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Strain relatedness in persistent and recurrent candiduria.

PURPOSE: We assessed the value of determining strain relatedness in differentiating persistent from recurrent candiduria. MATERIALS AND METHODS: Prospective monitoring of patients with candiduria (10(4) or greater colony forming units per ml.) during a 5-month period. All patients with persistent or recurrent infection after documented clearance were selected. Pair isolates were typed using restriction endonuclease analysis of genomic deoxyribonucleic acid with SfiI. Isolates were considered related if all deoxyribonucleic acid bands matched. RESULTS: We encountered 22 and 5 patients with persistent and recurrent infection, respectively. The isolates were recovered 1 to 140 days apart (21.56 +/- 28.97). Most patients were women (85.2%) with a mean age of 66.41 +/- 18.11 years. Risk factors included antibiotics (100%), indwelling catheter (88.9%) and diabetes mellitus (40.7%). Of 15 individuals who received antifungal therapy candiduria persisted in 10 and resolved but recurred within 4 to 26 days (13.00 +/- 9.08) after treatment in 5. Candida albicans accounted for 34 of 58 isolates (58.6%), and it was mixed with other species in 4 cultures. Paired strains were genetically identical in 26 of 27 patients. Strain persistence was documented in 21 of 22 cases with persistent infection and in all 5 patients with recurrent disease. CONCLUSIONS: These findings show that strain persistence is exceedingly frequent in candiduria. These results imply that determining strain relatedness of Candida urinary isolates may not be reliable in differentiating persistent from recurrent infection.

Aged↗

Influence of persistent occiput posterior position on delivery outcome.

OBJECTIVE: To evaluate the influence of intrapartum persistent occiput posterior position of the fetal head on delivery outcome and anal sphincter injury, with reference to the association with epidural analgesia. METHODS: We conducted a prospective observational study of 246 women with persistent occiput posterior position in labor during a 2-year period, compared with 13,543 contemporaneous vaginal deliveries with occiput anterior position. RESULTS: The incidence of persistent occiput posterior position was significantly greater among primiparas (2.4%) than multiparas (1.3%; P <.001; 95% confidence interval 1.4, 2.4) and was associated with significantly higher incidences of prolonged pregnancy, induction of labor, oxytocin augmentation of labor, epidural use, and prolonged labor. Only 29% of primiparas and 55% of multiparas with persistent occiput posterior position achieved spontaneous vaginal delivery, and the malposition was associated with 12% of all cesarean deliveries performed because of dystocia. Persistent occiput posterior position was also associated with a sevenfold higher incidence of anal sphincter disruption. Despite a high overall incidence of use of epidural analgesia (47% versus 3%), the institutional incidence of persistent occiput posterior position was lower than that reported 25 years ago. CONCLUSION: Persistent occiput posterior position contributed disproportionately to cesarean and instrumental delivery, with fewer than half of the occiput posterior labors ending in spontaneous delivery and the position accounting for 12% of all cesarean deliveries for dystocia. Persistent occiput posterior position leads to a sevenfold increase in the incidence of anal sphincter injury. Use of epidural analgesia was not related to the malposition.

Anal Canal↗

Persistent pulmonary hypertension of the neonate and asymmetric growth restriction.

OBJECTIVE: To evaluate the possible associations between persistent pulmonary hypertension of the neonate, need for extra-corporeal membranous oxygenation, small for gestational age (SGA), and low ponderal index for gestational age in infants with persistent pulmonary hypertension of the neonate and in matched controls. METHODS: Eighty-six infants with persistent pulmonary hypertension of the neonate delivered from 1991 to 1994 at our hospital were matched with 430 contemporaneous control singleton neonates. Birth weight and ponderal indices (100 x weight/length3) less than the tenth percentile for gestational age and gender were defined as SGA and low ponderal index, respectively. We assessed associations between these markers, the presence of persistent pulmonary hypertension of the neonate, and the need for extracorporeal membranous oxygenation. RESULTS: Low ponderal index was associated with persistent pulmonary hypertension of the neonate (odds ratio [OR] 5.4), whereas SGA was not. Low ponderal index (OR 4.0) was an independent correlate of persistent pulmonary hypertension of the neonate after adjustment with logistic regression for 5-minute Apgar scores less than 7, umbilical arterial pH less than 7.10, and presence of meconium. Low ponderal index was associated with need for extracorporeal membranous oxygenation in neonates with persistent pulmonary hypertension (P < .001). CONCLUSION: Fetal developmental events may significantly affect neonatal pulmonary status. Diminished neonatal nutritional status, as measured by low ponderal index for gestational age, is associated with increased risk of persistent pulmonary hypertension of the neonate and severity of the disease process.

