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PubMedDate not supplied

[The effect of myelopeptides on the persistence of tick-borne encephalitis virus in monkeys].

Myelopeptides (MP), bioregulatory molecules of bone marrow origin, exert a protective effect in persistence of tick-borne encephalitis virus in cynomolgus monkeys (Macaca fascicularis). The experiments involved 32 monkeys. The effect of MP was observed after one or two subcutaneous injections in a dose of 1 mg within 1.5-2 months after virus infection. The effect consists in 25-fold reduction of the frequency of virus persistence, marked limitation of the zone of spread of the persisting virus, including the central nervous system (CNS), decrease in virulence of the persisting virus, and lack of morphological signs of progress of the pathological process in the CNS. The protective effect was also observed when the infected monkeys were treated with MP and inactivated concentrated TBE vaccine. At the same time, the vaccine alone exerted a much less marked effect on the persisting TBE virus producing only a 2-fold reduction in the frequency of persistence without limitation of the zones of virus spread. In acute TBE in BALB/c mice, the effect of MP is observed irregularly. The marked protective effect of MP in TBE virus persistence in monkeys is not associated with stimulation of humoral immunity but is mediated by other immunological mechanisms requiring further study.

Acute Disease↗
PubMedDate not supplied

Persistence of Mycoplasma hominis after therapy: importance of tetracycline resistance and of coexisting vaginal flora.

In past studies Mycoplasma hominis has persisted after treatment with placebo, penicillins, or rifampin in 88-97% of women and 49-77% of men with infections of the lower genital tract. Among women with nonspecific vaginitis, M. hominis persisted in only a third of those treated with metronidazole as compared with at least 70% of those treated with ampicillin (P = 0.01), even though M. hominis is resistant in vitro to metronidazole and to its acid and hydroxy metabolites. Persistence of M. hominis after treatment with metronidazole was significantly associated with persistence of Bacteroides species in the vagina (P = .03). These results suggest that colonization of the vagina with M. hominis is partly dependent on other components of the vaginal microbial flora. In prior studies, M. hominis has persisted in zero to 50% of women and in zero to 30% of men after treatment with tetracycline or lincomycin, but the role of tetracycline resistance in treatment failure was not defined. The susceptibility of M. hominis to tetracycline is bimodal; and the minimal inhibitory concentration (MIC) of tetracycline for strains isolated before or soon after treatment was greater than or equal to 16 micrograms/ml for seven (78%) of nine that did persist and for two (17%) of 12 that did not persist after tetracycline therapy for cervicitis in women (P = .002). The MIC of tetracycline was greater than or equal to 16 micrograms/ml for two (12%) of 17 isolates from women in Seattle in 1972-1973, as compared with 27 (34%) of 79 isolates from Seattle men and women in 1979-1982.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2024

Adaptation for Staphylococcus aureus to hosts via insertion mutation in the accessory gene regulator agrC gene: decreased virulence and enhanced persistence capacity.

