Strain distribution of mice in discriminated Y-maze avoidance learning: Genetic and procedural differences.

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57?×?SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57?×?SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57?×?SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interferon-gamma mediates long-term persistent Chlamydia psittaci infection in vitro

The long-term anti-chlamydial effects of recombinant ovine interferon gamma (rOvIFN-gamma) were studied in ovine ST-6 fibroblasts infected with the S26/3 strain of Chlamydia psittaci. Chlamydial multiplication was assessed by enzyme-linked immunosorbent assay analysis of supernate lipopolysaccharide, titration of inclusion-forming units in culture supernates, and enumeration of inclusion bodies in cultured cells at 7-day intervals. Concentrations of 250 and 1000 U/ml of rOvIFN-gamma resulted in a microbistatic inhibition of C. psittaci growth, which appeared to become microbicidal when rOvIFN-gamma was maintained in the cultures for 14 days or more. There were no signs of C. psittaci multiplication when cultures were maintained in 25 or 100 U/ml of rOvIFN-gamma. However, subsequent removal of rOvIFN-gamma from these cultures resulted in a re-emergence of viable, infectious chlamydiae, which eventually killed all the fibroblasts. This re-emergence was more rapid in cultures initially treated with 25 U/ml of rOvIFN-gamma than in those treated with 100 U/ml.     

Dissociation of demyelination and viral clearance in congenitally immunodeficient mice infected with murine coronavirus JHM

Radiolabelled vitellogenin produced by juvenile grouper following injection of 3H-leucine, 32P-orthophosphate and estradiol-stimulation was purified by anion-exchange and gel filtration chromatography and characterized by electrophoresis and chemical analysis. The radiolabelled product was found to exist in two heterogeneous molecular weight forms by electrophoresis under nondenaturing conditions on polyacrylamide gel with M(r), of 260,000 and 525,000. It showed two protein monomers (M(r) 113,000 and 140,000) on electrophoresis under denaturing condition on a sodium dodecyl sulphate-polyacrylamide gel. The purified material contained 17.2% total lipid with 1.3% cholesterol and 2.1% triglycerides, 8-21 micrograms/mg protein total carbohydrate and 6.8 micrograms phosphate/mg protein; amino acid analysis showed a profile comparable to that found for vitellogenins isolated from the grouper, medaka, goldfish and rainbow trout. The study showed grouper vitellogenin to be a glycophospholipoprotein similar in composition to vitellogenins from other teleosts and demonstrated that vitellogenins can be induced in juveniles by injection with estradiol-17 beta.     

Deficits in complex motor functions, despite no evidence of procedural learning deficits, among HIV+ individuals with history of substance dependence.

Human immunodeficiency virus (HIV) and drugs of abuse affect common neural systems underlying procedural memory, including the striatum. The authors compared performance of 48 HIV seropositive (HIV+) and 48 HIV seronegative (HIV-) participants with history of cocaine and/or heroin dependence across multiple Trial Blocks of three procedural learning (PL) tasks: Rotary Pursuit (RP), Mirror Star Tracing (MST), and Weather Prediction (WP). Groups were well matched on demographic, psychiatric, and substance use parameters, and all participants were verified abstinent from drugs. Mixed model analyses of variance revealed that the individuals in the HIV+ group performed more poorly across all tasks, with a significant main effect of HIV serostatus observed on the Mirror Star Tracing and a trend toward significance obtained for the Rotary Pursuit task. No significant differences were observed on the Weather Prediction task. Both groups demonstrated significant improvements in performance across all three procedural learning tasks. It is important to note that no significant Serostatus × Trial Block interactions were observed on any task. Thus, the individuals in the HIV+ group tended to perform worse than those in the HIV- group across all trial blocks of procedural learning tasks with motor demands, but showed no differences in their rate of improvement across all tasks. These findings are consistent with HIV--associated deficits in complex motor skills, but not in procedural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection

Generally, it has been assumed that memory T cells are dormant and inactive cells in the absence of their specific Ag. Recent work has challenged this assumption by showing that a portion of the CD8+ memory T cell pool is in cycle. In this study, we demonstrate that a significant number of blast-size memory CD8+ T cells in mice, long after lymphocytic choriomeningitis virus (LCMV) infection, mediate cytolysis against highly sensitive targets without any in vivo or in vitro restimulation and expansion with Ag. Peptide-coated RMA-S targets were sufficiently sensitive to detect low but significant cytolytic activity in bulk 51Cr release assays in nonstimulated LCMV-specific splenic memory CTL populations. Most of the directly cytotoxic activity was against the GP33 epitope, and this persisted throughout the lifetime of the mouse following infection. The cytotoxic activity was not inhibited by cyclosporin A, indicating that these cells were already in an active state and not dependent on further stimulation in vitro. It was formally shown that the cytotoxic activity was mediated by the CD8+ CTL by sorting for the blast-size CD8+ population and by blocking target cell lysis with anti-CD8 Ab. Thus, at any time after the original infection some portion of the memory CD8+ T cell pool is cycling, and it remains cytolytically active long after resolution of the original infection. These CTL may provide a rapidly acting defense mechanism against reinfection.     

Deficits of spatial learning and working memory in spontaneously hypertensive rats

It is possible that behavioral dysfunction, including cognitive, perceptual and psychomotor impairments in hypertensive subjects, can be the result of the high blood pressure. The aim of this study was to evaluate the performance of the spontaneously hypertensive rats (SHR) in the acquisition and execution of tasks in an 8-arm radial maze. Male Wistar normotensive rats (CON, n = 11) and SHR (n = 12), 3 months old, were first submitted to a series of training sessions to enter each of the 8 arms once in a given session (task acquisition), and errors (revisiting an arm in the same session) were computed. Errors before and after two delay intervals (5 s and 1 h, introduced between the fourth and fifth arm choice) were measured. These delayed tests allowed us to evaluate the working memory in different terms. It was observed that the SHR group made slightly more errors during the acquisition sessions and in the execution of the post-delay of 5-s interval tests, and significantly in the execution of the post-delay of 1-h interval tests compared to the CON. These results show that the SHR has a deficiency in the performance of the radial maze, suggestive of impairment of learning and working memory, mainly for a long-term memory, corroborating the hypothesis about the possible behavioral consequences of hypertension.     

Characterization of defective viral RNA produced during persistent infection of Vero cells with Murray Valley encephalitis virus

Defective interfering viral particles are readily produced in cell culture after a high multiplicity of infection with many animal RNA viruses. Due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus. In many instances, this may cause the abrogation of a lytic cycle of the parental virus, leading to a persistent infection. In this paper, we describe for the first time the presence of truncated or defective interfering viral RNAs produced in Vero cells persistently infected with the flavivirus Murray Valley encephalitis virus. While these RNAs have not been detected in acutely infected Vero cells, their appearance coincided with the establishment of persistent infection. We also show for the first time that the defective viral RNAs replicate well in both cell culture and cell-free virus replication systems, indicating that they may interfere with the replication of parental virus at the level of viral RNA synthesis. Significantly, structural analyses of these RNA species including nucleotide sequencing have revealed that they carry similar nucleotide deletions encompassing the genes coding for the prM and E proteins and various gene segments coding for the N terminus of the NS1 protein. These deletions are in frame, allowing the synthesis of truncated NS1 proteins to occur in persistently infected cells. This may have further implications for the interference with the parental virus at the level of viral RNA synthesis in addition to a major one at the level of virion assembly and release.     

Deficits in visual learning produced by posterior temporal lesions in cats.

Eight cats with lesions in the posterior temporal (PT) cortex, 7 cats with lesions in the basolateral amygdala (BLA), and 8 intact controls were observed on 8 tests of visual discrimination learning and spontaneous responses to salient visual stimuli. The effects of the 2 lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and response to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetics of resistance to Trypanosoma congolense in inbred mice: efficiency of apparent clearance of parasites correlates with long-term survival

To study the genetic parameters of resistance to Trypanosoma congolense infection, highly susceptible BALB/c and relatively resistant C57BL/6 mice were crossed to produce reciprocal F1 and F2 offspring. Mice were infected with T. congolense and monitored for parasitemia within the first 2 wk and also for their survival periods. BALB/c mice showed unrestrained parasite growth to the time of death (median survival period, msp = 12.0 days), whereas in C57BL/6 mice, parasitemia reached an initial peak on day 6 and was followed by a rapid apparent clearance of the parasites in an average period of 3 days. Their msp was 163.0 days. The F1 mice cleared the parasites, following the first peak of parasitemia, in an average period of 4 days and had an msp of 69.5 days. Thus, the F1 offspring displayed an intermediate phenotype between susceptible and resistant parents in terms of parasite clearance and survival period. Resistance in F2 mice, as measured by survival times, was inherited as a polygenic trait. Among F2 mice, there was an inverse correlation between the time taken to clear the initial wave of parasitemia and the survival period, r = -0.58; P < 0.05. Thus, the pattern of control of the parasites following the first peak of parasitemia appears to be a good predictive factor for the survival period of mice infected with T. congolense.     

