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PubMed2006

A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (-13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, -13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

Adult↗
PubMed1998

Poor induction of interferon-induced 2',5'-oligoadenylate synthetase (2-5 AS) in cells persistently infected with mumps virus is caused by decrease of STAT-1 alpha.

Poor induction of interferon-induced 2',5'-oligoadenylate synthetase (2-5AS) has been demonstrated in cells persistently infected with mumps virus as compared with uninfected cells. As for the number of interferon (IFN) receptors and the level of IFN regulatory factors (IRF-1 and IRF-2) mRNAs, there was little difference between them. Therefore, it is suggested that the IFN-alpha signaling system is ineffective in the persistently infected cells. Components of IFN-stimulating gene factor 3 alpha (ISGF-3 alpha), STAT-1 alpha (p91) and STAT-2 (p113), were investigated in human amnion (FL), human nasopharyngeal cancer (KB), human T-lymphoid (HUT 78), and human B-lymphoid (Akata) cells persistently infected with mumps virus. STAT-1 alpha, but not STAT-2, disappeared in these persistently infected cells, and this factor was not restored by treatment of these cells with IFN. However, no difference was observed between the levels of STAT-1 alpha mRNA transcript in persistently infected and uninfected control cells. It is reasonable to infer that the poor induction of 2-5AS activity is due to the decrease of STAT-1 alpha in correlation with the IFN-signal transduction pathway. Furthermore, induction of other IFN-stimulated genes (ds-RNA activated protein kinase, PKR, and MxA protein) was also reduced in the cells persistently infected with mumps virus.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

Visible persistence in paranoid schizophrenics.

A visual temporal integration (i.e., visible persistence) task was performed by normal controls and paranoid schizophrenics. The task evaluated the critical duration (CD), which approximates the duration of peripheral persistence duration and post-CD persistence, which is possibly more associated with central processes. Subjects were required to report when temporally modulated spatial frequency patterns, which are known to have characteristic temporal processing rates, were pulsing "on-off" with a distinct "off" period. The dependent measure was the duration of visible persistence. An analysis of groups X spatial frequency duration (50, 75, 150, 300 msec) X spatial frequency (high, medium, low), with repeated measures on the last two variables, revealed that the second-order interaction was significant (p less than 0.05). Schizophrenics had shorter visible persistence only for the 300-msec presentation for the high spatial frequency pattern. Also, the CD of schizophrenics did not conform to the duration of normals on the high spatial frequency. The results are discussed in terms of the role high spatial frequencies plays in visual information processing and how shorter visible persistence by paranoid schizophrenics may reflect a premature termination of information necessary for synthesis into accurate percepts.

Adolescent↗
PubMed1984

Visible persistence as a function of spatial frequency, number of cycles and retinal area.

Using a variety of measures it has been shown that processing time increases with increasing spatial frequency. Long and Sakitt (1981) [Vision Res. 21, 1387-1393] investigated duration of visible persistence as a function of both spatial frequency and number of cycles present. They concluded that number of cycles and not spatial frequency is the crucial variable in determining duration of visible persistence. The present paper investigates this issue in three experiments. Experiments 1 and 2 determined duration of visible persistence with spatial frequencies of 2, 4, 8 and 10 c/deg while holding both number of cycles and grating area constant in a dark surround and in a light surround. Stimulus durations of 50 and 300 msec were used in Experiments 1 and 2 respectively. The results at each stimulus duration showed an increase in duration of visible persistence with increasing spatial frequency similar to that found in most previous reports. This increase was less with a 300 than with a 50 msec stimulus duration. Whether the gratings were presented in a light or a dark surround had no significant effect. Experiment 3 showed that at 2 c/deg duration of visible persistence increased with increasing size of the grating stimuli when all stimulus sizes fell within the area of spatial summation. This effect was greater in a dark than in light surround. It is concluded that visible persistence does increase with spatial frequency. Previous results inconsistent with this conclusion are explained in terms of spatial summation.

Afterimage↗
PubMed1985

Visual persistence from brief letters and pictures.

The visual persistence from briefly presented letters and pictures was assessed by the popular probe-matching procedure over a range of background and target luminance levels and for several color conditions. It was determined that the fading visible persistence measured in this way increased with increasing target luminance and with decreasing background luminance. For small foveal presentations, photopically-matched targets of differing wavelength produced equivalent persistences; but for larger, parafoveal presentations, scotopically-matched targets of differing wavelength produced equivalent persistences. This was true for both letter and picture targets. Results were discussed in terms of an early sensory locus to such persistence effects. The strong consistency of these findings to some previous work and the apparent inconsistency with other work were treated in terms of different kinds of visual persistence effects assessed by different experimental methods.

