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PubMed2001

Persistent expression of cytokines in the chronic stage of CVB3-induced myocarditis in NMRI mice.

Coxsackievirus B3 (CVB3)-induced myocarditis in NMRI mice represents a model for studying the pathogenesis of this chronic heart disease. Previously, we reported on specific cytokine patterns during the acute stage of myocarditis since cytokines are thought to play the important role in this cardiomyopathy. In this study, the expression of various cytokine mRNAs and CVB3-RNA kinetics was examined with particular emphasis on the late phase of myocarditis, by using reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). In addition, replicating and persisting CVB3-RNAs were semiquantified by PCR-ELISA. Distinct histopathological changes responsible for ongoing heart disease were found and characterized by increased fibrosis, persistent cellular infiltration and degenerated necrotic myocytes. One of the most important findings of this study was that the mRNA-expression of TNF- alpha, IL-1 alpha, interferon- gamma, IL-10, IL-18, macrophage inflammatory protein-1 alpha (MIP-1 alpha), transforming growth factor- beta (TGF- beta) and inducible nitric oxide synthase (iNOS) persisted as long as 98 days after the virus infection. The induction of IL-10 as well as IFN- gamma mRNAs was also verified by ISH and IHC at days 28 and 98 p.i. The clearly apparent persistence of the viral genomes in the myocardium of infected mice was confirmed by seminested PCR, ISH, and PCR-enzyme linked immunoabsorbent assay (ELISA), showing the highest amount of viral RNA in myocardial cells at day 7 after infection. These data indicate that the persistence of viral RNA is associated with persistently high levels of cytokine mRNAs which, when translated, could severely contribute to pathological changes and injury of connective tissue in the chronic stage of myocarditis.

Animals↗
PubMed1998

Environmental Variability and the Persistence of Parasitoid-Host Metapopulation Models.

Parasitoid-host metapopulation models (after Reeve) were simulated with varying amounts of spatio-temporal or spatial environmental variability, as well as varying dispersal rates and instability of within-population dynamics. Persistence with environmental variability occurred over broad ranges of low dispersal rates, the amount of variability required for persistence increased with increasing dispersal, and the range of values giving persistence was less when within-population dynamics where more unstable. Fixed spatial variation was found to be sometimes more effective than spatio-temporal variability at producing persistence, but with greater variance among replicates. Metapopulations also could persist without environmental variability (as found by Adler), but this occurred at very particular dispersal rates, quite different from those allowing persistence with environmental variability. Copyright 1998 Academic Press.

Journal Article↗
PubMed2002

Habitat destruction in a simple predator-prey patch model: how predators enhance prey persistence and abundance.

We model a metapopulation of predator-prey patches using both spatially implicit or mean-field (MF) and spatially explicit (SE) approaches. We show that in the MF model there are parameter regimes for which prey cannot persist in the absence of predators, but can in their presence. In addition, there are parameter regimes for which prey may persist in isolation, but the presence of predators will increase prey patch density. Predators may thus enhance prey persistence and overall abundance. The key mechanism responsible for this effect is the occurrence of prey dispersal from patches that are occupied by both prey and predators. In addition, these patches should be either long-lived, such as that occurs when predators keep prey from overexploiting its local resource, or the presence of a predator on a patch should significantly enhance the prey dispersal out of that patch. In the SE approach these positive effects of predators on prey persistence and abundance occur for even larger parameter ranges than in the MF model. Prey dispersal from predator-prey patches may thus be important for persistence of both species as a community, independent of the modeling framework studied. Comparison of the MF and SE approaches shows that local dispersal constraints can have the edge over global dispersal for the persistence of the metapopulation in regimes where the two species have a beneficial effect on each other. In general, our model provides an example of feedback in multiple-species metapopulations that can make the implementation of conservation schemes based on single-species arguments very risky.

Animals↗
PubMed1999

In vivo disturbance of hematopoiesis in mice persistently infected with murine cytomegalovirus: impairment of stromal cell function.