Deficits in discrimination and maze learning resulting from maternal histidinemia in rats.

Plasma histidine levels in female albino rats during pregnancy were elevated in 2 different ways: (a) Histidine deaminase was inactivated by periodic injection of nitromethane. (b) Rats were maintained on a high-histidine diet. Postnatal maze performance indicated that high-histidine levels impaired later learning ability. The deficit appeared to be cumulative; however, a ceiling was reached beyond which further increases in histidine levels did not result in additional learning impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short- and long-term efficacy of hexadecylphosphocholine against established Leishmania infantum infection in BALB/c mice

In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against established Leishmania infantum infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropic Leishmania species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established Leishmania infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for at least 7 to 8 weeks. Orally administered HDPC--the safe doses and side effects of which are at least partially known--appears to be a promising candidate for the treatment of VL.     

Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load

Although vigorous activated and memory CTL have been associated with HIV-1 infection, data are lacking regarding the breadth of epitopes recognized in a given individual and the relationship to the viral quasispecies present in vivo. In this study we performed a detailed analysis of the HIV-1-specific CTL response in a seropositive person with documented HIV-1 infection of 15 yr duration, stable CD4 counts above 500 cells/ml, and viral load persistently below 500 molecules of RNA/ml of plasma. Epitope mapping studies revealed the presence of HLA class I-restricted CTL responses to six different epitopes in p17, p24, RT, Env, and Nef, which conferred broadly cross-reactive recognition of reported HIV-1 variants. Sequence analysis of autologous viruses revealed the absence of immune escape variants within five of the six epitopes. Despite consistently low viral RNA levels in plasma and viral DNA levels in PBMC, in vivo-activated circulating CTL were detected against three of the epitopes. Five of the six epitopes, including the three dominant epitopes, have been detected in persons with progressive disease, suggesting that nonprogressors may not target unique epitopes. This study demonstrates that HIV-1-specific CTL can be highly activated and broadly directed in the setting of an extremely low viral load, and that neither high viral load nor antigenic diversity is required for the generation of a multispecific CTL response. Although the detection of strong CTL responses, low viral load, and lack of immune escape are consistent with the hypothesis that CTL may contribute to lack of disease progression in this individual, the contribution of these responses to maintenance of the asymptomatic state remains to be determined.     

Deficits in cross-race face learning: Insights from eye movements and pupillometry.

The own-race bias (ORB) is a well-known finding wherein people are better able to recognize and discriminate own-race faces, relative to cross-race faces. In 2 experiments, participants viewed Asian and Caucasian faces, in preparation for recognition memory tests, while their eye movements and pupil diameters were continuously monitored. In Experiment 1 (with Caucasian participants), systematic differences emerged in both measures as a function of depicted race: While encoding cross-race faces, participants made fewer (and longer) fixations, they preferentially attended to different sets of features, and their pupils were more dilated, all relative to own-race faces. Also, in both measures, a pattern emerged wherein some participants reduced their apparent encoding effort to cross-race faces over trials. In Experiment 2 (with Asian participants), the authors observed the same patterns, although the ORB favored the opposite set of faces. Taken together, the results suggest that the ORB appears during initial perceptual encoding. Relative to own-race face encoding, cross-race encoding requires greater effort, which may reduce vigilance in some participants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of persistent infection in experimental syphilis by PCR

The studies described herein were designed to evaluate the usefulness of the PCR in detecting persistent syphilitic infection. Three groups of animals were used: a nonimmune group infected with Treponema pallidum (NI/TP), a nonimmune group injected with heat-killed treponemes (NI/HKTP), and an immune and reinfected group (I/TP). All animals were inoculated with similar numbers of organisms distributed at 10 sites on the clipped back and in both testes. The persistence of the treponemes was examined by PCR and the rabbit infectivity test (RIT). The kinetic studies and statistical analysis of their results demonstrated that the rate of bacterial clearance from the NI/TP group was very low and incomplete at 4 months after infection. It was significantly different from those of both the NI/HKTP (P < 0.001) and I/TP (P < 0.05) groups. No statistically significant differences in treponemal elimination were found between the NI/HKTP and I/TP groups. PCR can detect the DNA of dead organisms, but the latter are eliminated by the host relatively quickly (15 to 30 days) as compared to elimination of live treponemes (>120 days). PCR results correlated well with RIT results. These data suggest that PCR-positive specimens obtained from an untreated patient(s) or collected weeks after treatment indicate persistent infection. They also show that the process of elimination of T. pallidum from primary sites of infection is prolonged and incomplete.     

