Biomedical subjects
Publications and source records attributed to Keith Gordon.
Ten years have passed since follitropin-beta first became commercially available. It is estimated that more than one million children have been born after ovarian stimulation and/or ovulation induction with this recombinant FSH in assisted reproduction.
A series of novel zinc metalloporphyrins, cyano-3-(2'-(5',10',15',20'-tetraphenylporphyrinato zinc(II))yl)-acrylic acid (Zn-3), 3-(trans-2'-(5',10',15',20'-tetraphenylporphyrinato zinc(II))yl)-acrylic acid (Zn-5), 2-cyano-5-(2'-(5',10',15',20'-tetraphenylporphyrinato zinc(II))yl)-penta-2,4-dienoic acid (Zn-8), 4-(trans-2'-(2' '-(5' ',10' ',15' ',20' '-tetraphenylporphyrinato zinc(II))yl)ethen-1'-yl))-1,2-benzenedicarboxylic acid (Zn-11), and 2-cyano-3-[4'-(trans-2' '-(2' ''-(5' '',10' '',15' '',20' ''-tetraphenylporphyrinato zinc(II))yl) ethen-1' '-yl)-phenyl]-acrylic acid (Zn-13) were synthesized and characterized by using various spectroscopic techniques. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations show that key molecular orbitals (MOs) of porphyrins Zn-5 and Zn-3 are stabilized and extended out onto the substituent by pi-conjugation, causing enhancement and red shifts of visible transitions and increasing the possibility of electron transfer from the substituent. The porphyrins were investigated for conversion of sunlight into electricity by constructing dye-sensitized TiO(2) solar cells using an I(-)/I(3)(-) electrolyte. The cells yield close to 85% incident photon-to-current efficiencies (IPCEs), and under standard AM 1.5 sunlight, the Zn-3-sensitized solar cell demonstrates a short circuit photocurrent density of 13.0 +/- 0.5 mA/cm(2), an open-circuit voltage of 610 +/- 50 mV, and a fill factor of 0.70 +/- 0.03. This corresponds to an overall conversion efficiency of 5.6%, making it the most efficient porphyrin-sensitized solar cell reported to date.
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Activation of T cells is necessary for efficient retroviral-mediated gene transfer. In addition, if the population of infused cells is to be limited to transduced cells, a means of positive selection is required. We describe a clinical scale procedure for activation of donor T cells with anti-CD3/CD28 beads followed by transduction with a retroviral construct expressing the herpes simplex virus thymidine kinase (HSV-tk) and human nerve growth factor receptor (NGFR). Optimization of transduction parameters was performed, testing the timing of transduction, centrifugation, and the use of serum. In large-scale experiments, 3-5 x 10(8) peripheral blood mononuclear cells (PBMC) were activated with anti-CD3/CD28 beads and expanded to day 13. Transduction was accomplished using MFG-TKiNG supernatant produced from the PG13 packaging line 48 hr after T-cell activation. The mean transduction frequency was 37.5% based on NGFR expression, and the mean expansion observed was 42.6-fold (mean final cell number 1.85 x 10(10)). A comparison of the ability of the Baxter Isolex 300i and the Miltenyi CliniMACS to perform purification of NGFR+ cells suggests that greater purity can be achieved with the CliniMACS device (67.4% vs. 97.7%), while the yield of transduced cells appears higher with the Isolex 300i (41.3% vs. 23.5%). We conclude that a strategy based on activation of human T cells with anti-CD3/CD28 beads can result in sufficient transduction, expansion, and purification based on NGFR expression for clinical trials.
This article reviews the past, present, and future of gonadotrophin therapy, including purification of gonadotrophins from animal or human urine sources and production of gonadotrophins through recombinant technology. With the advent of recombinant DNA methodologies combined with site-directed mutagenesis, a variety of structural modifications becomes possible.