Archaebacterial DNA polymerases tightly bind uracil-containing DNA

We show that archaebacterial DNA polymerases are strongly inhibited by the presence of small amounts of uracil-containing DNA. Inhibition appears to be competitive, with the DNA polymerase exhibiting approximately 6500-fold greater affinity for binding the inhibitor than a DNase I-activated DNA substrate. All six archaebacterial DNA polymerases tested were inhibited, while no eubacterial, eukaryotic, or bacteriophage enzymes showed this effect. Only a small inhibition resulted when uracil was present as the deoxynucleoside triphosphate, dUTP. The rate of DNA synthesis was reduced by approximately 40% when dUTP was used in place of dTTP for archaebacterial DNA polymerases. Furthermore, an incorporated dUMP served as a productive 3'-primer terminus for subsequent elongation. In contrast, the presence of an oligonucleotide containing as little as a single dUrd residue was extremely inhibitory to DNA polymerase activity on other primer-template DNA.     

Who is driving when unrestrained children and teenagers are hurt?

This paper examines driver characteristics in crashes where child and teenage motor vehicle crash victims were injured, in particular factors that determine whether or not the victim was restrained. Analyzing the data on children and teenagers who are injured revealed that the presence of a second adult in a vehicle increased the likelihood that these passengers were unrestrained. Other findings are more predictable: victim restraint use generally mirrored driver restraint use; a male driver, a young driver, a drinking driver, a speeding or reckless driver, an unlicenced or suspended driver, and a night-time trip each independently raised the odds that child and teenage passengers were not restrained when they were injured.     

Impact of gender on coronary bypass operative mortality

I examine trends in single mothers' living arrangements using data from the 1970-1995 Current Population Surveys. I create a consistent trend by correcting a coding problem that stemmed from the misidentification of children living in multigenerational households before 1984. Revised estimates show that the number of single mothers in each of these years was undercounted by 200,000-300,000. All of these women were subfamily heads living with their parents, and the problem occurred disproportionately among teens and black women. The uncorrected trend falsely indicates a large increase in the share of single mothers living with their parents. In reality, there was little change in the percentage of single mothers living in this arrangement over the time period. However, the data indicate a large increase in the rate of cohabitation and a comparable decline in the rate of living independently among this population.     

Coronal and sagittal clefts in skeletal dysplasias

Objective. To assess the role of coronal and sagittal vertebral clefts in diagnosing skeletal dysplasias. Material and Methods. A search in the database at the International Skeletal Dysplasia Registry revealed 40 different diagnoses in which coronal or sagittal clefts were present, the major groups being: atelosteogenesis, chondrodysplasia punctata, dyssegmental dysplasia, Kniest dysplasia and short rib polydactyly syndrome. We reviewed all firm cases with both AP and lateral films of the spine in these major groups (n = 143), with patients' ages ranging from 20 weeks of gestation up to 26 years of age. Results. Ninety-four percent of all clefts were found in children less than 1 year of age, mainly located in the thoracolumbar region. Fifty-six percent of the clefts were observed in boys. Coronal clefts were more common than sagittal clefts. Clefts were most frequently observed in atelosteogenesis (88%), followed by chondrodysplasia punctata (79%), dyssegmental dysplasia (73%), Kniest dysplasia (63%) and short rib polydactyly syndrome (53%). Conclusion. Vertebral clefts are of major diagnostic value in the groups mentioned above, especially before 1 year of age. The search did not come up with new entities in which vertebral clefts are of major diagnostic value.     

Survival and disability at 7-8 years of age in New Zealand infants less than 28 weeks gestation

AIMS: To determine the survival and disability rates at 7-8 years in infants of less than 28 weeks gestation born in New Zealand in 1986 and admitted to a neonatal unit. METHODS: In 1986, all infants with birthweight less than 1500 g and admitted to neonatal units were enrolled in a prospective audit of retinopathy of prematurity. Surviving infants, including the subset born at less than 28 weeks gestation, have been assessed at a home visit. Parents completed a comprehensive questionnaire and children underwent a visual assessment and were tested on the Wechsler Intelligence Scale for Children. RESULTS: Of 126 liveborn infants less than 28 weeks gestation, 80 (64%) survived to 7-8 years. Sixty eight children (97% survivors resident in New Zealand) were assessed: 72% had no, and 86% no or only mild disability, 77% had some visual problem, with close to one-third having myopia, strabismus or requiring spectacles and 32% received Ministry of Education funded special needs assistance. CONCLUSIONS: There have been few long-term follow-up studies of infants of less than 28 weeks gestation born in a defined geographical area. The outcome for New Zealand infants is comparable with that in other published data.     

