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PubMed2006

The persistence of depression score.

OBJECTIVE: To construct a score that allows prediction of major depressive episode (MDE) persistence in individuals with MDE using determinants of persistence identified in previous research. METHOD: Data were derived from 250 subjects from the general population with new MDE according to DSM-III-R. These subjects were recruited from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), using the Composite International Diagnostic Interview. Determinants for persistence were transformed into a practical risk score using proportional hazards models and bootstrapping techniques. RESULTS: The risk of MDE persistence after 12 months was 23%. The score comprised measures of physical illness, social support, depression severity and recurrency, and duration of previous episodes. With increasing categories of these measures, the predicted risks increased from 7 to 40%. CONCLUSION: We constructed the Persistence of Depression Score (PDS) showing reasonable performance. The PDS could be of importance in clinical practice to support treatment decisions.

Adolescent↗
PubMed1992

Persistent diarrhea as a cause of childhood mortality in rural Bangladesh.

To determine the importance of persistent diarrhea in childhood mortality a multiple-step verbal autopsy method was used to study 1934 deaths in Matlab, Bangladesh. We found that most of the deaths from acute watery diarrhea occurred in infancy, whereas the peak of non-watery diarrhea deaths was in children over 12 months of age. Children suffering from persistent diarrhea and malnutrition were at highest risk of dying during their third year of life. Children with infectious diseases have a two to four times higher risk of dying if they are malnourished, and for diarrhea the risk is 17 times as high. Forty-nine percent of the diarrheal deaths were in children with malnutrition associated with persistent diarrhea. These results imply that fluid and dietary management are key aspects in the treatment of diarrhea, particularly for those episodes which persist. We conclude that attempts to reduce diarrhoeal deaths with vertical ORT programmes will not have major impact unless other interventions are directed to the persistent diarrhoea-malnutrition complex.

Acute Disease↗
PubMed1992

Epidemiology of persistent diarrhea among Guatemalan rural children.

A prospective, longitudinal two-year study to determine the epidemiology of persistent (> or = 14 days' duration) diarrhea in rural children of Guatemala was undertaken. Three-hundred and twenty-one children aged 0-35 months were kept under surveillance by twice-a-week home visits. The overall incidence of diarrhea was 0.147 per child-week; the incidence of persistent diarrhea was 0.014 per child-week. The peak of persistent diarrhea was observed in infants below six months of age, with a continuous decline thereafter. This trend in incidence of persistent diarrhea was associated with a higher proportion (16%) of illnesses persisting for more than 13 days in children younger than six months of age as compared to children 30-35 months old (4%). Males had more diarrhea (0.156 per child-week) than females (0.139 per child week). Among children above 18 months of age, the proportion of episodes that lasted for more than 13 days was lower in females than in males.

Acute Disease↗
PubMed1992

Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú.

In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Perú, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re-infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries.

Acute Disease↗
PubMed1992

Small intestinal mucosal histology in the syndrome of persistent diarrhoea and malnutrition: a review.

Prolonged injury to the small intestinal mucosa is probably the final common pathway by which a variety of noxious influences--nutritional, infective and possibly allergic--perpetuate the syndrome of persistent diarrhoea in children in developing countries. Animal studies have helped to separate the individual effects of malnutrition and diarrhoea on the gut in a way that is not possible in the clinical situation. Early studies in children provided somewhat subjective or semi-quantitative data on intestinal morphology. More recently, the application of computer-assisted quantitative morphological techniques to intestinal mucosae from children with persistent diarrhoea have revealed a spectrum of changes consistent with a cell-mediated immune form of damage. The nature of the antigens that provoke these responses remains to be elucidated. Several reports indicate that in children with persistent diarrhoea clinical severity and prognosis do not necessarily correlate with the degree of small intestinal mucosal damage. Nutritional rehabilitation can be shown to produce a demonstrable improvement in small intestinal crypt cell proliferative activity in children with persistent diarrhoea. It is not yet known for how long nutritional rehabilitation should be continued to ensure complete recovery of the intestinal damage following persistent diarrhoea.

Animals↗
PubMed1992

Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study.

The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population-based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast-feeding was associated with an odds ratio of 0.06 (95% CI 0.002-2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0-9.9) in favour of developing persistence of acute diarrhoea (p = 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0-228.8) (p = 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea.

Acute Disease↗
PubMed2005

Persistent sexual arousal syndrome: a descriptive study.

INTRODUCTION: Persistent sexual arousal disorder (PSAS) is a poorly documented condition characterized by persistent genital arousal in the absence of conscious feelings of sexual desire. AIM: To determine whether there are replicable features associated with PSAS, to describe salient characteristics of women reporting this condition, and to determine predictors of distress. METHODS: A 46-item Internet survey containing demographic information, symptom description, triggers, exacerbation and relief measures, distress ratings, and life and sexual satisfaction was placed on a secure server. MAIN OUTCOME MEASURES: Frequency analyses of descriptive data, and stepwise multiple regression analysis to identify independent predictors of level of distress. RESULTS: Of the 103 respondents, most were in good health, well educated, and in long-term relationships. Ninety-eight percent of respondents met at least one criterion for PSAS and 53% met all five criteria. Involuntary genital and clitoral arousal persisting for extended time periods, genital arousal unrelated to subjective feelings of sexual desire, and genital arousal not relieved with orgasms were the most frequently endorsed features associated with this syndrome. Symptom triggers included sexual stimulation, masturbation, stress, and anxiety. Distress about the condition was low in 25%, moderate in 35%, and high in 40% of respondents. The strongest predictors of distress were intrusive and unwanted feelings of genital arousal (P < 0.0001), continuous symptoms (P < 0. 001), feelings of unhappiness (P < 0.03), shame (P = 0.0001) and worry (P = 0.01), reduced sexual satisfaction (P < 0.004), enjoyment of symptoms some of the time (P = 0.01), and relationship status (P < 0.004). CONCLUSIONS: The results of this research support the description of a condition (persistent sexual arousal) involving involuntary genital and clitoral arousal unrelated to subjective feelings of sexual desire which persists despite one or more orgasms and which usually feels intrusive and unwanted. Varying levels of distress were identified with this condition as well as a variety of primarily negative emotional reactions.

Adolescent↗
PubMed1987

Persistent calcium-sensitive potassium current and the resting properties of guinea-pig myenteric neurones.

1. Intracellular recordings were made from neurones in the guinea-pig myenteric plexus which show a long-lasting after-hyperpolarization following the action potential (AH neurones). In most experiments membrane currents were measured using a single-electrode voltage clamp. Tetrodotoxin was present. 2. A step depolarization (10-15 mV, 5-10 s) from a holding potential close to the resting level (typically -60 mV) caused a slowly developing outward current. The current increased exponentially with a time constant of about 1.3 s at -50 mV. At the termination of the step the current declined over a similar time period (time constant congruent to 2.5 s). Hyperpolarizing step commands resulted in a slowly declining outward current (tau congruent to 3.5 s at -70 mV) which developed again at the termination of the hyperpolarization (tau congruent to 2.1 s at -60 mV); these tail currents reversed at the potassium equilibrium potential. 3. The current was not observed in solutions containing no calcium, high magnesium concentrations and cobalt. It did not inactivate during changes in holding potential of up to 5 min. The current is therefore called the persistent calcium-sensitive potassium current. 4. A brief depolarizing command to less-negative potentials (typically to -10 mV for 10-30 ms) was followed by a potassium current which increased and decreased according to the sum of two exponentials having time constants tau on congruent to 0.4 s and tau off congruent to 2.5 s. This after-current disappeared in calcium-free, high-magnesium and cobalt solution. 5. Both the after-current and the persistent calcium-sensitive current were similarly sensitive to tetraethylammonium ions, being unaffected by 5 mM but substantially reduced by 20 mM solutions. The time constant of decline of the persistent calcium-sensitive current at the end of a depolarizing step was not different from tau off for the after-current; these time constants had a similar sensitivity to voltage and temperature. 6. The conductance underlying the after-current became progressively smaller as the persistent calcium-sensitive current was increased by membrane depolarization. In a given neurone, the sum of the two conductances was constant. This finding implies that the persistent calcium-sensitive potassium conductance is the same conductance as that which is increased during the after-hyperpolarization.

Action Potentials↗
PubMed2002

Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits.

Micafungin (FK463) is an echinocandin that demonstrates potent in vitro antifungal activities against Candida and Aspergillus species. However, little is known about its comparative antifungal activities in persistently neutropenic hosts. We therefore investigated the plasma micafungin pharmacokinetics and antifungal activities of micafungin against experimental disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. The groups with disseminated candidiasis studied consisted of untreated controls (UCs); rabbits treated with desoxycholate amphotericin B (DAMB) at 1 mg/kg of body weight/day; or rabbits treated with micafungin at 0.25, 0.5, 1, and 2 mg/kg/day intravenously. Compared with the UCs, rabbits treated with micafungin or DAMB showed significant dosage-dependent clearance of Candida albicans from the liver, spleen, kidney, brain, eye, lung, and vena cava. These in vivo findings correlated with the results of in vitro time-kill assays that demonstrated that micafungin has concentration-dependent fungicidal activity. The groups with invasive pulmonary aspergillosis studied consisted of UCs; rabbits treated with DAMB; rabbits treated with liposomal amphotericin B (LAMB) at 5 mg/kg/day; and rabbits treated with micafungin at 0.5, 1, and 2 mg/kg/day. In comparison to the significant micafungin dosage-dependent reduction of the residual burden (in log CFU per gram) of C. albicans in tissue, micafungin-treated rabbits with invasive pulmonary aspergillosis had no reduction in the concentration of Aspergillus fumigatus in tissue. DAMB and LAMB significantly reduced the burdens of C. albicans and A. fumigatus in tissues (P < 0.01). Persistent galactomannan antigenemia in micafungin-treated rabbits correlated with the presence of an elevated burden of A. fumigatus in pulmonary tissue. By comparison, DAMB- and LAMB-treated animals had significantly reduced circulating galactomannan antigen levels. Despite a lack of clearance of A. fumigatus from the lungs, there was a significant improvement in the rate of survival (P < 0.001) and a reduction in the level of pulmonary infarction (P < 0.05) in micafungin-treated rabbits. In summary, micafungin demonstrated concentration-dependent and dosage-dependent clearance of C. albicans from persistently neutropenic rabbits with disseminated candidiasis but not of A. fumigatus from persistently neutropenic rabbits with invasive pulmonary aspergillosis.

Animals↗
PubMed2003

High-dose azithromycin versus high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent acute otitis media.

Infants and young children, especially those in day care, are at risk for recurrent or persistent acute otitis media (AOM). There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients. In this double-blind, double-dummy multicenter clinical trial, we compared a novel, high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM. Three hundred four children were randomized; 300 received either high-dose azithromycin (20 mg/kg of body weight once a day for 3 days) or high-dose amoxicillin-clavulanate (90 mg/kg divided twice a day for 10 days). Tympanocentesis was performed at baseline; clinical response was assessed at day 12 to 16 and day 28 to 32. Two-thirds of patients were aged < or =2 years. A history of recurrent, persistent, or recurrent plus persistent AOM was noted in 67, 18, and 14% of patients, respectively. Pathogens were isolated from 163 of 296 intent-to-treat patients (55%). At day 12 to 16, clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients (86 versus 84%, respectively) and for children aged < or =2 years (85 versus 79%, respectively). At day 28 to 32, clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients (72 versus 61%, respectively; P = 0.047) and for those aged < or =2 years (68 versus 51%, respectively; P = 0.017). Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens. The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42%, respectively (P = 0.095). Corresponding compliance rates were 99 and 93%, respectively (P = 0.018). These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM.

Acute Disease↗
PubMed1984

Persistence of Nosema locustae Spores in Soil as Determined by Fluorescence Microscopy.

Nosema locustae, a protozoan parasite of grasshoppers, is used as a bioinsecticide. In the present study, the persistence of N. locustae spores in soil and the interaction of these spores with the indigenous soil microflora were examined with various forms of microscopy and staining. Fluorescence microscopy was found to be better than phase-contrast or bright-field microscopy for detecting and viewing spores in soil. Fluorescein isothiocyanate was a better fluorescent stain than acridine orange or fluorescein diacetate; water-soluble aniline blue did not stain spores. The eight bright-field microscopy stains tested (phenolic erythrosin, phenolic rose bengal, malachite green, crystal violet, safranin, Congo red, methyl red, and eosin B) were not satisfactory, as spore staining characteristics were either poor or masked by overstained soil debris. A procedure was developed which allowed spores to be extracted from soil with a peptone-phosphate buffer, recovered on a membrane filter, and stained with fluorescein isothiocyanate for microscopic counting. This procedure was used to assess the persistence of N. locustae spores in field and laboratory soils. The number of N. locustae spores in a laboratory model soil system persisted at a high level for over 8 weeks when the soil was incubated at 5 degrees C but exhibited a 1,000-fold decrease after 1 week of incubation at 27 degrees C. Persistence was related to the temperature-dependent activity of the indigenous soil microflora, which, on the basis of microscopic observations, appeared to prey on N. locustae spores. N. locustae spores were detected in an N. locustae-treated field soil at a low level consistent with the level for laboratory soil incubated at 27 degrees C, and they persisted at this level for over 2 months. No spores were detected on vegetation from this field or in the soil from an adjacent, nontreated control field. N. locustae-like spores were also detected in soil from nontreated fields supporting large grasshopper populations.

Journal Article↗
PubMed2000

Persistent colonization of sheep by Escherichia coli O157:H7 and other E. coli pathotypes.

Shiga toxin-producing Escherichia coli (STEC) is an important cause of food-borne illness in humans. Ruminants appear to be more frequently colonized by STEC than are other animals, but the reason(s) for this is unknown. We compared the frequency, magnitude, duration, and transmissibility of colonization of sheep by E. coli O157:H7 to that by other pathotypes of E. coli. Young adult sheep were simultaneously inoculated with a cocktail consisting of two strains of E. coli O157:H7, two strains of enterotoxigenic E. coli (ETEC), and one strain of enteropathogenic E. coli. Both STEC strains and ETEC 2041 were given at either 10(7) or 10(10) CFU/strain/animal. The other strains were given only at 10(10) CFU/strain. We found no consistent differences among pathotypes in the frequency, magnitude, and transmissibility of colonization. However, the STEC strains tended to persist to 2 weeks and 2 months postinoculation more frequently than did the other pathotypes. The tendency for persistence of the STEC strains was apparent following an inoculation dose of either 10(7) or 10(10) CFU. One of the ETEC strains also persisted when inoculated at 10(10) CFU. However, in contrast to the STEC strains, it did not persist when inoculated at 10(7) CFU. These results support the hypothesis that STEC is better adapted to persist in the alimentary tracts of sheep than are other pathotypes of E. coli.

Animals↗
PubMed2001

Evidence that certain clones of Campylobacter jejuni persist during successive broiler flock rotations.

Through the national surveillance program for Campylobacter spp., nine broiler chicken farms that were infected with Campylobacter jejuni in at least five rotations in 1998 were identified. One additional farm, located at the island of Bornholm where divided slaughter is used extensively, was also selected. Twelve broiler houses located on 10 farms were included in the study. The C. jejuni isolates collected from the selected houses during the surveillance were typed using fla typing and macrorestriction profiling (MRP), and a subset of the isolates, representing each of the identified clones, was serotyped according to the Penner scheme. Pulsed-field gel electrophoresis typing using SmaI and KpnI revealed that the majority of houses (11 of 12) carried identical isolates in two or more broiler flocks. Such persistent clones were found in 63% of all flocks (47 of 75). The majority of persistent clones (7 of 13) had fla type 1/1, but MRPs distinguished between isolates from different houses, and fla type 1/1 clones belonged to different serotypes. Seven houses carried persistent clones that covered an interval of at least four broiler flock rotations, or at least one half year. The dominant fla type (1/1) was represented by 44% of isolates, or by at least one isolate from 31 of 62 broiler flocks. This significantly exceeded the prevalence of fla type 1/1 C. jejuni isolates that we have estimated from other studies and suggests that isolates carrying this fla type are overrepresented in flocks with recurrent Campylobacter problems. The MRPs of clones belonging to fla type 1/1 serotype O:2 isolated from persistently infected flocks shared a high percentage of bands compared to the remaining isolates, indicating that some clones that have the ability to cause persistent infections in broiler farms are highly related to each other.

