Effect of 8-week leucine supplementation and resistance exercise training on muscle hypertrophy and satellite cell activation in rats.

We investigated the effects of regular leucine intake and/or resistance exercise training on skeletal muscle hypertrophy and satellite cell activity after the administration of different doses of leucine. Ten-week-old Sprague-Dawley rats were assigned to six groups (n = 7 per group): a control group (Con), two groups receiving either 10% (0.135 g/kg.wt) (Leu10) or 50% (0.675 g/kg.wt) (Leu50) leucine supplementation, and three exercise groups receiving 0% (Ex), 10% (Leu10Ex), and 50% (Leu50Ex) leucine supplementation. The rats performed ladder climbing exercises thrice per week for 8 weeks, and received leucine supplements at the same time daily. Muscle phenotypes were assessed by immunohistochemistry. MyoD, myogenin, and IGF1 protein levels were determined by western blot. The Leu50Ex group displayed significantly higher numbers of positive embryonic myosin fibers (0.35 ± 0.08, 250%) and myonuclei (3.29 ± 0.3, 118.7%) than all other groups. And exercise training groups increased the cross-sectional area, the number of satellite cells and protein expression of MyoD, myogenin, and IGF1alpha relative to the Control group (P < 0.05). However, Only leucine supplementation group did not increase skeletal muscle hypertrophy and satellite cell activity, regardless of the dose (P > 0.05). Leucine intake accompanied by regular exercise training may increase satellite cell activation in skeletal muscles, and improve muscle quality more effectively than continuous leucine ingestion alone.

Satellite cell activation and mTOR signaling pathway response to resistance and combined exercise in elite weight lifters.

PURPOSE: Our aim was to compare the effects of a single exercise training mode (resistance exercise) with a combined exercise training (resistance and plyometric exercise) mode on satellite cell activity and anabolic signaling at the molecular level. METHODS: Eighteen male weight lifters (20 ± 4 years, BMI 27 ± 6 kg/m2) were randomly assigned to either a series of resistance exercise or a series of combined exercise group. The intensity of the exercise was set at 60% of their 1 RM weight and subjects completed three sets each of six repetitions. The combined exercise group performed three different types of resistance exercise alternating with three different types of plyometric exercise, whereas the resistance exercise group performed only the three different types of resistance exercise which was repeated twice. Muscle biopsies were obtained the vastus lateralis muscle immediately before and 3 h after one bout of exercise. RESULTS: Exercise induced increases in satellite cell activation and myofibrillar protein synthesis following both exercise modes, but the resistance exercise group was superior compared to the combined exercise group in satellite cell activity expressed by Ki67/CD56 (165 vs 232%) and PI3K/Akt protein expression (121 vs 157%), mTOR protein expression (117 vs 288%), p70S6K protein expression (253 vs 809%), and 4E-BP1 protein expression (70 vs 139%) of anabolic signaling pathway. CONCLUSIONS: These results suggest that the previous findings showing a greater effect of combined as opposed to a single exercise mode could be the effect of a greater training volume rather than a true-training effect of a combined exercise program.

Immunodominant "asymptomatic" herpes simplex virus 1 and 2 protein antigens identified by probing whole-ORFome microarrays with serum antibodies from seropositive asymptomatic versus symptomatic individuals.

Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes.

The herpes simplex virus 1 latency-associated transcript promotes functional exhaustion of virus-specific CD8+ T cells in latently infected trigeminal ganglia: a novel immune evasion mechanism.

Following ocular herpes simplex virus 1 (HSV-1) infection of C57BL/6 mice, HSV-specific (HSV-gB(498-505) tetramer(+)) CD8(+) T cells are induced, selectively retained in latently infected trigeminal ganglia (TG), and appear to decrease HSV-1 reactivation. The HSV-1 latency-associated transcript (LAT) gene, the only viral gene that is abundantly transcribed during latency, increases reactivation. Previously we found that during latency with HSV-1 strain McKrae-derived viruses, more of the total TG resident CD8 T cells expressed markers of exhaustion with LAT(+) virus compared to LAT(-) virus. Here we extend these findings to HSV-1 strain 17syn+-derived LAT(+) and LAT(-) viruses and to a virus expressing just the first 20% of LAT. Thus, the previous findings were not an artifact of HSV-1 strain McKrae, and the LAT function involved mapped to the first 1.5 kb of LAT. Importantly, to our knowledge, we show here for the first time that during LAT(+) virus latency, most of the HSV-1-specific TG resident CD8 T cells were functionally exhausted, as judged by low cytotoxic function and decreased gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. This resulted in LAT(-) TG having more functional HSV-gB(498-505) tetramer(+) CD8(+) T cells compared to LAT(+) TG. In addition, LAT expression, in the absence of other HSV-1 gene products, appeared to be able to directly or indirectly upregulate both PD-L1 and major histocompatibility complex class I (MHC-I) on mouse neuroblastoma cells (Neuro2A). These findings may constitute a novel immune evasion mechanism whereby the HSV-1 LAT directly or indirectly promotes functional exhaustion (i.e., dysfunction) of HSV-specific CD8(+) T cells in latently infected TG, resulting in increased virus reactivation.

High prevalence of ceftazidime-resistant Klebsiella pneumoniae and increase of imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. in Korea: a KONSAR program in 2004.

A nationwide antimicrobial resistance surveillance has been conducted since 1997 in Korea. In this study, susceptibility test data generated in 2004 by KONSAR group hospitals were analyzed and compared to those at a commercial laboratory. In hospitals, the rank orders of organisms in 2004 were identical to those in 2003. The most prevalent species was Staphylococcus aureus (20.2%) in hospitals, but Escherichia coli (29.7%) in the commercial laboratory. The proportions of Enterococcus faecium to all isolates of Enterococcus faecalis plus E. faecium were 47.2% in hospitals and 24.9% in the commercial laboratory. The mean resistance rates of significant antimicrobial-organism combinations in hospitals were: oxacillin-resistant S. aureus (68%), oxacillin-resistant (penicillin- nonsusceptible) Streptococcus pneumoniae (68%), vancomycin-resistant E. faecium (25%), cefotaxime-resistant E. coli (14%), ceftazidime- and cefoxitin-resistant Klebsiella pneumoniae (34% and 32%, respectively), and imipenem-resistant Acinetobacter spp. and Pseudomonas aeruginosa (17% and 24%, respectively). In conclusion, oxacillin-resistant staphylococci, expanded-spectrum cephalosporin-resistant K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa were prevalent in 2004. Increasing trends were observed for vancomycin-resistant E. faecium, cefoxitin- resistant E. coli and K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa. Certain antimicrobial- organism combinations were also prevalent among the commercial laboratory-tested strains.