High mobility group proteins 1 and 2 recognize chromium-damaged DNA

Chromium (Cr) is a human carcinogen and a potent DNA damaging agent. Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to DNA and, at concentrations >20 microM, altered the electrophoretic mobility of a 100 bp oligonucleotide. We also demonstrate that high mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein binding was lesion density-dependent, with maximal binding to DNA treated with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of approximately 10(-9) M. These proteins also bound DNA obtained from chromate-treated cells. These results suggest that the covalent attachment of Cr to DNA induces alterations in DNA structure which are recognized by HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA recognition proteins in vivo and as a consequence of binding, may play a role in directing the cellular response to Cr-DNA adduct formation.      

Sexual precocity: sex incidence and aetiology

The aetiology of 197 girls and 16 boys presenting with sexual precocity was reviewed. Ninety one girls and four boys had central precocious puberty (M:F 23:1); a cause was identified in all the boys but in only six girls. All boys with precocious puberty need detailed investigation; in girls investigation should be based on clinical findings, particularly the consonance of puberty.     

Incidence of maternal tachycardia during the second stage of labor: a prospective observational cohort study

Objective: To our knowledge, this is the largest prospective study reporting on maternal heart rate (MHR) levels in laboring women (30 patients), and maternal tachycardia that is a potential risk factor in fetal monitoring confusion. Our objective was to analyze a large population of contiguous laboring patients and to assess the MHR levels attained during the second stage.

Methods: We performed a prospective study that analyzed MHR levels of second-stage laboring patients evaluating numerous predisposing maternal conditions. Univariate and stepwise multivariate logistic regression analysis were performed.

Results: A total of 1105 contiguous patients were analyzed and 33.9% had a sustained MHR ≥100; 18.8% had an MHR ≥110; and 9.1% had an MHR ≥120. Multivariate analysis of all potential predisposing maternal conditions did not reveal any specific variable as uniformly significant for predicting maternal tachycardia across all levels of analysis.

Conclusions: The incidence of maternal tachycardia in the second stage of labor is common. We recommend that if the MHR is ≥100 during labor, the simultaneous maternal and fetal heart rate (FHR) monitoring will be used to minimize the potential for fetal monitoring confusion and risking poor fetal outcome if the fetus is in distress.     

Descriptive analysis of patients with community-onset and hospital-onset methicillin-resistant Staphylococcus aureus infections.

Three hundred sixty-seven hospital- and community-onset methicillin-resistant Staphylococcus aureus (MRSA) infections diagnosed in a Dallas-Fort Worth Metroplex community hospital are described. Differences in age, gender, ethnicity, and susceptibility to four antibiotics between the two groups of patients are explored.     

A specific allele of the histidine-rich glycoprotein (HRG) locus is linked with elevated plasma levels of HRG in a Dutch family with thrombosis

Recent studies describe families with both elevated plasma HRG levels and thrombosis. In order to study the possibility that allelic variants of the HRG locus are associated with differences in HRG level, we studied linkage between HRG levels and a dinucleotide repeat polymorphism in a Dutch family which was selected on the presence of both thrombosis and elevated plasma HRG levels. No other known risk factors from thrombosis were found in this family. Linkage was calculated between the dinucleotide repeat and the HRG level considering the HRG level as a quantitative phenotype assuming a population prevalence of elevated HRG of 5%. Two classes of HRG levels were defined by a mean and a variance: one class with normal HRG levels and a second class with high HRG levels. Using a mean HRG level of 99% for individuals with a normal HRG level and 145% for individuals with high HRG, a maximum lod score of 4.17 (odds in favour of linkage of 22 000:1) was found at a recombination fraction of 0, indicating linkage. Considering the pedigree, an association was found between the presence of a specific allele (no. 6) of the dinucleotide repeat polymorphism and plasma HRG levels. Family members carrying allele 6 were found to have higher HRG plasma levels compared with family members lacking allele 6 (149% v 109% respectively). We conclude that in this family, linkage is found between the HRG locus and the HRG level, and that a HRG gene coupled to allele 6 of the dinucleotide polymorphism is associated with elevated plasma HRG levels. No evidence was found for a causal relationship between elevated plasma HRG levels and thrombosis in this family.     

Reduction of sound levels with antinoise in MR imaging

A combination of active and passive techniques was used to reduce the sound levels in magnetic resonance imagers. These techniques were integrated into an existing audio system. Measurements of sound reduction varied with the protocol being used and averaged 9.9 dB with coaxial cabling and 14.2 dB with fiberoptic conduction of the feedback signal to a controller. Patient comfort and communication were improved.     

Cell-autonomous induction of functional tumor suppressor 15-lipoxygenase 2 (15-LOX2) contributes to replicative senescence of human prostate progenitor cells

Normal human prostatic (NHP) epithelial cells undergo senescence in vitro and in vivo, but little is known about the tissue-specific molecular mechanisms. Here we first characterize young primary NHP cells as CK5(+)/CK18(+) intermediate basal cells that also express several other putative stem/progenitor cell markers including p63, CD44, alpha2beta1, and hTERT. When cultured in serum- and androgen-free medium, NHP cells gradually lose the expression of these markers, slow down in proliferation, and enter senescence. Several pieces of evidence implicate 15-lipoxygenase 2 (15-LOX2), a molecule with a restricted tissue expression and most abundantly expressed in adult human prostate, in the replicative senescence of NHP cells. First, the 15-LOX2 promoter activity and the mRNA and protein levels of 15-LOX2 and its multiple splice variants are upregulated in serially passaged NHP cells, which precede replicative senescence and occur in a cell-autonomous manner. Second, all immortalized prostate epithelial cells and prostate cancer cells do not express 15-LOX2. Third, PCa cells stably transfected with 15-LOX2 or 15-LOX2sv-b, a splice variant that does not possess arachidonate-metabolizing activity, show a passage-related senescence-like phenotype. Fourth, infection of early-passage NHP cells with retroviral vectors encoding 15-LOX2 or 15-LOX2sv-b induces partial cell-cycle arrest and big and flat senescence-like phenotype. Finally, 15-LOX2 protein expression in human prostate correlates with age. Together, these data suggest that 15-LOX2 may represent an endogenous prostate senescence gene and its tumor-suppressing functions might be associated with its ability to induce cell senescence.