Case-Control Studies↗

Suppression of interferon response gene expression in cells persistently infected with mumps virus, and restoration from its suppression by treatment with ribavirin.

Persistent infections with mumps virus were established in human B-lymphoid cell line Akata and in the human chronic myelogenous leukaemia cell line K562. Even after IFN treatment a drastic decrease in STAT-1alpha (signal transducers and activators of transcription-1alpha), STAT-2 and p48 (ISGF-3gamma: IFN-stimulated gene factor-3gamma), which are closely correlated with the IFN-signaling pathway, was found in these persistently infected cells (Akata-MP1 and K-MTP). Therefore, the IFN-signaling pathway is thought to be defective in these persistently infected cells. In other words, most of the IFN-inducible genes in these cells persistently infected with mumps virus may not be able to respond to IFN treatment. Indeed, poor induction of 2',5'-oligoadenylate synthetase (2-5AS), dsRNA activated protein kinase (PKR), and MxA protein mRNAs were demonstrated in these cell lines after IFN treatment. Expression of MHC class-I antigen was also significantly reduced in the persistently infected cell lines as compared with that of uninfected control cells. HLA antigen was augmented by IFN-alpha in Akata and K562 cells, but not in persistently infected cells. Furthermore, suppression of IFN-induced 2-5AS induction and MHC class-I expression was restored by treatment of persistently infected cells with ribavirin through inhibition of virus replication. The result of restoration was also confirmed by IFN-induced STAT-1 induction in persistently infected cells treated with ribavirin.

Antiviral Agents↗

Salvage brachytherapy for patients with locally persistent nasopharyngeal carcinoma.

