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PubMed2000

Sialylation of the host receptor may modulate entry of demyelinating persistent Theiler's virus.

Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus of the Cardiovirus genus. Certain strains of TMEV may cause a chronic demyelinating disease, which is very similar to multiple sclerosis in humans, associated with a persistent viral infection in the mouse central nervous system (CNS). Other strains of TMEV only cause an acute infection without persistence in the CNS. It has been shown that sialic acid is a receptor moiety only for the persistent TMEV strains and not for the nonpersistent strains. We report the effect of sialylation on cell surface on entry and the complex structure of DA virus, a persistent TMEV, and the receptor moiety mimic, sialyllactose, refined to a resolution of 3.0 A. The ligand binds to a pocket on the viral surface, composed mainly of the amino acid residues from capsid protein VP2 puff B, in the vicinity of the VP1 loop and VP3 C terminus. The interaction of the receptor moiety with the persistent DA strain provides new understanding for the demyelinating persistent infection in the mouse CNS by TMEV.

Animals↗
PubMed2001

High numbers of viral RNA copies in the central nervous system of mice during persistent infection with Theiler's virus.

The low-neurovirulence Theiler's murine encephalomyelitis viruses (TMEV), such as BeAn virus, cause a persistent infection of the central nervous system (CNS) in susceptible mouse strains that results in inflammatory demyelination. The ability of TMEV to persist in the mouse CNS has traditionally been demonstrated by recovering infectious virus from the spinal cord. Results of infectivity assays led to the notion that TMEV persists at low levels. In the present study, we analyzed the copy number of TMEV genomes, plus- to minus-strand ratios, and full-length species in the spinal cords of infected mice and infected tissue culture cells by using Northern hybridization. Considering the low levels of infectious virus in the spinal cord, a surprisingly large number of viral genomes (mean of 3.0 x 10(9)) was detected in persistently infected mice. In the transition from the acute (approximately postinfection [p.i.] day 7) to the persistent (beginning on p.i. day 28) phase of infection, viral RNA copy numbers steadily increased, indicating that TMEV persistence involves active viral RNA replication. Further, BeAn viral genomes were full-length in size; i.e., no subgenomic species were detected and the ratio of BeAn virus plus- to minus-strand RNA indicated that viral RNA replication is unperturbed in the mouse spinal cord. Analysis of cultured macrophages and oligodendrocytes suggests that either of these cell types can potentially synthesize high numbers of viral RNA copies if infected in the spinal cord and therefore account for the heavy viral load. A scheme is presented for the direct isolation of both cell types directly from infected spinal cords for further viral analyses.

Animals↗
PubMed2006

Persistence of cooperatively stabilized signaling clusters drives T-cell activation.

Antigen recognition triggers the recruitment of the critical adaptor protein SLP-76 to small macromolecular clusters nucleated by the T-cell receptor (TCR). These structures develop rapidly, in parallel with TCR-induced increases in tyrosine phosphorylation and cytosolic calcium, and are likely to contribute to TCR-proximal signaling. Previously, we demonstrated that these SLP-76-containing clusters segregate from the TCR and move towards the center of the contact interface. Neither the function of these clusters nor the structural requirements governing their persistence have been examined extensively. Here we demonstrate that defects in cluster assembly and persistence are associated with defects in T-cell activation in the absence of Lck, ZAP-70, or LAT. Clusters persist normally in the absence of phospholipase C-gamma1, indicating that in the absence of a critical effector, these structures are insufficient to drive T-cell activation. Furthermore, we show that the critical adaptors LAT and Gads localize with SLP-76 in persistent clusters. Mutational analyses of LAT, Gads, and SLP-76 indicated that multiple domains within each of these proteins contribute to cluster persistence. These data indicate that multivalent cooperative interactions stabilize these persistent signaling clusters, which may correspond to the functional complexes predicted by kinetic proofreading models of T-cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed1989

Endogenous formation of prostanoids in neonates with persistent pulmonary hypertension.

