Showing papers by "Seth M. Cohen published in 2001"

Cisplatin: from DNA damage to cancer chemotherapy.

Abstract: Cisplatin [cis-DDP, cis-diamminedichloroplatinum(II)] is a potent anticancer drug that has been used successfully to treat tumors of the head, neck, lungs, and genitourinary tract. The biological activity of cisplatin was discovered serendipitously more than 30 years ago, and since that time research efforts have focused on elucidating its mechanism of action. The present review provides a historical perspective of our attempts to understand this complex phenomenon and the results of recent work that guides our current activities in this field. Continued efforts to understand the mechanism of genotoxicity of cisplatin are expected to lead to the discovery of new drugs and combinations for the improvement of cancer chemotherapy.

Synthesis and metal binding properties of salicylate-, catecholate-, and hydroxypyridinonate-functionalized dendrimers.

Abstract: The synthesis, characteriza- tion, and metal-binding studies of che- late-functionalized dendrimers is report- ed. Salicylate, catecholate, and hydroxy- pyridinonate bidentate chelators have been coupled to the surface of both poly(propyleneimine) (Astramol) and poly(amidoamine) (Starburst, PA- MAM) dendrimers up to the fifth gen- eration (64 endgroups). A general meth- od has been developed for the facile and high quality chromatographic purifica- tion of poly(propyleneimine) and poly- (amidoamine) dendrimer derivatives. One- and two-dimensional (TOCSY) 1 H NMR experiments and electrospray ionization mass spectrometry (ESI-MS) have confirmed the exhaustive coupling of these chelators to the primary amine functionalities of the dendrimers. Spec- trophotometric titrations were used to investigate the metal binding ability of these macrochelates. Spectral analysis shows that ferric iron binding to these ligands is localized to the chelating endgroups. The ability of these dendritic polymers to bind large numbers of metal ions may lead to applications as metal sequestering agents for waste remedia- tion technologies.

Synthesis of homochiral tris(2-alkyl-2-aminoethyl)amine derivatives from chiral alpha-amino aldehydes and their application in the synthesis of water soluble chelators

Abstract: A novel synthesis of 3-fold symmetric, homochiral tris(2-alkyl-2-aminoethyl)amine (TREN) derivatives is presented. The synthesis is general in scope, starting from readily prepared chiral alpha-amino aldehydes. The optical purity of the N-BOC protected derivatives of tris(2-methyl-2-aminoethyl)amine and tris(2-hydroxymethyl-2-aminoethyl)amine has been ascertained by polarimetry and chiral NMR chemical shift experiments. An X-ray diffraction study of the L-alanine derivative (tris(2-methyl-2-aminoethyl)amine.3 HCl, L-Ala(3)-TREN) is presented: crystals grown from ether diffusion into methanol are cubic, space group P2(1)3 with unit cell dimensions a = 11.4807(2) A, V = 1513.23(4) A(3), and Z = 4. Attachment of the triserine derived backbone tris(2-hydroxymethyl-2-aminoethyl)amine (L-Ser(3)-TREN) to three 3-hydroxy-1-methyl-2(1H)-pyridinonate (3,2-HOPO) moieties, followed by complexation with Gd(III) gives the complex Gd(L-Ser(3)-TREN-Me-3,2-HOPO)(H(2)O)(2), which is more water soluble than the parent Gd(TREN-Me-3,2-HOPO)(H(2)O)(2) and a promising candidate for magnetic resonance imaging (MRI) applications. Crystals of the chiral ferric complex Fe(L-Ser(3)-TREN-Me-3,2-HOPO) grown from ether/methanol are orthorhombic, space group P2(1)2(1)2(1), with unit cell dimensions a = 13.6290(2) A, b = 18.6117(3) A, c = 30.6789(3) A, V = 7782.0(2) A(3), and Z = 8. The solution conformation of the ferric complex has been investigated by circular dichroism spectroscopy. The coordination chemistry of this new ligand and its iron(III) and gadolinium(III) complexes has been studied by potentiometric and spectrophotometric methods. Compared to the protonation constants of previously studied polydentate 3,2-HOPO-4-carboxamide ligands, the sum of protonation constants (log beta(014)) of L-Ser(3)-TREN-Me-3,2-HOPO (24.78) is more acidic by 1.13 log units than the parent TREN-Me-3,2-HOPO. The formation constants for the iron(III) and gadolinium(III) complexes have been evaluated by spectrophotometric pH titration to be (log K) 26.3(1) and 17.2(2), respectively.

Use of Rigid and Flexible Bronchoscopy Among Pediatric Otolaryngologists

Abstract: Objective To explore how rigid and flexible bronchoscopy are used in pediatric otolaryngologic practice. Design Survey. Participants Members of the American Society of Pediatric Otolaryngology who practice in the United States and Canada and were listed in the membership directory were eligible. Of the 206 members, 24 practicing outside the United States or Canada and 11 without an e-mail address or a fax machine were excluded. Hence, a questionnaire was e-mailed or faxed to 171 pediatric otolaryngologists. Main Outcome Measures Questions concerned the practice setting, type and number of bronchoscopies, indications, complications, and medicolegal cases. Results Responses were received from 120 subjects (70.2%), with 3 retired and 2 practicing only otology, leaving 115 respondents who completed at least some of the questionnaire. Rigid and flexible bronchoscopy were performed by 72.7% (56/77) of those in academic settings and by 71.1% (27/38) of those in group or solo practices. In the last 12 months, approximately 10 454 total bronchoscopies were performed, with 2052 flexible and 9117 rigid bronchoscopies. Stridor, suspected foreign body inhalation, and laryngomalacia were the most common indications for bronchoscopy. Of the 83 respondents practicing rigid and flexible bronchoscopy, 25 (30.1%) used both instruments to manage complex or repeated foreign bodies, 25 (30.1%) used both to manage patients with cystic fibrosis, and 15 (18.1%) used both to manage simple foreign bodies. Complications were reported by 15.7% of the respondents, the most common being arrhythmia. Familiarity with a case resulting in medicolegal action was reported by 32.2% of the respondents. Conclusions Rigid and flexible bronchoscopy have multiple uses in pediatric otolaryngologic practice. Also, flexible bronchoscopy appears to be emerging as a more frequently used diagnostic and therapeutic tool.