PURPOSE: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. This study was conducted to evaluate the outcomes of patients with locally persistent NPC as treated by high-dose-rate (HDR) intracavitary brachytherapy, and to explore whether routine brachytherapy boost could improve the local control. METHODS AND MATERIALS: Eighty-seven patients with locally persistent NPC treated during 1990-1998 with HDR intracavitary brachytherapy were retrospectively analyzed. Fibreoptic nasopharyngoscopy was performed 3-6 weeks after completion of the primary external radiation therapy (ERT). Biopsies were only taken from suspicious areas. Those with complete regression of local disease were put on observation. Eighty-seven patients were shown to have persistent viable disease at a median time of 6 weeks post-RT. The distribution according to Ho's staging system at initial diagnosis was as follows: Stage I-8, II-33, III-41, IV-5; T1-19, T2-48, T3-20; N0-32, N1-22, N2-28, N3-5. CT scan for restaging was not performed after the documentation of persistent disease. Our policy was to treat all patients with persistent disease with brachytherapy irrespective of the extent of disease just prior to brachytherapy. They were treated with HDR intracavitary brachytherapy, with either cobalt sources or an iridium source, giving 22.5-24 Gy in 3 weekly sessions in all but 4 patients. This dose was prescribed at a distance of 1.5 cm from the center of the surface as defined by the sources in the first six patients and subsequently reduced to 1 cm for the others. Twelve patients were treated with neoadjuvant chemotherapy. To compare the efficacy of brachytherapy, another 383 consecutive nonmetastatic patients, treated with curative intent by ERT, during the years 1990-1993, were evaluated. Multivariate analysis was performed using the Cox regression proportional hazards model. RESULTS: The 5-year actuarial local failure-free survival (LFFS) rates and disease-specific survival rates for the brachytherapy group and ERT group were 85% and 76.6% (p = 0.15), and 72% and 67.8% (p = 0.2), respectively. The corresponding 5-year actuarial LFFS rates for T1, T2, and T3 disease were 94.7%, 88.2%, 67.4%, and 84.1%, 79.8%, 62.6%. In assessing the local control, only the T staging was significant on multivariate analysis (p = 0.0004). Other parameters such as age, sex, and persistence of disease (giving brachytherapy) were all nonsignificant. Complications were comparable between the two groups. In the persistent group, the local failure rates of the patients treated with and without neoadjuvant chemotherapy were 17% (2/12) and 13% (10/75) respectively. When analyzed according to different brachytherapy sources, the 5-year LFFS rates of the T1, T2, and T3 patients treated with iridium and cobalt sources were 100% vs. 85.7 (p = 0.19), 93.6% vs. 70% (p = 0.04), and 67.7% vs. 60% (p = 0.72). The difference was statistically significant for the T2 groups. When early T-stage (T1 and T2) patients were grouped together for analysis, the iridium group again showed a statistically significant improvement in 5-year LFFS rate when it was compared with the cobalt group (95.3% vs. 76.5%, p = 0.03) and the ERT alone group (95.3% vs. 81.5%, p = 0.03). The improvement of local control is attributed to a higher nasopharyngeal mucosal dose that is achieved by using small-size flexible applicators with an iridium source. It is interesting to note that the 5-year LFFS rates for the ERT alone group (T1: 84.1%, T2: 79.8%, T3: 62.6%) are comparable to the corresponding rates of the cobalt group. This information supports our speculation that an adequate booster treatment could compensate for inadequate primary treatment. The prognosis of patients with locally recurrent NPC is grave. Maximizing the local control is therefore crucial for the survival of the patients. (ABSTRACT TRUNCATED)

Analysis of Variance↗

Persister cells and tolerance to antimicrobials.

Bacterial populations produce persister cells that neither grow nor die in the presence of microbicidal antibiotics. Persisters are largely responsible for high levels of biofilm tolerance to antimicrobials, but virtually nothing was known about their biology. Tolerance of Escherichia coli to ampicillin and ofloxacin was tested at different growth stages to gain insight into the nature of persisters. The number of persisters did not change in lag or early exponential phase, and increased dramatically in mid-exponential phase. Similar dynamics were observed with Pseudomonas aeruginosa (ofloxacin) and Staphylococcus aureus (ciprofloxacin and penicillin). This shows that production of persisters depends on growth stage. Maintaining a culture of E. coli at early exponential phase by reinoculation eliminated persisters. This suggests that persisters are not at a particular stage in the cell cycle, neither are they defective cells nor cells created in response to antibiotics. Our data indicate that persisters are specialized survivor cells.

Anti-Bacterial Agents↗

Sensory registration and informational persistence.

The traditional view of iconic memory as a precategorical, high-capacity, quickly decaying visible memory has recently come under attack (e.g., Coltheart, 1980). Specifically, distinctions have been drawn between visible persistence, or the phenomenal trace of an extinguished stimulus, and informational persistence, knowledge about the visual properties of the stimulus. In the present research we tested two alternative conceptions of informational persistence. One conception is that visual information persists in a visual memory that begins at stimulus offset and lasts for 150-300 ms, independently of exposure duration. The second is that informational persistence arises from a nonvisual memory that contains spatial coordinates for displayed items along with identity codes for those items. Three experiments were conducted in which 3 X 3 letter arrays were presented for durations ranging from 50 to 500 ms. A single character mask presented at varying intervals after array offset cued report of an entire row of the array. Comparison of the cued row's masked and unmasked letters revealed that spatially-specific visual (i.e., maskable) information persisted after stimulus offset, regardless of exposure duration. This result favors the visual conception of informational persistence. But there was also support for the nonvisual conception: Accuracy increased and item intrusion errors decreased as stimulus duration increased. The implications of these results for models of informational persistence and for transsaccadic integration during reading are discussed.