Endogenous formation of thromboxane A2 and prostacyclin were evaluated in seven neonatates with persistent pulmonary hypertension by serial gas chromatographic mass spectrometric determination of their urinary metabolites dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha, respectively. The patients were studied until their hypertension had resolved on clinical criteria. Urinary excretion of dinor-thromboxane B2 and dinor-6-keto-prostaglandin F1 alpha was increased when the persistent pulmonary hypertension was associated with group B streptococcal (n = 2) and pneumococcal (n = 1) sepsis. Based on urinary metabolite excretion, endogenous formation of thromboxane A2 and prostacyclin did not consistently differ from normal neonates in four patients with non-septic persistent pulmonary hypertension (hyaline membrane disease (n = 2), asphyxia, and meconium aspiration). These data suggest that thromboxane A2 is not a universal mediator of persistent pulmonary hypertension. It may, however, have a role in the pathophysiology of early onset group B streptococcal disease, and persistent pulmonary hypertension of other infectious aetiology. If these findings are confirmed by further studies, thromboxane synthetase inhibition or receptor antagonism may offer a potential therapeutic approach in neonates with persistent pulmonary hypertension associated with sepsis.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Associations of health related behaviour, social relationships, and health status with persistent physical activity and inactivity: a study of Finnish adolescent twins.

OBJECTIVE: To examine the association between leisure time physical activity over a three year period and health related behaviour, social relationships, and health status in late adolescence as part of a nationwide longitudinal study. METHODS: Five birth cohorts of adolescent twins aged 16 at baseline (n = 5028; 2311 boys and 2717 girls) participated in the study. Questionnaires on leisure time physical activity, other health related behaviour, social relationships, and health status were sent to the twins on their 16th and 17th birthdays and six months after their 18th birthday. The combined response rate to the three questionnaires was 75.8% for boys and 81.7% for girls. Those who answered in all three questionnaires that their frequency of physical activity was 4-5 times a week or more were defined as persistent exercisers, and those who exercised at most twice a month in all three were defined as persistently inactive. Logistic regression analyses were used to identify baseline variables associated with outcome measures. RESULTS: Overall, 20.4% of boys and 13.0% of girls were persistent exercisers and 6.5% of boys and 5.3% of girls were persistently inactive. In both sexes, smoking, irregular breakfast eating, attending vocational school, and poor self perceived current health were significantly associated with persistent inactivity. CONCLUSIONS: Persistent physical inactivity in adolescents is associated with a less healthy lifestyle, worse educational progression, and poor self perceived health. Tailoring methods to promote physical activity may prove useful for influencing other health habits. Such programmes are indicated for vocational schools in particular.

Adolescent↗
PubMed1988

Risk factors for persistent diarrhoea.

With a systematically sampled population of children aged under 5 attending this centre for diarrhoeal disease research during 1983-5 a retrospective analysis of persistent diarrhoea (defined as greater than 14 days' duration) was performed to identify the possible risk factors for this syndrome. Of the 4155 children included in the analysis, 410 (10%) gave a history of persistent diarrhoea. A comparison with children with acute diarrhoea matched for age showed that 11 factors were correlated with persistent diarrhoea, and strongly associated factors were stools with blood or mucus, or both, lower respiratory tract infection, malnutrition, vitamin A deficiency, and antibiotic use before presentation. The peak age was 2 years, and there was no sex difference. Deaths occurred more often in the group with persistent diarrhoea. Although Shigella spp, Campylobacter jejuni, and Giardia lamblia were frequently identified, their rates of isolation were not significantly higher among patients with persistent diarrhoea. No seasonal variation was observed in the rates of persistent diarrhoea. Although the introduction of family food to the diet was associated with higher rates, this factor was difficult to separate from the age dependent risks.

Acute Disease↗
PubMed1991

Prospective hospital based study on persistent diarrhoea.

A total of 383 children aged less than 5 years suffering from acute watery diarrhoea or dysentery were studied in hospital to determine the rate of persistent diarrhoea. Altogether 335 (87.5%) recovered within 13 days. Only in 48 (12.5%) did the diarrhoea continue for 14 days or more, and they were considered as having persistent diarrhoea. Children aged between 7 and 18 months had a significantly increased incidence of persistent diarrhoea. Children suffering from grade II-IV malnutrition constituted the majority (70.8%) of those with persistent diarrhoea. Higher rates of isolation of Shigella flexneri, Shigella dysenteriae 1, and Salmonella typhimurium were observed among patients with persistent diarrhoea than in those with diarrhoea of shorter duration. No positive correlations were observed between the clinical severity of disease at hospital admission and measles. Breast fed babies were not prone to persistent diarrhoea.

Acute Disease↗
PubMed1978

General features of persistent virus infections.

Persistent virus infections are discussed from the virus point of view in terms of the bodily sites in which the infection persists. Glands and body surfaces are thought to be significant because they give the virus protection at the topographical level from immune forces, and because they are appropriate sites for the shedding of virus to the exterior. Germ cells are relevant sites because infection can thus be transmitted vertically from generation to generation in the host. The central nervous system, however, is generally a 'dead end' from which there is no shedding to the exterior. Persistance in blood may be relevant when continued arthropod transmission becomes possible. Most persistent viruses infect lymphoreticular tissues, and this is interpreted by suggesting that it results in an impaired immune response to the infecting virus, which in turn favours persistence. It is suggested that the biological function of virus transformation and the integration of viral into host cell DNA is that it enables the infection to persist in the host and undergo reactivation. Papovaviruses, adenoviruses and oncornaviruses are considered from this point of view.

