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Biomedical subjects

C Whitacre

Publications and source records attributed to C Whitacre.

15 recordsLinked to original sources

Physical and observational practice afford unique learning opportunities.

In 2 experiments, the authors studied the effectiveness of physical and observational practice on learning and the effect on learning of combining physical practice and observation, as compared with providing physical practice alone. In Experiment 1, retention and transfer performance of 30 university students after physical, observational, or no practice were contrasted. Consistent with findings from other studies, the retention results indicated that observational practice is inferior to physical practice. The transfer data indicated no differences between observation and physical practice groups. In Experiment 2, retention and transfer performance of 30 participants in physical and combined (alternating physical and observational) practice groups were contrasted. The retention results showed no differences between the combined and physical practice groups, but the combined group performed significantly better than the physical practice group on the transfer test. Those findings suggest that a combination of observation and physical practice permits unique opportunities for learning beyond those available via either practice regimen alone.

Analysis of Variance↗

Effects of oral tolerance induction by myelin basic protein on Vbeta8+ Lewis rat T cells.

Encephalitogenic T cells from Lewis rats use a restricted T cell receptor (TCR) gene combination, Vbeta8.2 and Valpha2. The oral administration of myelin basic protein (MBP) to Lewis rats prior to encephalitogenic challenge results in a marked inhibition of clinical neurologic signs of encephalitis, reduced central nervous system pathology, suppressed T cell reactivity to MBP, and decreased serum anti-MBP antibody responses. The present study determined the TCR Vbeta8 gene usage in rats rendered orally tolerant to MBP as compared with vehicle-fed or unfed controls. Total RNA was extracted from lymph node cells (LNC), Northern blots run, and hybridizations performed using a rat beta chain V region probe positive for Vbeta8.2. The results indicate that feeding MBP results in a decrease in Vbeta8+ TCR RNA expression in lymph nodes draining the site of encephalitogenic challenge. T cell proliferation was reduced in LNC of tolerized rats relative to control rats. No change in the Vbeta8+ TCR RNA expression or MBP reactivity was observed in the mesenteric lymph nodes (MLN) of vehicle-fed or MBP-fed rats, although an increase in cell number was found in the MLN of both groups. These results suggest that the mechanisms of orally induced tolerance involve local clonal deletion or migration of Vbeta8+ T cells, of which MBP-specific T cells are a part.

Administration, Oral↗

Pharmacokinetics and pharmacodynamics of the leukotriene B4 receptor antagonist CP-105,696 in man following single oral administration.

AIMS: CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)-4-hydroxy-chroman-7-yl] cyclopropane carboxylic acid is a potent, novel LTB4 receptor antagonist advanced to clinical trials to determine its efficacy in inflammatory diseases. The pharmacokinetics and pharmacodynamics of CP-105,696 were investigated in healthy male volunteers following oral administration of single doses of 5 to 640 mg. METHODS: Forty-eight subjects participated in a randomized, double-blind, parallel group study. Plasma and urine concentrations of CP-105,696 were determined at intervals after drug administration. As an indication of LTB4 receptor antagonism following oral administration of CP-105,696, the inhibiton of LTB4-induced upregulation of the neutrophil cell surface complement receptor (CR3), CD11b/CD18, was monitored at 4 h following drug administration using an ex vivo whole blood flow cytometry assay. RESULTS: Cmax and AUC(0, infinity) increased in a dose-related manner. Respective mean Cmax values were 0.54 to 30.41 microg ml(-1) following doses of 5 to 640 mg. Respective mean AUC(0, infinity) values were 1337 to 16819 microg ml(-1) h for the 40 to 640 mg dose groups. Plasma concentrations declined in a monoexponential manner, with terminal elimination half-lives ranging from 289 to 495 h. Group mean terminal elimination half-lives were dose-independent. Urinary excretion of unchanged drug accounted for < 1% of the administered dose. A linear relationship was observed between CP-105,696 plasma concentrations and inhibition of LTB4-mediated CD11b upregulation on human neutrophils in whole blood. CP-105,696 plasma concentrations of 5-6 microg ml(-1) were necessary to elicit a two-fold shift to the right of the LTB4 concentration response curve for CD11b upregulation. CONCLUSIONS: These studies demonstrate pharmacologically significant LTB4-receptor antagonism following a single dose of CP-105,696 and pharmacokinetics consistent with once-daily dosing.

Administration, Oral↗

Gallium nitrate suppresses lupus in MRL/lpr mice.