Cues↗

Persistent fetal intraocular vasculature in the European ferret (Mustela putorius): clinical and histological aspects.

OBJECTIVE: To describe the clinical and histological appearance of persistent fetal intraocular vasculature in a colony of ferrets. Design Prospective study. ANIMALS STUDIED: Eighty-six European ferrets (Mustela putorius). Procedure Both eyes of 76 genetically related progeny and 10 breeding, adult, colony-raised ferrets were studied using a slit lamp biomicroscope and an indirect ophthalmoscope. Ferret progeny were examined after eyelid opening at 5-6 weeks of age, and at 12 months of age. After euthanasia, globes were enucleated and examined histologically. RESULTS: Persistent fetal intraocular vasculature was evident in 21 progeny ferrets at 5-6 weeks of age and in three mature progenitor ferrets. Clinical appearance of diminutive vasculature was characterized by focal remnants of the posterior tunica vasculosa lentis, muscae volitantes, and an occluded hyaloid artery extending from the optic papilla and terminating in the anterior vitreous body. Extensive persistent vasculature was characterized by a perfused hyaloid artery, vasa hyaloidea propria and posterior tunica vasculosa lentis, posterior cortical and capsular cataract, and proliferation of fibrovascular tissue along the posterior lens capsule. Fetal vasculature persisted in 7 of 21 progeny ferrets at one year of age and in three progenitor ferrets. Results of histologic examination showed persistence of the hyaloid vasculature, proliferation of retrolental fibrovascular tissue with osseous metaplasia, posterior capsular and cortical cataract, and occasional retinal detachment. CONCLUSIONS: Persistent fetal intraocular vasculature in ferrets appears similar clinically and histologically to persistent fetal intraocular vasculature reported in humans and dogs. The ferret may be a suitable animal model for vasculogenic mechanisms of persistent fetal intraocular vasculature and for evaluating vasoinhibitory growth factors and angiostatic test compounds.

Animals↗

Persistent elevation of C-reactive protein and ischemic heart disease in patients with continuous ambulatory peritoneal dialysis.

We evaluated the association between a persistent elevation of C-reactive protein (CRP) level and the presence or severity of ischemic heart disease (IHD) in patients with continuous ambulatory peritoneal dialysis (CAPD). Seventy-three patients, who were over 40 years old, underwent dipyridamole thallium single photon emission computed tomography (SPECT), and followed-up for more than 1 year were enrolled. We measured stored plasma for CRP every 3 months. Elevation of CRP was defined as greater than or equal to 5 mg/L and persistent elevation of CRP as elevated CRP levels that lasted longer than 6 months. Serum albumin, cholesterol, lipoprotein(a), and plasma fibrinogen were measured at 3 months after the start of CAPD. Twenty-six patients showed an elevation of CRP for more than 6 months during the follow-up period. Twenty-eight patients showed positive findings on thallium SPECT. Coronary angiography showed significant stenosis (narrowing of the diameter more than 50%) in 23 of the 25 patients studied. Seventeen (65%) of 26 patients who had an elevated CRP level for longer than 6 months had positive thallium SPECT. The presence of diabetes, albumin, fibrinogen, and the presence of a persistent elevation of CRP were different between the patients with positive (n = 28) or negative thallium SPECT (n = 45). A multivariate logistic regression analysis showed that a persistent elevation of CRP is the only predictor of positive thallium SPECT (P = 0.002). There was a tendency of association, although it was not statistically significant, between the persistence of CRP elevation and the severity of IHD (P = 0.066). Three of 9 patients who had a persistent elevation of CRP and a negative thallium SPECT had a history of cerebral infarction or peripheral vascular disease. Therefore, 77% (20/26) of an elevated CRP level that lasted longer than 6 months can be explained by the presence of IHD or other atherosclerotic vascular disease. In conclusion, a persistent elevation of CRP level in patients with CAPD was strongly associated with IHD. For patients who have a persistent elevation of CRP without an apparent cause, we recommend a workup for IHD or other atherosclerotic cardiovascular disease.

