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This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.

HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Extensive information is recorded for each variant and mutation, including sequence alterations, biochemical and hematological effects, associated pathology, ethnic occurrence and references. In addition to the regular updates to entries, we report two significant advances: (i) The frequencies for a large number of mutations causing beta-thalassemia in at-risk populations have been extracted from the published literature and made available for the user to query upon. (ii) HbVar has been linked with the GALA (Genome Alignment and Annotation database, available at http://globin.cse.psu.edu/gala/) so that users can combine information on hemoglobin variants and thalassemia mutations with a wide spectrum of genomic data. It also expands the capacity to view and analyze the data, using tools within GALA and the University of California at Santa Cruz (UCSC) Genome Browser.

Following the discovery of the enediyne anticancer antibiotics, investigations were initiated directed toward the design, synthesis, and study of simple monocyclic conjugated enediynes. In this article the synthesis of the parent 10-membered ring enediyne found in the enediyne natural products and its properties are described. In addition to the parent hydrocarbon 27, the synthetic methodology developed based on the Ramberg-Backlund reaction delivers a series of higher ring homologs (17-22) and the water soluble version of the 10-membered ring compound 47. Molecular mechanics calculations on these systems led to a number of geometrical parameters which correlated well with their tendencies to undergo the Bergman cycloaromatization reaction. Kinetic studies on the Bergman cycloaromatization of the 10-membered ring enediynes 27 and 47 led to the following thermodynamic values: 27, energy of activation (E(a)) = 23.8 kcal/mol, DELTA-G double dagger (37-degrees-C) = 24.6 kcal/mol; 47, energy of activation (E(a)) = 31.5 kcal/mol, DELTA-G double dagger (37-degrees-C) = 24.8 kcal/mol. The designed enediyne 47 showed potent DNA-cleaving properties becoming the first synthetic molecule to mimic the action of the naturally occurring enediynes in this regard.