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PubMed2006

Associations among health behaviors and time perspective in young adults: model testing with boot-strapping replication.

Previous research suggests that time perspective relates to health behavior; however, researchers have frequently employed inconsistent operational definitions and have often used projective or unpublished measures. The Zimbardo Time Perspective Inventory was created to provide a sound, objective measure of five distinct time perspective components. We examined the independent prediction of both risky and protective health behaviors from future, hedonistic, and fatalistic time perspective in 1,568 undergraduates using the Zimbardo Time Perspective Inventory. Health behaviors included alcohol, drug, tobacco, and seat belt use, sex behaviors, and exercise. Future time perspective was related to increased protective and decreased risky health behaviors, whereas hedonism exhibited an opposite pattern though was a stronger predictor; fatalism was related only to health-destructive behaviors. Gender interactions reveal that hedonism is a stronger predictor of risky health behaviors for females.

Adolescent↗
PubMed1988

Replication program of active and inactive multigene families in mammalian cells.

In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cell lines exhibiting different tissue-specific functions. Some of the rules we have determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (iii) Nontranscribed genes can replicate during any interval of S phase. (iv) Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of contiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.

Animals↗
PubMed1999

Eukaryotic DNA replication.

One of the fundamental characteristics of life is the ability of an entity to reproduce itself, which stems from the ability of the DNA molecule to replicate itself. The initiation step of DNA replication, where control over the timing and frequency of replication is exerted, is poorly understood in eukaryotes in general, and in mammalian cells in particular. The cis-acting DNA element defining the position and providing control over initiation is the replication origin. The activation of replication origins seems to be dependent on the presence of both a particular sequence and of structural determinants. In the past few years, the development of new methods for identification and mapping of origins of DNA replication has allowed some understanding of the fundamental elements that control the replication process. This review summarizes some of the major findings of this century, regarding the mechanism of DNA replication, emphasizing what is known about the replication of mammalian DNA. J. Cell. Biochem. Suppls. 32/33:1-14, 1999.

Animals↗
PubMed2001

Are estimates of MAC reliable?

BACKGROUND: Potency of inhaled anesthetics (minimum alveolar concentration [MAC]) is typically studied in humans using an "up-down" approach in which the (quantal) response to skin incision is assessed only once for each individual, so that each individual's MAC is never determined. The authors examined the influence of interindividual variability and study design issues (e.g., the number of patients enrolled in a study) on the accuracy of MAC estimates. METHODS: The typical sequence of a MAC study was simulated. The authors varied and tested the impact of several factors: anesthetic concentration used to start a study; number of "crossovers" (successive patients having different responses to skin incision) to terminate a study; concentration increment between consecutive patients; interindividual variability; and "measurement error." For each factor, simulations were replicated 500 times, and the resulting estimates were summarized. RESULTS: Starting an experiment below or above the "true" value led to slightly biased MAC estimates; in contrast, variability was underestimated with starting concentrations close to the true value. More than six crossovers improved MAC estimates minimally but increased variability estimates toward true values. A larger increment size affected MAC minimally and increased variability estimates toward true values. A larger interindividual variability led to more "outlier" estimates for MAC. Under many conditions, several of 500 replicates yielded MAC estimates that deviated more than 10% or even more than 25% from the "true" value. CONCLUSION: Individual experiments may yield inaccurate MAC estimates. This inaccuracy is minimized as the number of crossovers increases; however, improvement diminishes as the number of crossovers exceeds six.

Anesthesia, Inhalation↗
PubMed1992

Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells.

