Gaisbock's Syndrome: A Case Study.

A 73-year-old hypertensive was found to have new-onset polycythemia during his routine health check up. A workup revealed no evidence of polycythemia rubra vera or a secondary cause of his polycythemia (his erythropoietin level was normal, he had no splenomegaly, and a test for JAK2 v617F mutation was negative). Over the next year of follow up, his hematological profile returned to normal levels. We conclude that this patient had Gaisbock's syndrome, a relative polycythemia that occurs when there is clinically evident contraction of the intravascular fluid space (plasma volume) in smokers and people who received diuretics.

High magnetic field measurement utilizing Faraday rotation in SF11 glass in simplified diagnostics.

With the commercialization of powerful solid-state lasers as pointer lasers, it is becoming simpler nowadays for the launch and free-space reception of polarized light for polarimetric applications. Additionally, because of the high power of such laser diodes, the alignment of the received light on the small sensor area of a photo-diode with a high bandwidth response is also greatly simplified. A plastic sheet polarizer taken from spectacles of 3D television (commercially available) is simply implemented as an analyzer before the photo-receiver. SF11 glass is used as a magneto-optic modulating medium for the measurement of the magnetic field. A magnetic field of magnitude more than 8 Tesla, generated by a solenoid has been measured using this simple assembly. The measured Verdet constant of 12.46 rad/T-m is obtained at the wavelength of 672 nm for the SF11 glass. The complete measurement system is a cost-effective solution.

Mapping of shoot fly tolerance loci in sorghum using SSR markers.

Sorghum (Sorghum bicolor (L.) Moench) is one of the most important crops in the semiarid regions of the world. One of the important biotic constraints to sorghum production in India is the shoot fly which attacks sorghum at the seedling stage. Identification of the genomic regions containing quantitative trait loci (QTLs) for resistance to shoot fly and the linked markers can facilitate sorghum improvement programmes through marker-assisted selection. A simple sequence repeat (SSR) markerbased skeleton linkage map of two linkage groups of sorghum was constructed in a population of 135 recombinant inbred lines (RIL) derived from a cross between IS18551 (resistant to shoot fly) and 296B (susceptible to shoot fly). A total of 14 SSR markers, seven each on linkage groups A and C were mapped. Using data of different shoot fly resistance component traits, one QTL which is common for glossiness, oviposition and dead hearts was detected following composite interval mapping (CIM) on linkage group A. The phenotypic variation explained by this QTL ranged from 3.8%-6.3%. Besides the QTL detected by CIM, two more QTLs were detected following multi-trait composite interval mapping (MCIM), one each on linkage groups A and C for the combinations of traits which were correlated with each other. Results of the present study are novel as we could find out the QTLs governing more than one trait (pleiotropic QTLs). The identification of pleiotropic QTLs will help in improvement of more than one trait at a time with the help of the same linked markers. For all the QTLs, the resistant parent IS18551 contributed resistant alleles.

Serum surfactant protein-A levels in chronic bronchitis and its relation to smoking.

BACKGROUND: Surfactant protein-A (SP-A), which is an important constituent of natural surfactant, occurs physiologically in small amounts in blood. Tobacco smoke induces increased alveolo-capillary leakage of surfactant proteins into blood and its level in blood may help in the assessment of lung injury caused by smoke. Little is known on the SP-A levels in patients with chronic obstructive pulmonary disease (COPD). METHODS: Prospective analytical study of 30 patients with clinical diagnosis of chronic bronchitis, which was made on the basis of symptoms, signs and chest radiographic findings. Serum SP-A and serum cotinine levels were measured. RESULTS: Out of 30 patients, 21 were smokers and nine were non-smokers. The serum SP-A level in smokers with chronic bronchitis is significantly higher than the non-smokers. The plasma cotinine levels are also high in smokers. However, there was no correlation between the serum SP-A level and plasma cotinine level (r=0.044). Serum SP-A levels were related to age in smokers (r=0.566, p<0.01) but not in non-smokers with chronic bronchitis (r=0.017, p>0.05). CONCLUSION: The increase in SP-A level in smokers with chronic bronchitis suggests that tobacco smoking causes a chronic increase in permeability of the lung parenchyma. The SP-A, a lung-specific secretory protein, is a potential marker for non-invasive assessment of the integrity of the lung epithelium. Further studies are required to find out whether SP-A can be used as a marker for early identification of smokers who are at risk of COPD.

An all-atom solution-equilibrated model for human extrinsic blood coagulation complex (sTF-VIIa-Xa): a protein-protein docking and molecular dynamics refinement study.