Adenoviridae Infections↗
PubMed1982

Detection of transient and persistent feline leukaemia virus infections.

A study was made of cats persistently or transiently viraemic with feline leukaemia virus (FeLV) following experimental oronasal infection. Cats of two ages were exposed to the virus. One group was infected when eight weeks old in the expectation that most of the cats would become persistently viraemic, and the second group when 16 weeks old, so that some would show signs of a transient infection and then recover. The periods following infection when virus was detectable in the blood and in the oropharynx were determined for each group. Three methods for detecting viraemia were compared: virus isolation, immunofluorescence on blood smears and an enzyme-linked immunosorbent assay (ELISA). There was good overall agreement among the three tests in detecting virus-positive cats. Virus was found sooner after infection by virus isolation than by the other methods, and virus appeared in the blood slightly sooner in cats which developed persistent viraemia than in transiently viraemic cats. Infectious FeLV was isolated from the oropharynx of all of the persistently viraemic cats, in most cases simultaneously with virus in the plasma. Virus was also isolated from the mouth of most transiently viraemic cats. Under field conditions such transient excretion of virus lasting only a few days would rarely be detected in a single sampling. This might explain how FeLV is maintained in free range urban cats in the absence of a large number of cats with persistent active FeLV infection. For routine diagnosis, immunofluorescence would appear to offer the best chance of differentiating transient and persistent infections by FeLV.

Age Factors↗
PubMed1998

Persistence of the efficacy of doramectin against Ostertagia ostertagi and Cooperia oncophora in cattle.

The persistence of the efficacy of doramectin injectable against Ostertagia ostertagi and Cooperia oncophora was evaluated in two studies in calves. In both, the calves were allocated to six groups of six. Calves in the first control group (C1) and first treated group (T1) received a daily infection of 200 L3 of O ostertagi and 200 L3 of C oncophora; the calves in groups C2 and T2 received a daily infection of 1000 L3 of each species, and groups C3 and T3 received 10,000 L3 of each species per day. The calves in the three treated groups each received 0.2 mg/kg doramectin injectable on day 0. In the first study, the calves were infected for 21 days with Cooperia and for 28 days with Ostertagia, and they were slaughtered on day 33. In the second study, the calves were infected for 21 days with both species, the infections with Cooperia and Ostertagia starting from eight and 15 days, respectively, after the treatment, and the animals were slaughtered on day 40. The calculation of the persistence of the activity of doramectin was based on its efficacy against the different developmental and adult stages of the two parasites. The data from both studies indicated that the efficacy of doramectin against Ostertagia persisted for at least five weeks, but no conclusions could be drawn about the effect of the size of the infective doses on the persistence of the activity. In contrast, the Cooperia worm counts from the second study suggested that the efficacy of doramectin against Cooperia persisted for at least four weeks when the calves were exposed to a low or moderate infection level, whereas at the highest infection level it persisted for between three and four weeks.

Animals↗
PubMed1981

Mechanisms of persistence in arenavirus infections: a brief review.

A characteristic of the arenaviruses is persistent infections in their natural host. Age at infection is an important factor in the establishment of persistence. Infections early in life regularly result in persistence and this appears to be related to the immaturity of the immune system. Persistently infected animals make antibodies to the viral antigens, which indicates that the animals are not tolerant with respect to B cell functions. However, cytotoxic T cells cannot be demonstrated in persistently infected animals, suggesting a defect in effector T cell functions. The mechanisms leading to this defect in cytotoxic T cells have not been resolved. Persistence of arenaviruses in cell cultures is also regularly observed but the molecular basis for survival of the virus and cell in long-term cultures has yet to be clarified.

Animals↗
PubMed1992

Relative persistence capacity of BCG substrains in mouse spleen. Computerized statistical analysis. Multiple comparison.