Afterimage↗
PubMed1993

On the confounding effects of phosphor persistence in oscilloscopic displays.

Phosphor persistence has been a source of confounding in studies of temporal integration in vision. We examined the confounding by assessing the effects of the persistence of two commonly-used phosphors (P15 and P31) on performance of a temporal-integration task. In one experiment we eliminated the visibility of phosphor persistence by closing two mechanical shutters upon display termination. In a second experiment we estimated the duration of phosphor persistence by displaying the image behind closed shutters which opened upon display termination. No detectable persistence was every produced by P15 phosphor. By contrast, P31 phosphor produced persistence that lasted several hundred milliseconds even when a veiling light was projected on the screen. We ascribe the earlier instances of confounding to inadequate interpretation of the technical data on phosphor decay.

Humans↗
PubMed1994

Effect of the ISI on the visible persistence of a stimulus in apparent motion.

The persistence of briefly flashed stimuli undergoing a horizontal apparent motion is assessed as a function of the temporal interval (inter-stimulus interval or ISI) between successive locations. The main result is that the duration of persistence is increased when the ISI is reduced (within the range 1-15 msec). An increase of persistence also occurs when the spatial separation (delta chi) between successive presentations of the moving stimulus becomes larger, a well established result which is replicated here. In both cases, the elevation of persistence suggests that inhibitory processes, which are assumed to underlie the persistence-suppression, have become less efficient. According to the data, it seems that the spatio-temporal parameters of motion, and not the speed as such, are responsible for the strength of inhibition. Namely, optimal inhibition, and thus suppression, would need a minimum amount of time to take place, and would improve with proximity (i.e. with smaller delta chi). Finally, a persistence-suppression decrease is observed when the angular size of the flashed stimuli is reduced (i.e. when higher spatial frequencies become more predominant). A model of transient-on-sustained inhibition accounts well for these results.

Afterimage↗
PubMed1996

Efficient induction of persistent and prenatal parvovirus infection in rats.

Parvoviruses are prevalent and disruptive infectious agents of laboratory rats. Risks to rat-based research from infection are increased by the persistence of virus in immune rats and by prenatal transmission of infection. The mechanisms leading to viral persistence and prenatal infection are poorly understood and have been difficult to study for lack of reliable and humane induction methods. We report here protocols for inducing persistent and prenatal infection without causing clinical disease using the UMass strain of rat virus (RV), a common rat parvovirus. Infant rats inoculated by the oronasal route at 6 days of age had greater than 90% prevalence of persistent infection. RV-UMass also induced intrauterine infection in pregnant rats inoculated by the oronasal route. Inoculation of dams at gestation day 9 frequently caused severe disease in the fetuses whereas inoculation at gestation day 12 caused primarily asymptomatic fetal infection that persisted post partum RV-UMass infection facilitates study of parvoviralhost interactions that are relevant to laboratory rats and which also may improve understanding of persistent and prenatal human parvovirus infection.

Animals↗
PubMed1989

Persistent albuminuria as an index of diabetic nephropathy in type 2 diabetic patients in Osaka, Japan-incidence, risk factors, prognosis and causes of death.

A group of 1196 type 2 (non-insulin-dependent) diabetic patients was followed for a mean of 10 years to determine the incidence of persistent albuminuria, its associated risk factors and prognosis, as well as causes of death in patients. None of the patients studied had albuminuria on entry. The mean annual incidence rate of persistent albuminuria per 1000 person-years in the patients was higher in males than in females (18.42 and 12.57, respectively). Development of persistent albuminuria was associated with age at entry, duration of known diabetes, systolic blood pressure, fasting glucose level, presence of diabetic retinopathy and type of treatment. Among 193 patients who developed persistent albuminuria during the observation period, 66 (34.2%) died before the end of the observation period, with a mean survival period (+/- SD) of 3.0 +/- 3.1 years after the onset of persistent albuminuria, indicating an extremely poor prognosis. Renal disease was the predominant cause of death in patients who developed persistent albuminuria, followed by heart disease and cerebrovascular disease.

Adult↗
PubMed1991

Disturbed secretion of atrial natriuretic peptide in patients with persistent atrial standstill: endocrinologic silence.

Persistent atrial standstill is a very rare pathophysiologic condition whose diagnosis is established when both electrical and mechanical silence of the atria are confirmed. To test the hypothesis that secretion of atrial natriuretic peptide is disturbed in patients with persistent atrial standstill, the response of atrial natriuretic peptide secretion and other neurohormonal factors during exercise was investigated in three patients with a rate-responsive ventricular demand (VVI) pacemaker implanted for confirmed persistent atrial standstill. The results were compared with those observed in eight normal subjects and patients with a rate-responsive VVI (Group A) or atrial demand (AAI) (Group B) pacemaker implanted for confirmed sick sinus syndrome. Patients in Group A displayed significant elevation of alpha-human atrial natriuretic peptide secretion both before and during exercise (122.5 +/- 14.8 and 207.5 +/- 8.3 pg/ml, respectively) compared with those in Group B (55 +/- 14.1 and 116.4 +/- 51.5 pg/ml, respectively) and the normal subjects (18.9 +/- 9.8 and 30.8 +/- 19.2 pg/ml, respectively). This indicated development of a nonphysiologic increase in atrial volume or pressure overload, or both, in rate-responsive VVI pacing because of lack of atrioventricular synchrony. However, patients with persistent atrial standstill had undetectable (less than 10 pg/ml) or almost undetectable secretion of atrial natriuretic peptide as well as lower levels of cyclic guanosine monophosphate in the circulation both before and during exercise. Changes in plasma catecholamines during exercise were similar in patients with persistent atrial standstill compared with the other groups. This study indicates that "endocrinologic silence" accompanies electrical and mechanical silence of the atria, which may constitute a third diagnostic clue to persistent atrial standstill.

Adult↗
PubMed2006

Relationship between self-reported task persistence and history of quitting smoking, plans for quitting smoking, and current smoking status in adolescents.

The task persistence construct has previously been measured primarily behaviorally (e.g., with a mirror-tracing task, or breath holding), and only in adults. It has been shown to differentiate between adult smokers and non-smokers and to predict smoking cessation in adult smokers trying to quit. This theory-based analysis is the first to examine task persistence in adolescent smokers and to examine a two-item, internally consistent, self-report measure of task persistence. Results indicate that task persistence is greater among adolescent non-smokers as compared to adolescent current smokers, and those planning to quit smoking as compared to those with no plans to quit. Contrary to hypotheses, task persistence was not found to be related to prior successful attempts to quit smoking. Our results suggest that a brief, self-report measure of task persistence may be a methodologically sound, practical clinical tool for this population.

Adolescent↗
PubMed2006

The effect of dosing frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women: a comparison of studies in the United States, the United Kingdom, and France.

OBJECTIVES: The aim of this study was to determine the effect of dose frequency on compliance and persistence with bisphosphonate therapy in postmenopausal women and to compare findings from 3 different health care systems. METHODS: Three independently performed retrospective cohort analyses were performed using observational data sources. In the United States, bisphosphonate-naive postmenopausal women were identified from a database providing information on health plan prescription drug claims; in the United Kingdom and France, bisphosphonate-naive postmenopausal women were identified from a database of medical records supplied by general practice physicians. The women were grouped into 2 cohorts: those who were initiated on a weekly regimen of alendronate 70 mg or risedronate 35 mg and those initiated on a daily regimen of alendronate 5 or 10 mg or risedronate 5 mg. Compliance was measured in terms of the medication possession ratio (MPR), which was defined as the proportion of days in the 12-month follow-up period for which patients were covered by prescriptions for bisphosphonates. Persistence was measured as the number of days from the date of the index prescription to the last day of prescription coverage within the followup period. Women were classified as nonpersistent if the gap between prescriptions was > 30 days. RESULTS: The study included 2741 postmenopausal women with osteoporosis from the United States, 7567 from the United Kingdom, and 5332 from France. The mean (SD) age of the women was 73.0, 71.7, and 69.7 years in the 3 countries, respectively. The overall MPR was 61% in the United States, 74% in the United Kingdom, and 58% in France. In all 3 countries, women on a weekly regimen had a significantly greater MPR than women on a daily regimen (69% vs 58%, respectively, in the United States; 76% vs 64% in the United Kingdom; and 59% vs 53% in France; all, P < 0.001). Women on a weekly regimen of bisphosphonates persisted with treatment significantly longer than women on a daily regimen (227 vs 185 days, respectively, in the United States; 249 vs 208 in the United Kingdom; and 179 vs 155 in France; all, P < 0.001). A significantly greater proportion of the women on a weekly regimen persisted with treatment for 12 months compared with those on a daily regimen (44% vs 32%, respectively, in the United States; 52% vs 40% in the United Kingdom; and 51% vs 44% in France; all, P < 0.001). CONCLUSIONS: In all 3 countries, postmenopausal women prescribed a weekly regimen of bisphosphonates had significantly greater rates of compliance than women prescribed a daily regimen, and they persisted longer with treatment. However, compliance and persistence rates were suboptimal for both regimens.

Cohort Studies↗
PubMed2006

Persistent structural priming from language comprehension to language production.

To examine the relationship between syntactic processes in language comprehension and language production, we compared structural persistence from sentence primes that speakers heard to persistence from primes that speakers produced. [Bock, J. K., & Griffin, Z. M. (2000). The persistence of structural priming: transient activation or implicit learning? Journal of Experimental Psychology: General, 129, 177-192.] showed that the production of target priming structures increased the probability of spontaneously using the same structures to describe events in subsequent pictures that were semantically unrelated to the primes. These priming effects persisted across as many as ten intervening filler trials. The present studies replicated these results using auditorily presented primes to which participants only listened. The results indicated persistence of priming across all lags, with relative magnitudes of priming as large as those observed by Bock and Griffin. The implication is that structural priming is persistent regardless of the modality in which language structures are experienced, underscoring the power of priming as an implicit learning mechanism.

Cognition↗
PubMed2006

Exploring beliefs and practice of opioid prescribing for persistent non-cancer pain by general practitioners.

Persistent non-cancer pain is a common reason for consultation in primary care but treatment options, including non-opioid analgesics, are limited, and neither strong evidence nor established guidelines address when and how primary care doctors should prescribe opioid analgesics for persistent non-cancer pain. The aim of this study was to investigate associations between doctors' prescribing patterns for persistent non-cancer pain in primary care and their personal and practice characteristics and beliefs about appropriateness and risks of opioids. A pilot survey sampled beliefs concerning the need for and risks of opioid prescribing for persistent non-cancer pain among volunteers from primary care practices and postgraduate educational events, using a self-report questionnaire, and related these beliefs to their reported opioid prescribing. One quarter of the sample prescribed no opioids for persistent non-cancer pain. Prescribing opioids was predicted by moderate belief in the appropriateness of opioids within certain constraints, and to a lesser extent by younger age. While some beliefs distinguished prescribers from non-prescribers, predicting non-prescribing was poor. Both prescribers and non-prescribers expressed concern about the risks of opioids. In addition, most primary care doctors were dissatisfied with their training on pain; few had prescribing guidelines; and neither training nor guidelines influenced prescribing. In conclusion, whether or not GPs prescribe opioids for persistent non-cancer pain is mainly determined by their personal beliefs about appropriateness of opioids for this problem.

Adult↗
PubMed2005

The care provided by general practitioners for persistent depression.

PURPOSE: To examine the care provided by general practitioners (GPs) for persistent depressive illness and its relationship to patient, illness and consultation characteristics. SUBJECTS AND METHOD: Using the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC) a sample of 264 patients with ICD-10 depression was identified among consecutive primary care patients in the Netherlands. At 1-year follow-up 78 of these patients (30%) still fulfilled the criteria of an ICD-10 depression and were considered persistent cases. At baseline and follow-up the GPs specified their diagnosis and treatment. The extent of recognition as a mental health problem, accuracy of diagnosis as a depression and treatment in accordance with clinical guidelines for depression was examined. In addition it was examined whether these steps in adequate GP care for persistent depression were related to patient, illness and consultation characteristics. RESULTS: Twenty percent of the persistent depression cases were not recognized at baseline or during follow-up, 28% was recognized but not accurately diagnosed, 17% was accurately diagnosed, but did not receive adequate treatment and 35% was treated adequately. Recognition was associated with psychological reason for encounter; accurate diagnosis with absence of activity limitation days; and adequate treatment with severity of depression and higher educational level. CONCLUSION: Non-recognition, misdiagnosis and inadequate treatment are not limited to patients with a relatively mild and brief depression but are also prominent in patients with a persistent depression, who consulted their GP 8.2 times on average during the year their depression persisted.

Adult↗
PubMed2005

Inhibition of Qi site of mitochondrial complex III with antimycin A decreases persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells.

Hypoxia-induced inhibition of Qi site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. In this paper, we used Qi site inhibitor antimycin A to mimic the inhibition of the Qi site of mitochondrial complex III and studied the effects of the inhibition of this site on persistent sodium currents, transient sodium currents, and neuronal excitability in rat hippocampal CA1 cells with whole cell patch-clamp methods. The results showed that antimycin A decreased the amplitude of both persistent and transient sodium currents; antioxidant 2-mercaptopropionylglycine or 1,10 phenanthroline abolished the effect of antimycin A; the complex III Qo site inhibitor stigmatellin, the protein kinase C inhibitor chelerythrine, but not the protein kinase A inhibitor H89, canceled the effect of antimycin A; antimycin A decreased the amplitude of both persistent and transient sodium currents only at more depolarized membrane potentials and the decrease percentage of both persistent and transient sodium currents after antimycin A at potentials above -50 mV increased with the change in potentials toward more depolarized direction; exogenous application of H2O2 inhibited the amplitude of both persistent and transient sodium currents; the amount of current required to trigger spikes was increased and the number of spikes produced by varying levels of currents was decreased by antimycin A. These results suggest that the inhibition of Qi site of mitochondrial complex III decreases both persistent and transient sodium currents via reactive oxygen species and protein kinase C in rat hippocampal CA1 cells.

Action Potentials↗
PubMed2005

Persistent left superior vena cava: case reports and clinical implications.

We report four cases of persistent left superior vena cava (LSVC) incidentally recognized during device implantation. Persistent LSVC is the commonest venous anomaly of the thorax and drains into the right atrium via the coronary sinus. Persistent LSVC demonstrates several congenital variations including variable communication with right-sided superior vena cava (SVC), absence of right-sided SVC, drainage into the left atrium creating a right to left shunt, and association with other congenital anomalies of the heart and great vessels. Abnormal persistent fetal dispersion of specialized pacemaker and conduction tissue, which occurs in some individuals with persistent LSVC, may provide an arrhythmogenic substrate. In this article we discuss embryology, diagnostic approaches, clinical features, technical difficulties in accessing the right ventricle, and a review of literature related to persistent LSVC.

Aged↗
PubMed2004

Three-dimensional conformal radiotherapy versus intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma.

PURPOSE: To compare the outcomes of three-dimensional conformal radiotherapy (3D-CRT) and intracavitary brachytherapy (ICBT) as salvage treatment for locally persistent nasopharyngeal carcinoma. METHODS AND MATERIALS: Between March 1994 and November 2001, a total of 117 patients with locally persistent nasopharyngeal carcinoma received salvage treatment for 2-8 weeks (median, 4 weeks) after a full course of conventional external beam RT. Of the 117 patients, 54 were salvaged with 3D-CRT (3D group) and 63 with ICBT (BT group). No statistically significant differences were found in the patient characteristics between the two groups (p >0.05). In the 3D group, the planning target volume for 3D-CRT was defined as the persistent disease plus a 5-mm margin; three to seven static conformal coplanar or noncoplanar portals were delivered for each fraction. The median salvage dose was 24 Gy (range, 18-38 Gy), with fraction size of 2.0 Gy/d. In the BT group, a median salvage dose of 20 Gy (range, 15-30 Gy) was delivered with a (192)Ir source, at 5 Gy/fraction, twice weekly. The brachytherapy dose was prescribed at a distance of 1 cm from the center of the surface as defined by the sources, irrespective of the extent of persistent disease. The actuarial rates of survival were estimated using the Kaplan-Meier method. Potential differences in the actuarial outcomes between groups were evaluated using the Mantel log-rank test. Multivariate analyses were performed with the Cox regression proportional hazards model. RESULTS: The 5-year actuarial rates of overall survival, disease-specific survival, and local failure-free survival for the 3D group and BT group were 64.50% vs. 55.78% (p = 0.33), 70.03% vs. 59.56% (p = 0.11), and 88.93% vs. 76.28% (p = 0.07), respectively. Subgroup analysis showed that the 5-year actuarial local failure-free survival rate of patients with initially diagnosed T3-T4 disease for the 3D group and BT group was 84.01% vs. 60.50% (p = 0.03). The incidence of Grade 3-4 late complications was comparable between the two groups. Multivariate analyses performed in the whole group showed that T stage at initial diagnosis and the salvage technique (3D-CRT or ICBT) were the statistically significant, independent prognostic factors for local failure-free survival (p = 0.00 and p = 0.02, respectively). CONCLUSION: 3D-CRT seemed to provide better local control than ICBT as a salvage treatment for locally persistent nasopharyngeal carcinoma, especially in patients with initially diagnosed T3-T4 disease. CT/MRI evaluation of the extent of persistent disease is recommended for technique selection of salvage RT. Patients should be cautioned about the potentially increased complications. The optional time for salvage treatment remains controversial.

Adult↗