Biomarkers↗

Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in paroxysmal, persistent and permanent atrial fibrillation. Effects of cardioversion and return of left atrial function.

BACKGROUND: Atrial fibrillation is associated with increased risk of stroke and thromboembolism, possibly by conferring a prothrombotic or hypercoagulable state. However, it is unclear whether or not this differs in the clinical subgroups of chronic atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. We therefore hypothesized that: (i) there are differences in the prothrombotic state between these patients; and (ii) reduction in indices of hypercoagulability would follow elective electrical cardioversion of persistent atrial fibrillation and the return of left atrial function. PATIENTS AND METHODS: We studied 69 patients with chronic atrial fibrillation: 23 with paroxysmal atrial fibrillation (16 males; mean age 65 years+/-SD 13); 23 with persistent atrial fibrillation (16 males; 65 years+/-13), with a mean duration of atrial fibrillation of 3 months (range 2 to 6 months); and 23 with permanent atrial fibrillation (16 males; 67 years+/-10). Blood results were compared to 20 age- and sex-matched healthy controls. The patients with persistent atrial fibrillation then underwent elective DC cardioversion, with Doppler echocardiographic examinations and bloods tests performed prior to cardioversion, and at 3 and 12 weeks afterwards. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P-selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). RESULTS: Permanent atrial fibrillation was associated with significantly raised levels of von Willebrand factor, soluble P-selectin and fibrinogen (all P<0.001); paroxysmal atrial fibrillation with significantly elevated levels of plasma von Willebrand factor (P=0.0067) and fibrinogen (P=0.0001) but not soluble P-selectin (P=0.472); and persistent atrial fibrillation with normal levels of fibrinogen, von Willebrand factor and soluble P-selectin when compared to healthy controls (all P=ns). Stepwise multiple regression analyses demonstrated that the presence of atrial fibrillation was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P-selectin levels. Electrical cardioversion of the patients with persistent atrial fibrillation did not significantly alter levels of von Willebrand factor (P=0.766), soluble P-selectin (P=0.726) or fibrinogen (P=0.50) despite maintenance of sinus rhythm and a significant return of left atrial systolic function (as quantified by the presence of A wave on Doppler echocardiography) at 3 months. CONCLUSION: There were significant differences in the prothrombotic state when patients with paroxysmal and permanent atrial fibrillation are compared to matched patients with persistent atrial fibrillation or controls in sinus rhythm. Cardioversion of persistent atrial fibrillation did not significantly alter indices of hypercoagulability even after 3 months maintenance of sinus rhythm, despite the return of atrial systole.

Adult↗

Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation.

Chlamydia trachomatis is an obligatory intracellular prokaryotic parasite that causes a spectrum of clinically important chronic inflammatory diseases of humans. Persistent infection may play a role in the pathophysiology of chlamydial disease. Here we describe the chlamydial transcriptome in an in vitro model of IFN-gamma-mediated persistence and reactivation from persistence. Tryptophan utilization, DNA repair and recombination, phospholipid utilization, protein translation, and general stress genes were up-regulated during persistence. Down-regulated genes included chlamydial late genes and genes involved in proteolysis, peptide transport, and cell division. Persistence was characterized by altered but active biosynthetic processes and continued replication of the chromosome. On removal of IFN-gamma, chlamydiae rapidly reentered the normal developmental cycle and reversed transcriptional changes associated with cytokine treatment. The coordinated transcriptional response to IFN-gamma implies that a chlamydial response stimulon has evolved to control the transition between acute and persistent growth of the pathogen. In contrast to the paradigm of persistence as a general stress response, our findings suggest that persistence is an alternative life cycle used by chlamydiae to avoid the host immune response.

Cell Division↗

Persistent poliovirus infection of human neuroblastoma cells.

