Cancer incidence estimation at a district level without a national registry: A validation study for 24 cancer sites using French health insurance and registry data

Background: District-level cancer incidence estimation is an important issue in countries without a national cancer registry. This study aims to both evaluate the validity of district-level estimations in France for 24 cancer sites, using health insurance data (ALD demands – Affection de Longue Durée) and to provide estimations when considered valid. Incidence is estimated at a district-level by applying the ratio between the number of first ALD demands and incident cases (ALD/I ratio), observed in those districts with cancer registries, to the number of first ALD demands available in all districts. These district-level estimations are valid if the ratio does not vary greatly across the districts or if variations remain moderate compared with variations in incidence rates. Methods: Validation was performed in the districts covered by cancer registries over the period 2000–2005. The district variability of the ALD/I ratio was studied, adjusted for age (mixed-effects Poisson model), and compared with the district variability in incidence rate. The epidemiological context is also considered in addition to statistical analyses. Results: District-level estimation using the ALD/I ratio was considered valid for eight cancer sites out of the 24 studied (lip–oral cavity–pharynx, oesophagus, stomach, colon–rectum, lung, breast, ovary and testis) and incidence maps were provided for these cancer sites. Conclusion: Estimating cancer incidence at a sub-national level remains a difficult task without a national registry and there are few studies on this topic. Our validation approach may be applied in other countries, using health insurance or hospital discharge data as correlate of incidence.     

Collagenase in mineralized tissues of human teeth

A collagenase cleaving native type I [14C]collagen but inactive against the synthetic substrate Pz-Pro-Leu-Gly-Pro-D-Arg was extracted from mineralized human dental tissue. The enzyme specifically degrades native collagen into characteristic products (3/4) and (1/4). Its apparent molecular mass of 68 kDa is relatively high in comparison with collagenases from other oral tissues. The enzyme is a metalloproteinase inhibited by low concentrations of the chelating agents EDTA, 1, 10-phenanthroline, alpha alpha'-dipyridyl, and not affected by diisopropylfluorophosphate, soybean trypsin inhibitor, and p-chloromercuribenzoate. It is stable to lyophilization and can be stored at-20 degrees C for at least 6 months.     

Variation in Wolbachia cidB gene,but not cidA,is associated with cytoplasmic incompatibility mod phenotype diversity in Culex pipiens

Endosymbiotic Wolbachia bacteria are, to date, considered the most widespread symbionts in arthropods and are the cornerstone of major biological control strategies. Such a high prevalence is based on the ability of Wolbachia to manipulate their hosts' reproduction. One manipulation called cytoplasmic incompatibility (CI) is based on the death of the embryos generated by crosses between infected males and uninfected females or between individuals infected with incompatible Wolbachia strains. CI can be seen as a modification‐rescue system (or mod‐resc) in which paternal Wolbachia produce mod factors, inducing embryonic defects, unless the maternal Wolbachia produce compatible resc factors. Transgenic experiments in Drosophila melanogaster and Saccharomyces cerevisiae converged towards a model where the cidB Wolbachia gene is involved in the mod function while cidA is involved in the resc function. However, as cidA expression in Drosophila males was required to observe CI, it has been proposed that cidA could be involved in both resc and mod functions. A recent correlative study in natural Culex pipiens mosquito populations has revealed an association between specific cidA and cidB variations and changes in mod phenotype, also suggesting a role for both these genes in mod diversity. Here, by studying cidA and cidB genomic repertoires of individuals from newly sampled natural C. pipiens populations harbouring wPipIV strains from North Italy, we reinforce the link between cidB variation and mod phenotype variation fostering the involvement of cidB in the mod phenotype diversity. However, no association between any cidA variants or combination of cidA variants and mod phenotype variation was observed. Taken together our results in natural C. pipiens populations do not support the involvement of cidA in mod phenotype variation.     

