Study on quantitative structure-toxicity relationships of benzene derivatives acting by narcosis

Hydrophobicity (logP) as well as quantiative structure-toxicity relationships (QSTRs) of some benzene derivatives acting by narcosis have been established based on narcotic mechanisms of action and toxicity data to the fathead minnow, Daphnia magna and Vibrio fischeri using information-theoretic topological index (Id). Excellent results are obtained in multiparametric regression upon introduction of dummy parameters (indicator variables). Consistent increase in R(2)(A) values indicated that inspite of collinarity between Id and one of the indicator variables (I(3-6)) the proposed models are statistically significant.     

Rapid genotyping of loci involved in antifolate drug resistance in Plasmodium falciparum by primer extension

Current methods used to genotype point mutations in Plasmodium falciparum genes involved in resistance to antifolate drugs include restriction digestion of PCR products, allele-specific amplification or sequencing. Here we demonstrate that known point mutations in dihydrofolate reductase and dihydropteroate synthase can be scored quickly and accurately by single-nucleotide primer extension and detection of florescent products on a capillary sequencer. We use this method to genotype parasites in natural infections from the Thai-Myanmar border. This approach could greatly simplify large-scale screening of resistance mutations of the type required for evaluating and updating antimalarial drug treatment policies. The method can be easily adapted to other P. falciparum genes and will greatly simplify scoring of point mutations in this and other parasitic organisms.     

Fine needle aspiration cytology of bursal cyst

OBJECTIVE: To evaluate the cytomorphology of bursal cyst and assess the efficacy of aspiration cytology in its diagnosis and treatment. STUDY DESIGN: Nineteen cases of bursal cyst seen over four years were studied. Material was obtained by fine needle aspiration. The smears were stained with May-Grünwald-Giemsa stain and hematoxylin and eosin. RESULTS: Eight cysts were in the popliteal fossa, 4 on the elbow, 3 on the knee, 2 on the shoulder and 2 in the calf. Gelatinous material was aspirated in all the cases. In some cases the cyst collapsed after aspiration. The key diagnostic features were hypocellular smears in a mucoid background. Histiocytelike (synovial) cells were seen lying in all cases and as pseudopapillary structures in two. CONCLUSION: The presence of a cyst at a classic location with aspiration of gelatinous material and the presence of singly occurring histiocytelike cells in a mucoid background in smears is diagnostic of bursal cyst. The procedure is therapeutic in some cases.     

Proteome analysis of the plasma membrane of Mycobacterium tuberculosis

The plasma membrane of Mycobacterium tuberculosis is likely to contain proteins that could serve as novel drug targets, diagnostic probes or even components of a vaccine against tuberculosis. With this in mind, we have undertaken proteome analysis of the membrane of M. tuberculosis H37Rv. Isolated membrane vesicles were extracted with either a detergent (Triton X114) or an alkaline buffer (carbonate) following two of the protocols recommended for membrane protein enrichment. Proteins were resolved by 2D-GE using immobilized pH gradient (IPG) strips, and identified by peptide mass mapping utilizing the M. tuberculosis genome database. The two extraction procedures yielded patterns with minimal overlap. Only two proteins, both HSPs, showed a common presence. MALDI-MS analysis of 61 spots led to the identification of 32 proteins, 17 of which were new to the M. tuberculosis proteome database. We classified 19 of the identified proteins as 'membrane-associated'; 14 of these were further classified as 'membrane-bound', three of which were lipoproteins. The remaining proteins included four heat-shock proteins and several enzymes involved in energy or lipid metabolism. Extraction with Triton X114 was found to be more effective than carbonate for detecting 'putative' M. tuberculosis membrane proteins. The protocol was also found to be suitable for comparing BCG and M. tuberculosis membranes, identifying ESAT-6 as being expressed selectively in M. tuberculosis. While this study demonstrates for the first time some of the membrane proteins of M. tuberculosis, it also underscores the problems associated with proteomic analysis of a complex membrane such as that of a mycobacterium.     