Two human neuroblastoma cell lines were persistently infected with poliovirus strains of all three serotypes. In persistently infected IMR-32 cells, which were studied in greatest detail, viral antigens were present in most cells, and over a 9-month period virions were found in the medium at high titers. Persistently infected cells were resistant to superinfection by Sabin 1, 2, and 3 poliovirus but sensitive to coxsackievirus B3. The viruses recovered from persistently infected cells were studied for conservation of epitopes, host cell specificity, and temperature resistance phenotype. The antigenic site 1 carried by the major capsid protein VP1 was modified on the persistent viruses of all three serotypes. This was confirmed for one virus by sequencing the corresponding genomic region in which two mutations were detected. The titers of persistent viruses were 1-3 log10 units higher on IMR-32 cells than on nonneuronal HEp-2 cells, while parental viruses had similar titers on both lines. When thermosensitive viruses were used to initiate the infection, the persistent viruses were found to be thermoresistant at 39 degrees C. Together the results indicate that the persistent infection correlated with the selection of highly mutated viral strains. Poliovirus-infected neuroblastoma cell lines thus constitute an in vitro model of chronic viral infections, which are increasingly implicated in human neural diseases.

Cell Line↗

Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells.

Persistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA-dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1beta converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K-AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-alpha synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.

Apoptosis↗

The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia.

Persistence and recurrence of Staphylococcus aureus bacteraemia (SAB) have been linked primarily with difficult-to-eradicate foci of infection such as endocarditis, osteomyelitis or abscess formation. Although vancomycin therapy has been suggested as a predictor of relapse of SAB, it has never been shown to be associated with persistent SAB. The purpose of this study was to examine the possible association of vancomycin therapy and persistence of SAB. Two groups of patients were retrospectively studied. One group consisted of 124 patients who completed > or =10 d of appropriate anti-staphylococcal therapy (from among a total of 284 patients with SAB during 2 y, 1997-8). In this group, persistence of SAB (methicillin resistant and susceptible combined) for >3 d while on therapy, occurred in 11 (22%) of 55 vancomycin recipients and in none of 52 cloxacillin recipients (p = 0.002). When calculated for methicillin susceptible SAB alone, the numbers were 3 of 13 vs 0 of 52, respectively (p = 0.007). The second study group included all patients with persistence and/or relapse of SAB while on appropriate anti-staphylococcal therapy during 4 y (1997-2000). In this group, the persistence occurred while on vancomycin therapy, in 32 (94%) of 34 patients with >3 d of persistence of SAB. In the majority of these patients a secondary focus of infection serving as the site of persistence was identified in addition to the primary focus (or portal of entry). It was concluded that vancomycin is inferior to cloxacillin therapy in terminating SAB and therefore may predispose to prolonged bacteraemia and secondary seeding of infection during therapy.

Adult↗

Ethnic differences in predictors of initiation and persistence of adolescent cigarette smoking in the National Longitudinal Survey of Youth.

AIMS: To identify and compare predictors of adolescent smoking initiation and persistence among African American, Hispanic and White adolescents in a longitudinal national sample. DESIGN: The sample includes 1537 mother-child dyads from the National Longitudinal Survey of Youth (NLSY). Family, youth, peer and sociodemographic risk and protective factors were analyzed. FINDINGS: White adolescents reported the highest rates of smoking initiation and persistence; African Americans and Hispanics the lowest. Multivariate analyses revealed mostly common and few ethnic-specific predictors of smoking initiation and persistence. For initiation, maternal current smoking, child age, child problem behavior, and perceived peer pressure to smoke were predictive across ethnic groups; female gender and ineffective parenting were predictive among Whites only. For persistence, child age, child problem behavior and perceived scholastic competence were predictive across ethnic groups; negative mood was predictive among Whites only. CONCLUSIONS: More common than unique factors predict smoking initiation and persistence among adolescents of different ethnicity. However, the power to detect ethnicity-by-predictor interactions with respect to persistence was low. Social factors are more important for smoking initiation, whereas individual factors are more important for persistence, although child problem behaviors are common determinants both of initiation and persistence. With few exceptions, universal anti-smoking interventions should be targeted to youths of different ethnicity.

