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Serum antibodies to giardial surface antigens: lower titres in persistent than in non-persistent giardiasis.

Antisera to two antigens of Giardia lamblia--plasma membrane (PM) protein and an affinity-purified surface antigen (SA56)--were raised in rabbits, and shown to agglutinate and kill trophozoites in vitro. These antibodies were also demonstrated by ELISA in the sera of paediatric patients with giardiasis. The titres of both antibodies were significantly higher in non-persistent (acute) and asymptomatic cases than in patients with persistent infection; and the latter group did not respond to anti-giardial therapy. The inability of this group to clear G. lamblia infection, in spite of therapy, may result from the low level of antibodies which mediate the killing of trophozoites.

Animals↗

Prolonged persistence of cytopathogenic bovine viral diarrhea virus (BVDV) in a persistently viremic cattle.

A bull persistently viremic with noncytopathogenic (ncp) BVDV was inoculated with the cytopathic (cp) BVDV strain TGAC, which had been found to be antigenically different from the endogenous ncpBVDV (ncpW8). Neutralizing antibodies against strains NADL and TGAC were detectable 12 days and four weeks post infection, respectively. The animal developed fever and diarrhea 15 weeks post infection. On days 3 and 8 after onset of diarrhea a cpBVDV (cpX) was isolated from feces. Antigenic analysis using monoclonal antibodies (MoAbs) showed that cpX and the endogenous ncpBVDV (ncpW8) had identical reactivity patterns except for one epitope that was neither expressed on TGAC nor on ncpW8. Using polymerase chain reaction analysis it was shown that both TGAC and cpX contained a p8 phi gene duplication combined with genomic insertions of identical size. Restriction enzyme analysis of the TGAC and cpX amplicons using four enzymes showed an identical cleavage pattern, except for HaeIII digestion where an additional fragment was observed with cpX. These results suggest that cpBVDV strain TGAC persisted in the viremic animal and apparently caused disease after 15 weeks.

Animals↗

Leishmania major reaches distant cutaneous sites where it persists transiently while persisting durably in the primary dermal site and its draining lymph node: a study with laboratory mice.

So far, studies of Leishmania persistence in mice have used injections of parasites administered either intravenously in the tail vein or subcutaneously in the footpad. These routes poorly reflect the natural conditions when the sandfly delivers metacyclic promastigotes intradermally. In this study B10D2 and BALB/c mice were inoculated within the ear dermis with 10(4) Leishmania major metacyclic promastigotes. The parasite load was monitored by quantitative PCR in different tissues from the dermal inoculation site to distant tissues. The two sites of multiplication and persistence of parasites were the site of L. major inoculation and the draining lymph node (DLN), with a different pattern in the two mouse inbred lines. These two organs were the only sites harboring parasites 12 months postinoculation, with the DLN of BALB/c mice harboring around 10(7) parasites, a stable load from months 3 to 12. In these two sites, 8 and 12 months after inoculation, interleukin 4 (IL-4), gamma interferon, and inducible nitric oxide synthase transcripts parallel the parasite load while IL-10 transcript levels remain high. In addition, at early time points until month 3, parasite DNA was also detected in distant tissues such as the contralateral noninoculated ear or the tail skin, indicating that blood was at least transiently disseminating the parasites. In contrast, L. major DNA in liver, spleen, and femoral bone marrow remained sporadic in mice of both lines. This study is discussed within the framework of Leishmania transmission from the vertebrate host to the sandfly vector, a complex process still poorly understood.

Animals↗

Disruption of the genes for ClpXP protease in Salmonella enterica serovar Typhimurium results in persistent infection in mice, and development of persistence requires endogenous gamma interferon and tumor necrosis factor alpha.

The enteric pathogen Salmonella enterica serovar Typhimurium, similar to other facultative intracellular pathogens, has been shown to respond to the hostile conditions inside macrophages of the host organism by producing a set of stress proteins that are also induced by various environmental stresses. The stress-induced ClpXP protease is a member of the ATP-dependent proteases, which are known to be responsible for more than 90% of all proteolysis in Escherichia coli. To investigate the contribution of the ClpXP protease to the virulence of serovar Typhimurium we initially cloned the clpP and clpX operon from the pathogenic strain serovar Typhimurium chi3306 and then created insertional mutations in the clpP and/or clpX gene. The Delta clpP and Delta clpX mutants were used to inoculate BALB/c mice by either the intraperitoneal or the oral route and found to be limited in their ability to colonize organs of the lymphatic system and to cause systemic disease in the host. A variety of experiments were performed to determine the possible reasons for the loss of virulence. An oxygen-dependent killing assay using hydrogen peroxide and paraquat (a superoxide anion generator) and a serum killing assay using murine serum demonstrated that all of the serovar Typhimurium Delta clpP and Delta clpX mutants were as resistant to these killing mechanisms as the wild-type strain. On the other hand, the macrophage survival assay revealed that all these mutants were more sensitive to the intracellular environment than the wild-type strain and were unable to grow or survive within peritoneal macrophages of BALB/c mice. In addition, it was revealed that the serovar Typhimurium ClpXP-depleted mutant was not completely cleared but found to persist at low levels within spleens and livers of mice. Interferon gamma-deficient mice and tumor necrosis factor alpha-deficient mice failed to survive the attenuated serovar Typhimurium infections, suggesting that both endogenous cytokines are essential for regulation of persistent infection with serovar Typhimurium.

Adenosine Triphosphatases↗

Cells persistently infected with newcastle disease virus: I. Properties of mutants isolated from persistently infected L cells.

The strain of Newcastle disease virus (NDV(pi)) present in persistently infected L cells differed markedly from the Herts strain (NDV(0)) used to initiate the infection. NDV(pi) produced small plaques (less than 1 mm) in chick embryo cell cultures, whereas the wild type (NDV(0)) produced large plaques (2 to 3 mm). The two viruses differed in a number of additional properties. Whereas 80% of adsorbed NDV(0) eluted from chicken red blood cells at 37 C, only about 20% of NDV(pi) was recovered under similar conditions. There was no significant difference in the neuraminidase content of the two viruses. The infectivity of NDV(0) was stable for 1 hr at 48 C, whereas 99.9% of the infectivity of NDV(pi) was destroyed. The two viruses also differed in lethality for chick embryos; NDV(pi) had significantly reduced lethality for 9-day-old chick embryos when compared to NDV(0). In contrast to NDV(0), which produced an abortive infection in L cells, NDV(pi) not only replicated effectively and destroyed these cells, but also induced significantly higher quantities of interferon than did NDV(0). These data furnished additional evidence for the lack of relationship of interferon production to abortive infection of L cells with NDV(0). In contrast, interferon was found to play a significant role in the maintenance of persistent infection.

Journal Article↗

Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence.

Isolates of lymphocytic choriomeningitis virus (LCMV) that elicit a cytotoxic T-lymphocyte response (CTL+) have been compared with isolates that suppress the CTL response (CTL-) in an effort to map this phenotype. A single amino acid change in the glycoprotein of the LCMV Armstrong (ARM) strain is consistently associated with the CTL- trait and the ability of the virus to persist (P+). The CTL+ P- parental strain spontaneously gives rise to CTL- P+ variants within lymphoid tissues of mice persistently infected from birth. To map the structural basis of the phenotype, the complete RNA sequence of LCMV ARM 53b (CTL+) was compared with that of its variant ARM clone 13 (CTL-). Differences in 5 of 10,600 nucleotides were found. Three changes are noted in the large L RNA segment, and two are noted in the small S RNA segment. Only two of the changes distinguishing CTL+ from CTL- isolates affect amino acid coding: lysine to glutamine at amino acid 1079 of the polymerase protein, and phenylalanine to leucine at amino acid 260 of the envelope glycoprotein (GP). We also analyzed two additional CTL- variants and four spontaneous CTL+ revertants. All three CTL- variants differ from the original CTL+ parental strain at GP amino acid 260, indicating that this amino acid change is consistently associated with the CTL- phenotype. By contrast the other four mutations in LCMV are not associated with the CTL- phenotype. Sequence analysis of the coding regions of four CTL+ revertants of ARM clone 13 did not reveal back mutations at the GP 260 locus. This finding indicates that the GP 260 mutation is necessary but not sufficient for a CTL- P+ phenotype and that the reversion to CTL+ P- is likely either due to secondary mutations in other regions of the viral genome or to quasispecies within the revertant population that make significant contributions to the phenotype.

Amino Acid Sequence↗

Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients.

AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients.

AIDS-Related Opportunistic Infections↗

Changes in uterine estrogen receptor concentrations in persistent estrous and persistent diestrous rats.

Changes in uterine weight and the estrogen receptor concentrations were examined in persistent estrous (PE) and persistent diestrous (PD) rats at 80 days of age. To prepare PE rats, 100 micrograms estradiol benzoate (EB) was injected sc into 3-day-old females. PD rats were obtained by daily injections of 10 micrograms EB into females for 10 consecutive days from the day of birth. The uterine weight in PE rats at 80 days was comparable to that in metestrous controls. The uteri of PD rats were smaller than those in PE rats. The concentrations of estrogen receptor in nuclear fractions in PE and PD rats were much lower than those in proestrous controls. Receptor concentrations in cytosol fractions were significantly lower in PE and PD rats than in control diestrous, proestrous and estrous rats. The dissociation constants and sedimentation coefficients of estrogen receptors in PE and PD rats were found to be in the same range as those in control rats. Thus, the reduction in the activity of cytosol receptors in these rats is attributable to a quantitative change in the amount of estrogen receptor protein. To study the response of the uterus to estrogen, ovariectomized rats were injected daily with 10 micrograms estradiol for 7 consecutive days. The uterine growth of PE and PD rats after administration of estradiol was less marked than in controls, indicating a reduction of estrogen sensitivity of the uterus. Seven daily administrations of estradiol continued to increase the concentration of uterine cytosol estrogen receptor in controls. In contrast, in PE and PD rats, the receptor concentrations continued to increase during the first 3 days, and then remained constant. These data suggest that EB in neonatal treatment may directly affect the mechanism of receptor synthesis in uterine tissues. This effect may contribute to the reduction of the uterine response to estrogen.

Animals↗

[Persistent influenza virus infection. Molecular genetic characteristics of ts mutants selected during persistence].

Properties of ts mutants isolated from systems of persistent influenza infection formed in MDCK cell culture by A/Victoria/35/72 virus were studied. The ts mutants isolated at later intervals of persistent infection (158 days) were characterized by thermolability of hemagglutinin and neuraminidase, changes in the EP mobility of HA2 polypeptide, decrease in the molecular weight of this polypeptide, appearance of multiple ts mutations in genes 3, 5, 6, 7, and 8, coding for P2, NP, NA, M, and NS proteins, respectively.

Animals↗

[Therapeutic efficacy of ursodeoxycholic acid in persistent gallbladder lithiasis and persistent biliary sludge: preliminary results of a multicenter experience].

A prospective and multicenter study was performed to determine the efficacy and tolerance of ursodeoxycholic acid (UDCA) in the treatment of gallstones and biliary sludge. Criteria for entry into the trial were radiolucent gallbladder stones; until 20 mm of size and visualization of the gallbladder by oral cholecystography. Too were treatment the patients with persistent biliary sludge (PBS) defined by the persistence of the biliary sludge in two consecutive echography along three months. Without severe gallbladder disease. Then daily UDCA doses of 600 mg were suminstred divided in two postprandial times for a six months period. The control to the treatment were: basal ultrasonography (US) of the gallbladder and by follow-up gallbladder US for six months; clinical examination every month and cholecystography before and after the treatment. Of 110 admitted patients, 19 (17%) stopped the treatment for no-medical reasons and 91 (83%) arrived to the and point. After six months of treatment, complete dissolution was observed in 50% of the patients (46/91), partial in the 43% (39/91) and failed the treatment in 6.5% (6/91) who presented high density stones for computed tomography, CT (greater than 60 UH). According to pattern of lithiasis dissolution was complete in 100% (22/22) of the patients with PBS; 71.4% (10/14) in microlithiasis and 25% (14/55) in macrolithiasis. Minor adverse effects were acidism in the 7.7% (7/91) and diarrhea in the 1.1% (1/91). In the other hand, one patient presented acute pancreatitis (1/91; 1.1%), it must be discussed if was a complication of the lithiasis or an therapeutic effect. The UDCA was a safe and effective treatment without lethality in PBS and in microlithiasis while in case of macrolithiasis must be standardized response criterion, for example density stones for CT.

Adult↗

[The characteristics of labour course and perinatal prognosis in cases of fetal persistent occiput-transverse position and persistent occiput-posterior position].

OBJECTIVES: To study the characteristics of the labour course and perinatal prognosis in cases of fetal persistent occiput-transverse position (POTP) and persistent occiput-posterior position (POPP). METHODS: All the cases, delivered with POTP and POPP in or hospital from Nov, 1995 to July 1996 were analyzed retrospectively. RESULTS: In abnormal fetal occipital position group, the following indices were significantly higher than those of normal group: fetal macrosomia, uterine inertia, and duration of each labour course. The speed of descending of presentation was obviously slower. The incidence of abnormal labour course was markedly increased. The rate of operative delivery was significantly higher. The total rate of operative delivery was 82.81% in the POTP group, and 92.31% in the POPP group. The incidence fetal hypoxia and neonatal asphyxia was markedly high in the abnormal occiput group. CONCLUSIONS: The POTP and POPP are major cases of dystocia. If management is unsuitable, perinatal prognosis will be poor.

Adult↗

Persistent pulmonary hypertension of the neonate (persistent fetal circulation syndrome).

This 15-year-old disease has been clearly described anatomically. Some understanding of possible in utero predisposing conditions has emerged from clinical and animal studies. However, we have very little understanding of the cellular processes that trigger and/or prolong the abnormal medial smooth muscle hypertrophy underlying the condition. Empiric observation has resulted in the development of hyperventilation as a fairly successful treatment modality, although the underlying mechanism of this salubrious effect is unknown. Drugs, a major focus of clinical and laboratory investigations, sometimes are marginally successful (and sometimes are utter failures). Translated into the neonatal intensive care unit, the disease is more frequently accurately diagnosed than in the past, but it remains frustratingly difficult to manage, and thus far is impossible to prevent. The research foundations laid in the past decade provide impetus for accelerated search into the fundamental cellular and biochemical derangements that cause persistent pulmonary hypertension. It is to be hoped that the next decade will yield major advances in both mechanistic understanding and in treatment.

Acetylcholine↗

Effect of interferon on Vero cells persistently infected with Sendai virus compared to Vero cells persistently infected with SSPE virus.

Persistent infections with Sendai and SSPE virus were established in Vero cells. Sequential passages of these cells were monitored by immunofluorescence and for their sensitivity to the antiviral and antiproliferative effects of interferon (IFN). The cells rapidly developed resistance to the antiviral effect of IFN as judged by the inability of IFN to inhibit the replication of exogenous Sindbis virus. This decrease was accompanied by a reduction in the induction of the 2'-5' oligo A synthetase. Both cell lines were resistant to the antiproliferative effect of IFN. A decrease or absence of IFN receptors on the surface of the cells was not found to be the cause of their resistance to IFN.

2',5'-Oligoadenylate Synthetase↗

Intensity and persistence profiles of flavor compounds in synthetic solutions. Simple model for explaining the intensity and persistence of their aftersmell.

