Search

Recent findings regarding the existence of functional brown adipose tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling protein 1 (UCP1)-linked thermogenesis in energy balance.To investigate whether UCP1 polymorphism was associated with resting energy expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity in humans.A total of 82 healthy females (20-22 years) were genotyped for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele-specific DNA primer assay system. REE was measured by indirect calorimetry. The thermoregulatory SNS activity was assessed by heart rate variability power spectral analysis according to our previously reported method. Each subject was studied in the morning, after an overnight fast. Nutritional values were calculated on the basis of 2-day food records.The frequencies of A/A, A/G and G/G genotypes were 0.27, 0.45 and 0.28, respectively. No significant difference was found in anthropometric indexes among the three groups. However, in the G/G group, the percentage of energy consumed as fat was lower (A/A: 30.7 ± 1.1%, A/G: 31.3 ± 1.0%, G/G: 26.0 ± 1.2%, P0.01), and energy intake tended to be lower (A/A: 7209 ± 310 kJ d(-1), A/G: 7075 ± 280 kJ d(-1), G/G: 6414 ± 264 kJ d(-1), P=0.16). With regard to metabolic parameters, group differences were observed in REE (A/A: 5599 ± 170 kJ d(-1), A/G: 5054 ± 115 kJ d(-1), G/G: 4919 ± 182 kJ d(-1), P0.01) and in thermoregulatory SNS activity (A/A: 313 ± 47 ms(2), A/G: 333 ± 42 ms(2), G/G: 185 ± 23 ms(2), P0.05).Diminished REE in G-allele carriers as well as reduced thermoregulatory SNS activity for the G/G genotype, suggest that attenuated UCP1-linked thermogenesis has an adverse effect on the regulation of energy balance.

Percutaneous low-frequency electrical muscle stimulation (LF-ES) is a new alternative exercise prescription for individuals who cannot adequately perform voluntary exercise. However, substantial undesirable elevation of both systolic blood pressure (SBP) and cardiac afterload occurs during LF-ES and must be resolved. Therefore, this study examined whether or not the synchrony between cardiac systole and skeletal muscle contraction affects instantaneous blood pressure and cardiac afterload during intermittent evoked muscle contractions. In eight subjects, the quadriceps and biceps femoris muscles of each limb were simultaneously stimulated at 20Hz with a duty cycle of 0.3s stimulation and 0.7s pause for 15min. The phase difference between the ECG R-peak and the onset of muscle contraction ( τ c–s ) was measured for all heartbeats. Then, instantaneous SBP, tension-time index (TTI), and peripheral vascular resistance (PVR) associated with each heartbeat were plotted as functions of τ c–s . The results showed that SBP, TTI, and PVR were significantly lowered at positive τ c–s (i.e., the moment at which a muscle contraction started during the cardiac recovery phase). These results suggest that a well-designed stimulator, one that induces muscle contractions coupled with heartbeats with appropriate phase difference, would effectively attenuate the elevation of SBP and cardiac afterload during LF-ES.

We developed fully automated software for dynamic susceptibility contrast (DSC) MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical hemodynamic information for acute stroke treatment decisions. Brain MR PWI was performed in 80 consecutive patients with acute nonlacunar ischemic stroke within 24h after onset of symptom from January 2008 to August 2009. These studies were automatically processed to generate hemodynamic parameters that included cerebral blood flow and cerebral blood volume, and the mean transit time (MTT). To develop reliable software for PWI analysis, we used computationally robust algorithms including the piecewise continuous regression method to determine bolus arrival time (BAT), log-linear curve fitting, arrival time independent deconvolution method and sophisticated motion correction methods. An optimal arterial input function (AIF) search algorithm using a new artery-likelihood metric was also developed. Anatomical locations of the automatically determined AIF were reviewed and validated. The automatically computed BAT values were statistically compared with estimated BAT by a single observer. In addition, gamma-variate curve-fitting errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two observes independently assessed the quality and area of hypoperfusion mismatched with restricted diffusion area from motion corrected MTT maps and compared that with time-to-peak (TTP) maps using the standard approach. The AIF was identified within an arterial branch and enhanced areas of perfusion deficit were visualized in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.) without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a standard personal computer. The MTT map produced with our software adequately estimated brain areas with perfusion deficit and was significantly less affected by random noise of the PWI when compared with the TTP map. Results of image quality assessment by two observers revealed that the MTT maps exhibited superior quality over the TTP maps (88% good rating of MTT as compared to 68% of TTP). Our software allowed fully automated deconvolution analysis of DSC PWI using proven efficient algorithms that can be applied to acute stroke treatment decisions. Our streamlined method also offers promise for further development of automated quantitative analysis of the ischemic penumbra.