Mitochondrial adenine nucleotide translocase is modified oxidatively during aging

The purpose of this study was to test the hypothesis that elevation in protein oxidative damage during the aging process is a targeted rather than a stochastic phenomenon. Oxidative damage to proteins in mitochondrial membranes in the flight muscles of the housefly, manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl antibodies. Adenine nucleotide translocase (ANT) was found to be the only protein in the mitochondrial membranes exhibiting a detectable age-associated increase in carbonyls. The age-related elevation in ANT carbonyl content was correlated with a corresponding loss in its functional activity. Senescent flies that had lost the ability to fly exhibited a relatively higher degree of ANT oxidation and a greater loss of functional activity than their cohorts of the same age that were still able to fly. Exposure of flies to 100% oxygen resulted in an increase in the level of ANT carbonyl content and a loss in its activity. In vitro treatment of mitochondria with a system that generated hydroxyl free radicals caused an increase in ANT carbonyl level and a decrease in ANT exchange activity. ANT was also the only mitochondrial membrane protein exhibiting adducts of the lipid peroxidation product 4-hydroxynonenal. Results of this study indicate that proteins in mitochondrial membranes are modified selectively during aging.     

Two-year experience with rate-modulated pacing controlled by mixed venous oxygen saturation

Mixed venous oxy-hemoglobin saturation (MVO2) is a physiological variable with several features that might be desirable as a control parameter for rate adaptive pacing. Despite these desirable characteristics, the long-term reliability of the MVO2 sensor in vivo is uncertain. We, therefore, designed a study to prospectively evaluate the long-term performance of a permanently implanted MVO2 saturation sensor in patients requiring VVIR pacing. Under an FDA approved feasibility study, eight patients were implanted with a VVIR pulse generator and a right ventricular pacing lead incorporating an MVO2 sensor. In order to accurately assess long-term stability of the sensor, patients underwent submaximal treadmill exercise using the Chronotropic Assessment Exercise Protocol (CAEP) at 2 weeks, 6 weeks, and 3, 6, 9, 12, 18, and 24 months following pacemaker implantation. Paired maximal exercise testing using the CAEP was also performed with the pacing system programmed to the VVI and VVIR modes in randomized sequence with measurement of expired gas exchange after 6 weeks and 12 months of follow-up. During maximal treadmill exercise the peak exercise heart rate (132 +/- 9 vs 71.5 +/- 5 beats/min, P < 0.00001) and maximal rate of oxygen consumption (1,704 +/- 633 vs 1382 +/- 407 mL/min, P = 0.01) were significantly greater in the VVIR than in the VVI pacing mode. Similarly, the duration of exercise was greater in the VVIR than the VVI pacing mode (8.9 +/- 3.6 min vs 7.6 +/- 3.7 min, P = 0.04). The resting MVO2 and the MVO2 at peak exercise were similar in the VVI and VVIR pacing modes (P = NS). However, the MVO2 at each comparable treadmill exercise stage was significantly higher in the VVIR mode than in the VVI mode (CAEP stage 1 (P = 0.005), stage 2 (P = 0.04), stage 3 (P = 0.008), and stage 4 (P = 0.04). The correlation between MVO2 and oxygen consumption (VO2) was excellent (r = -0.93). Telemetry of the reflectance of red and infrared light and MVO2 in the right ventricle during identical exercise workloads revealed no significant change over the first 12 months of follow-up (ANOVA, P = NS). The chronotropic response to exercise remained proportional to VO2 in all patients over the first 12 months of follow-up. The time course of change in MVO2 during maximal exercise was significantly faster than for VO2. At the 18- and 24-month follow-up exercise tests, a significant deterioration of the sensor signal with attenuation of chronotropic response was noted for 4 of the 8 subjects with replacement of the pacing system required in one patient because of lack of appropriate rate modulation. Rate modulated VVIR pacing controlled by right ventricular MVO2 provides a chronotropic response that is highly correlated with VO2. This parameter responds rapidly to changes in workload with kinetics that are more rapid than those of VO2. Appropriate rate modulation provides a higher MVO2 at identical workloads than does VVI pacing. Although the MVO2 sensor remains stable and accurate over the first year following implantation, significant deterioration of the signal occurs by 18-24 months in many patients.     

DNA damage and cell cycle checkpoints

DNA is prone to numerous forms of damage that can injure cells and impair fitness. Cells have evolved an array of mechanisms to repair these injuries. Proliferating cells are especially vulnerable to DNA damage due to the added demands of cellular growth and division. Cell cycle checkpoints represent integral components of DNA repair that coordinate cooperation between the machinery of the cell cycle and several biochemical pathways that respond to damage and restore DNA structure. By delaying progression through the cell cycle, checkpoints provide more time for repair before the critical phases of DNA replication, when the genome is replicated, and of mitosis, when the genome is segregated. Loss or attenuation of checkpoint function may increase spontaneous and induced gene mutations and chromosomal aberrations by reducing the efficiency of DNA repair. Defects in checkpoint control have been seen in certain hereditary cancer syndromes and at early stages of cell transformation. Mutations in checkpoint control genes therefore may contribute to the genetic instability that appears to drive neoplastic evolution.