Although the pathogenic effects of a primary cytomegalovirus (CMV) infection on hematopoiesis has been largely investigated so far, the effects of a persistent or latent infection have yet to be elucidated. The effects of persistent CMV infection on hematopoiesis thus were examined using BALB/c mice at 4 weeks postinfection with 0. 2 LD50 of murine CMV (MCMV) infection as a persistent infection model. The parameters of constitutive hematopoiesis of MCMV persistently infected mice were completely identical to those of the control. However, the inductive hematopoiesis, examined by the autologous marrow reconstitution after 5-fluorouracil administration, was significantly impaired in the MCMV persistently infected mice (P < 0.05). In a colony-forming unit-spleen assay and a long-term bone marrow culture system, a decreased capacity of bone marrow stromal cells to support hematopoiesis was observed in the MCMV-infected mice in comparison with the controls. The existence of MCMV DNA in the adherent cells of long-term bone marrow culture from the MCMV-infected mice were confirmed by a polymerase chain reaction but not in the nonadherent cells. Furthermore, the increased expression level of tumor necrosis factor-alpha by stromal cells was also observed by semiquantitative reverse transcriptase-polymerase chain reaction. These results therefore strongly suggest that MCMV remains to infect the stromal cells while also inhibiting inductive hematopoiesis through the impairment of the stromal cell functions in the MCMV persistently infected mice.

Animals↗
PubMed1988

Suppression of neuroleptic-induced persistent abnormal movements in Cebus apella monkeys by enantiomers of 3-PPP.

Effects of the enantiomers of the dopamine (DA) autoreceptor agonist 3-PPP (0.5-8.0 mg/kg body weight, i.m.) were studied in three Cebus apella monkeys with persistent abnormal movements induced by prior long-term treatment with fluphenazine enanthate. In 2 of the animals, (-)-3-PPP abolished the abnormal movements while producing only negligible acute motor effects (trembling and stereotypy). (+)-3-PPP, administered to one of these monkeys, also produced a dose-dependent suppression of the persistent abnormal movements, along with the appearance of acute motor signs including tongue protrusions, hyperkinesia, and stereotypy; at the highest dose, there was a biphasic effect. In the first phase, there were pronounced acute motor signs but no persistent abnormal movements. In the second phase, there were neither acute nor persistent abnormal movements. One monkey was unaffected by (-)-3-PPP or low doses of (+)-3-PPP; a higher dose (4 mg/kg) produced hyperkinesia and increased persistent abnormal movements in one experimental setting. The suppression of neuroleptic-induced persistent abnormal movements by 3-PPP enantiomers may be related to their ability to act as autoreceptor agonists, while the acute motor signs produced by higher doses of (+)-3-PPP may be due to activation of postsynaptic DA receptors. The present findings suggest that (-)-3-PPP and drugs with a similar pharmacological profile might be effective as symptomatic treatments for tardive dyskinesia, with little chance of inducing acute extrapyramidal side-effects.

Animals↗
PubMed1983

Persistent baculovirus infections: Spodoptera frugiperda NPV and Autographa californica NPV in Spodoptera frugiperda cells.

Establishment of a persistent infection of Spodoptera frugiperda nuclear polyhedrosis virus (NPV) in Spodoptera frugiperda (S.f.) cells occurred in three phases: the first phase was characterised by high levels of cell infection and death, the second phase by decreasing cell infection levels leading to the final phase where less than one per cent of the cells were infected during any subculture. The virus persisted at this level of infection provided the cells were maintained by regular subculturing and incubated at the optimum growth temperature of 27 degrees C. Because of the low proportion of cells infected, cultures of virus-free cells could be selected ('cured') by dilution of the persistent infection without the use of viral antiserum. Unlike the parent S.f. cells, cultures of cured cells were partially resistant to infection with S. frugiperda NPV or infection with an unrelated baculovirus Autographa californica NPV. A. californica NPV, which is cytolytic for the parent S.f. cell line, established a persistent infection in the cured cells. The establishment pattern was similar to that previously found for S. frugiperda NPV and only one to five per cent of the cells were infected at equilibrium. Cured cells from the A. californica NPV persistent infection were highly resistant to infection with both S. frugiperda NPV and A. californica NPV. All attempts to find a viral interference phenomenon to explain the resistance of the cured cells were unsuccessful. All cell types adsorbed virus equally well. Slower growth of S.f. cells cured from the persistent A. californica NPV infection is the only difference so far observed between any of the S.f. cell types.

Animals↗
PubMed1988

A model virus-cell system to study the persistence of African swine fever virus.

The persistence of African swine fever virus (ASFV) on Vero cells was induced by using 5-iodo-2'-deoxyuridine (IDU). After the persistence was established, several cycles of decreasing virus production were observed with intervals in which no virus could be detected. These latency-like periods could last from 15 to 25 days. After three and a half months the cells appeared to be "cured" and no virus was detected during almost three years. These "cured" cells (Vero-L) were more resistant to superinfection with the wild type virus, and when infected they always established persistence without drug addition characterized by a continuous virus production. The persistent virus isolated at passage 23rd from ASFV persistently infected Vero-L cells was different from wild type in a) the morphology of the plaque, b) its ability to replicate in Vero-L cells, and c) greater resistance to be inhibited by IDU in normal Vero cells (Vero-N). These results suggest that both, Vero cells and ASFV have changed during persistent infection.