Early sub-clinical assessment of severity of cardiac autonomic neuropathy (CAN) and intervention are of prime importance for risk stratification and early treatment in preventing sudden death due to silent myocardial infarction. The Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical disease and requires patient cooperation. Time and frequency domain analysis have several shortcomings including sensitivity to recording length, respiratory activity and non-stationarities in the ECG signal. An important step forward is to have a non-invasive method of detecting CAN that is robust against these shortcomings and has a higher sensitivity for the presence of both sub-clinical and overt clinical disease. This study presents a novel parameter, tone-entropy (T-E) that analyses heart rate variability (HRV) of 20 min lead II ECG recordings. Tone (T) represents sympatho-vagal balance and entropy (E) the autonomic regularity activity. Thirteen normal subjects without (CAN-) and 21 with CAN (CAN+) participated in this study. Among 21 CAN+ subjects, 13 are early CAN+ (eCAN+), eight are definite CAN+ (dCAN+) according to autonomic nervous system function tests as described by Ewing. The results showed that tone was higher and the entropy was lower in the dCAN+ group (T=-0.033 to -0.010 and E=1.73-2.24) compared with the eCAN+ (T=-0.0927 to -0.0311 and E=2.0-2.65) and normal (T=-0.128 to -0.0635 and E=2.64-3.15) group. The research verified that T-E is a suitable method to determine the presence of CAN that correctly identifies experimentally induced changes in cardiac function akin to parasympathetic and sympathetic dysfunction and differentiates between stages in CAN disease progression identified using the Ewing battery.

本研究の目的は, スープ摂取後の安堵感（心がほっと安らぐ感覚）の定量的評価を行い, スープの種類による安堵感の違い, および安堵感に影響を及ぼす心理的, 生理的要因を検討することである。予備試験では, 訓練された6名のパネルによる官能検査を4種類のサンプル（コーンポタージュ[90 kcal], チキンコンソメ[43 kcal], および等エネルギーで風味に乏しいコーン・プラセボ, チキン・プラセボ）について行い, 各サンプルの特性を位置づけた。本試験では, 前夜から絶食した11名の女性（22.6±0.3歳）に, スープサンプルを朝食として, 異なる4日間にランダムな順序で負荷した。安堵感スコア, 満腹感スコア, 心拍数, 交感・副交感神経活動（心拍変動解析による), エネルギー消費量（呼気ガス分析による）を, スープ摂取前および摂取1時間後まで経時的に測定した。サンプルへの嗜好スコアは, コーンポタージュ, チキンコンソメの順に高く, 両プラセボで最も低かった。スープ摂取後の安堵感は, コーンポタージュでは他のスープサンプルより有意に高値を示した。安堵感は, 嗜好スコア, 満腹感スコア, 心拍数と正相関し, 副交感神経活動と負の相関を示した。本結果から, コーンポタージュ摂取後の高い安堵感には, スープへの嗜好性, および摂取後の満腹感と心拍数の上昇が関連していることが示唆された。

The present study aimed to examine whether a single bout of percutaneous low-frequency electrical muscle stimulation (EMS) can attenuate postprandial hyperglycemia in human subjects. Ten obese and 4 pre-obese Japanese men participated in two experimental sessions, one involved 20 min of EMS just after a breakfast (EMS trial) and the other involved complete rest after a breakfast (Control trial). In each trial, blood samples were taken before and at 30, 60, 90, and 120 minutes after the meal. Blood lactate concentration and respiratory gas exchange were measured during EMS and at complete rest after a meal in the EMS and Control trials, respectively. The results showed that the postprandial hyperglycemia was significantly attenuated in the EMS trial (P

Background The lower limb muscle may play an important role in decreasing the heart’s pumping workload. Aging and inactivity cause atrophy and weakness of the muscle, leading to a loss of the heart-assisting role. An electrical lower limb muscle stimulator can prevent atrophy and weakness more effectively than conventional resistance training; however, it has been reported to increase the heart’s pumping workload in some situations. Therefore, more effective tools should be developed. Methods We newly developed a cardiac cycle-synchronized electrical lower limb muscle stimulator by combining a commercially available electrocardiogram monitor and belt electrode skeletal muscle electrical stimulator, making it possible to achieve strong and wide but not painful muscle contractions. Then, we tested the stimulator in 11 healthy volunteers to determine whether the special equipment enabled lower limb muscle training without harming the hemodynamics using plethysmography and a percutaneous cardiac output analyzer. Results In 9 of 11 subjects, the stimulator generated diastolic augmentation waves on the dicrotic notches and end-diastolic pressure reduction waves on the plethysmogram waveforms of the brachial artery, showing analogous waveforms in the intra-aortic balloon pumping heart-assisting therapy. The heart rate, stroke volume, and cardiac output significantly increased during the stimulation. There was no change in the systolic or diastolic blood pressure during the stimulation. Conclusion Cardiac cycle-synchronized electrical muscle stimulation for the lower limbs may enable muscle training without harmfully influencing the hemodynamics and with a potential to reduce the heart’s pumping workload, suggesting a promising tool for effectively treating both locomotor and cardiovascular disorders.

Background: In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)−45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. Aim: Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. Subjects and methods: Thirty-two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay system and FRET probe assay system. Results: After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the T/T genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). Conclusion: Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet.

Objectives The mitochondrial uncoupling proteins UCP2 and UCP3 are implicated in energy metabolism and regulation of reactive oxygen species, which are closely involved in autonomic nervous system function. Heart rate variability (HRV) reflects cardiac autonomic regulation and has been used to evaluate dysfunction of the autonomic nervous system in hypertension and cardiovascular diseases. We examined the association between polymorphisms in the UCP2 and UCP3 genes and HRV in healthy young Japanese men. Methods The 45 bp insertion/deletion polymorphism in exon8 of UCP2 and the -55C/T polymorphism in the UCP3 promoter region were genotyped (n = 255). Cardiac autonomic function was evaluated by power spectral analysis of HRV during supine rest and in a standing position. Low-frequency ( 0.15 Hz) components of HRV were quantified by frequency domain analysis. Results The I/I genotype of the UCP2 45 bp insertion/ deletion polymorphism was associated with relatively higher blood pressure and HRV sympathetic indices (low frequency percentage and low frequency:high frequency ratio) at supine rest. For the -55C/T polymorphism of UCP3, individuals carrying the -55T allele had significantly lower HRV sympathetic indices, but higher HRV parasympathetic indices (high frequency and high frequency percentage), than carriers of the C/C genotype at standing. Both UCP2 and UCP3 polymorphisms were significantly associated with a third-degree family history of hypertension, diabetes, and obesity. Additionally, carriers of the UCP2 45 bp I allele -UCP3 -55C/C combined genotype had the lowest HRV sympathetic and the highest HRV parasympathetic indices at standing among the combined genotypes. Conclusion UCP2 and UCP3 polymorphisms were associated with HRV in young and healthy states, suggesting a significant relationship between autonomic cardiovascular regulation and UCP2/UCP3 polymorphisms.

胃電図は, 腹部に装着した表面電極から経皮的に胃筋電活動を記録する非侵襲的な胃運動評価法である。本研究では, 胃電図を指標として朝食欠食と朝の胃運動の関連を検討するために, 朝食摂取習慣のある女性11名 (21.5±0.2歳) に, 1週間の朝食欠食および1週間の再摂食試験を連続して行った。各試験の前後に検査日を設け, 前夜から絶食した被験者の体組成, 空腹感と食欲 (Visual analog scaleによる) を測定し, 午前9時より胃電図と心電図を同時に記録した。得られた胃の電気信号を解析し, 1分間に約3回生じる正常波パワー (Normal power), 正常波パワー含有率 (% Normal power) およびその出現頻度 (Dominant frequency; DF) を定量した。心電図からは心臓自律神経活動を定量した。1週間の朝食欠食は, 有意ではないが% Normal powerとDFを低下させた。DFは欠食後から再摂食後にさらに低下した (p=0.074 versus baseline) 。朝食欠食後の空腹感スコア (r=0.55, p=0.077), 食欲スコア (r=0.60, p=0.051) と % Normal powerの相関には有意傾向が認められた。以上の結果より, 1週間の朝食欠食が習慣的に朝食を摂取している若年女性の胃運動を減弱させる傾向が認められたこと, および, 胃収縮運動の強さが空腹感や食欲の強さと関連している可能性が示唆された。

The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 ± 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.

Experiments were performed to determine whether spinal and supraspinal components of reciprocal inhibition (a neural mechanism responsible for the prevention of muscular co-ordination during voluntary movement) were present in groups of non-disabled children and children with cerebral palsy. Changes in the gastrocnemius-soleus H reflex were examined during voluntary dorsiflexion and plantarflexion of the ankle and during a vibration applied to the anterior tibial tendon. The results indicate that children with cerebral palsy have impairments in reciprocal inhibition, both before and during voluntary movement. These deficits, which involve damage to supraspinal centres, contribute to their inability to perform smooth, co-ordinated movements.

Background: Asian people are divided into the individuals who can ingest alcohol and cannot because of the difference of aldehyde dehydrogenase-2 (ALDH2) genotype. The purpose of the present study was to investigate the effect of ALDH2 genotype on cardiac autonomic nervous responses to moderate alcohol ingestion. Methods: Subjects were 17 healthy male students at Kyoto University. According to the difference of ALDH2 genotype, they were divided into two groups: the STRONG (n = 10) and WEAK (n = 7) group. The subjects ingested 10 (the LITTLE trial) or 30 g (the MUCH trial) of pure alcohol on a separate day randomly. We collected ECG data and analyzed QT interval. Results: ECG QT interval, the important marker for sudden cardiac death in cardiac patients as well as healthy people, of the STRONG group were not prolonged after alcohol ingestion, but that of the WEAK group were significantly prolonged, compared to control. Moreover, with respect to the comparison of the change of QT interval between the LITTLE and MUCH trials, there were also no significant differences in the STRONG group. In the WEAK group, however, the change was more marked at MUCH trial. Conclusions: It is concluded that the cardiovascular response to alcohol ingestion is influenced by ALDH2 genotype and that the drinking assumed to be in moderation puts a strain on the hearts for the ALDH2-deficient individuals. The results of this investigation show that moderate drinking does not have a good effect on everybody with respect to QT interval. This study also shows that moderate alcohol intake does not have a bad effect on the immune system regardless of ALDH2 genotype.

We examined the effects of acute exercise on reaction time to visual stimuli presented in the central portion and periphery of the visual field. Twelve participants performed reaction time tasks at rest and during cycling at 65 % peak oxygen uptake in two visual conditions. We used circular black-and-white checkerboard patterns as visual stimuli. The participants were asked to respond as quickly as possible to pattern reversal of the visual stimulus by releasing a response button. Reaction time was fractionated into Premotor time and Motor time. Premotor time in the peripheral condition significantly increased (p < 0.025) during exercise (mean +/- SE; 195.9 +/- 7.9 ms) from that at rest (183.7 +/- 6.8 ms). Premotor time in the central condition did not differ between at rest (185.3 +/- 7.6 ms) and during exercise (188.4 +/- 6.6 ms). These data suggest that the ability to respond to visual stimuli presented in the periphery of the visual field is vulnerable to moderate to severe exercise, as compared with the ability to respond to visual stimuli presented in the central portion of the visual field. An exercise-induced increase in arousal level and a consequent narrowing of attentional focus would explain the present results.

現代人の多忙な生活の中で，簡便で即効性のある栄養補助食品が求められている。本研究では，GABAを30 mg含有したカプセルの経口摂取によるリラクセーション効果を，自律神経活動の観点から評価することを試みた。12名の健康な若年男性（21.7±0.8歳）を対象に，GABAとプラセボカプセルを摂取させ，摂取前（安静時），摂取30分および60分後の心電図を胸部CM5 誘導より測定した。自律神経活動は，心拍のゆらぎ（心電図R-R間隔）をパワースペクトル解析し，非観血的に交感神経活動と副交感神経活動を弁別定量化した。その結果，GABA摂取前と比較して，総自律神経活動は摂取30分後 (p

Summary Uncoupling protein-1 (UCP1) activity in brown adipose tissue increases energy expenditure, and contributes to diet-induced or cold-induced thermogenesis. We previously reported that children with −3826 A → G nucleotide variant of the UCP1 gene had lowered postprandial thermogenesis in response to a high-fat meal. In this study, we investigated whether the UCP1 polymorphism was associated with cold-induced thermogenesis in healthy children. Resting energy expenditure was measured in 19 children (6–10 years) by indirect calorimetry for 30 min under thermoneutral (25 °C) or cold conditions (10 °C) in an environmental chamber. The activity of autonomic nervous system (ANS) was assessed by power spectral analysis of heart rate variability (HRV). Samples of saliva were collected for cortisol determination at the end of the experimental session. Each experiment was performed on 2 consecutive days. Children were genotyped for the UCP1 polymorphism with a PCR-restriction fragment length analysis using buccal samples. During cold exposure, total power of the HRV, an index of the overall ANS activity, as well as the salivary cortisol concentration significantly increased in the children with homozygous (GG) for the UCP1 polymorphism while only cortisol response was found in the carriers of the wild-type (AA) and heterozygous (AG) alleles; however, the GG allele group showed a lower cold-induced thermogenesis compared to the AA + AG group. In conclusion, despite cold-induced autonomic stimulation, the GG allele carriers have a reduced capacity for thermogenesis in response to acute cold exposure, suggesting that such reduced UCP1-linked thermogenesis may have adverse effects on the regulation of body weight.

We investigated whether capsaicin ingestion (150 mg) enhances substrate oxidation associated with thermogenic sympathetic activity as an energy metabolic modulator without causing prolongation of the cardiac OT interval during aerobic exercise in humans. Ten healthy males [24.4 (4.3) y] volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis, energy metabolism, and ECG QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilatory threshold (50% VT(max)) on a stationary ergometer with placebo or capsaicin oral administration chosen at random. The results indicated that there were no significant differences in heart rate during rest or exercise between the two trials. Autonomic nervous activity increased in the capsaicin tablet trial during exercise, but the difference did not reach statistical significance. Capsaicin, however, significantly induced a lower respiratory gas exchange ratio [0.92 (0.02) vs. 0.94 (0.02), means (SE), p0.05] and higher fat oxidation [0.17 (0.04) vs. 0.12 (0.04) g/min, means (SE), p0.05] during exercise. On the other hand, the data on the cardiac OT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, it may be considered that capsaicin consumption 1 h before low intensity exercise (50% VT(max)) is a valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity because it improves lipolysis without any adverse effects on the cardiac depolarization and repolarization process.

L-カルニチンがヒトの空腹感に及ぼす影響を明らかにするために, 若年健常女性12名 (21.3±0.3歳) を対象として, L-カルニチン300mgを含有するフォーミュラ食と通常のフォーミュラ食を用いた二重盲検プラセボ対照試験による検証を行った (ウォッシュアウト : 1週間)。前夜からの絶食の後, フォーミュラ食を朝食として摂取させ, 食前および食後6時間まで満腹感スコア (ビジュアルアナログスケールズ ; VASs), 唾液コルチゾール, 血清カルニチン濃度, 血糖値, および心拍変動パワースペクトル解析を用いた自律神経活動指標を経時的に測定した。実験結果から, L-カルニチン摂取により主観的空腹感が軽減される可能性があること, および, 空腹感の軽減には血清総カルニチン濃度が関連していることが示唆された。さらに, 唾液コルチゾールはL-カルニチン摂取30分後, 2時間後には低値を示したが, 空腹感軽減との明確な関連は明らかではなかった。

Recently, we demonstrated region-specific electromyography (EMG) responses along the rectus femoris (RF) muscle during gait in healthy young men (Watanabe et al., 2014b). For the RF muscle, regional EMG response should be tested to characterize neuromuscular control and/or to assess its dysfunction and/or pathology during gait. We aimed to identify spatial distribution of EMG pattern within the RF muscle in elderly during gait. Seven young men (age: 20.4±1.0 years) and 8 elderly men (age: 73.8±5.9 years) walked on treadmill with three different speed: slow (preferred -1km/h), preferred, and fast (preferred +1km/h). The spatial distribution of surface EMG was tested by central locus activation (CLA), which is calculated from 18 surface electrodes along the longitudinal line of the muscle. CLA were not different between the groups for slow and preferred gait speed (p>0.05) during a gait cycle. In fast gait speed, CLA at 80% of a gait cycle (swing phase) for the elderly were significantly located at more distal site than the young group (p

