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D Ranganathan

Publications and source records attributed to D Ranganathan.

22 records · Page 2Linked to original sources

Racemization of tyrosine in the insoluble protein fraction of brunescent aging human lenses.

With increase in age, proteins of the eye lens undergo covalent modifications associated with interprotein cross-linking, loss of protein solubility, generation of protein-associated pigments, and racemization of some optically active residues. Precipitated protein aggregates localized in the nucleus of brunescent lenses are modified to such an extent that they become resistant to the commonly used methods of extraction by reducing agents or detergents. Thus, little information is available on the types of protein modifications that occur in the nuclear region of the lens. Here we report the simultaneous solubilization and digestion of the entire nuclear pellet of brunescent human cataract lenses into constituent amino acids and their derivatives through protease action at neutral pH. Fractionation of the resulting hydrolyzate by reverse phase chromatography, followed by spectroscopic and biochemical analysis of one of the purified fractions, showed the presence of racemic tyrosine in the amino acid mixture. Racemization of L-amino acid residues in protein chains is associated with the aging process. This is the first report of racemization of tyrosine in any system studied so far.

Aging↗

Protein-associated pigments that accumulate in the brunescent eye lens. Identification of a quinoline derivative.

Brunescent (dark brown) cataract is particularly prevalent in the tropics. Enzymatic digestion of the insoluble protein fraction of brunescent cataractous eye lenses from India, followed by high performance liquid chromatographic separation of the pigments and spectroscopic investigations, have led to the identification of one of the pigments as 4-hydroxyquinoline-3-[alpha-aminoacetic acid] (compound A). The 4-hydroxyquinoline moiety is shown to be a photodynamic agent that generates O2.- and leads to protein crosslinking. This suggests that the compound A may play a long-term deleterious role in situ in the lens.

Cataract↗

Conformation of the oxalamide group in retro-bispeptides. Three crystal structures.

We have determined the structures of a range of peptides having the oxalamide (-NH-CO-CO-NH-) unit located at their center. The oxalamide group has the trans conformation in two retropeptides and an approximately orthogonal conformation in the peptide with Pro residues. Torsional angles about the CO-CO bond are 180 degrees in MeO-Aib-CO-CO-Aib-OMe (1), 175 degrees in MeO-L-Leu-CO-CO-L-Leu-OMe (2), and -108 and -106 degrees for the two independent molecules in the crystal of MeO-L-Pro-CO-CO-L-Pro-OMe (3), owing to steric hindrance between CO and the pyrolidine ring. Crystal data are: (1) C12H20N2O6, triclinic, space group P1, a = 6.190(1), b = 10.044(2), c = 11.989(2) A, alpha = 86.13(12), beta = 83.13(2), gamma = 80.16(2) degrees, R = 0.057 for 1646 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)]; (2) C16H28N2O6, tetragonal, space group P4(1), a = b = 11.121(3), c = 15.775(6) A, R = 0.058 for 1216 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)]; (3) C14H20N2O6, monoclinic space group P2(1), a = 9.556(2), b = 17.864(3), c = 9.618(2) A, beta = 104.35(1) degree; R = 0.051 for 2100 observed reflections [magnitude of Fo > 3 sigma (magnitude of Fo)].

Amides↗

Group B streptococcus: to culture or not to culture?

OBJECTIVE: To determine if universal Group B Streptococcus (GBS) culturing and antibiotic prophylaxis of obstetric patients decreased the incidence of neonatal early-onset GBS sepsis and mortality and maternal chorioamnionitis. STUDY DESIGN: A time series observational study was conducted to compare the cohort of all obstetric patients delivering at the University of Chicago neonatal center from January 1989 through December 1993, before a GBS surveillance policy existed, with the cohort delivering January 1994 through December 1996, after initiation of a GBS policy. Included in the policy were universal GBS cultures at 28 weeks' gestation, antibiotic prophylaxis at the time of labor for all those with positive cultures and for all with risk factors of preterm delivery, preterm premature rupture of membranes, prolonged rupture of membranes greater than 18 hours, and a previous child affected by GBS or maternal fever in labor. Predictor variables were GBS culturing and antibiotic usage; outcome variables were incidence of GBS sepsis and mortality in the neonates and maternal chorioamnionitis. chi-squared and Fisher exact analyses were used with p < 0.05 being significant. RESULTS: Before the GBS policy, there were 16,272 deliveries with a 2.24/1000 deliveries rate of early-onset GBS sepsis (n = 35); after initiating the GBS policy, 9130 deliveries occurred with an early-onset GBS sepsis rate of 2.29/1000 (n = 20). Early-onset GBS sepsis case fatality rates before and after initiation of the policy were 14.3% and 0%, respectively (p = 0.09). Antibiotic use almost doubled (relative risk = 1.84; confidence interval, 1.74 to 1.93, p < 0.001) over the two time periods, and the relative risk of chorioamnionitis decreased to 0.95 (confidence interval, 0.73 to 0.99, p = 0.04). CONCLUSION: Despite universal GBS culturing and very liberal use of antibiotics in labor, we were unable to effect a statistically significant change in the rate of early-onset GBS sepsis or mortality, and there was only a slightly decreased chorioamnionitis rate.

Anti-Bacterial Agents↗