UV-induced radical formation and isomerization of 4-methoxyindole and 5-methoxyindole
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Authors: Lopes Jesus, A. J.; Rosado, Mario T. S.; Fausto, R.; Reva, I.
Abstract
Monomers of 4-methoxyindole and 5-methoxyindole trapped in low-temperature xenon matrices (15-16 K) were characterized by IR spectroscopy, in separate experiments. Each compound was shown to adopt the most stable 1H-tautomeric form. The photochemistry of the matrix-isolated compounds was then investigated by exciting the matrices with narrowband UV light with lambda <= 305 nm. Two main photoproducts, similar for each compound, have been detected: (1) 4-methoxy- or 5-methoxy-indolyl radical, resulting from cleavage of the N-H bond; (2) 3H-tautomers (4-methoxy- or 5-methoxy-) with the released hydrogen atom reconnected at the C3 ring carbon atom. The presence of the two types of photoproducts in the UV-irradiated matrices was confirmed by comparison of their B3LYP/6-311++G(d,p) calculated IR spectra with the experimental spectra emerging upon the irradiations. The mechanism of the observed phototransformations was elucidated by Natural Bond Orbital and Natural Resonance Theory computations on the methoxy-substituted indolyl radicals resulting from the N-H bond cleavage. The highest natural atomic spin densities were predicted at the C3 and N1 positions of the indolyl ring, corresponding to a predominance of the resonance structures with the radical centres located at these two atoms. As a whole, the obtained experimental and theoretical data allowed establishing a general pattern for the photochemistry of methoxyindoles under matrix-isolation conditions.
Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients
PEDIATRIC NEPHROLOGY
Authors: Miller, Paul; Xiao, Andrew Y.; Kung, Vanderlene L.; Sibley, Richard K.; Higgins, John P.; Kambham, Neeraja; Charu, Vivek; Lenihan, Colin; Uber, Amanda M.; Talley, Elizabeth M.; Arora, Neiha; Walavalkar, Vighnesh; Laszik, Zoltan G.; Nast, Cynthia C.; Troxell, Megan L.
Abstract
Background Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children. Methods We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition. Results Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-lambda, two showed IgG3-kappa, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course. Conclusions Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID.