The elevation of natural killer cell activity induced by laughter in a crossover designed study.

The elevation of natural killer cell activity (NKCA) by laughter was not confirmed due to incomplete methodology of previous studies although positive emotion is believed to be favorable for health. To verify NKCA elevation by laughter in a crossover design, we measured NKCA before and after watching films, presenting 75-min comic film and non-emotional control film at different days to the same 21 healthy male subjects. Electromyogram of left major zygomatic muscle was obtained during the films to quantify the magnitude of laughter as an index of emotional expression. As indices of emotional experience, the self-rated pleasantness of the comic film and mood state before and after film were measured using visual analogue scale and Profiles of Mood State (POMS), respectively. The comic film significantly elevated NKCA (26.5-29.4%, p<0.05), whereas the control film did not (27.1-24.8%, not significant). This is the first study to demonstrate NKCA elevation by laughter in a crossover designed study. To examine the contribution of experiential and expressive aspects of laughter to NKCA elevation, correlation of NKCA elevation with the self-rated pleasantness, mood scores before and after comic film and the magnitude of laughter was statistically tested. We found that NKCA elevation was negatively correlated with the scores of negative mood scales of POMS while NKCA elevation had no significant correlation with self-rated pleasantness and the magnitude of laughter. Further group analysis revealed that high scores of depression and anger-hostility suppressed NKCA elevation by laughter. We also found that NKCA before and after comic film had tendency of correlation with self-rated pleasantness of the comic film while NKCA had no correlation with the magnitude of laughter. These findings suggest that NKCA elevation and NKCA before and after comic film seem to be related with the experiential aspects of laughter rather than with the expressive aspects.

Exercise training and autonomic nervous system activity in obese individuals.

PURPOSE: This study was designed to investigate the effects of 12 wk of exercise training on autonomic nervous system (ANS) in 18 obese middle-aged men (N = 9) and women (N = 9) (age: 41.6 +/- 1.2 yr; BMI: 27.3 +/- 0.4 kg x m(-2); %fat: 29.6 +/- 1.3%, mean +/- SE). METHODS: Each subject participated in an aerobic exercise training at anaerobic threshold (AT), consisting of 30 min/session, 3 times/wk, for 12 consecutive weeks. The ANS activities were assessed by means of power spectral analysis of heart rate variability (HRV) at resting condition before, at 5 wk, and after the exercise program. RESULTS: The exercise training resulted in a significant decrease in body mass, BMI, and % fat (P < 0.01) but not in lean body mass (P > 0.05) together with a significant increase in the AT VO2 (P < 0.01). Our power spectral data indicated that there were significant increases in the low-frequency component associated with the sympathovagal activity (0.03--0.15 Hz, 348.5 +/- 66.8 vs 694.7 +/- 91.5 ms(2), P < 0.01), the high-frequency vagal component (0.15--0.4 Hz, 146.3 +/- 30.4 vs 347.7 +/- 96.5 ms(2), P < 0.05), and the overall autonomic activity as evaluated by total power (0.03--0.4 Hz, 494.8 +/- 88.5 vs 1042.4 +/- 180.9 ms(2), P < 0.01) of HRV after the training. CONCLUSIONS: Twelve weeks of exercise training has significantly improved both the sympathetic and parasympathetic nervous activities of the obese individuals with markedly reduced ANS activity, suggesting a possible reversal effect of human ANS functions. These favorable changes may also have an influence on the thermoregulatory control over the obesity.

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Comparison of thermogenic sympathetic response to food intake between obese and non-obese young women.

OBJECTIVE: Sympathetic nervous system abnormality in humans is still a matter of debate. The present study was designed to examine diet-induced autonomic nervous system activity and metabolic change in obese and non-obese young women. RESEARCH METHODS AND PROCEDURES: Sixteen age- and height-matched obese and non-obese young women participated in this study. Sympathovagal activities were assessed by means of our newly developed spectral analysis procedure of heart-rate variability during the resting condition and after mixed-food ingestion (480 kcal). Energy expenditure was also measured under these two conditions. RESULTS: There was no significant difference in any of the parameters of the heart-rate variability between the obese group and control group during the resting condition. In the control group, both absolute values (221.5 +/- 54.5 vs. 363.8 +/- 43.7 ms2, p < 0.05) and relative values (0.23 +/- 0.03 to 0.36 +/- 0.02, p < 0.05) of a very-low-frequency component and global sympathetic nervous system index (1.46 +/- 0.19 vs. 3.26 +/- 0.61, p < 0.05) were significantly increased after mixed-food ingestion compared with the values obtained after resting condition. However, no such sympathetic response was found in the obese group. Energy expenditure increased in the two groups after the meal, but the magnitude of the increase above the preprandial resting condition was significantly greater in the control group than in the obese group (11.2 +/- 2.3 vs. 6.7 +/- 0.8%, p < 0.05). DISCUSSION: Our data suggest that despite identical sympathovagal activities at the resting condition, obese young women may possess a reduced sympathetic response to physiological perturbation such as mixed food intake, which might be related to lowered capacity of thermogenesis and the state of obesity.

Assessment of lower-back muscle fatigue using electromyography, mechanomyography, and near-infrared spectroscopy.

We have investigated the etiology of lower-back muscle fatigue using simultaneous recordings of electromyography (EMG), mechanomyography (MMG), and near-infrared spectroscopy (NIRS) in an attempt to shed some light on the electrophysiological, mechanical, and metabolic characteristics, respectively. Eight male subjects performed isometric back extensions at an angle of 15 degrees with reference to the horizontal plane, for a period of 60 s. Surface EMG, MMG and NIRS signals were recorded simultaneously from the center of the erector spinae at the level of L3. NIRS was measured to determine the level of muscle blood volume (BV) and oxygenation (Oxy-Hb). The root mean square amplitude value (RMS) of the EMG signal was significantly increased at the initial phase of contraction and then fell significantly, while mean power frequency (MPF) of the EMG signal decreased significantly and progressively as a function of time. There were also significant initial increases in RMS-MMG that were followed by progressive decreases at the end of fatiguing contractions. MPF-MMG remained unchanged. Muscle BV and Oxy-Hb decreased dramatically at the onset of the contraction and then remained almost constant throughout the rest of the contraction. These results, obtained by simultaneous recordings of EMG, MMG, and NIRS, demonstrate that the restriction of blood flow due to high intramuscular mechanical pressure is one of the most important factors in muscle fatigue in the lower-back muscles. In addition, the simultaneous recording system described here can be used to obtain more reliable information regarding the mechanism(s) of lower-back muscle fatigue.

Effects of capsaicin-containing yellow curry sauce on sympathetic nervous system activity and diet-induced thermogenesis in lean and obese young women.

The present study was designed to investigate the effect of capsaicin, a pungent component of red pepper, on the sympathetic nervous system (SNS) activity and energy metabolism in 16 age- and height-matched lean and obese young women. The sympatho-vagal activities were assessed by means of spectral analysis of heart rate variability (HRV) during the resting condition and after the meal (2,016 kJ) with capsaicin (3 mg). Energy expenditure was also measured under the two conditions. There was no significant difference in any of the parameters of the HRV between the obese and control groups at rest. After the capsaicin diet, however, the very low frequency component (0.007-0.035 Hz) associated with thermogenesis (315.8+/-78.0 vs. 814.8+/-211.7 ms2 x Hz(-1), p<0.05) as well as its responsiveness (delta changes: 14.6+/-104.4 vs. 369.2+/-121.7 ms2 x Hz(-1), p<0.05) were significantly lower in the obese than the control group. Energy expenditure was significantly increased in the control group after the meal (5,574.7+/-221.2 to 6,114.7+/-239.0 kJ day(-1); p<0.01), but no such significant thermogenic response was detected in the obese group despite nearly identical lean body mass of the control group. Our data indicate that regardless of the resting level of sympatho-vagal activities, the reduced sympathetic responsiveness to physiological perturbation such as a capsaicin diet, which may cause impaired diet-induced thermogenesis and further weight gain, could be an important etiological factor leading to obesity in young women.

Autonomic responsiveness to acute cold exposure in obese and non-obese young women.

OBJECTIVE: Conflicting results have emerged over the nature of autonomic nervous system abnormalities in human obesity. This present study was designed to investigate the sympatho-vagal activities and their responsiveness to acute cold exposure in age- and height-matched obese and non-obese young women. SUBJECTS: Twenty-four age- and height-matched obese (Weight: 68.1 +/- 2.64 kg, BMI: 26.3 +/- 0.74 kg/m2, %Fat: 39.9 +/- 1.23%) and non-obese young women (Weight: 46.9 +/- 0.77 kg, BMI: 18.5 +/- 0.18 kg/m2, %Fat: 22.9 +/- 0.8%). MEASUREMENTS: Plasma leptin, insulin, glucose and lipid concentrations were measured at rest. The sympathetic (SNS) and parasympathetic (PNS) nervous system activities were assessed by means of power spectral analysis of heart rate variability (HRV) for 15 min under control (25 degrees C) or acute cold exposure (10 degrees C) conditions. The very low (VLO) frequency component, and SNS (low/high power), and PNS (high/total power) indexes were used to evaluate thermoregulatory sympathetic function, and cardiac sympathetic and parasympathetic nervous activities, respectively. RESULTS: Plasma leptin concentration was significantly greater in the obese than in the control group (47.3 +/- 7.00 vs 12.1 +/- 1.22 ng.ml-1, P < 0.001). There was a highly positive correlation between plasma leptin concentration and percent of body fat (r = 0.863, P < 0.001). During the resting condition, there was no significant difference in any of the parameters of the HRV between the obese and control groups. Upon acute cold exposure, the VLO frequency component associated with thermoregulation (309 +/- 49.9 vs 578 +/- 142.2 ms2, P < 0.05) as well as its responsiveness (25-10 degrees C delta changes: 17 +/- 82.9 vs 326 +/- 138.2 ms2, P < 0.05) were significantly lower in the obese than in the control group. CONCLUSION: Our data indicate that a reduced autonomic, especially sympathetic responsiveness associated with thermoregulation and possibly leptin resistance might be aetiological factors of obesity in young women.

The association between Trp64Arg polymorphism of the beta3-adrenergic receptor and autonomic nervous system activity.

The beta3-adrenergic receptor plays a significant role in the control of lipolysis and thermogenesis in brown adipose tissue through autonomic nervous system (ANS) activity. As the Trp64Arg polymorphism of the beta3-adrenergic receptor gene might affect ANS activity, we investigated the association of the polymorphism with ANS activity. The prevalence of the polymorphism was determined in 204 subjects. Ten normal homozygous, 10 heterozygous, and 1 variant homozygous subjects were examined for ANS activity during supine rest and standing by electrocardiogram R-R interval power spectral analysis. Subjects with the variant did not differ from subjects without the variant in body mass index, plasma glucose, plasma insulin, or family history of diabetes or obesity. The total power of heterozygotes at supine rest was lower than that of normal subjects (1124.6 +/- 191.6 vs. 3029.8 +/- 758.8 ms2; mean +/- SE). With a postural change to standing, the parasympathetic and sympathetic nervous system activity indexes of heterozygotes showed a higher response than those of normal subjects (parasympathetic nervous system index, 0.10 +/- 0.02 vs. 0.17 +/- 0.02; sympathetic nervous system index, 10.55 +/- 1.47 vs. 6.26 +/- 1.09), and the difference in total power disappeared. These findings show that subjects with the variant, even the heterozygotes, had lower resting ANS activity than normal subjects.

The pH-dependent changes of the enzymic activity and spectroscopic properties of iron-substituted manganese superoxide dismutase. A study on the metal-specific activity of Mn-containing superoxide dismutase.

Manganese-containing superoxide dismutases (Mn-SODs) and iron-containing superoxide dismutases (Fe-SODs) from aerobic bacteria often show high metal specificity for their enzymic activities by a standard assay system using xanthine-xanthine oxidase and cytochrome c. In this study, we have attempted to characterize the structural basis of the metal specificity of manganese-containing SOD (Mn-SOD) using Fe-substituted Mn-SOD prepared from apo-Mn-SOD from Serratia marcescens. The Fe3+ content of the Fe-substituted enzyme was 1.71 +/- 0.14 mol/mol dimer and the specific activity was 34.8 +/- 4.8 units.mg protein-1.mol Fe3+(-1).mol subunit-1. Fe-substituted Mn-SOD was found to react with the superoxide anion at pH 8.1 with a second-order rate constant of 6 x 10(6) M-1 s-1, which is approximately 1% of that of native Mn-SOD at the same pH. However, the rate constant increased with decreasing pH to approximately 10% (5 x 10(7) M-1 s-1) that of native Mn-SOD at pH 6.0 with a pK of 7.0. The visible absorption spectrum and EPR spectrum of Fe-substituted Mn-SOD also showed pH-dependent changes with pK values of 6.6 and 7.2, respectively. Similarly, the affinity of the azide ion, an analog of the superoxide ion, for iron of Fe-substituted Mn-SOD increased with decreasing pH, with a pK value of 7.0 (e.g. Kd = 0.1 mM at pH 6.2 and 0.9 mM at pH 8.2). The similarity of these pK values suggests that the activity, the spectral changes and the affinity of the azide ion for iron are derived from the same change in the metal environment. After comparison with the reported pK values (around 9) of similar pH-dependent changes in the spectra, the enzymic activity and the affinity of azide for iron of Fe-SOD from Escherichia coli, we proposed that the difference in the pK values of a hydroxide ion binding to iron between Fe-substituted Mn-SOD and Fe-SOD may cause the different pH dependencies of these changes in each SOD.

Relation between functions and conformational characteristics of modified nucleosides found in tRNAs.

Conformational characteristics of N4-acetyl-2'-O-methylcytidine (ac4Cm), 5-methyl-2'-O-methylcytidine (m5Cm) and N2-dimethyl-2'-O-methylguanosine (m2(2)Gm) found in tRNAs from extremely thermophilic archaebacteria were analyzed by proton NMR spectroscopy. The 2'-O-methylation of ac4C, m5C and m2(2)G was found to stabilize the C3'-endo form and therefore cause "conformational rigidity". In particular, the ac4Cm was found to be extremely rigid due to additive effects of the N4-acetylation and 2'-O-methylation. Therefore, tRNAs from the extremely thermophilic archaebacteria use the base modifications in combination with the 2'-O-methylation, resulting in stabilization of the A-type conformation at specific positions in the tRNAs even at very high temperatures. In contrast, mesophile tRNAs use for a given site only one of these ribose and base modifications each of which is effective enough by itself at ordinary temperatures. These findings are consistent with our previous findings that roles of a variety of post-transcriptional modifications are to regulate the conformational rigidity/flexibility which is essential for the tRNA functions.