Daily energy intake per person in Japan reached a peak of 2,226 Kcal in 1975 and dropped dramatically to 1,902 Kcal in 2004, nearly identical to the value during the immediate post-World War II period. However, since 1975 obesity has sharply increased despite this dramatic decline in energy intake. This may be, in part, the result of a “relative energy surplus” caused by a decline in energy expenditure due to modern industrialization that far exceeds the decreased energy intake. Bray (J Nutr 121:1146–1162, 1991) has proposed the “MONA LISA” (Most Obesities kNown Are Low In Sympathetic Activity) hypothesis, suggesting that obesity is associated with a relative or absolute reduction in the activity of the thermogenic component of the sympathetic nervous system. It is now well recognized that “middle age obesity” is strongly associated with both aging and depressed autonomic nervous system (ANS) activity, particularly the sympathetic thermogenic responses to a high-fat diet and an irregular food intake pattern. Our series of studies have suggested the decline in ANS activity that regulates fat metabolism and appetite control is potentially reversible by regular exercise training in middle-aged individuals and obese children with depressed ANS activity. In other words, habitual exercise plays a vital role in enhancing not only fat and glucose metabolism, but also in preventing obesity and enhancing appetite control. Recent studies have clearly indicated that exercising obese individuals have a much lower mortality rate and incidence of disease than lean individuals with little or no exercise. A possible explanation could be that exercise effects immune functions and myocytokines, preventing and improving lifestyle-related diseases. Finally, our recent studies on the effect of functional muscle electrical stimulation on glucose utilization during hyperinsulinemic-euglycemic clamp will be discussed together with the most recent topics on brain derived neurotrophic factors (BDNFs) that appear to influence energy metabolism, appetite, and aspects of neurocognitive function. These data strongly suggest that a lack of exercise or a sedentary lifestyle combined with an unhealthy diet may lead to accelerated ageing, diseases of the body and brain, and an overall decline in the quality of life.

Background Clock genes regulate circadian rhythm and are involved in various physiological processes, including digestion. We therefore investigated the association between the CLOCK 3111T/C single nucleotide polymorphism and the Period3 (PER3) variable-number tandem-repeat polymorphism (either 4 or 5 repeats 54 nt in length) with morning gastric motility. Methods Lifestyle questionnaires and anthropometric measurements were performed with 173 female volunteers (mean age, 19.4 years). Gastric motility, evaluated by electrogastrography (EGG), blood pressure, and heart rate levels were measured at 8:30 a.m. after an overnight fast. For gastric motility, the spectral powers (% normal power) and dominant frequency (DF, peak of the power spectrum) of the EGG were evaluated. The CLOCK and PER3 polymorphisms were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism analysis. Results Subjects with the CLOCK C allele (T/C or C/C genotypes: n = 59) showed a significantly lower DF (mean, 2.56 cpm) than those with the T/T genotype (n = 114, 2.81 cpm, P < 0.05). Subjects with the longer PER3 allele (PER34/5 or PER35/5 genotypes: n = 65) also showed a significantly lower DF (2.55 cpm) than those with the shorter PER34/4 genotype (n = 108, 2.83 cpm, P < 0.05). Furthermore, subjects with both the T/C or C/C and PER34/5 or PER35/5 genotypes showed a significantly lower DF (2.43 cpm, P < 0.05) than subjects with other combinations of the alleles (T/T and PER34/4 genotype, T/C or C/C and PER34/4 genotypes, and T/T and PER34/5 or PER35/5 genotypes). Conclusions These results suggest that minor polymorphisms of the circadian rhythm genes CLOCK and PER3 may be associated with poor morning gastric motility, and may have a combinatorial effect. The present findings may offer a new viewpoint on the role of circadian rhythm genes on the peripheral circadian systems, including the time-keeping function of the gut.

