PubMed Health⌕ Search

Biomedical subjects

John Wade

Publications and source records attributed to John Wade.

9 recordsLinked to original sources
PubMed2006

Acetylated Tat regulates human immunodeficiency virus type 1 splicing through its interaction with the splicing regulator p32.

The human immunodeficiency virus type 1 (HIV-1) potent transactivator Tat protein mediates pleiotropic effects on various cell functions. Posttranslational modification of Tat affects its activity during viral transcription. Tat binds to TAR and subsequently becomes acetylated on lysine residues by histone acetyltransferases. Novel protein-protein interaction domains on acetylated Tat are then established, which are necessary for both sustained transcriptional activation of the HIV-1 promoter and viral transcription elongation. In this study, we investigated the identity of proteins that preferentially bound acetylated Tat. Using a proteomic approach, we identified a number of proteins that preferentially bound AcTat, among which p32, a cofactor of splicing factor ASF/SF-2, was identified. We found that p32 was recruited to the HIV-1 genome, suggesting a mechanism by which acetylation of Tat may inhibit HIV-1 splicing needed for the production of full-length transcripts. Using Tat from different clades, harboring a different number of acetylation sites, as well as Tat mutated at lysine residues, we demonstrated that Tat acetylation affected splicing in vivo. Finally, using confocal microscopy, we found that p32 and Tat colocalize in vivo in HIV-1-infected cells.

Acetylation↗
PubMed2005

Relaxin research in the postgenomic era.

Because of the coevolution of ligands and their cognate receptors, analysis of human genomic sequences allows prediction of the pairing of these elements. Initially, we identified a group of five human leucine-rich repeat-containing G-protein-coupled receptor (LGR) genes homologous to LH, FSH, and TSH receptors. Based on common phenotypes of INSL3 null mice and transgenic mice with LGR8 gene deletion, we hypothesized that INSL3, relaxin, and related genes are likely ligands for the paralogous LGR7 and LGR8 genes. Matching the relaxin family peptides with these two orphan LGRs led to the finding that relaxin is capable of activating LGR7 and LGR8 through the Gs pathway. In addition, INSL3 and relaxin 3 were found to be specific ligands for LGR8 and LGR7, respectively. Based on the known production of INLS3 by testicular Leydig cells and ovarian theca cells, we demonstrated the expression of the INSL3 receptor LGR8 in oocytes in ovary and in male germ cells in the testis. Furthermore, we found that LH stimulates INSL3 transcripts in ovarian theca and testicular Leydig cells. INSL3, in turn, binds LGR8 expressed in germ cells to initiate the meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo and to suppress male germ cell apoptosis in vivo. INSL3 interacts with germ cells to activate the inhibitory G protein, thus leading to decreases in cAMP production. Our data demonstrate the importance of the INSL3-LGR8 paracrine system in mediating gonadotropic actions in both ovary and testis.

Animals↗
PubMed2005

Clinical effects of intraarticular injection of high molecular weight hyaluronan (Orthovisc) in osteoarthritis of the knee: a randomized, controlled, multicenter trial.

OBJECTIVE: To evaluate the efficacy and safety of injection of high molecular weight (HMW) hyaluronan (Orthovisc) in patients with mild, moderate, and severe knee osteoarthritis (OA). METHODS: A randomized, arthrocentesis-controlled, multicenter trial. Patients (n = 372) were randomized to 4 weekly HMW hyaluronan injections (O4, n = 128), 3 weekly HMW hyaluronan injections followed by one arthrocentesis (O3A1, n = 120), or 4 arthrocenteses without injection (control group, A4, n = 124). All patients had knee OA, as determined by Kellgren-Lawrence (K-L) grade, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score > or = 200 mm and < 400 mm in index knee and < 150 mm in contralateral knee. The primary outcome measure was the proportion of patients achieving a 20% relative and 50 mm absolute improvement from baseline in WOMAC pain score at Weeks 8, 12, 16, and 22 post-baseline in the index knee. Secondary outcomes were Patient Global score, Investigator Global score, and Pain on Standing score. RESULTS: The evaluable subgroup consisted of patients with K-L grade 2 or 3 at baseline. The comparison of O4 versus A4 for the primary outcome approached, but did not reach, significance in the evaluable subgroup: 76% of O4 patients had > or = 20% improvement in WOMAC pain score at Week 8 compared to 62% of A4 patients. More O4 patients had > or = 40% improvement in WOMAC pain score compared to A4. The effectiveness of the 3-injection regimen (O3A1) was masked by a possible placebo effect from the needle injection procedure in the A4 (control) group. No differences between groups were observed with respect to incidence of adverse events. CONCLUSION: Our findings indicate that HMW hyaluronan is safe and seems to be effective in the treatment of mild to severe OA of the knee.

Adult↗
PubMed2004

Installation of a multiplexed Raman system in a chemical process.

A 785 nm laser dispersive Raman system was installed in a hazardous chemical production plant to monitor two reactors, a still, and a holding tank with measurement directly through sight glasses. Compositional information for several raw materials, intermediates, and products was obtained using partial least squares (PLS) calibrations. Discriminate analysis was used to exclude extremely poor spectra while including usable ones. Derivative/standard normal variate (SNV) treatment was found to be effective for correcting for background fluorescence and for large differences in spectral intensity. Final regression equations incorporated temperature fluctuations, occasional fluorescence, some sunlight effects, large intensity variations, and large compositional changes. Various installation problems were solved via data treatment or mechanical changes. The Raman system provides information for control of the process, resulting in cost savings and improved safety.

Algorithms↗
PubMed2002

Consumerism: automating patient and provider interactions.

Healthcare is essentially an information industry that is seeking to automate its processes and use Internet technology to support its consumers. The healthcare industry understands that, without computerization, it would be nearly impossible to reduce medical errors, analyze the delivery of care, and provide real-time clinical decision support to healthcare providers to support patient care via the Internet. Without progressive steps, use of Internet technology to care for patients will be limited. The only way to meet the information challenges of tomorrow is to begin capitalizing on today's technology and implement the necessary tools now. Most important, healthcare organizations need to adopt a full array of technology to support their consumers in the electronic world of today and tomorrow.

Consumer Advocacy↗