AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins

Recent studies show that Hox homeodomain proteins from paralog groups 1 to 10 gain DNA binding specificity and affinity through cooperative binding with the divergent homeodomain protein Pbx1. However, the AbdB-like Hox proteins from paralogs 11, 12, and 13 do not interact with Pbx1a, raising the possibility of different protein partners. The Meis1 homeobox gene has 44% identity to Pbx within the homeodomain and was identified as a common site of viral integration in myeloid leukemias arising in BXH-2 mice. These integrations result in constitutive activation of Meis1. Furthermore, the Hoxa-9 gene is frequently activated by viral integration in the same BXH-2 leukemias, suggesting a biological synergy between these two distinct classes of homeodomain proteins in causing malignant transformation. We now show that the Hoxa-9 protein physically interacts with Meis1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis1 site (TGACAG) and an AbdB-like Hox site (TTTTACGAC). Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b, while Hox proteins from other paralogs do not appear to interact with Meis1 proteins. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.     

Tetracycline-resistant Chlamydia trachomatis in Toulouse, France

Host immunity to Epstein-Barr Virus Patterns of Epstein-Barr Virus latent gene expression in EBV posttransplantation lymphoproliferative disorders Cytokines network in posttransplantation lymphoproliferative disorders associated with EBV Lymphomagenesis and EBV Morphology and clonality of posttransplantation lymphoproliferative disorders associated with EBV Treatment of posttransplantation lymphoproliferative disorders associated with EBV.     

A decade of clinical trial developments in postmyocardial infarction, congestive heart failure, and sustained ventricular tachyarrhythmia patients: from CAST to AVID and beyond. Cardiac Arrhythmic Suppression Trial. Antiarrhythmic Versus Implantable Defibrillators

Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients: (1) postmyocardial infarction; (2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and (3) with sustained ventricular tachycardia and those who have survived an out-of-hospital cardiac arrest. This article reviews some of the key findings and limitations of completed and ongoing trials. We also make recommendations for the current treatment of such patients based on the results of these trials.     

Successful long-term ventricular pacing via the coronary sinus after the Fontan operation

A man with double inlet left ventricle and severe subpulmonary stenosis underwent a Fontan operation at the age of 29 years. Eight years later he developed atrial flutter with complete heart block. To avoid a further thoracotomy, a unipolar carbon tipped electrode was placed into the posterior cardiac vein via the coronary sinus. More than 8 years after implantation of the original lead, and after two generator changes, telemetric thresholds remain between 1.8-2.1 volts. Percutaneous transvenous ventricular pacing via the coronary sinus can produce an excellent long-term result and should be the initial approach of choice after a Fontan-type operation.     

Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings

Tribal warfare is a way of life in the highlands of Papua New Guinea. In earlier times direct confrontation with bushknives and axes, and shooting with bows and arrows were common. In recent years there have not been as many instances of direct confrontation with bushknives and axes, but the use of bows and arrows is on the rise. Since 1993, guns have been increasingly used, with devastating results. In 1993, 18 deaths were reported from tribal warfare in one area of the Southern Highlands Province, especially from gunshots, while in 1994, 24 deaths were reported from another area. A five-year review of tribal fight admissions to Mendi Hospital, from 1990 to 1994, showed an increase in the number and proportion of gunshot wounds; there were none in 1990-1992 but they constituted 18% of tribal fight injuries in 1993 and 33% in 1994.     

Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians

Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19q13.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p = 0.009), and with common GYS1 alleles (p = 0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of GYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25% reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t-test p = 0.024; Wilcoxon's rank-sum test, p = 0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance. We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element.     

Rapid tamoxifen-induced inactivation of an estrogenic response is accompanied by a localized epigenetic modification but not by mutations

Ethidium was found to be efficiently cross-linked to DNA by glyoxal. Kinetic studies showed that the rate of the cross-linking reaction is strongly dependent on the glyoxal concentration. Comparative studies using a series of phenanthridines and acridines showed that NH2 groups at both the 2 and 7 positions on the phenanthridine ring are necessary for efficient cross-linking. Studies using synthetic polydeoxynucleotides showed that the 2-amino group of guanine is absolutely required for cross-linking. Fluorescence contact energy transfer and relative viscosity experiments showed that the cross-linked drug remains intercalated into DNA. DNA gel electrophoresis and melting studies demonstrated that cross-linked ethidium does not dissociate the DNA double helix to single strands.