Gallium (Ga) nitrate, a drug which prevents a variety of experimental autoimmune diseases, was investigated in a murine model of systemic lupus erythematosus (SLE). In one experiment, female MRL/Mp lpr/lpr (MRL/lpr) mice were randomized into 2 groups of 6: 1) vehicle (trisodium citrate) and 2) Ga. Subcutaneous injections began at 3 weeks of age and continued weekly until the mice were euthanized a week after the thirteenth injection. The loading dose of Ga (calculated as elemental Ga) was 45 mg/kg, followed by 15 mg/kg/week. In another experiment (n = 18) with 3 males and 3 females per group, mice received 1) vehicle, 2) Ga x 1 (one 45 mg/kg dose), and 3) Ga x 13. In the experiment with 12 mice, axillary lymph nodes from Ga-treated mice were significantly smaller than those from vehicle-treated mice (91+/-42 and 360+/-358 mg respectively, mean+/-SD), and spleens as well as lymph nodes from the former showed significantly less lymphoid infiltrate. In the experiment with 18 mice, prescapular lymph nodes weighed 312+/-98, 217+/-52, and 42+/-34 mg, and spleens weighed 732+/-492, 409+/-164, and 192+/-93 mg in the groups which received vehicle, Ga x 1, and Ga x 13 respectively. Control mice had significantly more lymphoid infiltrates in the lungs, spleen, and lymph nodes and, unlike Ga x 13 mice, exhibited glomerulitis and renal vasculitis. Within groups, females developed more severe disease than males. The Ga x 13 group had increased percentages of CD4-bearing and CD8-bearing lymphocytes in lymph nodes and increased CD4-bearing lymphocytes in the spleen, with an increased proliferative response to mitogen stimulation in vitro in lymph nodes, although not in the spleen. The Ga x 13 group also gained less weight and developed osteosclerosis. Although preliminary, our findings suggest that clinical trials with Ga in SLE are merited.

Animals↗

Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group.

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, combined treatment with several agents may increase the effectiveness of antiviral therapy. We studied the safety and efficacy of saquinavir, an HIV-protease inhibitor, given with one or two nucleoside antiretroviral agents, as compared with the safety and efficacy of a combination of two nucleosides alone. METHODS: In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine. The 302 patients enrolled had CD4+ counts of 50 to 300 cells per cubic millimeter and had previously received zidovudine for a median of 27 months. The study lasted 24 weeks, with an optional double-blind extension period of an additional 12 to 32 weeks. RESULTS: Ninety-six percent of the patients completed the 24-week study. In all three treatment groups, CD4+ cell counts rose at first and then fell gradually. The normalized area under the curve for the CD4+ count was greater with the three-drug combination than with either saquinavir and zidovudine (P=0.017) or zalcitabine and zidovudine (P<0.001). There were significantly greater reductions in plasma HIV with the three-drug combination than with the other regimens when peripheral-blood mononuclear cells were cultured for HIV and HIV RNA was assessed, and there were greater decreases in serum neopterin and beta2-microglobulin levels. There were no major differences in toxic effects among the three treatments. CONCLUSIONS: Treatment with saquinavir, zalcitabine, and zidovudine was well tolerated. This drug combination reduced HIV-1 replication, increased CD4+ cell counts, and decreased levels of activation markers in serum more than did treatment with zidovudine and either saquinavir or zalcitabine. Studies are warranted to evaluate whether the three-drug combination will reduce morbidity and mortality.

Adult↗

Contextual dependencies during perceptual-motor skill acquisition: gone but not forgotten!

The development and resiliency of contextual dependencies developed during perceptual-motor skill acquisition was assessed. Incidental aspects of the stimulus used to instigate the production of previously practised typing sequences were manipulated during either an immediate or delayed retention test. The findings from the immediate test offered further support for the existence of contextual-dependent performance for perceptual-motor responding. However, the dependency was attenuated by using a delayed retention test. Experiment 2 pursued two alternative explanations for the diminished dependency effect revealed in Experiment 1. In Experiment 2 some subjects were explicitly encouraged to reinstate aspects of the incidental contextual information that was present during training prior to administration of a delayed test. The dependency present only in the immediate test in Experiment 1 reemerged after contextual reinstatement. The present data are discussed with respect to the inclusion of incidental contextual stimuli as part of the long-term sensorimotor memory representation.

Analysis of Variance↗

Suppression of experimental autoimmune encephalomyelitis by gallium nitrate.

We examined the effect of gallium (Ga) nitrate on the development of the development of experimental autoimmune encephalomyelitis (EAE). Weekly subcutaneous injections of 10-30 mg/kg prevented clinical signs as well as histopathological changes of EAE. The optimal timing of a single injection of Ga was 6 days after induction of EAE, with amelioration also apparent following a single injection on day 3 or 9 but not day 12. Ga administered in vivo suppressed myelin basic protein (MBP) and purified protein derivative-specific lymphocyte proliferative responses in vitro. Addition of Ga to MBP-specific T lymphocyte line cultures at various times after initiation of culture revealed that Ga exerts an effect at an early stage of cellular activation.

Animals↗

The contribution of elaborative processing to the contextual interference effect.

This study examined the influence of supplemental intertask and intratask processing on the retention of three motor sequences practiced in conditions of high and low contextual interference. Subjects practiced in either a blocked or random practice format and experienced additional intratask processing, intertask processing, or no additional processing. Each of three movement sequences were practiced for 18 trials. The subjects were required to perform the sequences as fast and as accurately as possible. Retention performance and recall of the movement sequences were assessed after a 21-day retention interval. The results replicated those of Wright (1991), indicating a benefit for individuals engaging intertask processing during a low contextual interference practice condition. Furthermore, supplementing random practice with additional intertask processing not only slowed the rate of task acquisition, but also resulted in retention performance that was significantly poorer than that exhibited by individuals exposed to random practice with no additional processing. This suggests there may be a limit to the extent of interference that can be established during practice that will lead to a facilitation in retention performance.