Difference spectroscopic studies on binding of Cibacron blue F3GA to ribosome inactivating proteins: Effect of β-mercaptoethanol on the interaction with ricin

The interaction of Cibacron blue F3GA with ribosome inactivating proteins, ricin, ricin A-chain and momordin has been investigated using difference absorption spectroscopy. Ricin was found to bind the dye with a 20- and 2-fold lower affinity than ricin A-chain and momordin, respectively. A time dependent increase in the amplitude of Cibacron blue difference spectrum in the presence of ricin was observed on addition of β-mercaptoethanol. Analysis of the kinetic profile of this increase showed a biphasic phenomenon and the observed rates were found to be independent of the concentration of β-mercaptoethanol. Kinetics of reduction of the intersubunit disulphide bond in ricin by β-mercaptoethanol showed that reductionper se is a second order reaction. Therefore, the observed changes in the difference spectra of Cibacron blue probably indicate a slow change in the conformation of ricin, triggered by reduction of the intersubunit disulphide bond.     

An induced blood pressure rise does not alter upper airway resistance in sleeping humans

Wilson, Christine R., Shalini Manchanda, David Crabtree,James B. Skatrud, and Jerome A. Dempsey. An induced blood pressurerise does not alter upper airway resistance in sleeping humans.J. Appl. Physiol. 84(1): 269-276, 1998.Sleep apnea is associated with episodic increases in systemicblood pressure. We investigated whether transient increases in arterialpressure altered upper airway resistance and/or breathingpattern in nine sleeping humans (snorers and nonsnorers). Apressure-tipped catheter was placed below the base of the tongue, andflow was measured from a nose or face mask. Duringnon-rapid-eye-movement sleep, we injected 40- to 200-µg iv boluses ofphenylephrine. Parasympathetic blockade was used if bradycardia wasexcessive. Mean arterial pressure (MAP) rose by 20 ± 5 (mean ± SD) mmHg (range 12-37 mmHg) within 12 s and remained elevated for105 s. There were no significant changes in inspiratory or expiratorypharyngeal resistance (measured at peak flow, peak pressure, 0.2 l/s orby evaluating the dynamic pressure-flow relationship). Atpeak MAP, end-tidal CO₂ pressure fell by 1.5 Torr and remained low for 20-25 s. At 26 s after peak MAP, tidal volume fell by 19%, consistent with hypocapnic ventilatory inhibition. We conclude that transient increases in MAP of a magnitude commonly observed during non-rapid-eye-movement sleep-disordered breathing do not increase upper airway resistance and, therefore, willnot perpetuate subsequent obstructive events.

     

Invasive marine algae: An ecological perspective

The significance of marine algal invasion is undisputed in the global context; however, this topic has not received as much attention as it deserves. Although substantial evidence supports the fact of marine algal introduction and invasion, the underlying ecological principles need more attention to better explain such invasions. Marine algal invasions transcend national boundaries, so the problem must be considered an international problem. Commercial exploitation of invasive marine algae (and under this category we include deliberate introductions) should be undertaken, if at all, with great care and with a full understanding of all aspects of the biology and ecological consequences of the new exotic species. The aim of this article is to define algal invaders from a marine ecosystem standpoint and to discuss the different vectors, their dispersal patterns, and mechanisms of their dominance in their naturalized or introduced range     

Effect of cholesterol and 7beta-hydroxycholesterol on glutathione status and expression of Hsp70 in cultured murine peritoneal macrophages

Using cultured murine peritoneal macrophages, the change in redox ratio (oxidized/reduced glutathione) was studied at different incubation intervals (6, 12, 18 and 24 hr) with different concentrations (2.5, 5 and 7.5 microg/ml) of cholesterol and 7beta-hydroxycholesterol (7beta-OH), using fluorimeter. The changes in the levels of heat shock protein, hsp70 was determined using ELISA. Both cholesterol/7beta-OH caused a decrease in hsp70 protein levels at all the incubation intervals in dose dependent manner but the decrease was significantly higher with 7beta-OH. Treatment with 7beta-OH also resulted in significantly increased levels of oxidized glutathione (GSSG) and decreased reduced glutathione (GSH) while cholesterol showed no effect on GSSG levels. Moreover, GSH levels were lowered only at the highest concentration (7.5 microg/ml) at longer incubation intervals (18 and 24 hr) with cholesterol exposure. This altered the redox status in both cholesterol/7beta-OH treated macrophages. These results suggest that cholesterol and more likely 7beta-OH may exert their pro-atherogenic effects by lowering hsp70 protein production and inhibiting glutathione synthesis by macrophages present in the arterial wall.