Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track Gene Expression by Both Partners during Initiation of Symbiosis.

The establishment of a productive symbiosis between Euprymna scolopes, the Hawaiian bobtail squid, and its luminous bacterial symbiont, Vibrio fischeri, is mediated by transcriptional changes in both partners. A key challenge to unraveling the steps required to successfully initiate this and many other symbiotic associations is characterization of the timing and location of these changes. We report on the adaptation of hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) to simultaneously probe the spatiotemporal regulation of targeted genes in both E. scolopes and V. fischeri. This method revealed localized, transcriptionally coregulated epithelial cells within the light organ that responded directly to the presence of bacterial cells while, at the same time, provided a sensitive means to directly show regulated gene expression within the symbiont population. Thus, HCR-FISH provides a new approach for characterizing habitat transition in bacteria and for discovering host tissue responses to colonization.

Half mustard (CEES) induced damage to rabbit cornea: attenuating effect of taurine-pyruvate-alpha-ketoglutarate-pantothenate mixture.

Studies have been conducted on the corneal damage by half mustard (2-chloroethyl-ethyl sulfide, CEES) and its possible prevention by a mixture of taurine, alpha-ketoglutarate, pyruvate and pantothenate. CEES has been found to damage the membrane permeability function of the corneal epithelium as evidenced by increased flux of the rubidium ion from the epithelial to the endothelial side. The cornea also loses its transparency. These damaging effects are preventable by the above mixture labeled as VM. It is conceived that use of such a mixed formulation may provide a pharmacological means of prophylactic and post-exposure treatment against the tissue damage caused by exposure to the mustards.

Corneal damage by half mustard (2-chloroethyl ethyl sulfide, CEES) in vitro preventive studies: a histologic and electron microscopic evaluation.

The effect of half-mustard (2-chloroethyl ethyl sulfide, CEES) on the morphology and ultrastructure of the cornea has been studied in vitro. Extensive necrotic changes were observed histologically as well as electron microscopically. The outer layer of corneal epithelium was observed to undergo vacuolization and globulization prior to its denudation. The epithelium becomes separated from the Bowman's membrane. These necrotic changes are prevented from taking place in the presence of a mixture of taurine, pyruvic acid, alpha-keto glutaric acid and pantothenic acid suggesting the use of this mixture in the prevention of mustard damage.

Structure-activity relationship for DNA topoisomerase II-induced DNA cleavage by azatoxin analogues.

Eighteen analogues of the nonintercalative DNA topoisomerase II (topo II)-active epipodophyllotoxin-ellipticine hybrid, azatoxin, were synthesized and evaluated for their ability to induce topo II-mediated DNA strand breaks in vitro. In general, the SAR profile of the azatoxins showed more homology with that of the epipodophyllotoxins than with the ellipticines. Of the compounds studied, only fluoro substitution at the 8-, 9, and 10-positions of azatoxins enhanced activity, with 9-fluoroazatoxin being the most active compound in this series.

[Transfusion medicine in unified Europe. Brief report on the status of transfusion medicine in central and east European countries]. / Transfusionsmedizin im geeinten Europa. Kurzbericht über den Stand der Transfusionsmedizin in den zentralen und osteuropäischen Ländern.

Requests of the Council of Europe are harmonization of policies, encouragement of voluntary, unremunerated donation, self-sufficiency and introduction of EC quality standards. Present conditions were evaluated by a study in 11 countries of Eastern and Central Europe. Quality control is usually done according to USSR guidelines. Alarming are decreasing numbers of blood donations of 15% within 2 years. For satisfaction of FVIII needs plasma production has to be increased 3 times. In the countries of Western Europe too self-sufficiency is not yet reached. Strong efforts should be taken in Eastern, Central and also in Western Europe to reach self-sufficiency in the evolving unified Europe.

Chemistry of artemisinin: an overview.

The endoperoxide sesquiterpene lactone, artemisinin, and its derivatives have become increasingly important as antimalarial drugs with impressive activity against multidrug resistant forms of Plasmodium falciparum. Artemisinin has a novel structure among known antimalarial compounds with a unique 1,2,4-trioxane ring that is essential for activity. This paper gives an overview of the chemistry of artemisinin and comments on future prospects for artemisinin and its derivatives.

Rational design and molecular effects of a new topoisomerase II inhibitor, azatoxin.

Azatoxin [NSC 640737-M; 5.R,11aS-1H,6H,3-one-5,4,11,11a-tetrahydro-5-(3,5-dimethoxy-4-hydr oxyphenyl) oxazolo (3',4':1,6)pyrido-(3,4-b)indole] was rationally designed from a model for the pharmacophore of drugs with topoisomerase II inhibition activity. This pharmacophore has at least 2 domains: a quasiplanar polycyclic ring system proposed to bind between the DNA base pairs and a pendant substituent proposed to interact with the enzyme and/or to the DNA grooves. The present study shows that, in cell free systems, azatoxin induces a large number of double strand-breaks in linear Simian virus 40 and human c-myc DNA. These breaks yield cleavage patterns that are different from those of well established topoisomerase II inhibitors (epipodophyllotoxins, amsacrine, mitoxantrone). Azatoxin also inhibits the catalytic activity of purified topoisomerase II, and is a nonintercalator. The structure-activity relationship of 3 isomers and 6 derivatives of azatoxin shows a stringent stereochemical requirement for activity. The effects of azatoxin pendant ring substitution on topoisomerase II mediated DNA cleavage activity were similar to the relationship observed for etoposide.

Cytotoxicity of acridine compounds for Leishmania promastigotes in vitro.

The effect of mammalian and bacterial topoisomerase II inhibitors on Leishmania promastigotes was studied in vitro. Parasites were incubated with drugs, and cytotoxicity was assessed on the basis of the loss of flagellar motility and cell lysis after 48 h. 9-Aminoacridines, which are structurally related to the known antileishmanial compounds quinacrine and chlorpromazine, showed activity against the parasite at concentrations in the range of 10 to 20 microM. Adriamycin showed far less activity, while etoposide and several quinolones were inactive at 100-microM concentrations. These results demonstrate that a particular structural class of compounds is cytotoxic to Leishmania species. The unique structure-activity relationship discovered suggests that leishmanial topoisomerase II could be a useful target for chemotherapy.