This study was aimed at dissecting the cellular mechanisms that underly the growth of actively expanding human goiter nodules. Thirty-two nodules from different patients, all removed because of steady recent growth, were serially sectioned and screened for 1) histomorphological signs of cell proliferation and 2) in situ expression of the immunohistochemically stained p21ras protooncogene product. Bovine, porcine, and rat thyroid glands (the latter from both T4- and perchlorate-treated animals) were used as controls. In normal glands, only a few follicular cells contain substantial amounts of stainable p21ras. Some of these cells are unusually large, but do not proliferate. In contrast, all goiter nodules contain areas where the epithelial cells are morphologically grossly altered and heavily loaded with p21ras. Cells of this type are mostly clustered in large cohorts coating whole follicles or entire groups of follicles. Only a small fraction of these activated cells actually proliferates at any one point in time. Actively replicating cells are scattered in tiny foci all over the nodules. The earliest proliferating buds are solid, but soon begin to generate microfollicles that enlarge by adding new cells to the follicular epithelium. Regionally heterogeneous p21ras content in morphologically identical cells suggests that growth occurs in bursts and waves. We conclude that goiter nodules grow by episodic proliferation of heterogeneous cohorts of epithelial cells from which new follicles are generated. Only a tiny fraction of all goiter cells proliferate at any one point in time. The molecular mechanisms governing these growth processes are unknown.

Adolescent↗
PubMed1979

Object Investigation by the oestrous rat and guinea-pig: the oestrous cycle and the effects of oestrogen and progesterone.

The time spent investigation small objects in an arena was found to vary systematically with the oestrous cycle of rats and guinea-pigs. Both the total time spent and the mean time per object were greater for oestrous animals, which show more long bouts of investigation per test than do dioestrous animals. The changes in investigation time were replicated by administering oestradiol benzoate followed after 40 h by progesterone, to ovariectomized rats, suggesting an endocrine basis. Most bouts of investigation were terminated by a move straight to another object, suggesting that it had been chosen before the move was made.

Animals↗
PubMed1985

Chromosome structure and DNA replication in nurse and follicle cells of Drosophila melanogaster.

In the nurse cells of Drosophila, nuclear DNA is replicated many times without nuclear division. Nurse cells differ from salivary gland cells, another type of endoreplicated Drosophila cell, in that banded polytene chromosomes are not seen in large nurse cells. Cytophotometry of Feulgen stained nurse cell nuclei that have also been labeled with 3H-thymidine shows that the DNA contents between S-phases are not doublings of the diploid value. In situ hybridization of cloned probes for 28S + 18S ribosomal RNA, 5S RNA, and histone genes, and for satellite, copia, and telomere sequences shows that satellite and histone sequences replicate only partially during nurse cell growth, while 5S sequences fully replicate. However, during the last nurse cell endoreplication cycle, all sequences including the previously under-replicated satellite sequences replicate fully. In situ hybridization experiments also demonstrate that the loci for the multiple copies of histone and 5S RNA genes are clustered into a small number of sites. In contrast, 28S + 18S rRNA genes are dispersed. We discuss the implications of the observed distribution of sequences within nurse cell nuclei for interphase nuclear organization. In the ovarian follicle cells, which undergo only two or three endoreplication cycles, satellite, histone and ribosomal DNA sequences are also found by in situ hybridization to be underrepresented; satellite sequences may not replicate beyond their level in 2C cells. Hence the pathways of endoreplication in three cell types, salivary gland, nurse, and follicle cells, share basic features of DNA replication, and differ primarily in the extent of association of the duplicated chromatids.

Animals↗
PubMed1992

Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication.