Animal Husbandry↗
PubMed1967

Quantitative studies on fabrics as disseminators of viruses. 3. Persistence of vaccinia virus on fabrics impregnated with a virucidal agent.

Eight compounds were tested in vitro for virucidal and antiviral activity against poliovirus and vaccinia virus. These compounds included five quaternary ammonium salts, two bromosalicylanilides, and neomycin sulfate, an antibiotic. None of the compounds was active against poliovirus, but virucidal activity was demonstrated against vaccinia virus with three of the quarternary ammonium compounds: n-alkyl (C14, C12, C16) dimethyl benzyl ammonium chloride, di-isobutyl cresoxy ethoxy ethyl dimethyl benzyl ammonium chloride monohydrate, and n-alkyl (60% C14, 30% C16, 5% C12, 5% C18) dimethyl benzyl ammonium chlorides plus n-alkyl (50% C12, 30% C14, 17% C16, 3% C18) dimethyl ethylbenzyl ammonium chlorides. Wool blanketing, wool gabardine, and cotton sheeting materials were impregnated with the first of the above virucidal compounds, and the persistence of vaccinia virus on these fabrics was compared with the persistence of the agent on nonimpregnated fabrics of the same type held at 25 C in 35 and 78% relative humidity. No virus could be recovered from the chemically treated fabrics at any time after virus exposure, whereas the virus persisted as long as 4 weeks on nonimpregnated materials. Viable vaccinia virus was also found to persist less than 1 day on a cotton fabric finished with a wash-and-wear modified triazone resin. Poliovirus persisted less than 5 days on this wash-and-wear fabric.

Anilides↗
PubMed2002

Screening of neonatal calves for persistent infection with bovine viral diarrhea virus by immunohistochemistry on skin biopsy samples.

Detection and elimination of cattle that are persistently infected with bovine viral diarrhea virus (BVDV) is important for controlling the transmission of this virus. Colostrum-derived antibodies make the detection of persistently BVDV-infected neonatal calves cumbersome and expensive. The objective of this study was to evaluate the use of immunohistochemical staining of skin biopsy samples from neonatal calves as a method for the early detection of persistent BVDV infection. Three hundred thirty-two 1- to 4-week-old dairy calves were screened for BVDV as part of a routine control program. Formalin-fixed skin biopsy samples were stained for BVDV antigen by immunohistochemistry (IHC), and the results were compared to those of virus isolation (VI) from white blood cell preparations. Six calves were positive by both IHC and VI and remained positive for BVDV upon subsequent follow-up testing; thus, they were classified as persistently infected with BVDV. One calf was positive by VI but negative by IHC. On subsequent testing, the calf was negative by VI, suggesting that the initial VI result was due to an acute BVDV infection. One calf was positive by IHC but negative by VI. This calf remained negative by VI on follow-up testing. Immunohistochemical staining of skin biopsy samples is a reliable method for screening neonatal calves for persistent BVDV infection and would be a useful management tool as an aid for controlling and preventing BVDV infection.

Animals↗
PubMed1980

Persistent infection of mouse fibroblasts (L cells) with Chlamydia psittaci: evidence for a cryptic chlamydial form.