Tissue factor (TF)-bound factor (F)VIIa plays a critical role in activating FX, an event that rapidly results in blood coagulation. Despite recent advances in the structural information about soluble TF (sTF)-bound VIIa and Xa individually, the atomic details of the ternary complex are not known. As part of our long-term goal to provide a structural understanding of the extrinsic blood coagulation pathway, we built an all atom solution-equilibrated model of the human sTF-VIIa-Xa ternary complex using protein-protein docking and molecular dynamics (MD) simulations. The starting structural coordinates of sTF-VIIa and Xa were derived from dynamically equilibrated solution structures. Due to the flexible nature of the light-chain of the Xa molecule, a three-stage docking approach was employed in which SP (Arg195-Lys448)/EGF2 (Arg86-Arg139), EGF1 (Asp46-Thr85) and GLA (Ala1-Lys45) domains were docked in a sequential manner. The rigid-body docking approach of the FTDOCK method in conjunction with filtering based on biochemical knowledge from experimental site-specific mutagenesis studies provided the strategy. The best complex obtained from the docking experiments was further refined using MD simulations for 3 ns in explicit water. In addition to explaining most of the known experimental site-specific mutagenesis data pertaining to sTF-VIIa, our model also characterizes likely enzyme-binding exosites on FVIIa and Xa that may be involved in the ternary complex formation. According to the equilibrated model, the 140s loop of VIIa serves as the key recognition motif for complex formation. Stable interactions occur between the FVIIa 140s loop and the FXa -strand B2 region near the sodium-binding domain, the 160 s loop and the N-terminal activation loop regions. The helical-hydrophobic stack region that connects the GLA and EGF1 domains of VIIa and Xa appears to play a potential role in the membrane binding region of the ternary complex. The proposed model may serve as a reasonable structural basis for understanding the exosite-mediated substrate recognition of sTF-VIIa and to advance understanding of the TFPI-mediated regulatory pathway of the extrinsic blood coagulation cascade.

Structural properties of DNA:RNA duplexes containing 2'-O-methyl and 2'-S-methyl substitutions: a molecular dynamics investigation.

The physical properties of a DNA:RNA hybrid sequence d(CCAACGTTGG)*(CCAACGUUGG) with modifications at the C2'-positions of the DNA strand by 2'-O-methyl (OMe) and 2'-S-methyl (SMe) groups are studied using computational techniques. Molecular dynamics simu-lations of SMe_DNA:RNA, OMe_DNA:RNA and standard DNA:RNA hybrids in explicit water indicate that the nature of the C2'-substituent has a significant influence on the macromolecular conformation. While the RNA strand in all duplexes maintains a strong preference for C3'-endo sugar puckering, the DNA strand shows considerable variation in this parameter depending on the nature of the C2'-substituent. In general, the preference for C3'-endo puckering follows the following trend: OMe_DNA>DNA>SMe_DNA. These results are further corroborated using ab initio methods. Both gas phase and implicit solvation calculations show the C2'-OMe group stabilizes the C3'-endo conformation while the less electronegative SMe group stabilizes the C2'-endo conformation when compared to the standard nucleoside. The macromolecular conformation of these nucleic acids also follows an analogous trend with the degree of A-form character decreasing as OMe_DNA:RNA>DNA:RNA>SMe_DNA:RNA. A structural analysis of these complexes is performed and compared with experimental melting point temper-atures to explain the structural basis to improved binding affinity across this series. Finally, a possible correlation between RNase H activity and conformational changes within the minor groove of these complexes is hypothesized.

Tautomeric equilibria in 8-oxopurines: implications for mutagenicity.

Free-radical-induced DNA damage by ionizing radiation leads to a number of oxidized purines, of which 7H-8-oxoguanine (8OG) and 7H-8-oxoadenine (8OA) are predominant and known to cause an appreciable amount of cellular damage. A detailed quantum mechanical study at various levels of theory in both the gas phase and in an aqueous solution has been carried out in order to assess the tautomeric preferences of the bases. The calculated energies of various plausible tautomers suggest that at higher levels of ab initio theory with inclusion of electron correlation, the 8-keto-6-enolic form of 8-oxoguanine (8OG2) would predominate over the 6,8-diketo form (8OG1) in the gas phase whereas the 6-amino-8-keto form (8OA1) predominates over the other possible tautomers of 8-oxoadenine. Aqueous solvation, however, changes the gas-phase order for 8-oxoguanine, 8OG1 turning out to be the major tautomeric species in an aqueous medium. The estimated free energies of hydration by polarized continuum models are indicative that the mutagenically significant amounts of minor tautomeric forms of 8-oxoguanine and 8-oxoadenine exist in the aqueous phase and might be held responsible for inducing transversional as well as transitional mutations.