Hydroalcoholic solutions containing a single aroma-active compound were evaluated by a sensory panel to determine the difference between ortho and retronasal odor intensities (DeltaI(ro)), buccal savoring, and aftersmell duration. Eight compounds were used. Buccal perception seems to be just a physiologically restricted form of retronasal perception. DeltaI(ro) values were dependent on the panel, although results from the two panels were significantly correlated. Such differences and the aftersmell persistence were also significantly correlated with different physicochemical parameters related to volatility. A simple model to explain such dependence is proposed. The model considers the mouth-throat system as a perfect mixing tank with a finite amount of odorants being progressively diluted by swallowing and purging (both taken as continuous processes). Retronasal intensity is modeled from the odor properties of the liquid in such a tank calculated from orthonasal odor intensity versus concentration (I/log C) curves. The model explains successfully experimental results and has also been successfully applied to instrumental data from other authors.

Alcohols↗

Memory B-cell persistence is independent of persisting immunizing antigen.

Immunological memory in the antibody system is generated in T-cell-dependent responses and carried by long-lived memory B cells that recognize antigen by high-affinity antibodies. But it remains controversial whether these B cells represent true 'memory' cells (that is, their maintenance is independent of the immunizing antigen), or whether they are a product of a chronic immune response driven by the immunizing antigen, which can be retained in the organism for extended time periods on the surface of specialized antigen-presenting cells (follicular dendritic cells). Cell transfer experiments provided evidence in favour of a role of the immunizing antigen; however, analysis of memory cells in intact animals, which showed that these cells are mostly resting and can persist in the absence of detectable T-cell help or follicular dendritic cells, argued against it. Here we show, by using a genetic switch mediated by Cre recombinase, that memory B cells switching their antibody specificity away from the immunizing antigen are indeed maintained in the animal over long periods of time, similar to cells retaining their original antigen-binding specificity.

Alleles↗

Persistent infection with chicken anaemia virus and some effects of highly virulent infectious bursal disease virus infection on its persistency.

Chicken anaemia virus (CAV) infectivity and the effect of highly virulent infectious bursal disease virus (hv IBDV) infection on CAV's infectivity were examined in chickens inoculated with CAV or inoculated dually with CAV and hv IBDV. Five chickens inoculated dually with hv IBDV at 35 days old and then with CAV at 40 days old exhibited no clinical signs of disease, but showed atrophic bursae of Fabricius when necropsied 4 weeks later. Upon examining the chickens at 7 days postinoculation (dpi) with CAV, it was found that hv IBDV infection had inhibited production of virus neutralising (VN) antibody to CAV, and that it was possible to recover CAV from plasma of these chickens. Although VN antibody to CAV appeared after 14 dpi, CAV was recovered from blood cells (BC s) at high titres ranging from 10(2.5)to 10(5.5)TCID(50)/0.1 ml, 7 to 28 dpi in IBDV -induced immunosuppressed chickens. In addition, CAV was sporadically recovered, using rectal swabs, from the dually inoculated chickens at low titers, ranging from 10(1.0)to 10(2. 0)TCID(50)/0.1 ml). In contrast, although CAV was recovered from BC s in most of the chickens inoculated with CAV alone, the titers were lower (10(1.0)to 10(2.5)TCID(50)/0.1 ml). No CAV was detected from the rectal swabs of these chickens. The results of virus recovery were confirmed by polymerase chain reaction. This study first examined the persistency of CAV in BC s and the effective enhancement of primary CAV infection as a result of immunosuppression caused by hv IBDV infection.

Anemia↗

The concept of hardiness: persistent problems, persistent appeal.

Despite increased critical debate, the concept of hardiness continues to be a popular focus of research, and little has changed in how hardiness is defined, measured, and applied. The article argues that the concept of hardiness remains inherently problematic. In particular, hardiness is plagued by definitional problems, problems of construct validity, measurement problems, and class, gender, and age bias. The persistent appeal of the hardiness construct lies partially in researchers' desire to discover why some people are able to withstand the health-damaging effects of stress. More important, the article argues that hardiness is appealing because it continues to be easier to focus on individual problems and solutions rather than look for and try to change the social factors that affect health status and well-being.

Adaptation, Psychological↗