The dose and time dependency of peroxisome proliferation and hepatocyte replication was evaluated in the liver of rats fed the peroxisome proliferator and hepatocarcinogen, Wy-14,643. Male F344 rats were fed NIH07 diet blended with Wy-14,643 at 0, 5, 10, 50, 100, or 1000 ppm for 1, 3, 6, or 13 weeks. Hepatomegaly was induced by Wy-14,643 at all doses and at all time points. Peroxisome proliferation was present in rats fed 5 ppm Wy-14,643 as early as 1 week, as determined by the peroxisome-specific NAD+ reduction of palmitoyl CoA (PCO) and the peroxisome-associated activity of carnitine acetyltransferase (CAT) (5- and 11-fold over control, respectively). The elevations of PCO and CAT were dose-dependent from 5 to 50 ppm and then plateaued from 50 to 1000 ppm throughout the treatment period. Hepatocellular replication, evaluated by nuclear histoautoradiography ([3H]thymidine labeling, 6-day infusion), was increased in all Wy-14,643 dose groups after 1 week of treatment (5 ppm, 4-fold; 10 ppm, 5-fold; 50 ppm, 13-fold; 100 ppm, 12-fold; and 1000 ppm, 13-fold over controls). However, in 5 and 10 ppm groups this cell replication returned to control levels by 3 weeks. In contrast, 50, 100, and 1000 ppm groups had sustained increases in cell replication up to 13 weeks (13 weeks: 6-, 7-, and 9-fold over controls, respectively). We have demonstrated that Wy-14,643 can induce peroxisome proliferation at 5 ppm, a dose 200 times lower than the dose shown to be highly hepatocarcinogenic in rats (100% incidence by 60 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Paradoxes of eukaryotic DNA replication: MCM proteins and the random completion problem.

Eukaryotic DNA replication initiates at multiple origins. In early fly and frog embryos, chromosomal replication is very rapid and initiates without sequence specificity. Despite this apparent randomness, the spacing of these numerous initiation sites must be sufficiently regular for the genome to be completely replicated on time. Studies in various eukaryotes have revealed that there is a strict temporal separation of origin "licensing" prior to S phase and origin activation during S phase. This may suggest that replicon size must be already established at the licensing stage. However, recent experiments suggest that a large excess of potential origins are assembled along chromatin during licensing. Thus, a regular replicon size may result from the selection of origins during S phase. We review single molecule analyses of origin activation and other experiments addressing this issue and their general significance for eukaryotic DNA replication.

Animals↗
PubMed2006

Enhanced clinical utility of the NucliSens EasyQ RSV A+B Assay for rapid detection of respiratory syncytial virus in clinical samples.

The aim of the present study was to compare traditional methods for the detection of respiratory syncytial virus with a newly developed commercial assay based on real-time nucleic acid sequence based amplification. Respiratory syncytial virus is a major cause of severe respiratory infection in infants and in certain groups of older children and adults. Treatment options are limited, but a rapid diagnosis improves patient management and infection control. The rapid diagnosis of respiratory syncytial virus currently relies on antigen detection assays. These tests are limited to use in certain good-quality types of samples, which are rarely obtained from adult patients. Molecular-based assays for the detection of respiratory syncytial virus are shown to be highly sensitive, specific, and more rapid than cell culture techniques. This retrospective study compared traditional laboratory techniques for the detection of respiratory syncytial virus in 508 respiratory samples collected during the winter months of 2003-2004 against the recently developed, commercially available NucliSens EasyQ Respiratory Syncytial Virus A+B assay (bioMérieux, Marcy l'Etoile, France), which is based on real-time nucleic acid sequence based amplification using molecular beacons and an internal control. Using traditional techniques, the prevalence of respiratory syncytial virus in the samples tested was found to be 21%. Using the real-time nucleic acid sequence-based amplification assay, an additional 41 samples from patients with a clinically diagnosed respiratory illness were found to be positive for respiratory syncytial virus. The NucliSens EasyQ assay was shown to be sensitive and specific for the detection of respiratory syncytial virus A+B in different types of respiratory samples. Moreover, the time required to complete the assay was <4 h, so results could be obtained on the same day as sample receipt in the laboratory.

Adult↗
PubMed1986

Recognition of emotion in hemifaces presented to the left and right visual fields.

Thirty-two right-handed subjects (16 males and 16 females) participated in a choice reaction time experiment replicating two previous studies which demonstrated the superiority of the left hemisphere in rapidly identifying facial emotion as either positive or negative. Slides of hemifaces split along the vertical axis, showing either positive (happiness, surprise) or negative (anger, disgust, or sadness) affect were presented tachistoscopically to either the left or right visual field. A 2 X 2 X 2 mixed ANOVA revealed main effects for visual field and type of affect. In contrast to earlier studies which presented full face stimuli, presentation of hemifaces produced a strong left visual field advantage and, as expected, positive faces produced faster reaction times than negative faces.