129-Derived Mouse Strains Express an Unstable but Catalytically Active DNA Polymerase Iota Variant

Mice derived from the 129 strain have a nonsense codon mutation in exon 2 of the polymerase iota (Polι) gene and are therefore considered Polι deficient. When we amplified Polι mRNA from 129/SvJ or 129/Ola testes, only a small fraction of the full-length cDNA contained the nonsense mutation; the major fraction corresponded to a variant Polι isoform lacking exon 2. Polι mRNA lacking exon 2 contains an open reading frame, and the corresponding protein was detected using a polyclonal antibody raised against the C terminus of the murine Polι protein. The identity of the corresponding protein was further confirmed by mass spectrometry. Although the variant protein was expressed at only 5 to 10% of the level of wild-type Polι, it retained de novo DNA synthesis activity, the capacity to form replication foci following UV irradiation, and the ability to rescue UV light sensitivity in Polι^−/− embryonic fibroblasts derived from a new, fully deficient Polι knockout (KO) mouse line. Furthermore, in vivo treatment of 129-derived male mice with Velcade, a drug that inhibits proteasome function, stabilized and restored a substantial amount of the variant Polι in these animals, indicating that its turnover is controlled by the proteasome. An analysis of two xeroderma pigmentosum-variant (XPV) cases corresponding to missense mutants of Polη, a related translesion synthesis (TLS) polymerase in the same family, similarly showed a destabilization of the catalytically active mutant protein by the proteasome. Collectively, these data challenge the prevailing hypothesis that 129-derived strains of mice are completely deficient in Polι activity. The data also document, both for 129-derived mouse strains and for some XPV patients, new cases of genetic defects corresponding to the destabilization of an otherwise functional protein, the phenotype of which is reversible by proteasome inhibition.     

Magnetic resonance distinction between site bound and atmospherically bound paramagnetic counterions in polyelectrolyte solutions.

A combination of the water protons NMR chemical shifts, longitudinal and transversal relaxation rates and of the paramagnetic counterion EPR signal is shown to provide a clear distinction between site binding, atmospheric trapping and free counterions in solutions of polyelectrolyte TMA salts with increasing concentrations of the divalent counterions Co++ and Mn++. Site binding is defined by the loss of water in the counterion first hydration shell while atmospheric binding results in a change in the counterion correlation time as compared to a free ion.     

Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin

Acne vulgaris is a chronic inflammatory disorder of the sebaceous follicles. Propionibacterium acnes (P. acnes), a gram-positive anareobic bacterium, plays a critical role in the development of these inflammatory lesions. This study aimed at determining whether reactive oxygen species (ROS) are produced by keratinocytes upon P. acnes infection, dissecting the mechanism of this production, and investigating how this phenomenon integrates in the general inflammatory response induced by P. acnes. In our hands, ROS, and especially superoxide anions (O₂ ^•−), were rapidly produced by keratinocytes upon stimulation by P. acnes surface proteins. In P. acnes-stimulated keratinocytes, O₂ ^•− was produced by NAD(P)H oxidase through activation of the scavenger receptor CD36. O₂ ^•− was dismuted by superoxide dismutase to form hydrogen peroxide which was further detoxified into water by the GSH/GPx system. In addition, P. acnes-induced O₂ ^•− abrogated P. acnes growth and was involved in keratinocyte lysis through the combination of O₂ ^•− with nitric oxide to form peroxynitrites. Finally, retinoic acid derivates, the most efficient anti-acneic drugs, prevent O₂ ^•− production, IL-8 release and keratinocyte apoptosis, suggesting the relevance of this pathway in humans.     

Polarized fluorescence in an electric field. A model calculation with application to the geometry of the 2-hydroxy-4,4′-diamidinostilbene–DNA complex

Theoretical expressions are derived for the change in the polarized components of the fluorescence, resulting from the orientation of a rigid molecule bearing a chromophore with arbitrary angles for the absorption and transition moments \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _a $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _e $\end{document} with respect to the molecular axis. The break in the symmetry relation H_V = V_H is related to the tilt angle between \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _a $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ \vec \mu _e $\end{document}. The theory is applied to a sonicated DNA–2-hydroxy-4,4′-diamidinostilbene complex, in the blue and red emission bands of this peculiar dye. Simultaneous measurements of linear dichroism and fluorescence lead to the determination of an angle of 47° between a fluorescent bound dye and the DNA axis, with no difference for the blue- and red-emitting species, but confirm the presence of nonfluorescent bound dye in a more perpendicular arrangement.