Humans↗

Magnetic resonance imaging of white matter lesions in HIV infection.

Previous studies of the frequency of high-signal lesions in human immunodeficiency virus (HIV) infection have had methodological weaknesses regarding lack of control groups, differing machine strengths, and biased subject selection. To obtain a more accurate estimate of prevalence, MRI scans were performed on 243 HIV-positive and HIV-negative homosexual or bisexual men with no history of intravenous drug use. Axial T2-weighted (long TR/TE, spin-echo) MRI scans were rated blindly for presence of focal white matter high-signal lesions. Incidence of hyperintensities was low in all groups, although slightly higher in patients with AIDS, and was not associated with neuropsychological performance. The lower incidence of hyperintensities appears to relate to elimination of methodological problems in previous studies.

AIDS Dementia Complex↗

Lymphocyte supernatant-induced human monocyte tumoricidal activity: dependence on the presence of gamma-interferon.

Recently, gamma-interferon (IFN-gamma) has been shown to be have the capacity to activate macrophages in several murine and human systems. The studies reported here were undertaken to determine the identity of the lymphokine responsible for activation of human monocytes to a tumoricidal state. Macrophage-activating factor (MAF) activity was assessed using a 24-h 51Cr release assay with human monocytes as effector cells and K-562 targets. Stimulated lymphocyte supernatants were produced by stimulation of peripheral blood mononuclear cells with concanavalin A in serum-free media. Interferon was detected in an antiviral assay. Four lines of evidence lead to the conclusion that MAF and IFN-gamma are identical in this system: (a) fractionation of stimulated lymphocyte supernatants by adsorption chromatography, followed by anion or cation exchange chromatography (Mono-S, Mono-Q columns), resulted in nearly identical elution profiles of MAF and IFN activities. All of the individual fractions containing MAF activity were found to contain IFN in amounts corresponding to MAF activity. (b) Monoclonal antibody specific for IFN-gamma neutralized the ability of stimulated lymphocyte supernatants to induce human monocyte tumoricidal activity. This antibody also neutralized the MAF activity of purified IFN-gamma but not alpha-interferon. (c) The biological MAF activity of activated lymphocyte supernatants and IFN-gamma were similar. Dilution versus MAF activity for IFN-gamma and stimulated lymphocyte supernatants exhibited identical slopes. Lymphocyte supernatants and IFN-gamma demonstrated similar MAF activity on three effector cells: monocytes, in vitro-differentiated macrophages, and dexamethasone-differentiated macrophages. (d) Analysis of supernatants produced by five antigen-stimulated human T-cell clones demonstrated coordinate production of MAF and IFN. These results provide compelling evidence for support of the concept that IFN-gamma is the major human lymphokine capable of inducing monocyte-macrophage tumoricidal activity.

Antibodies, Monoclonal↗

Host immune responses after administration of inactivated Venezuelan equine encephalomyelitis virus vaccines--III. Kinetics for neutralizing antibody immunoglobulin class responses in donors and adoptively-immunized recipients.

C57B16 mice were immunized with either live, attenuated TC-83 strain VEE virus vaccine or formalin-inactivated VEE vaccine combined with Bordetella pertussis. The kinetics of specific donor and adoptively-immunized recipient anti-VEE neutralizing antibody responses were studied. Donor mice immunized with either live or inactivated VEE virus vaccine combined with potent adjuvants develop specific anti-VEE IgM and IgG responses as early as 7 days post-immunization. Anti-VEE IgM antibody responses comprise the majority of anti-VEE neutralizing antibody at this early time period. By 14 to 21 days post-immunization, anti-VEE IgG responses predominated. When adoptively-immunized recipients were studied, the anti-VEE IgM to IgG predominance seen in donors early after administration was reversed, and for each time-period studied, recipients' serum anti-VEE antibody class responses consisted principally of IgG rather than IgM antibody. Since T-cells cooperation with B-cells is critical in the IgM-IgG antibody shift, these studies support the critical role T-cells exert in adoptive transfer in a murine model of experimental VEE infection. Furthermore, immunization with either live or inactivated VEE vaccine coupled to a potent adjuvant induce comparable donor and adoptively-immunized recipient anti-VEE antibody class responses.

Animals↗

Characterization of IgG-containing DEAE fractions of canine serum.

A high-titered canine antilymphocyte serum was chromatographed on DE-52 cellulose and the fractions were assayed for cytotoxic activity. Although cytotoxicity was associated with the first 63% of the column effluent corresponding to fractions 1 through 7, significant activity (256) was demonstrable only in fractions 2, 3, 4, and 5. An immunoelectrophoretic study of fractions 1 through 5 showed only IgGa in fraction 1, IgGa and IgGb as electrophoretically separate arcs in fraction 2, and as electrophoretically inseparable arcs in fractions 3 through 5. Cytotoxicity is postulated to be associated with the IgGb subclass, since titers correspond with the distribution of IgGb in column fractions.

Animals↗