Adolescent↗
PubMed1995

Prediction of protein degradation of forages from solubility fractions.

Two experiments were conducted to determine the relationship between enzymatic digestion of forage protein and fractionation based on solubility. The first experiment used 42 forages, each replicated three times, including different species, stages of maturity, and methods of conservation. Crude protein was fractionated into six parts for each forage by sequential extraction in TCA, bicarbonate-phosphate buffer, acetone, detergent at pH 7, and detergent with acid. Multiple regression analysis, with all the solubility fractions as independent variables, resulted in prediction of CP degradation by ruminal enzyme extract at 2 and 24 h; R2 were .88 and .81, respectively. Greater solubility in the buffer and the detergent at pH 7 was associated with higher protein degradation; solubility in acetone, detergent with acid, and insolubility were associated with lower degradation. In the second experiment, eight forages each replicated twice were digested with ruminal enzyme for 0, 2, 6, and 24 h and then were extracted as described. Solubility in TCA and acetone increased during degradation, but solubility in buffer, detergent with acid, and insolubility decreased. For both experiments, buffer-soluble CP was the only uniform fraction across forages; other fractions contained proteins that degraded at diverse rates. Solubility of CP is related to degradation properties, but further research is needed to improve the accuracy of predictions based on solubility.

Animal Feed↗
PubMed2006

Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV-infected children.

OBJECTIVE: The use of antiretroviral therapy in HIV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children. METHODS: The study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis. RESULTS: A total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001). CONCLUSION: Triple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HIV-infected children. Therefore, triple therapy should be the treatment of choice.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Cloning of nascent monkey DNA synthesized early in the cell cycle.

To study the structure and complexity of animal cell replication origins, we have isolated and cloned nascent DNA from the onset of S phase as follows: African green monkey kidney cells arrested in G1 phase were serum stimulated in the presence of the DNA replication inhibitor aphidicolin. After 18 h, the drug was removed, and DNA synthesis was allowed to proceed in vivo for 1 min. Nuclei were then prepared, and DNA synthesis was briefly continued in the presence of Hg-dCTP. The mercury-labeled nascent DNA was purified in double-stranded form by extrusion (M. Zannis-Hadjopoulos, M. Perisco, and R. G. Martin, Cell 27:155-163, 1981) followed by sulfhydryl-agarose affinity chromatography. Purified nascent DNA (ca. 500 to 2,000 base pairs) was treated with mung bean nuclease to remove single-stranded ends and inserted into the NruI site of plasmid pBR322. The cloned fragments were examined for their time of replication by hybridization to cellular DNA fractions synthesized at various intervals of the S phase. Among five clones examined, four hybridized preferentially with early replicating fractions.

Animals↗
PubMed1991

The novel tertiary structure in delta RNA may function as a ribozyme control element.

The viroid-like domain making up the lefthand end of the delta hepatitis genome (Branch et al., 1989) has structural elements whose interactions may be essential for replication. This portion of the genome is highly conserved in primary sequence and contains two well-defined types of structural features: sites capable of self-cleavage, and those forming a UV-sensitive element of local tertiary structure which is very stable and contains non-Watson:Crick bonds that may form a distinctive surface for binding specific proteins. The proximity of the tertiary structure to the genomic self-cleavage site suggests that the photoreactive element may regulate the ribozyme. This element's stability would limit "breathing" in this region of the circular genome, maintaining the ribozyme in the "off" conformation; its tight structure could be relieved by protein binding at the time of replication. We previously mapped a novel local tertiary structure to a highly conserved portion of the viroid genome (Branch et al., 1985). The many additional properties shared by viroids, related infectious circular RNAs of plants, and the delta agent are discussed in a recent article (Branch et al., in press-a).

Base Sequence↗
PubMed2005

Inherent correlation between dose and clearance in therapeutic drug monitoring settings: possible misinterpretation in population pharmacokinetic analyses.

