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PubMed1992

Persistent poliovirus infection: establishment and maintenance involve distinct mechanisms.

Mutants of poliovirus (PV) with highly modified biological properties can be selected in vitro in cells of neural origin. Mutations accumulate in the genome of type 1 PV strains selected in human neuroblastoma cells, modifying cell specificity and conferring to the virus the ability to persist in such nonneural cells as HEp-2c (Pelletier et al., Virology 180, 729 1991). With this cell system, we have both parent lytic strains and persistent PV mutants; these were used to study the mechanisms of the establishment and maintenance of the persistent infection. We found that a persistent infection was established when the lytic potential of the virus was reduced; this involved both an early and a late event of the virus cycle for the type 1 mutants. In contrast, maintenance of the infection did not correlate with the reduced lytic potential of the viruses, but rather with the selection of mutant cell populations of various phenotypes. Two cell lines, representative of two phenotypes, were studied in greater detail. In the first one, HEp-S32 (cl7), the PV receptor was not detected by cytofluorometry and viral genomes were detected by in situ hybridization in 2% of the cells. In the second cell line, HEp-S31 (cl18), 97% of the cells expressed the PV receptor, viral genomes were detected in 9-10% of the cells, and viral antigens in 5-10% of the cells. With this cell line, the cure of the culture or, alternatively, the lysis of the majority of cells, could be induced under specific culture conditions. We propose a model involving an equilibrium between an abortive and a lytic infection to explain the properties of cells persistently infected with PV.

Animals↗
PubMed1983

The relationship between temporal integration and persistence.

We measured the persistence for gratings of three different spatial frequencies after they had been equated for visibility by manipulating: (1) the contrast of the stimulus, (2) the duration of the stimulus, or (3) both contrast and duration. When we presented gratings of equal apparent contrast and equal duration, persistence increased with increasing spatial frequency. This effect occurred when apparent contrast was equated in terms of extended-duration or brief duration contrast sensitivity. However, when we examined persistence using gratings equated for temporal integration (i.e. equal apparent contrast but unequal durations), no differences in persistence as a function of spatial frequency were observed. Thus, the increase in persistence which is typically found with higher spatial frequencies can be accounted for by knowledge of the spatio-temporal characteristics of the visual system. Our findings are discussed in terms of the notion of different filter time-constants for different spatial channels.

Afterimage↗
PubMed1979

Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus.

Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution.

Animals↗
PubMed1991

Changes in cell gene expression in human leukemic cells persistently infected with vaccinia virus.

Persistent viral infections in vitro are useful systems to study the coevolution of virus and cell populations. Persistent infection of mouse Friend erythroleukemic cells (FEL) with vaccinia virus results in profound changes of the virus as well as of the cells. To investigate phenotypic changes of other cell types, we have established a persistent infection with vaccinia virus in a human leukemic cell line (K562). This cell line can be induced to differentiate along the erythroid pathway synthesizing embryonic and fetal globins, thus providing a system in which specific genes can be stimulated. After serial passage, the persistently infected cells (K562vac) became spontaneously differentiated, as shown by the increase in the number of cells producing hemoglobin (benzidine positive cells), and resistant to superinfection. These phenotypic changes of the cells were not accompanied by changes in the viral population. Hybridization of cellular RNA with cloned embryonic and fetal globin genes indicated that uninduced K562 cells do not express these genes, whereas cells induced by hemin or butyrate express G gamma (fetal globin) epsilon and zeta (embryonic globins) genes. By contrast vaccinia infected cells spontaneously express the G gamma gene. These results demonstrate that persistent infection with vaccinia virus elicited phenotypic changes in the infected cell population; in this case the constitutive expression of fetal hemoglobin.

Cell Line↗
PubMed1993

A persistent infection in MDCK cells by an influenza type B virus.

A persistent infection in Madin Darby Canine Kidney (MDCK) cells by an influenza B virus (B/Tecumseh/63/80) has been established and characterized. Virus recovered from the persistent state titrated lower in relation to the parental wild-type (wt) that initiated the infection as measured by hemagglutination and egg and tissue culture infectious dose, suggesting that the virus is a less cytopathic variant of the original wt virus. The persistent virus (pv) has decreased cytopathology for both MDCK and primary chick kidney (PCK) cell lines, and exhibits different RNA and protein electrophoretic migrations. Plaques of the persistent virus are smaller and take longer to appear, indicating that the pv is a slower growing variant of the wt. The small plaque mutant phenotype may play a role in the maintenance of the persistent infection in MDCK cells. The pv differs from the wt antigenically and in its ability to form deposits of uric acid-like crystals beneath the culture monolayers.

Animals↗
PubMed1991

Prediction of persistent carbohydrate intolerance in patients with gestational diabetes.

A 12-month prospective study was carried out in 120 Chinese patients with gestational diabetes who were found to have persistent carbohydrate intolerance at 6 weeks postpartum. The 75 g OGTT and WHO diagnostic criteria were employed for both antepartum and postpartum assessment. By 12 months, persistent carbohydrate intolerance was found in 13.3% of the patients only, 6 patients were diabetic while 10 had impaired glucose tolerance. Of those whose carbohydrate tolerance reverted to normal, 85% did so within the first 6 months. The clinical variables were analysed by multiple discriminant analysis using the logistic model. Five prognostic variables which were predictive of persistent carbohydrate intolerance at 12 months were identified. In order of decreasing predictive value, these included a high fasting glucose during pregnancy and at the first postnatal visit, a high antepartum 2 h blood glucose, the requirement of insulin during pregnancy, and a high postpartum 2 h blood glucose. Macrosomia, gestational age at diagnosis and a family history of diabetes were not predictive of persistent carbohydrate intolerance. Multiparity, maternal age and body mass index were of marginal significance only. The fitted logistic model provides a mechanism to estimate the probability of persistent carbohydrate intolerance. Such information will be helpful in patient counselling and in the efficient planning of postpartum medical follow-up.

Adult↗
PubMed1988

Hepatitis B virus markers and persistent antigenemia in adolescents.

Adolescents attending a municipal outpatient adolescent clinic in New York City were evaluated for the prevalence of hepatitis B virus (HBV) markers and persistent antigenemia. Among 313 teenagers tested in 1 year, 11.8% were HBV marker positive, and 4.8% had persistent antigenemia. Hispanic teens had a marker rate of 6.4% and an antigenemia rate of 1.4%. Dominican Republic teens had a significantly higher marker rate than Puerto Rican teens. Among Hispanics, sexual activity status and foreign- vs. U.S.-born status were not significantly related to the presence of HBV markers. Asian teenagers had a 50% marker rate and a 27.2% rate for persistent antigenemia. Marker and antigenemia rates were highest in the most recent immigrants. Unexplained persistent hematuria occurred more frequently in patients with HBV markers than in patients without markers. We recommend routine hepatitis B surface antigen screening in Hispanic and Asian adolescents. The greatest at-risk groups are Asians, especially recent immigrants, immigrants from the Dominican Republic, and probably patients with unexplained persistent hematuria.

Adolescent↗
PubMed1991

Persistence length and bending dynamics of DNA from electrooptical measurements at high salt concentrations.

A new electrooptical apparatus has been used to characterize the dichroism decay time constants for a collection of nine blunt-ended DNA restriction fragments in the range of chain lengths from 41 to 256 base-pairs at physiological salt concentrations. The experimental data show an increase of rotational diffusion coefficients, when the monovalent salt concentration is increased from a few mM, used previously for standard electrooptical experiments, to the range of salt concentrations around 100 mM. The presence or absence of 10 mM Mg2+ in a buffer with 100 mM NaCl does not induce any large change of the rotational diffusion. Bending of double helices is reflected by a fast component in the dichroism decay for fragments greater than or equal to 90 bp; the time constant of the first bending mode is 7-9% relative to the time constant of overall rotational diffusion for fragments with 90 to 179 bp at the temperatures 2, 10 and 20 degrees C. Interpretation of the overall rotational diffusion time constants by different models on the hydrodynamics of flexible polymer chains leads to diverging values of the persistence length. The most accurate description is expected from a combination of the rotational diffusion coefficient for rigid rods given by Tirado and Garcia de la Torre (J. Chem. Phys. 73 (1980) 1986) with correction factors derived from Monte Carlo simulations (P.J. Hagerman and B.H. Zimm, Biopolymers 20 (1981) 1481). This model leads to 'average' values of the persistence length of 440, 400 and 380 A at the temperatures 20, 10 and 2 degrees C, respectively (in 110 mM Na+ and 10 mM Mg2+, pH 7.0); the hydrodynamic radius of the helix is approx. 12.5 A. The persistence lengths measured at various monovalent salt concentrations can be represented as a linear function of the reciprocal square root of the ionic strength. The rotational time constants measured for individual fragments at physiological salt show clearly larger deviations from the model average than corresponding time constants measured previously at low salt; 'apparent' persistence lengths of individual fragments as well as their temperature dependence show strong variations. Thus, it is hardly possible to define a 'standard' persistence length for mixed sequences--even though the sequences used in the present investigation do not show clear deviations from standard gel mobilities. These data indicate that formation of individual, sequence-directed structures of DNA fragments is favoured under physiological salt conditions.

Circular Dichroism↗
PubMed1993

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL: Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS: There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION: Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Adult↗
PubMed1990

Alterations in lymphocyte subpopulations in peripheral blood of sheep persistently infected with border disease virus.

Fourteen sheep persistently infected with border disease virus were investigated to examine the effects of persistent viraemia on lymphocyte subpopulations in peripheral blood and their responses to the mitogen phytohaemagglutinin (PHA) in vitro. Persistently infected sheep had significantly more CD8+ (cytotoxic-suppressor) T-lymphocytes than uninfected sheep of the same age (P less than 0.001). The total number of CD4+ (helper) T-lymphocytes were not significantly different but there were more T-lymphocytes (CD5+) which were CD4- and CD8- in normal sheep than persistently infected sheep (P less than 0.001). Peripheral lymphocytes obtained from persistently infected sheep showed significantly reduced blastogenesis induced by PHA than those obtained from normal sheep (P less than 0.001).

Animals↗
PubMed1987

The effects of O-antigen character and enterobacterial common antigen content on the in vivo persistence of aromatic-dependent Salmonella sp. live-vaccine strains.

Aromatic-dependent (aro) derivatives of Salmonella choleraesuis like aro S. typhimurium are non-virulent but, unlike them, are ineffective as live vaccines in mice, given i.p. An aro derivative of S. choleraesuis did not persist in the liver and spleen (RES) of mice after i.p. inoculation whereas a similar derivative of S. typhimurium persisted. S. choleraesuis (O group C1; O-6,7) and S. typhimurium [O group B; O-(1),4(5),12] differ in O antigen of LPS, determined by chromosomal locus, rfb. Three pairs of nearly-isogenic aro derivatives, one member O-6,7 and the other O-(1),4,(5),12, were constructed in two lines of S. typhimurium by replacement of their B-rfb genes with the C1-rfb genes of S. choleraesuis. In tests for persistence after mixed or separate i.p. inoculation of equal doses into BALB/c mice the O-(1),4,(5),12 member of each pair was recovered as CFU in the RES at ca. 100-fold greater number than the O-6,7 member at 24 hours post-inoculation and subsequently. O-6,7 derivatives of S. typhimurium constructed as described above by a simple replacement of group B with group C-rfb locus synthesise only trace (tr) amounts of enterobacterial common antigen (ECA). An ECA+ (able to make normal levels of ECA) derivative of one aro, O-6,7 S. typhimurium strain was constructed by replacement of its B-rfe locus with the C-rfe locus of S. choleraesuis. Tested by mixed inoculation i.p. this strain persisted in the RES in numbers 10-fold greater than its O-6,7 ECAtr but 5-10-fold lesser than its O-(1),4,(5),12 cousins. Thus both O-specificity and ECA contribute to the survival of salmonella species in mice as determined by in vivo persistence of non-multiplying aro derivatives.

Animals↗
PubMedDate not supplied

Prediction of persistent microalbuminuria in patients with diabetes mellitus.

Persistent microalbuminuria [albumin excretion rate (AER): 30-300 micrograms/min] is predictive of clinical nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and cardiovascular mortality in addition to nephropathy in patients with non-insulin-dependent diabetes. The clinical significance of intermittent microalbuminuria, however, is unknown. We performed serial measurements of urinary albumin excretion at intervals of approximately 6 months in 139 diabetic patients who at entry did not have persistent microalbuminuria to determine whether intermittent microalbuminuria occurs more frequently in those patients who subsequently develop persistent microalbuminuria. The relative risk for the development of persistent microalbuminuria in diabetic patients with a greater proportion than 3 out of 20 determinations in the microalbuminuric range was 17.4 (95% confidence interval, 3.92-77.2) in those with IDDM and 2.78 (0.99-7.8) in those with non-insulin-dependent diabetes when compared with matched diabetic patients with fewer elevated measurements. These data suggest that frequent intermittent microalbuminuria predicts the future development of persistent microalbuminuria particularly in IDDM patients and that AER should be assessed by serial rather than single measurements.

Adolescent↗
PubMed2006

Persistence and adherence to cholesterol lowering agents: evidence from Régie de l'Assurance Maladie du Québec data.

BACKGROUND: There is a concern that poor compliance to cholesterol lowering agents (CLA) may compromise their potential benefits. The objective of this study was to estimate compliance to CLAs, in the context of clinical practice in Quebec. METHODS: This study was performed using data from the Régie de l'Assurance Maladie du Québec Persistence and adherence to treatment were estimated separately. An index combining these 2 measures was also calculated. RESULTS: In a random sample of patients (n = 428304) from the Régie de l'Assurance Maladie du Québec administrative database, 14076 were new users of a CLA. After 24 months, the persistence rate with the statins was significantly higher than with other CLAs (83% vs 69%; P < .001). The proportion of patients who switched from their initial statin varied across the statins (ranging from 7% to 34%). The proportion of patients who were 80% adherent to their treatment was significantly lower with the other CLA than with statins (43% vs 60%, P < .001). A composite index combining monthly persistence and adherence was calculated. This index was significantly higher for atorvastatin than for the other CLAs (P < .001) and the other statins (P < .01), with the exception of simvastatin (P = .09). CONCLUSIONS: Over a 2-year period, a large proportion of patients using a statin remained persistent to treatment. The overall rate of compliance (persistence and adherence) after 2 years was >60% with some statins.

Adult↗
PubMed2005

Persistent effects on blood pressure and renal function of perindopril alone or combined with losartan in Lyon hypertensive rats.

BACKGROUND: In Lyon genetically hypertensive (LH) rats, an early and long-term angiotensin-converting enzyme (ACE) inhibition with perindopril prevents their hypertension and renal alterations. The present work aimed to determine whether: 1) these effects persist after treatment withdrawal; 2) a short-term additional angiotensin II type 1 (AT1) receptor blockade with losartan potentiates these effects; and 3) an early combination of low doses of perindopril and losartan produces the same prolonged effects as monotherapy with a higher dose of perindopril. METHODS: Perindopril (0.4 or 3 mg/kg/day orally) was given from 3 to 12 weeks of age to male LH rats. In other perindopril-treated LH rats, losartan (10 mg/kg/day orally) was added 1 week before perindopril withdrawal and during a 3-week period. In another group of LH rats, perindopril (0.1 mg/kg/day) and losartan (2.5 mg/kg/day) were given together from 3 to 12 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored using radio-telemetry and renal function studied in anesthetized rats. RESULTS: Eight weeks after perindopril withdrawal, a significant reduction (P < .05) in SBP and DBP was observed with the both doses (SBP: 135 +/- 3, 139 +/- 5 v 157 +/- 4; DBP: 89 +/- 4, 93 +/- 5 v 111 +/- 3 mm Hg for 0.4 and 3 mg/kg/day v untreated LH rats). This was accompanied by a persistent decrease in urinary protein excretion and a long-lasting improvement in pressure natriuresis. The persistent antihypertensive effect was not improved by short-term addition of losartan. Interestingly, the early combination of perindopril with losartan at fourfold lower doses produced similar persistent antihypertensive and renoprotective effects. CONCLUSIONS: The blood pressure reduction produced by an early ACE inhibition in LH rats persists long after treatment withdrawal and is associated with an improvement in renal function. The combination of low doses of perindopril and losartan reveals a long-term effect similar to that of a monotherapy with a higher dose of perindopril.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Persistence with bisphosphonate treatment for osteoporosis: finding the root of the problem.