The relative persistence capacity in mouse spleen of 10 and 9 BCG substrains from liquid and dried vaccines, respectively, was evaluated in two studies. Recoverable BCG colony counts from mouse spleen were determined at given days on solid medium in the two studies during a period of 1-360 and 1-345 days, respectively, after the intravenous BCG vaccination, performed with two different viable units. From 36,000 (study 1) and 21,600 (study 2) recoverable BCG colony counts, 180 and 108 mean relative persistence capacity values were estimated to test the residual virulence during the follow-up time, using computerized statistical analysis. The early and late trends of mean relative persistence capacity of the BCG substrains in mouse spleen were tested by linear regression analysis and analysis of variance and covariance; then with ranked adjusted group mean relative persistence capacity, Gabriel's simultaneous test procedure was performed for multiple comparison to diminish type 1 error in statistical inference and in objective interpretation of the experimental results. The associations of the ranked mean relative persistence capacity of the BCG substrains at the different sacrifice days of mice were also analyzed by Kendall's test of concordance. The early, late, and overall relative persistence capacity reflects the residual virulence of the BCG substrains and provides information on the required protective efficacy (immunogenicity) and adverse reactions (reactogenicity), allowing the appropriate vaccination dose, expressed in viable units of the substrain used, to be determined.

Animals↗
PubMed2005

The genetics of the persistent infection and demyelinating disease caused by Theiler's virus.

Theiler's virus causes a persistent and demyelinating infection of the central nervous system of the mouse, which is one of the best animal models to study multiple sclerosis. This review focuses on the mechanism of persistence. The virus infects neurons for a few weeks and then shifts to white matter, where it persists in glial cells and macrophages. Oligodendrocytes are crucial host cells, as shown by the resistance to persistent infection of mice bearing myelin mutations. Two viral proteins, L and L*, contribute to persistence by interfering with host defenses. L, a small zinc-finger protein, restricts the production of interferon. L*, a unique example of a picornaviral protein translated from an overlapping open reading frame, facilitates the infection of macrophages. Susceptibility to persistent infection, which varies among inbred mouse strains, is multigenic. H2 class I genes have a major effect on susceptibility. Among several non-H2 susceptibility loci, Tmevp3 appears to regulate the expression of important cytokines.

Amino Acid Sequence↗
PubMed2003

Persistent LIP activity in memory antisaccades: working memory for a sensorimotor transformation.

The lateral intraparietal area (LIP) contains neurons that are active during the memory interval of memory saccades. We call these "persistent neurons." Here we study the activity of the persistent neurons in memory antisaccades, "motor" (the saccade is made toward the response field, although the response field is not stimulated visually) and "visual" (the response field is stimulated visually, but the movement is away from the field). Most persistent neurons are active during parts of the memory intervals of both visual and motor memory-antisaccades. Typically, these parts significantly overlap each other and together span the entire memory interval. The amplitude of the activity changes systematically during the memory intervals of visual and motor memory antisaccades. These changes are reflected in an antisaccade differential activity, which turns first to the visual direction and then crosses over to the motor direction. Some persistent neurons appear to show the paradoxical activity previously characterized in visual neurons; paradoxical activity accelerates the transition of the neuron's activity from visual to motor. These observations suggest that the persistent neurons reflect working memory for the computation of the antisaccade sensorimotor transformation. Ensembles of persistent neurons with different response fields may make up modules of working memory.

Animals↗
PubMed2005

Perceptual continuity and the emergence of perceptual persistence in the ventral visual pathway.

Perceptual continuity is an important aspect of our experience of the visual world. In this study, we focus on an example of perceptual continuity involving the maintenance of figure-ground segregation despite the removal of binding cues that initiated the segregation. Fragmented line drawings of objects were superimposed on a background of randomly oriented lines. Global forms could be discriminated from the background based on differences in motion or differences in color/brightness. Furthermore, perception of a global form persisted after the binding cue had been removed. A comparison between the persistence of forms constructed from motion or color demonstrated that both forms produced persistence after the object defining cues were removed. Functional imaging showed a gradual increase in the persistence of brain activity in the lower visual areas (V1, V2, VP), which reached significance in V4v and peaked in the lateral occipital area. There was no difference in the location of persistence for color- or motion-defined forms. These results suggest that the retention of a global percept is an emerging property of the ventral visual processing stream and the maintenance of grouped visual elements is independent of cue type. We postulated that perceptual persistence depends on a system of perceptual memory reflecting the state of perceptual organization.

Attention↗
PubMedDate not supplied

Inhaled corticosteroids in COPD: determinants of use and trends in patient persistence with treatment.