When monolayers of mouse fibroblasts (L cells) were infected with enough Chlamydia psittaci (strain 6BC) to destroy most of the host cells, 1 in every 10(5) to 10(6) originally infected cells gave rise to a colony of L cells persistently infected with strain 6BC. In these populations, the density of L cells and 6BC fluctuated periodically and reciprocally as periods of host cell increase were followed by periods of parasite multiplication. Successive cycles of L-cell and 6BC reproduction were sustained indefinitely by periodic transfer to fresh medium. Isolation of L cells and 6BC from persistent infections provided no evidence that there had been any selection of variants better suited for coexistence. Persistently infected populations consisting mainly of inclusion-free L cells yielded only persistently infected clones, grew more slowly, and cloned less efficiently. They were also almost completely resistant to superinfection with high multiplicities of either 6BC or the lymphogranuloma venereum strain 440L of Chlamydia trachomatis. These properties of persistently infected L cells may be accounted for by assuming that all of the individuals in these populations are cryptically infected with 6BC and that cryptic infection slows the growth of the host cell and makes it immune to infection with exogenous chlamydiae. According to this hypothesis, the fluctuations in host and parasite density occur because some factor periodically sets off the conversion of cryptic chlamydial forms into reticulate bodies that multiply and differentiate into infectious elementary bodies in a conventional chlamydial developmental cycle.

Animals↗
PubMed1984

Persistent infection with mouse hepatitis virus 3 in mouse lymphoid cell lines.

The sensitivity of mice to mouse hepatitis virus 3 (MHV3) varies according to strain, age, and immune status of the animals. In semisusceptible strains, mice surviving the acute phase of infection develop a chronic disease characterized by the occurrence of paralysis, virus persistence, and immunodeficiency. Persistent MHV3 infections established in vitro in YAC and RDM -4 mouse lymphoid cell lines were characterized by virus production, presence of cytoplasmic viral antigens, and cell lysis. The occurrence of cell "crisis" in YAC cells was manifested by a sharp increase in cell lysis and in the number of fluorescent cells and, concomitantly, by a marked decrease in virus titers. A relationship was observed among the percentage of fluorescent cells, cell lysis, and virus yield and was modulated by renewal of culture media, change in temperature, or inhibition of cellular RNA synthesis. Cell cloning and antibody treatment experiments indicated that viral transmission was performed by viral infection of newly permissive cells produced by the division of uninfected cells in the culture and not by transmission of viral information by infected dividing cells. The biological and biochemical properties of MHV3 variants derived from persistently infected YAC lymphoid cells were characterized. Thermosensitivity and thermolability of cloned viruses originating from persistently infected YAC cells, as well as parent virus suspensions, were studied. A similar heterogeneity was observed when YAC-derived cloned substrains (YAC-MHV3) were compared with parent-derived cloned viruses, indicating that no selection of temperature-sensitive mutants was induced in persistently infected YAC cells. However, the capacity of MHV3 to induce a lethal acute disease when injected into susceptible mice was lost very rapidly. The absence of pathogenicity was related to the induction of a subclinical infection which elicited defense mechanisms. These data suggest, therefore, that MHV3 replication in lymphoid cell lines leads to induction or selection of variants which maintain pathogenicity in vitro but display reduced pathogenic effects in vivo.

Animals↗
PubMed1994

Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence.

Previous studies have shown that the immune-regulated cytokine gamma interferon (IFN-gamma) activates host cells to restrict intracellular growth of the bacterial pathogen Chlamydia trachomatis by induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Recently, subinhibitory levels of IFN-gamma were used to generate an in vitro persistent chlamydial infection characterized by large aberrant, noninfectious reticulate bodies from which infectious progeny could be recovered following the removal of IFN-gamma. Studies were done to determine if the mechanism functioning to induce chlamydiae to enter a persistent state in the presence of low levels of IFN-gamma was similar to that reported to inhibit chlamydial growth. Host cells treated with levels of IFN-gamma required to induce persistence were assessed for IDO activity by high-performance liquid chromatography analysis of tryptophan and its catabolic products. Substantial tryptophan catabolism was detected in acid-soluble cellular pools, indicating that the intracellular availability of this essential amino acid was limited under these conditions. In addition, a mutant cell line responsive to IFN-gamma but deficient in IDO activity was shown to support C. trachomatis growth, but aberrant organisms were not induced in response to IFN-gamma treatment. Analyses of infected cells cultured in medium with incremental levels of exogenous tryptophan indicated that persistent growth was induced by reducing the amount of this essential amino acid. These studies confirmed that nutrient deprivation by IDO-mediated tryptophan catabolism was the mechanism by which IFN-gamma mediates persistent growth of C. trachomatis.

Chlamydia trachomatis↗