Treatment with anti-interleukin-10 monoclonal antibody enhances early resistance to but impairs complete clearance of Listeria monocytogenes infection in mice

Mice that received an anti-interleukin-10 (anti-IL-10) neutralizing monoclonal antibody (MAb) (SXC-1) prior to infection with Listeria monocytogenes initially demonstrated resistance to the infection, as indicated by reduced recovery of L. monocytogenes from their spleens and livers during the first 5 days after challenge. Anti-IL-10 MAb-treated mice then demonstrated reduced resistance during the later stage of infection, as indicated by persistent infection with L. monocytogenes in their livers 11 days after challenge. Aspartate aminotransferase (AST) levels (a measure of liver damage) in the sera of control mice increased between 1 and 5 days after challenge, while anti-IL-10 MAb-treated mice maintained lower AST levels. At 7 days after challenge, AST levels in the sera of control mice decreased as the numbers of organisms declined. In contrast, AST levels increased as the infections persisted in anti-IL-10 MAb-treated mice. The AST levels in serum reflected liver histopathology as anti-IL-10 MAb-treated mice exhibited fewer granulomatous lesions and less necrosis of liver tissue than the control mice during the first 5 days after challenge. Anti-IL-10 MAb treatment altered the expression of inflammatory cytokine mRNAs during L. monocytogenes infection. Control MAb-treated mice exhibited increased expression of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor mRNA in their lives during L. monocytogenes infection, but this increase did not occur in anti-IL-10 MAb-treated mice. Gamma interferon mRNA expression in the livers of the control MAb-treated mice was increased between 1 and 5 days after L. monocytogenes challenge and then decreased at 7 days after challenge. In contrast, gamma interferon mRNA expression in the livers of anti-IL-10 MAb-treated mice was not decreased until 7 days after challenge. These results indicate that endogenous IL-10 has both beneficial and detrimental effects on the host response to L. monocytogenes infection in mice.     

Ethiopathogenesis of hepatitis B viral infection in chimpanzees

Oral glucose tolerance tests were performed on 16 addicts and 16 control subjects. A flat delayed glucose response was demonstrated, with hyperinsulinaemia, elevated plasma growth hormone and normal plasma cortisol in heroin addicts compared with control subjects. These studies suggest a relative insulin resistance in addicts which might be mediated by the elevated growth hormone or some other pharmacologic effect of the chronic opiate abuse.     

Autoimmunity develops in lupus-prone NZB mice despite normal T cell tolerance

NZB mice spontaneously develop an autoimmune disease characterized by production of anti-RBC, -lymphocyte, and -ssDNA Abs. Evidence suggests that the NZB mouse strain has all of the immunologic defects required to produce lupus nephritis but lacks an MHC locus that allows pathogenic anti-dsDNA Ab production. The capacity to produce diverse autoantibodies in these mice raises the possibility that they possess a generalized defect in self-tolerance. To determine whether this defect is found within the T cell subset, we backcrossed a transgene encoding bovine insulin (BI) onto the NZB background. In nonautoimmune BALB/c mice, the BI transgene induces a profound but incomplete state of T cell tolerance mediated predominantly by clonal anergy. Comparison of tolerance in NZB and BALB/c BI-transgenic mice clearly demonstrated that NZB T cells were at least as tolerant to BI as BALB/c T cells. NZB BI-transgenic mice did not spontaneously produce anti-BI Abs, and following antigenic challenge, BI-specific Ab production was comparably reduced in both BI-transgenic NZB and BALB/c mice. Further, in vitro BI-specific T cell proliferation and cytokine secretion were appropriately decreased for primed lymph node and splenic T cells derived from NZB BI-transgenic relative to their nontransgenic counterparts. These data indicate that a generalized T cell tolerance defect does not underlie the autoimmune disease in NZB mice. Instead, we propose that the T cell-dependent production of pathogenic IgG autoantibodies in these mice arises from abnormal activation of T cells in the setting of normal but incomplete tolerance.