African Swine Fever Virus↗
PubMed1976

Persistent infection of tissue culture cells by RNA viruses.

In this paper, the characteristics of cultured cells persistently infected with RNA viruses, other than leuko viruses are described. The roles that the host cell, interferon, virus mutants and defective interfering particles may play in the establishment and maintenance of persistent infection are discussed. It is proposed that the interaction of viruses with certain types of host cells can lead to persistent infection. The differences in virus-host interactions may be attributable to differences in membrane properties of various cells. Defective interfering particles may play a role in the establishment of persistent infections in cells which normally undergo lytic virus development. Mutant types of virus appear to be prominent in the virus released from persistently infected cells, but the role that various mutants play in the maintenance of persistent infections remains unclear.

Antibodies, Viral↗
PubMed1996

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.

Aged↗
PubMed1999

Persistent perineal sinus after proctocolectomy for Crohn's disease.

PURPOSE: Persistent perineal sinus is a source of morbidity after proctocolectomy for Crohn's disease. This study examined the factors responsible for persistent sinus after proctocolectomy for Crohn's disease. We also assessed the outcome of surgical treatment for persistent perineal sinus. METHODS: The records of 145 patients who underwent proctocolectomy for Crohn's disease between 1970 and 1997 were reviewed. RESULTS: Persistent sinus occurred in 33 (23 percent) patients after proctocolectomy. Factors associated with a significantly greater risk of perineal sinus were younger age (P = 0.006), rectal involvement (P = 0.02), perianal sepsis (P = 0.0005), high fistulas (P = 0.04), extrasphincteric excision (P = 0.0004), and fecal contamination at operation (P = 0.0003). Multivariate analyses showed that age (P = 0.0001), rectal involvement (P = 0.007), and fecal contamination (P = 0.009) were significant independent predictive factors for perineal sinus. Fifty-six operations, including 24 radical excisions, two rectus abdominis flaps, four gracilis transpositions, and two omentoplasties were performed in 24 patients with persistent sinus, but only 9 achieved healing. Long sinuses (>10 cm) and sinuses presenting late (>12 weeks after proctocolectomy) were seldom cured by surgical treatment. CONCLUSION: Persistent perineal sinus is more likely to occur if an extrasphincteric dissection is needed because of extensive anorectal disease or if fecal contamination occurs at operation. Attempted surgical eradication of perineal sinus is often ineffective.

Adrenal Cortex Hormones↗
PubMed1976

Persistent infection with bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) in cultured hamster cells.

Bovine herpesvirus-1 infection in hamster embryo cells was found to be dependent upon input multiplicity; productive infection was achieved at input multiplicities greater than one, while persistent infection was established when input multiplicities were about 0.5. This persistence was characterized by a noncyclic, minimal degree of cytopathic effect with a low level of released virus. Maintenance of the persistently infected cultures did not require external supportive measures. Subcultivation of the persistently infected cultures led to virus replication followed by CPE and then cell regrowth. With 3 to 4 weeks after subcultivation a persistent infection was re-established. The possible mechanism for the bovine herpesvirus persistence in hamster cells is discussed.

Animals↗
PubMed1999

Calcium metabolism in adolescents and young adults with type 1 diabetes mellitus without and with persistent microalbuminuria.

Alterations in calcium metabolism can be demonstrated in the course of insulin-dependent diabetes mellitus. In order to clarify if the presence of persistent microalbuminuria (MA) can affect the main parameters of calcium metabolism, we studied 22 diabetic adolescents and young adults with persistent MA and compared them with 24 patients without MA and 24 healthy controls. Mean values of serum calcium, phosphorus and magnesium were similar in diabetic children and young adults without persistent MA and in controls. In addition, the mean values of PTH and 25-OHD, 1,25 (OH)2D3 and OC did not differ between these diabetics and controls. Diabetics with persistent MA showed no significant difference from the values of either controls or the group of diabetics without persistent MA for the mean values of serum calcium, phosphorus and magnesium and PTH. In contrast, diabetics with persistent MA had significantly (p<0.01) lower 25-OHD (26.5+/-5.2 ng/ml) and 1,25 (OH)2D3 (24.7+/-5.6 pg/ml) as well as OC levels (9.8+/-2.5 ng/ml; p<0.001) than controls (38.1+/-4.9 ng/ml, 40.7+/-6.4 pg/ml and 16.5+/-5.8 ng/ml, respectively) and subjects with normoalbuminuria (36.0+/-4.5 ng/ml, 38.8+/-8.9 pg/ml and 14.5+/-3.2 ng/ml). In conclusion, our study suggests that abnormalities in 25-OHD, 1,25(OH)2D3 and OC can be present in diabetic adolescents and young adults with incipient nephropathy.

