study is warranted to evaluate the potential value of adjustable vs set-pressure valve systems.

Adolescent↗

PubMed2003

Retinoid X receptor is a nonsilent major contributor to vitamin D receptor-mediated transcriptional activation.

The vitamin D receptor (VDR) belongs to the thyroid hormone/retinoid receptor subfamily of nuclear receptors and functions as a heterodimer with retinoid X receptor (RXR). The RXR-VDR heterodimer, in contrast to other members of the class II nuclear receptor subfamily, is nonpermissive where RXR does not bind its cognate ligand, and therefore its role in VDR-mediated transactivation by liganded RXR-VDR has not been fully characterized. Here, we show a unique facet of the intermolecular RXR-VDR interaction, in which RXR actively participates in vitamin D3-dependent gene transcription. Using helix 3 and helix 12 mutants of VDR and RXR, we provide functional evidence that liganded VDR allosterically modifies RXR from an apo (unliganded)- to a holo (liganded)-receptor conformation, in the absence of RXR ligand. As a result of the proposed allosteric modification of RXR by liganded VDR, the heterodimerized RXR shows the "phantom ligand effect" and thus acquires the capability to recruit coactivators steroid receptor coactivator 1, transcriptional intermediary factor 2, and amplified in breast cancer-1. Finally, using a biochemical approach with purified proteins, we show that RXR augments the 1,25-dihydroxyvitamin D3-dependent recruitment of transcriptional intermediary factor 2 in the context of RXR-VDR heterodimer. These results confirm and extend the previous observations suggesting that RXR is a significant contributor to VDR-mediated gene expression and provide a mechanism by which RXR acts as a major contributor to vitamin D3-dependent transcription.

Allosteric Regulation↗

PubMed2002

A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand.

We provide evidence of a cross-talk between nuclear receptor and Ser/Thr protein phosphatases and show that vitamin D receptor (VDR) interacts with the catalytic subunit of protein phosphatases, PP1c and PP2Ac, and induces their enzymatic activity in a ligand-dependent manner. PP1c specifically interacts with VDR but not retinoic acid receptor alpha and retinoid X receptor alpha in yeast. Although VDR-PP1c and VDR-PP2Ac interaction is ligand-independent in vivo, 1alpha,25-dihydroxy-vitamin D(3) induces VDR-associated phosphatase activity. Further, VDR modulation of PP1c/PP2Ac activity results in a rapid and specific dephosphorylation and inactivation of their substrate, p70 S6 kinase (p70(S6k)). Finally, we demonstrate that the endogenous VDR, PP1c or PP2Ac, and p70(S6k) are present in a ternary complex in vivo, and the interaction of p70(S6k) with the VDR-PP complex is modulated by the phosphorylation state of the kinase. Since p70(S6k) is essential for G(1)-S transition, our results provide a molecular basis of 1alpha,25-dihydroxyvitamin D(3)-induced G(1) block in colon cancer cells.

G1 Phase↗