METHODS: The determinants of a new treatment with inhaled corticosteroids and secular trends in patient persistence with treatment among chronic obstructive pulmonary disease (COPD) patients were investigated. A cohort of 3768 physician-diagnosed, elderly COPD patients was selected between 1990 and 1996 from the health care administrative database of the Régie de l'assurance maladie du Québec. A nested case-control design was used to identify patient and physician characteristics that were associated with a new treatment with inhaled corticosteroids. Treatment persistence with inhaled corticosteroids was also estimated using Kaplan-Meier analysis. In addition to that, changes in treatment persistence over time, from 1990 to 1995, were investigated by estimating the yearly proportion of patients persisting for less than one year. RESULTS: Within the cohort, the yearly percentage of patients filling at least one prescription for inhaled corticosteroids was 42.2% in 1990 and increased to 53.1% in 1995 (P=0.001). Using a conditional logistic regression model, it was found that the patients most likely to initiate a treatment with inhaled corticosteroids were those who had severe COPD (rate ratio [RR] 1.7; 95% CI 1.4 to 2.0), those who were hospitalized for COPD (RR 10.0; 95% CI 5.6 to 17.9), those who consulted a respirologist in the previous month (RR 2.3; 95% CI 1.6 to 3.3) or those who visited more than three different physicians in the previous three months (RR 1.6; 95% Cl 1.3 to 1.9). The proportion of patients persisting with inhaled corticosteroids for less than one year rose by 19.4%, from 47.6% in 1990 to 67.0% in 1995 (P=0.011; test for trend). CONCLUSIONS: The use of inhaled corticosteroids increased while patient persistence decreased between 1990 and 1995. Disease severity, as well as recent consultation to a respirologist and multiple visits to a physician, were associated with a strong likelihood of being prescribed inhaled corticosteroids. The cost of this practice is far from negligible, while their clinical impact is still uncertain.

Administration, Inhalation↗
PubMed2006

Persistent human papillomavirus infection is associated with a generalized decrease in immune responsiveness in older women.

The development of cervical cancer and its precursors are linked to persistent infection with oncogenic types of human papillomavirus (HPV). Host immune responses seem to be determinants of risk for this disease. However, little is known about the immunologic determinants of HPV persistence. Here, we examined the association between lymphoproliferative responses to antigens/mitogens and persistent HPV infection in women older than 45 years. Women included in this study were participants in a 10,000-woman population-based cohort study of cervical neoplasia in Costa Rica. Women older than 45 years and HPV DNA positive at a screening visit were selected as cases (n = 283). We selected a comparably sized control group of HPV DNA-negative women, matched to cases on age and time since enrollment (n = 261). At an additional clinical visit, women were cytologically and virologically rescreened, and cervical and blood specimens were collected. Proliferative responses to phytohemagglutinin (PHA), influenza virus (Flu), and HPV16 virus-like particle (VLP) were lower among women with persistent HPV infection [median counts per minute (cpm): 72,849 for PHA, 1,241 for Flu, and 727 for VLP] than for the control group (median cpm: 107,049 for PHA, 2,111 for Flu, and 2,068 for VLP). The decreases were most profound in women with long-term persistence and were only observed for the oldest age group (>/=65 years). Our results indicate that an impairment in host immunologic responses is associated to persistent HPV infection. The fact that effects were evident for all studied stimuli is suggestive of a generalized effect.

Age Factors↗
PubMed2007

Type-specific persistence of high-risk human papillomavirus infections in the New Independent States of the former Soviet Union Cohort Study.

BACKGROUND: Prospective follow-up studies have recently suggested that persistent high-risk human papillomavirus (HPV) infections play a key role in the progression of CIN lesions and in the development of cervical cancer. However, data on type-specific persistence, viral integration, and the role of multiple infections are scanty. MATERIALS AND METHODS: A cross-sectional/cohort study was conducted between 1998 and 2002 in three New Independent States of the former Soviet Union comprising a cohort of 3,187 women, of whom 854 women were followed up for a mean of 17 months (SD, 11.6). HPV genotyping was done with real-time PCR, detecting HPV types 16, 18/45, 31, 33/52/58, 35, and 39. The integration status of HPV16 was examined by using a novel Taqman-based PCR method. RESULTS: The mean clearance time for the individual high- risk-type infection was 16.5 months (range = 0.9-34.9 months). HPV16 and HPV31 were the most persistent infections (clearance times = 18.1 and 16.2 months, respectively), whereas HPV39 infections cleared most rapidly. The mean copies per cell in HPV18/45, HPV31, HPV33/52/58, and HPV39 infections were higher in persisting HPV infections than in HPV infections that cleared, but the difference was not significant. Integration of HPV16 was not found to correlate with HPV persistence. CONCLUSIONS: A large proportion of women remained high-risk HPV positive after 18 months. Coinfection with multiple HPV types, viral load, or integration status did not correlate with persistence of high-risk HPV infections.

Adolescent↗