Adolescent↗

Persistence of nucleoli in short term and long term cell cultures and in direct bone marrow preparations in mammalian materials.

Persistent nucleoli were studied in Chinese hamster and human long term cultures, human peripheral blood short term cultures, as well as direct bone marrow preparations. No colchicine or hypotonic treatments were applied and the cells were differentially stained with the Feulgen method and light green. Nucleoli were found to persist in the three systems studied, although to a much greater extent in the long term culture. The persistent nucleolar materials were usually in the form of individualized nucleoli mainly at chromosome ends. They also sometimes existed in a fluidlike or dropletlike condition around the chromosomes. Association of acrocentrics in humans and end-to-end associations in hamsters are likely to result from persistence of nucleoli and the possible effects of colchicine and hypotonic treatments that are usually applied. Other phenomena, such as stickiness at metaphase and separation difficulties and fragmentation at anaphase, may result from persistence of nucleoli. Nucleoli were often associated with large chromosomes and sometimes at sites exhibiting faint or clear constrictions. The possibilities of a partial correspondence between sites of persistence and sites of organization, as well as of the organization of nucleolar materials at sites other than the main organizers, are discussed. The persistent nucleoli were not included in daughter nuclei. They either degenerated in the cytoplasm or were eliminated from the cell. The three systems used may represent different intensities of metabolism reflected in the amounts of nucleolar materials built up and the amount that persists.

Animals↗

Persistence and pathogenicity of defective Friend spleen focus-forming virus. Decreased transplantability of hemopoietic cells as a marker for preleukemic change.

A latent form of persistent infection can be established in susceptible adult mice inoculated with a preparation of defective Friend spleen focus-forming virus (SFFV) purified free from standard leukemia-inducing helper virus (LLV-F). SFFV persistence was initially observed using an in vivo rescue technique in which SFFV could be directly rescued to form splenic foci of malignant erythropoiesis in mice. At approximately 30 d after virus inoculation however, SFFV could not be rescued after inoculation of LLV-F indicating that persistently infected (i.e., SFFV+) mice were either immume to exogenous helper virus or able to express SFFV-associated defective-interfering (DI) function(s). Persistent infection by SFFV was further documented using an in vitro rescue technique and ultimately resulted in the induction by SFFV of erythroleukemia in the absence of polycythemia or overt virus production. However, SFFV rescued by LLV-F from persistently infected normal and transformed hemopoietic cells was able to induce polycythemia in adult mice suggesting that this is a helper controlled property of the Friend virus complex. Transplantable SFFV-induced erythroleukemic cells could be retrieved from persistently infected yet histologically normal mice. The duration of SFFV persistence in normal spleen tissue suggests that the SFFV provirus resides in either a long-lived or pluripotent hemopoietic cell. Further, certain changes occurred, presumably in the membranes of persistently infected cells, which preceded the overt development of Friend leukemia and facilitated the definition of an SFFV preleukemic phase. Cell surface alterations were revealed using cell transfer techniques. Hemopoietic cells harboring a rescuable SFFV failed to proliferate when inoculated into lethally irradiated, syngeneic adult mice. In contrast, the transformed progeny of preleukemic cell populations and spleen cells transformed by FV complex (i.e., cells replicating both SFFV and LLV-F) were not rejected. This result suggests that histologically normal SFFV+ preleukemic cells express an antigen recognition site which is not present on overtly transformed cells and which may be a pertinent surveillance target for host anti-leukemogenic reactions.

Animals↗

Lung epithelial cells are a major site of murine gammaherpesvirus persistence.

It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used microMT transgenic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell-deficient mice. Both episomal and linear forms of the virus genome were present in lungs, implying the presence of both latency and productive replication. In situ hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial cells. Infectious virus was recovered from the lungs of microMT mice after T cell depletion, showing that the persisting virus DNA was reactivatable. Finally, using adoptive transfer of B cells into B cell-deficient mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These results show that mucosal epithelia can act as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a two-way movement of virus between lymphoid and nonlymphoid compartments during persistence.

Animals↗