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PubMed2002

Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival crevicular fluid in matched clinical sites in smokers and non-smokers with persistent periodontitis.

BACKGROUND/AIMS: Smokers with persistent periodontitis may have granulocytes with impaired function. This study aimed to determine the levels of granulocyte elastase, matrix metalloproteinase-8 (MMP-8) and prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF) in smokers and non-smokers with persistent periodontitis. METHODS: We analyzed GCF from 70 matched sites in 29 periodontitis and 6 gingivitis sites in 34 subjects, 17 smokers, and 17 non-smokers. We also analyzed separately GCF from 28 of these subjects, 14 smokers and 14 non-smokers in 14 matched periodontitis sites. The following measurements were made: elastase complexed to alpha1-antitrypsin (EA-alpha1AT) and MMP-8 with ELISA, functional elastase with a chromogenic substrate, and PGE2 with radioimmunoassay (125I RIA). The significance of the findings was determined with Mann-Whitney test. RESULTS: In the 29 matched periodontitis sites, smokers had significantly more functional elastase (p<0.005) and more EA-alpha1AT (p<0.05) than non-smokers. In the 14 matched periodontitis sites in 14 smokers and 14 non-smokers, the former had significantly more functional elastase than the latter (p<0.001). A significant correlation was found between EA-alpha1AT and MMP-8 in smokers (p<0.05) and non-smokers (p<0.001) and a positive correlation between levels of functional elastase and MMP-8 in non-smokers (r2=0.98; p<0.001). CONCLUSIONS: Granulocyte function seems to be impaired in smokers with persistent periodontitis. The cells react to the bacterial challenge by releasing serine proteases, which reflect the degradation of connective tissue. The risk of progression of the disease is therefore higher in smokers with persistent periodontitis than in non-smokers.

Case-Control Studies↗
PubMed2001

Persistence of contact allergy among Danish adults: an 8-year follow-up study.

In 1990, a random sample of 567 persons of the 15-69-year-old population living in the Western part of Copenhagen County, Denmark, was patch tested in a cross-sectional study. In 1998, a follow-up study was performed. Out of 540 invited, 365 (68%) were re-patch tested. In the follow-up study, the persistence of allergic contact sensitivity, defined as 1 or more positive patch tests in both surveys, was 71% (37 out of 52 subjects). Nickel allergy persisted in 79% (19 out of 24 subjects), while 60% (21 out of 35 subjects) had a positive patch test reaction to 1 or more allergens, other than nickel, in both surveys. The lowest persistence was 50% (5 out of 10 subjects) and this was found for patch test reactivity to 1 or more of the cosmetic ingredients included in the patch test series. 8 years after the baseline study had demonstrated allergic contact sensitivity, 71% of the subjects still had at least 1 positive patch test. Nickel allergy persisted in 79%. Allergen avoidance should probably be lifelong to prevent elicitation of contact dermatitis.

Adolescent↗
PubMed1984

On the relationship between stimulus intensity and duration of visible persistence.

Stimulus intensity and duration of visible persistence have been found to vary directly in some studies but inversely in others. Hawkins and Shulman (1979) have proposed that this inconsistency can be resolved by separating the studies that employed a decrement-threshold measure of persistence (Type I measure) from those that measured the total duration of persistence (Type II measure). They suggested that Type I measures yield an inverse relationship, whereas Type II measures yield a direct relationship between intensity and persistence. Hawkins and Shulman's model is incomplete in ways that are easily remedied. However, the model is totally contradicted by the experimental evidence. A new resolution of the inconsistent results is proposed in terms of retinal afterimages.

Attention↗
PubMed1985

Suppression of visible persistence.

Five experiments were conducted to examine duration of visible persistence in sequences of stimuli. The basic display consisted of a point that stepped around a circular path on the face of an oscilloscope. Observers estimated the number of points seen simultaneously. Results were compared with a control condition in which the points were plotted in random order rather than sequentially. It was found that visible persistence of a point is suppressed if other points are shown nearby and after an appropriate delay. The degree of suppression depended on the spatial proximity of successive points. It was also found that both duration of visible persistence and degree of suppression increase with eccentricity in the visual field. The results are discussed in terms of two independent processes, persistence and suppression, that operate in a hierarchically antithetical relation.

