Temporal Association Between Ischemic Muscle Perfusion Recovery and the Restoration of Muscle Contractile Function After Hindlimb Ischemia.

During incomplete skeletal muscle recovery from ischemia, such as that occurs with critical limb ischemia, the temporal relationship between recovery of muscle capillary perfusion and contractile function is poorly defined. We examined this relationship in BALB/cJ mice (N = 24) following unilateral hindlimb ischemia (HLI), which pre-clinically mimics the myopathy observed in critical limb ischemia patients. Specifically, we examined this relationship in two phenotypically distinct muscles (i.e., "oxidative" soleus - Sol and "glycolytic" extensor digitorum longus - EDL) 14- or 56-days after HLI. Although overall limb blood flow (LDPI) reached its' recovery peak (48% of control) by HLI d14, the capillary networks in both the Sol and EDL (whole mount confocal imaging) were disrupted and competent muscle capillary perfusion (perfused lectin+µm2/muscle µm2) remained reduced. Interestingly, both Sol and EDL muscles recovered their distinct capillary structures and perfusion (Con Sol; 0.056 ± 0.02 lectin+µm2/muscle µm2, and Con EDL; 0.039 ± 0.005 lectin+µm2/muscle µm2) by HLI d56 (Sol; 0.062 ± 0.011 lectin+µm2/muscle µm2 and EDL; 0.0035 ± 0.005 lectin+µm2/muscle µm2), despite no further improvement in limb blood flow (LDPI). Both muscles suffered severe myopathy, indicated by loss of dystrophin positive immunostaining and the absence of stimulation induced isometric force production at HLI d14. Dystrophin immunofluorescence returned at HLI d56, although neither myofiber CSA (µm2) nor isometric force production (58 and 28% sustained deficits, Sol and EDL, respectively) recovered completely in either muscle. In summary, we reveal that the temporal relationship between the restoration of muscle capillary perfusion and functional ischemic skeletal muscle regeneration favors competent muscle capillary perfusion recovery in BALB/c mice in a phenotypically non-distinct manner.

C3d enhancement of neutralizing antibodies to measles hemagglutinin.

Measles remains a major cause of worldwide infant mortality despite the use of current live attenuated vaccines. New approaches to measles virus (MV) vaccine development are critical to interrupt the spread of MV. In this study, we report the results using a DNA vaccine expressing a fusion of the measles hemagglutinin (H) protein and the complement component, C3d, to enhance the titers of neutralizing antibody. Plasmids were generated that expressed a secreted (s) form of H and the same form fused to three tandem copies of the murine homologue of C3d (sH-3C3d). Analysis of titers of the antibody raised in vaccinated mice indicated that immunizations with the DNA expressing sH-3C3d had higher titers of anti-H antibodies compared to serum from mice vaccinated with DNA expressing sH only. In addition, sH-3C3d elicited higher neutralizing antibody titers that inhibited MV induced plaque formation.

Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins.

DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, we report that fusion of Env and the complement component, C3d, in a DNA vaccine, enhances the titers of antibody to Env. Plasmids were generated that expressed a secreted form of Env (sgp120) from three isolates of HIV and these same forms fused to three tandem copies of the murine homologue of C3d (sgp120-3C3d). Analyses of titers and avidity maturation of the raised antibody indicated that immunizations with each of the sgp120-3C3d-expressing DNAs accelerated both the onset and the avidity maturation of antibody to Env.

Accelerating antidepressant response in geriatric depression: a post hoc comparison of combined sleep deprivation and paroxetine versus monotherapy with paroxetine, nortriptyline, or placebo.

Speed of response is an important clinical issue in the treatment of depressed elderly patients. Our objective was to compare rapid response rates in a study combining therapeutic sleep deprivation (TSD) with paroxetine with two earlier randomized, double-blind studies in late-life depression, one of paroxetine versus nortriptyline and another of nortriptyline versus placebo. We measured depressive symptoms with the 17-item Hamilton Rating Scale of Depression (HRSD), defining rapid response as an HRSD < or = 10 by 2 weeks. With combination therapy (TSD + paroxetine), 9 of 13 patients (69%) experienced a rapid response. In the nortriptyline versus paroxetine study, nortriptyline brought about rapid response in 12 of 37 (32%) and paroxetine in 11 of 43 patients (26%). In the third study, rapid response to nortriptyline occurred in 10 of 41 patients (24%) and to placebo in 6 of 39 patients (15%). The overall chi square, including the rate of rapid response to placebo, was 14.87 (P = .005). The chi square on the four active treatment groups, excluding placebo, was 10.28 (P = .016). This preliminary observation suggests that combined therapy with TSD plus paroxetine may be twice as successful at achieving rapid response in elderly depressed patients than conventional monotherapy with medication or placebo. A prospective, placebo-controlled evaluation of this dual therapy is warranted.

Causal attribution and affective response as mediated by task performance and self-acceptance.

Predictions derived from cognitive consistency theories, self-esteem theories, and ego-serving-bias theory concerning how students would make attributional and affective responses to their academic performance were investigated. 202 university students completed a measure of self-acceptance of their college ability and made attributional and affective responses to an hypothetical examination performance. Analyses showed that students receiving positive feedback perceived greater internal causality and responded with greater positive affect than students receiving negative feedback. Self-acceptance did not moderate the attributions or affective reactions. The results supported the ego-serving-bias theory and provided partial support for self-esteem theory. Findings did not support predictions from cognitive-consistency theory.

Evaluation of a rapid peptide-based anti-human immunodeficiency virus-1 antibody immunoassay.

A qualitative, visually interpreted, rapid, and synthetic peptide-based anti-human immunodeficiency virus-1 (HIV) antibody immunoassay has been developed that may be of value in situations in which rapid determination of HIV-1 status is important. Because questions have been raised about the accuracy of rapid anti-HIV-1 assays, the sensitivity, specificity, interobserver and intraobserver variability of the Genie HIV-1 assay (Genetics Systems, Seattle, WA) were determined. Sera from 56 patients with HIV-1 infections documented by enzyme immunoassay and western blot tested positive by this assay. Enzyme immunoassay- and western blot-negative sera from 30 visceral organ transplant donors were negative using the Genie assay. Specificity was examined further by testing sera from 29 patients hospitalized with a variety of medical disorders, including acute bacterial pneumonia, acute myocardial infarction, monoclonal gammopathy, and high titer antinuclear or antimitochondrial antibodies. Two of these patients were reactive with the enzyme immunoassay, both of which tested negative by western blot. All 29 tested negative using the Genie assay. In addition, sera from five patients with repeatedly reactive enzyme immunoassays and negative western blots tested negative by the Genie system. There was 100% agreement in interobserver and intraobserver studies. With the western blot as the reference method, the Genie assay exhibited 100% sensitivity and specificity and there was no observer variability.

Implicit versus explicit learning processes in a probabilistic, continuous fine-motor catching task.

We compared the influences of explicit instruction and uninstructed implicit learning of correlations among visual events, in a fine-motor task. The task required visual tracking of a small "ball" of light and "catching" it by means of joystick manipulation. A general pattern of improvement with practice for instructed and "noninstructed" conditions was found. Additionally, both instructed and noninstructed conditions evidenced use of the predictive relationships among stimulus events. The improvement in overall performance caused by explicit verbal instructions was less than the improvement seen with the implicit learning condition. Further, instructed and noninstructed conditions showed different patterns of joystick activity. These findings suggest a qualitatively different approach to visual information processing and task performance for the instructional conditions