Poor compliance and persistence are among the most significant reasons for failed pharmacotherapy encountered in clinical practice. Consequences of poor compliance range from minor to serious, depending on drug characteristics, disease state, and severity of disease. Compliance and persistence are particular problems for patients with a disorder such as osteoporosis, which remains asymptomatic for long periods. Poor compliance with bisphosphonate therapy for osteoporosis has been associated with a smaller decrease in the rate of bone turnover and smaller improvements in bone mineral density, and may potentially result in a higher risk of fracture and disability. The compliance problem is additive; complex dosing guidelines may contribute to poor compliance with therapy, and the failure to follow these guidelines may result in treatment-related adverse events that further reduce compliance. In the long term, these issues often result in nonpersistence with treatment. In addition to direct consequences for the patient, poor compliance is associated with significant healthcare costs. Studies suggest that less-frequent dosing regimens improve compliance; however, even among patients receiving weekly bisphosphonates, persistence may remain suboptimal. Several strategies are available to improve compliance and persistence with osteoporosis therapies. Good communication between the healthcare provider and the patient--with continuous reinforcement of the importance of treatment--is a key approach to improving persistence. Patients should receive feedback to confirm that their treatment is having an effect, and individualized reminder systems should be recommended to help the patient adhere to the treatment plan. Potentially, every patient is liable to discontinue treatment even after a long period of regular dosing. It should be assumed that every patient receiving therapy for osteoporosis needs regular reinforcement of the importance of continuing therapy.

Bone Density↗
PubMed2006

Improving compliance and persistence with bisphosphonate therapy for osteoporosis.

The successful treatment of patients at increased risk for fracture requires proper diagnosis and the development of a treatment plan that permits the patient to take medications in accordance with dosing guidelines and on the correct schedule. Data indicate that patients with osteoporosis who have good long-term medication compliance experience substantially lower risk of fracture. Persistence with therapy also correlates with better bone mineral density and improved suppression of bone turnover markers. Although bisphosphonates are the most potent currently approved antiresorptive agents, they have special dosing issues that can have a negative impact on long-term persistence. The inconvenience and complexity of some dosing requirements; the potential for adverse effects, especially when dosing recommendations are not followed; and very low absorption rates--even under ideal conditions--all contribute to poor outcomes. Extension of the dosing interval from a once-daily to a once-weekly regimen is associated with comparable efficacy, theoretically may improve gastrointestinal safety, and is associated with substantial improvement in persistence with therapy. However, compliance with weekly regimens remains suboptimal. Monthly dosing of ibandronate, a bisphosphonate, was recently approved by the US Food and Drug Administration (FDA). Although extending the dosing interval may improve compliance and persistence with bisphosphonate therapy, it is important to recognize that missed doses or improper dosing may have greater consequences with extended dosing intervals. This article highlights the importance of educating patients about their diagnosis and long-term treatment plan, including the importance of persistence with therapy and compliance with dosing recommendations.

Bone Density↗
PubMed2006

Speech perception and short-term memory deficits in persistent developmental speech disorder.

Children with developmental speech disorders may have additional deficits in speech perception and/or short-term memory. To determine whether these are only transient developmental delays that can accompany the disorder in childhood or persist as part of the speech disorder, adults with a persistent familial speech disorder were tested on speech perception and short-term memory. Nine adults with a persistent familial developmental speech disorder without language impairment were compared with 20 controls on tasks requiring the discrimination of fine acoustic cues for word identification and on measures of verbal and nonverbal short-term memory. Significant group differences were found in the slopes of the discrimination curves for first formant transitions for word identification with stop gaps of 40 and 20 ms with effect sizes of 1.60 and 1.56. Significant group differences also occurred on tests of nonverbal rhythm and tonal memory, and verbal short-term memory with effect sizes of 2.38, 1.56, and 1.73. No group differences occurred in the use of stop gap durations for word identification. Because frequency-based speech perception and short-term verbal and nonverbal memory deficits both persisted into adulthood in the speech-impaired adults, these deficits may be involved in the persistence of speech disorders without language impairment.

Adolescent↗
PubMed2005

Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression.

In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies.

Cell Line↗