Figural Aftereffect↗
PubMed1990

On the relation between metacontrast masking and suppression of visible persistence.

Does the introduction of additional contours in a display sequence (an operation known to reduce the strength of suppression in metacontrast) also reduce suppression of visible persistence? In three experiments, duration of visible persistence was estimated by a method in which successful performance depends on the temporal integration of a pattern whose elements are displayed in two successive frames. In this procedure, the arrival of the trailing frame is known to exert a suppressive influence on the visible persistence of the leading frame. Embedding the elements of the leading frame within additional contours (a line grid) reduced the degree of suppression exerted by the trailing frame. This did not occur when the grid was part of the trailing display. We conclude that suppression of visible persistence and metacontrast masking belong to the same class of events.

Adult↗
PubMed1981

Duration of visible persistence in relation to range of spatial frequencies.

Five experiments examined the relationship between range of spatial frequencies contained in a visual display and duration of visible persistence. The high spatial frequency contents of the display were reduced by defocusing the image at the retina. Duration of visible persistence was measured by a task that required perceptual integration of a pattern whose parts were displayed sequentially in time. Experiments 1 and 2 showed that progressive reductions in the high-frequency contents of the display produced corresponding decrements in the duration of visible persistence. Experiments 3, 4, 5 showed that decrements in the duration of visible persistence could not be attributed to changes in the apparent size or in the brightness of the display brought about by defocusing. The results were interpreted in terms of the temporal response properties of perceptual mechanisms attuned to separate ranges of spatial frequencies. Strong parallels were drawn with the multichannel theory of visual information processing proposed by Breitmeyer and Ganz.

Discrimination Learning↗
PubMed2005

Perceptions of parental involvement and support as predictors of college students' persistence in a science curriculum.

As technological and scientific skills are increasingly needed, finding that science students encounter significant problems in their academic program causes serious concern. The authors examined how perceived parental involvement and support predict college students' persistence in science based on J. P. Connell and J. G. Wellborn's (1991) theoretical model: Perceived parental involvement and support should foster student persistence by promoting students' competence, autonomy, and relatedness. Results suggest that perceived parental autonomy supports predicted scientific persistence partly through students' autonomy. Perceived parental involvement, although unrelated to persistence, was a significant predictor of autonomy and relatedness. Results suggest that perceived parental involvement and support have specific roles in predicting student self-processes and achievement, highlighting the importance of sustaining parents' contribution for college students.

Adolescent↗
PubMed1988

Persistent protein kinase activity underlying long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a much-studied example of synaptic plasticity. Although the role of N-methyl-D-aspartate (NMDA) receptors in the induction of LTP is well established, the nature of the persistent signal underlying this synaptic enhancement is unclear. Involvement of protein phosphorylation in LTP has been widely proposed, with protein kinase C (PKC) and calcium-calmodulin kinase type II (CaMKII) as leading candidates. Here we test whether the persistent signal in LTP is an enduring phosphoester bond, a long-lived kinase activator, or a constitutively active protein kinase by using H-7, which inhibits activated protein kinases and sphingosine, which competes with activators of PKC (ref. 17) and CaMKII (ref. 18). H-7 suppressed established LTP, indicating that the synaptic potentiation is sustained by persistent protein kinase activity rather than a stably phosphorylated substrate. In contrast, sphingosine did not inhibit established LTP, although it was effective when applied before tetanic stimulation. This suggests that persistent kinase activity is not maintained by a long-lived activator, but is effectively constitutive. Surprisingly, the H-7 block of LTP was reversible; evidently, the kinase directly underlying LTP remains activated even though its catalytic activity is interrupted indicating that such kinase activity does not sustain itself simply through continual autophosphorylation (see refs 9, 13, 15).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Habitat structure and population persistence in an experimental community.

Understanding spatial population dynamics is fundamental for many questions in ecology and conservation. Many theoretical mechanisms have been proposed whereby spatial structure can promote population persistence, in particular for exploiter-victim systems (host-parasite/pathogen, predator-prey) whose interactions are inherently oscillatory and therefore prone to extinction of local populations. Experiments have confirmed that spatial structure can extend persistence, but it has rarely been possible to identify the specific mechanisms involved. Here we use a model-based approach to identify the effects of spatial population processes in experimental systems of bean plants (Phaseolus lunatus), herbivorous mites (Tetranychus urticae) and predatory mites (Phytoseiulus persimilis). On isolated plants, and in a spatially undivided experimental system of 90 plants, prey and predator populations collapsed; however, introducing habitat structure allowed long-term persistence. Using mechanistic models, we determine that spatial population structure did not contribute to persistence, and spatially explicit models are not needed. Rather, habitat structure reduced the success of predators at locating prey outbreaks, allowing between-plant asynchrony of local population cycles due to random colonization events.

Animals↗
PubMed2001

In vivo intracellular recording and perturbation of persistent activity in a neural integrator.

To investigate the mechanisms of persistent neural activity, we obtained in vivo intracellular recordings from neurons in an oculomotor neural integrator of the goldfish during spontaneous saccades and fixations. Persistent changes in firing rate following saccades were associated with step changes in interspike membrane potential that were correlated with changes in eye position. Perturbation of persistent activity with brief intracellular current pulses designed to mimic saccadic input only induced transient changes of firing rate and membrane potential. When neurons were hyperpolarized below action potential threshold, position-correlated step changes in membrane potential remained. Membrane potential fluctuations were greater during more depolarized steps. These results suggest that sustained changes in firing rate are supported not by either membrane multistability or changes in pacemaker currents, but rather by persistent changes in the rate or amplitude of synaptic inputs.

Action Potentials↗
PubMed1997

Expression of tissue type plasminogen activator and type 1 plasminogen activator inhibitor, and persistent fibrin deposition in chronic renal allograft failure.

Persistent fibrin deposition has been observed in kidneys undergoing chronic rejection, and has been suggested to contribute to the obliteration of the vasculature in these grafts. The mechanisms leading to it are not clear. Fibrinolysis, the process to remove fibrin in tissues, is initiated by tissue type plasminogen activator (tPA) and suppressed by type 1 plasminogen activator inhibitor (PAI-1). To investigate their roles in chronic rejection and fibrin deposition, we serially examined the expression of tPA and PAI-1 in an unmodified chronic rejection model, using a Fisher 344 to Lewis rat renal transplant, at 0, 2, 4, 6, 10, 12, 16 and 20 weeks post-transplantation (N = 4 rats/time point in each group). We also analyzed fibrin deposition and the development of chronic changes in the grafts. Our results show that tPA was up-regulated only in the acute phase of rejection (P < 0.05), whereas PAI-1 was induced and persistently expressed during the progressive phase of chronic rejection, together with persistent fibrin deposition in the grafts. Immunohistochemistry showed PAI-1 was mainly localized to the damaged/proliferative vascular intima. The results suggest that persistent induction of PAI-1 may be responsible for the continuance of fibrin deposition, which is associated with irreversible damage and chronic graft loss.

Animals↗
PubMed2003

Tuberculosis: a problem with persistence.

Mycobacterium tuberculosis is one of most successful pathogens of mankind, infecting one-third of the global population and claiming two million lives every year. The ability of the bacteria to persist in the form of a long-term asymptomatic infection, referred to as latent tuberculosis, is central to the biology of the disease. The persistence of bacteria in superficially normal tissue was recognized soon after the discovery of the tubercle bacillus, and much of our knowledge about persistent populations of M. tuberculosis dates back to the first half of the last century. Recent advances in microbial genetics and host immunity provide an opportunity for renewed investigation of this persistent threat to human health.

Animals↗
PubMed2000

Rapid desensitization of the TRH receptor and persistent desensitization of its constitutively active mutant.

We studied rapid desensitization of the thyrotropin-releasing hormone receptor (TRH-R) or the m1-muscarinic receptor (m1-R) to a short challenge of threshold TRH concentration and persistent desensitization due to constitutive activity of a mutant TRH-R. Xenopus oocytes expressing TRH-Rs and/or m1-Rs were challenged for 15 s with threshold concentrations of TRH ([TRH]) and then immediately with supraoptimal [TRH] or acetylcholine ([ACh]). The threshold challenge caused desensitization of 50 - 57% of responses to subsequent supraoptimal stimulation with TRH or ACh. The homologous desensitization was reversible within 60 s after removal of the agonist. The protein kinase C (PKC) inhibitor, chelerythrine, inhibited the control responses by 30 - 40%, without affecting the desensitized responses. Chelerythrine or the phosphatase inhibitor, okadaic acid, had little effect on the kinetics of resensitization, indicating limited involvement of PKC. In oocytes coexpressing wild type TRH-Rs or m1-Rs with a constitutively active TRH-R mutant (C335Stop TRH-R), a persistent desensitization (33 - 57%) of the responses to TRH or ACh was observed. Additionally, there was a complete loss of the rapid desensitization induced by threshold [TRH]. Chlorodiazepoxide (CDE), a competitive binding antagonist of TRH-Rs and an inverse agonist of C335Stop TRH-Rs, abolished the persistent desensitization induced by C335Stop TRH-Rs and enabled the rapid desensitization, conferring the wild type phenotype on C335Stop TRH-Rs. Chelerythrine had qualitatively the same effect as CDE. In conclusion, unlike the rapid desensitization, the persistent desensitization caused by the constitutively active C335Stop TRH-Rs is largely mediated by PKC. It abrogates, however, the rapid desensitization, suggesting a common mechanistic step(s).

Acetylcholine↗
PubMed2001

Increased persistence of lung gene expression using plasmids containing the ubiquitin C or elongation factor 1alpha promoter.

For effective gene therapy of chronic disease, persistent transgene expression at therapeutic levels is required. Clinical studies of airway gene transfer in patients with cystic fibrosis (CF) have resulted in short-lived transgene expression. We used intra-nasal dosing of naked plasmid DNA to the murine lung as a model for investigating the duration of airway gene transfer from a series of reporter expression plasmids. Transgene expression was transient when mediated by the viral promoters CMV, RSV and SV40, falling to less than 10% of peak expression after 2 weeks, although the presence of the adenoviral E4ORF3 gene in cis, resulted in extended duration of reporter activity from the CMV promoter. Transient expression from these promoters was not due to loss of the vector as determined by quantitative TaqMan PCR analysis. However, use of the promoters from the human polybiquitin C (UbC) and the elongation factor 1alpha (EF1alpha) genes resulted in persistent gene expression in the mouse lung. The UbC promoter directed high-level reporter activity which was maintained for up to 8 weeks and was still detectable 6 months after a single administration. Such persistent airway transgene expression from a nonviral vector without the concomitant expression of a potential antigen has not been reported previously. Thus, despite the persistence of vector DNA in vivo, attenuation of promoter function may lead to silencing of transgene expression and careful selection of promoter sequences is recommended for in vivo gene transfer.

Administration, Inhalation↗
PubMed2002

Persistent hepatic expression of human apo A-I after transfer with a helper-virus independent adenoviral vector.

Gene transfer with 'gutted' vectors is associated with persistent transgene expression and absence of hepatotoxicity, but the requirement of helper viruses hampers efficient production and leads to contamination of viral batches with these helper-viruses. In the present study, gene transfer with a helper-virus independent E(1)/E(3)/E(4)-deleted adenoviral vector induced persistent expression of human apo A-I (200 +/- 16 mg/dl at day 35, 190 +/- 15 mg/dl at 4 months, 170 +/- 16 mg/dl at 6 months) and stable transgene DNA levels (3.5 +/- 0.60 at day 35, 3.3 +/- 0.39 at 4 months, 3.1 +/- 0.47 mg/dl at 6 months) in C57BL/6 mice in the absence of significant toxicity. The vector contained the 1.5 kb human alpha(1)-antitrypsin promoter in front of the genomic human apo A-I sequence and four copies of the human apo E enhancer (hAAT.gA-I.4xapoE) and was deleted in E(1), E(3) and E(4). Reintroduction of E(4) ORF 3 and E(4) ORF 4 in the viral backbone caused a more than four-fold decline of transgene DNA between day 35 and 4 months after transfer both in wild-type and in C57BL/6 SCID and C57BL/6 Rag-1(-/-) mice, indicating that the effect of E(4) ORF 3 and E(4) ORF 4 is independent of a cellular immune response against viral epitopes. Co-injection of an E(1)-deleted vector containing no expression cassette and the E(1)/E(3)/E(4)-deleted vector containing the hAAT.gA-I.4xapoE expression cassette indicated that E(4) gene products destabilize transgene DNA in trans. Gene transfer with an E(1)/E(3)/E(4)-deleted vector containing only E(4) ORF 3 and the hAAT.gA-I.4xapoE expression cassette was associated with transgene DNA decline, but not with hepatotoxicity, indicating that transgene DNA persistence and hepatotoxicity are dissociated processes. After transfer with E(1)/E(3)/E(4)-deleted vectors containing expression cassettes with a different promoter or a different position of the apo E enhancers, transgene DNA levels were less stable than after transfer with the vector containing hAAT.gA-I.4xapoE, indicating that the expression cassette is an important determinant of episomal stability. In conclusion, gene transfer with an E(1)/E(3)/E(4)-deleted vector containing the hAAT.gA-I.4xapoE expression cassette induces persistent expression of human apo A-I in the absence of hepatotoxicity. Transgene DNA turnover is independent of an adaptive cellular immune response against viral epitopes and of hepatotoxicity. E(1)/E(3)/E(4)-deleted vectors containing transgenes under control of the hAAT promoter in combination with four copies of the human apo E enhancer may be suitable for hepatocyte-specific overexpression of transgenes after gene transfer. doi:10.1038/sj.gt.3301824

Adenoviridae↗
PubMed2005

Persistence and discontinuation patterns of antihypertensive therapy among newly treated patients: a population-based study.

The objective was to assess persistence with antihypertensive therapy (AHT) and discontinuation patterns in patients newly dispensed different antihypertensive drug classes in a natural Canadian population-based setting. Hypertensive patients initiating AHT monotherapy were included in this 3-year retrospective cohort study (N=21 326) using the Saskatchewan health-care databases. Persistence was defined as consistently refilling a new prescription for AHT within 90 days of a previous dispensing. New courses of AHT were also documented in nonpersistent patients. Kaplan-Meier and Cox regression analyses were used to compare persistence and new courses of therapy across initial drugs. Compared to the newer angiotensin II antagonists (AIIAs), the likelihood of discontinuing therapy over the 39-month study period was significantly higher for angiotensin-converting enzymes inhibitors (HR=1.29; 95% CI=1.16-1.43), calcium channel blockers (HR=1.42; 95% CI=1.27-1.60), beta blockers (HR=1.62; 95% CI=1.45-1.80) and diuretics (HR=1.92; 95% CI=1.73-2.14). In the year following treatment discontinuation, between 54 and 75% of patients initiated a second course of treatment. Patients initiated on an AIIA had a significantly higher likelihood of starting a new course of therapy after a first treatment discontinuation, compared to all other agents. In conclusion, hypertensive patients initiated on an AIIA not only had greater persistence to AHT but were also more likely to initiate a new course of AHT after discontinuation than those initiating treatment with other agents. Further studies are required that relate intermittent treatment behaviours to health outcomes and costs in hypertension.

Adrenergic beta-Antagonists↗
PubMed2006

Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood.

Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLG null variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that identification of FLG null alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

Adolescent↗
PubMed1999

The fate and persistence of polychlorinated biphenyls in soil.

The fate and persistence of PCBs 28, 52, 101, 138, and 180 artificially introduced into three soils was studied under a variety of field conditions for up to 415 d following initial contamination. A relationship was detected between ln Koa (octanol/air partition coefficient) and the experimentally observed first-order loss rate constant that was statistically significant at at least the 90% level in all but one instance. In nearly all experiments, PCB persistence was greater in soils of higher organic carbon content. Soil temperature and moisture content were also indicated as important influences on persistence. Significantly longer half-lives were observed in a soil in which initial PCB contamination had occurred ca. 1 year previously. A mass balance showed the most likely mechanism of loss to be volatilisation. Losses attributable to aerobic biodegradation could not be ruled out, but those due to leaching, uptake by biota, and soil erosion were demonstrated to be negligible. First-order rate constants (Kv) were determined for volatilisation of the same congeners from soil under a variety of controlled laboratory scenarios. Multiple linear regression analysis (MLRA) showed the most important influences on kv to be ln Koa (adjusted for soil temperature) and soil organic carbon content. Limited evidence was observed for a relationship between kv and soil moisture content, but not water flux. When tested against field measurements, the MLRA-derived relationship between kv and independent variables predicted to within a factor of 2.5, the persistence of PCBs 28, 52, and 101, However, it did not account for the influence of the age of contaminant association with the soil, soil moisture content or water flux, and failed to function for soils of high organic content, or where ln Koa exceeds ca. 23.

Biodegradation, Environmental↗