Adolescent↗
PubMed2000

Ecstasy (MDMA): a review of its possible persistent psychological effects.

RATIONALE: Recreational use of "ecstasy" (3,4-methylenedioxymethamphetamine; MDMA) has become increasingly widespread. Until recently, however, little was known about the possible persistent psychological effects of extensive use of this drug. OBJECTIVE: The aim of the present review is to evaluate recent empirical evidence concerning the persistent psychological sequelae of recreational ecstasy use. METHODS: The methodologies of open trial studies of recreational ecstasy users are evaluated and reports of the presence or absence of persistent psychological problems are related to the extent of past exposure to ecstasy. RESULTS: There is growing evidence that chronic, heavy, recreational use of ecstasy is associated with sleep disorders, depressed mood, persistent elevation of anxiety, impulsiveness and hostility, and selective impairment of episodic memory, working memory and attention. There is tentative evidence that these cognitive deficits persist for at least 6 months after abstinence, whereas anxiety and hostility remit after a year of abstinence. The possibility that some of these psychological problems are caused by ecstasy-induced neurotoxicity is supported by preclinical evidence of MDMA-induced neurotoxicity and behavioural deficits, evidence of depleted serotonin in heavy ecstasy users, and by dose-response relationships between the extent of exposure to ecstasy and the severity of cognitive impairments. CONCLUSIONS: An increasing number of young, heavy ecstasy users are at significant risk of persistent cognitive impairments and disturbances of affect and personality. Some of these problems may remit after abstinence, but residual neurotoxicity and decline of serotonergic function with age may result in recurrent psychopathology and premature cognitive decline.

Affect↗
PubMed2000

Relaparotomy in peritonitis: prognosis and treatment of patients with persisting intraabdominal infection.

Some patients are prone to persisting intraabdominal infection regardless of initial eradication of the source of infection. Our aim was to characterize patients who had to undergo relaparotomy for persisting abdominal sepsis using simple clinical parameters and to define those patients who are susceptible to benefit of aggressive surgical treatment by early and repeated reoperations to control multiple organ dysfunction syndrome (MODS) caused by ongoing intraabdominal infection. Persisting abdominal sepsis was the cause of death in all of our patients who had to undergo relaparotomy. Controlling persisting abdominal sepsis should achieve a reduction in the tremendously high mortality rate. Performing a case-control study, we retrospectively reviewed 523 consecutive patients with secondary peritonitis treated from 1986 to 1996 and focused our attention on 105 patients, in whom standard surgical treatment of secondary peritonitis failed and who had to undergo relaparotomy for persisting abdominal sepsis (study group). Overall, there was no significant difference in the postoperative mortality rate between "planned relaparotomy" and "relaparotomy on demand" (54.5% versus 50. 6%). Equally clear risk estimations were given preoperatively by both the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Goris scores. There was a significant difference between patients of the control group and patients of the study group with regard to preoperative APACHE II score, Goris score, age >70 years, albumin <30 g/L, extent of peritonitis, and outcome (p = 0.0001). Reexploration performed more than 48 hr after the initial operation resulted in a significantly higher mortality rate (76.5% versus 28%; p = 0.0001). However, the time of reoperation had no significant impact on survival in patients with an APACHE II score of > or = 26, because physiologic derangement is such that only a few patients could benefit from reoperation. The lowest mortality rate (9%) was achieved in patients who underwent reoperation on demand within 48 hr. We conclude that patients >70 years of age with secondary peritonitis extending over the entire abdomen and a greater degree of physiologic compromise (serum albumin levels <30 g/L, preoperative APACHE II scores >20, and existing organ failure measured by the Goris score) are at high risk for developing persistent intraabdominal infection. Our data show that timely relaparotomy provides the only surgical option that significantly improves outcome. However, aggressive surgical treatment has reached its limit in patients whose source of infection could not be controlled at the initial operation. To improve overall survival the decision to perform a relaparotomy on demand after an initially successful eradication of the source of infection must be made within 48 hr, at least before MODS emerges.

Abdomen↗
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↗