During the course of therapeutic drug monitoring (TDM), doses are adjusted to attain a target concentration range and a correlation between clearance (CL) and dose is introduced. In population pharmacokinetic analyses of such TDM data, CL has frequently been modeled as a function of dose. This paper demonstrates by simulation methodology that the TDM process does indeed introduce a correlation between dose and CL which can be interpreted as a nonlinearity. Using literature values of carbamazepine pharmacokinetics, three steady-state concentrations were simulated following a standard 1000 mg total daily dose (TDD) regimen in 100 in silico subjects. A set of clinical rules was established to adjust the TDD based on these three concentrations, as might be done in the clinical setting. Another set of concentrations using these TDM-derived TDDs for each subject (600-1600 mg) was simulated. A standard population pharmacokinetic analysis of the post-TDM data was conducted using NONMEM. This process was replicated 100 times to estimate the type II error rate. When CL was modeled without TDD, plots of WRES versus PRED demonstrated a clear pattern, as did the delta plots of CL (CL minus TVCL) versus TDD, suggesting the covariate TDD should be incorporated into the model. After TDD was included in the model for CL, the objective function value decreased by an average of 75.7 (p < 0.001). In addition, the inter-individual variability in CL expressed as a coefficient of variation decreased by an average of 9.9% and the diagnostic plots improved. Although CL was simulated to be independent of TDD, it was identified as an important covariate using standard approaches in a simulated TDM setting in 100% of the replicated simulation studies. The TDM process introduces a correlation between CL and TDD that can be misinterpreted as nonlinearity in the system.

Analgesics, Non-Narcotic↗
PubMed2006

Continued evolution of HIV-1 circulating in blood monocytes with antiretroviral therapy: genetic analysis of HIV-1 in monocytes and CD4+ T cells of patients with discontinued therapy.

The role of blood monocytes in HIV-1 infection is a relatively new field of interest. What happens to HIV-1 in monocytes and their relationship to CD4+ T cells before, during, and after suppressive antiretroviral therapy (ART) is largely unstudied. Here, considering that diversity is a good indicator of continued replication over time, we evaluated the effect of ART on HIV-1 in blood monocytes and CD4+ T cells by examining the diversity of HIV-1 from 4 infected patients who underwent and stopped therapy. We determined diversity and compartmentalization of HIV-1 between blood monocytes and CD4+ T cells in each patient in relationship to their ART regimens. Our data indicate that the rate of HIV-1 diversity increase in monocytes during therapy was significantly higher than in CD4+ T cells (P<0.05), suggesting that HIV-1 present in monocytes diversify more during therapy than in CD4+ T cells. Increased rates of HIV-1 compartmentalization between monocytes and CD4+ T cells while on therapy were also observed. These results suggest that ART inhibits HIV-1 replication in CD4+ T cells more than in blood monocytes and that better treatments to combat HIV-1 in monocytes/macrophages may be needed for a more complete suppression of HIV replication.

Anti-HIV Agents↗
PubMed1994

Rapid increases in load of human immunodeficiency virus correlate with early disease progression and loss of CD4 cells in vertically infected infants.

The relationship between viral burden, timing of transmission, and clinical progression was investigated in 110 children at risk for vertical human immunodeficiency virus (HIV) infection using quantitative polymerase chain reaction, coculture, and immune complex-dissociated p24 antigen assay. In a cross-sectional study, the mean HIV DNA copy number in 19 symptomatic children was significantly higher than in 31 infected, asymptomatic children (420 +/- 125 vs. 87 +/- 78; P < .0001). In a second group of 8 vertically infected infants followed prospectively from birth, 4 defined as infected in utero showed a more rapid increase in virus load, an accelerated loss of CD4 cells, and early progression to symptomatic disease (3-12 weeks) compared with 4 children with late in utero or intrapartum transmission (10-31 months). These data suggest that a direct relationship exists between HIV replication, the timing of transmission and onset and progression of HIV disease in vertically infected children.

Acquired Immunodeficiency Syndrome↗