UNLABELLED: Staphylococcus aureus is an important human pathogen due to its vast array of virulence factors regulated by multiple regulatory mechanisms, including the accessory gene regulator. In this study, two S. aureus strains were simultaneously isolated from the blood of a febrile patient, belonging to the same clone, designated as 23H with a complete hemolytic phenotype, and 23B, exhibiting an incomplete hemolytic phenotype. The genomic comparison between strains 23B and 23H revealed that 23B had a single adenine base insertion at position 923 in the agrC gene, leading to a functional loss of the encoded AgrC. Experimental findings showed that strain 23B had decreased hemolytic activity, lower cytotoxicity against human alveolar epithelial A549 cells and in the Galleria mellonella model, and a reduced ability to survive intracellularly after infecting macrophages, in comparison to 23H. Conversely, 23B exhibited enhanced biofilm formation, greater adherence to A549 cells, and increased persistence in the face of vancomycin and daptomycin treatment. Transcriptomic analysis revealed that 23B upregulated surface protein-encoding genes while simultaneously reducing the expression levels of virulence factors, highlighting the intricate regulatory adjustments facilitating its persistence and reducing pathogenic potential. ATP assay results indicated that 23B maintained elevated ATP levels during the exponential phase yet exhibited reduced levels in the stationary phase when compared with 23H. Our findings suggested that the mutation in the agrC gene of S. aureus results in diminished virulence but markedly enhances persistence. This mutated strain warrants clinical attention because it may lead to treatment failures and persist in patients. IMPORTANCE: In clinical antimicrobial therapy, bacterial strains often develop resistance to antimicrobial agents. Additionally, mutations in their gene regulatory networks can increase their persistence, especially in immunocompromised patients. This study identified an insertion mutation in the accessory gene regulator, agrC gene, carried by a Staphylococcus aureus strain isolated from the blood of a febrile patient, leading to the functional loss of AgrC. Further research revealed that despite the reduced virulence of the mutated strain, it significantly bolstered the capacity to adapt and endure within the host during prolonged infections. This was evidenced by increased adhesion and biofilm formation capabilities, development of antimicrobial tolerance, and decreased ATP levels linked to persistence. Therefore, monitoring these mutations in S. aureus is crucial clinically, as they can complicate treatment strategies.

Staphylococcus aureus↗
PubMed2023

Teicoplanin associated gene tcaA inactivation increases persister cell formation in Staphylococcus aureus.

Staphylococcus aureus is part of normal human flora and is widely associated with hospital-acquired bacteremia. S. aureus has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant S. aureus (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. S. aureus has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the S. aureus glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in S. aureus persister cells formation, and ΔtcaA dependent persisters' ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of glyS and sgtB. The RNA-seq data revealed a significant decrease in tcaA (p = 0.008) and tcaB (p = 0.04) expression while tcaR was not significantly altered. We knocked down tcaA, tcaB, and tcaR using CRISPR-dCas9 and the results showed that when tcaA was suppressed by dCas9, a significant increase was witnessed in persister cells while tcaB suppression did not induce persistence. The results were further evaluated by creating a tcaA mutant that showed ΔtcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that tcaA is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in S. aureus.

MRSA↗
PubMed1989

Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn.

Ureaplasma urealyticum was isolated from the lower respiratory tract of three infants with persistent pulmonary hypertension of the newborn. In one, cultures positive for U urealyticum were obtained on multiple occasions from trachea, blood, and pleural fluid prior to the infant's death on postnatal day 6. Autopsy findings confirmed the presence of severe pneumonia and the organism was again recovered from multiple sites. A second infant had no apparent predisposing factors for development of persistent pulmonary hypertension of the newborn but U urealyticum and Staphylococcus epidermidis were recovered from the trachea antemortem and from lung tissue obtained during autopsy on the 12th postnatal day. The third infant had persistent pulmonary hypertension of the newborn and a pulmonary infiltrate within hours after birth with tracheal cultures positive for both U urealyticum and Mycoplasma hominis. Erythromycin was given for ten days, and the infant gradually improved. Prolonged ventilation with supplemental oxygen was necessary, and chronic lung disease developed. This is the first report of neonatal ureaplasmal pneumonia with sepsis and persistent pulmonary hypertension of the newborn as well as the first time a microorganism other than streptococci has been specifically implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Respiratory infections with U urealyticum or other bacteria should be considered as possible causative or contributory factors in infants with persistent pulmonary hypertension of the newborn.

Female↗
PubMed1990

Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Macular Photocoagulation Study Group.

The persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 247 eyes assigned to krypton red laser photocoagulation in the Age-Related Macular Degeneration Study-Krypton Laser were examined to describe the incidence, timing, visual impact, and potential risk factors for persistence and recurrence. Persistent neovascularization detected within 6 weeks of initial treatment was observed in 32% of treated eyes, and recurrent neovascularization was estimated by life-table methods to develop in an additional 47% over a 5-year period. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. The persistence rate among eyes having 10% or more of the foveal side of the neovascular membrane not covered by treatment was twice as high as in eyes having more extensive coverage. Patients having a fellow eye with a neovascular membrane or scar, a fellow eye with 20 or more drusen in the central macula, or a fellow eye with nongeographic atrophy at initial visit had more recurrences than patients without these characteristics. Ophthalmologists treating similar lesions may be able to reduce persistent neovascularization and the associated visual loss by covering the entire lesion with treatment.

Age Factors↗
PubMed1986

Persistent tardive dyskinesia in bipolar patients.

The prevalence and outcome of persistent tardive dyskinesia (TD) was studied in 131 bipolar patients. There were 34 cases of persistent TD in the subgroup (n = 96) with a history of neuroleptic treatment (prevalence, 35.4%; 95% confidence interval, 25% to 45%); there were no cases of persistent TD in the subgroup (n = 35) without such treatment history. Except in one patient, signs of TD persisted in spite of lithium carbonate treatment in 23 patients (median duration, 16 months; range, five to 24 months), of whom 15 remained off of a neuroleptic regimen during the study period for a median duration of 14 months (range, four to 24 months). Using multiple regression analysis, two variables were found to predict the presence of persistent TD and account for 36% of the variance: longer cumulative duration of maintenance neuroleptic treatment and shorter duration of previous lithium carbonate treatment. There appears to be a significant risk of persistent TD among neuroleptic-treated bipolar patients. High-risk subgroups within this category need to be identified.

Adult↗
PubMed1989

Genetic epidemiology of persistent islet cell antibodies among IDDM patients.

The persistence of cytoplasmic islet cell antibodies (ICA) more than a year after diagnosis of insulin-dependent diabetes mellitus (IDDM) was investigated in 43 families with at least two children with IDDM. The prevalence of persistent ICA among IDDM patients was 16%. Persistence of ICA appeared to be familial in that siblings with IDDM were significantly more concordant for the presence or for the absence of ICA than expected by chance (P = 0.04). Patients with persistent ICA were older on average at onset of IDDM than patients without persistent ICA after adjusting for duration of disease (P = 0.004). Persistence of ICA was not significantly associated with HLA DR type, immunoglobulin genotype, insulin allele class, sex, history of viral diseases, or prior vaccinations.

Autoantibodies↗
PubMed1977

A persistent infection of baby hamster kidney-21 cells with mumps virus and the role of temperature-sensitive variants.

A persistent infection of baby hamster kidney-21 (BHK-21) cells with mumps virus (BHKpi) was maintained for over 60 cell passages in the absence of antiserum. Viral persistence was demonstrated in the cultures by hemadsorption, immunofluorescence, multinucleate syncytia, and released mumps virus at the level of 10(2)--10(3) fluorescent focus-forming units/ml. No detectable levels of interferon were found in cultures persistently infected with mumps virus. Approximately 85--95% of the cells contained viral antigens. Nuclear fluorescence was observed in the persistently infected cells. Mumps virus from persistently infected clutures (MuVpi) was more heat-labile than wild-type mumps (MuVo) when subjected to 40 degrees C. BHKpi cells had a more rapid doubling time and a higher cloning efficiency in soft agar in comparison to BHK-21 cells. MuVpi was also found to be temperature-sensitive. The temperature-sensitivity of MuVpi was determined by the efficiency of plating at 33 degrees and 39 degrees C. MuVpi readily established a persistent infection in BHK-21 cells with less cytopathology than MuVo, and released temperature-sensitive virus.

Animals↗
PubMed1995

Effect of persistent mouse hepatitis virus infection on MHC class I expression in murine astrocytes.

Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I-restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H-2 Kb molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma-interferon (IFN-gamma) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction.

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↗
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↗
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↗