alpha(1A)-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation, and alpha(2A)-AR and alpha(2C)-AR subtypes are essential for presynaptic feedback regulation of catecholamine release from the central and peripheral sympathetic nerve. Genetic variations in each human alpha-AR subtype gene have been identified and have been implicated in hypertension and cardiovascular disease. It is not yet clear whether these genetic variations actually have an effect on sympatho-vagal modulation. The aim of the present study was to evaluate the relation between the five representative genetic polymorphisms of alpha-AR subtypes (Arg347Cys of alpha(1A)-AR; C-1291G, Asn251Lys, and DraI RFLP of alpha(2A)-AR; and Del322-325 of alpha(2C)-AR) and autonomic nervous system (ANS) function in young and healthy Japanese males. One hundred forty-nine subjects were genotyped for each alpha-AR polymorphism, and underwent evaluation of ANS function by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. In a supine position, the alpha(1A)-AR 347Cys allele was significantly associated with lower HRV sympathetic index (normalized low frequency power [LF(%)] and LF:HF ratio) and higher HRV parasympathetic index [HF(%)]. Meanwhile, subjects with the alpha(2C)-AR Del322-325 allele had markedly higher LF(%) and LF:HF ratio and lower HF(%) than noncarriers. Thus, the alpha(1A)-AR and alpha(2C)-AR genetic variations influence sympatho-vagal balance even in young and healthy normotensive states, which could be postulated to constitute an intermediate phenotype for future pathological episodes of various ANS dysfunction-related diseases.

Tremendous numbers of heart rate variability studies have aimed to elucidate age-associated alterations of autonomic function in the past decades. However, the studies, far from clarifying ageing mechanisms, fell into confusion by a lack of common scales. The purpose of this study is to show a possibility to establish a comparative scale of autonomic function through a method, tone-entropy (T-E) analysis on heart period variation, whose validity has been already examined on typical physiological cases (Oida et al. in J Appl Physiol 82:1794-1801, 1997; Oida et al. in J Gerontol 54A:M219-M224, 1999a; Oida et al. in Acta Physiol Scand 165:129-134, 1999b; Oida et al. in Acta Physiol Scand 165:421-422, 1999c; Amano et al. in Eur J Appl Physiol 94:602-610, 2005). In this study, 276 subjects from teens to seventies were examined at rest by T-E analysis together with conventional time and frequency domain analyses. The tone (negativity represents vagal predominance) became significantly high [-0.174 +/- 0.026 (teens) to -0.024 +/- 0.004 (seventies), P0.05 for one-way ANOVA], and the entropy (total autonomic activity), significantly low [4.40 +/- 0.12 (teens) to 2.90 +/- 0.09 bit (seventies), P0.05] with advancing age. The result, plotted in 2-D T-E space, showed that the ageing traced a curvi-linear relation from right-bottom to left-top, and was consistent with previously studied typical physiological cases. The conventional analyses showed almost the same autonomic reduction as T-E did, but failed in detecting delicate alteration of autonomic balance. The results, showing that autonomic activity reduced in both pathways impairing vagal predominance significantly with ageing, suggested a possibility to assess autonomic function in 2-D T-E space in a comparative way.

In achondroplasia, venous narrowing associated with a small skull base leads to elevated venous pressure which impairs cerebrospinal fluid (CSF) absorption, resulting in communicating hydrocephalus. We correlated venous narrowing at the jugular foramina and collateral circulation on magnetic resonance venography (MRV) with ventricular size in 17 patients. Patients were divided into three groups: Group I: progressive hydrocephalus; Group II: nonprogressive hydrocephalus; and Group III: normal ventricular size. The grades of venous narrowing and types of collaterals were well correlated with hydrocephalus groups.

The majority of women of reproductive age experience a regular recurrence of various symptoms in the premenstrual phase. The etiopathogenesis of premenstrual symptomatology, however, remains inconclusive. The present study was proposed to evaluate whether the activity of the autonomic nervous system (ANS), which largely contributes to the relative stability of a human's internal environment, is altered during the menstrual cycle of women with premenstrual symptomatology. Thirty eumenorrheic young women participated in this study. All subjects were investigated during the follicular and late luteal phases. The ANS activity was assessed by means of heart rate variability power spectral analysis during supine rest. No intramenstrual cycle differences in the ANS activity were found in women experiencing no or small increases in premenstrual symptoms. In contrast, the sympathetic nervous system (SNS) activity significantly increased and the parasympathetic nervous system (PNS) activity apparently decreased in the late luteal phase in subjects whose premenstrual symptomatology was not unbearable, but substantially increased (> 20%) compared to the symptom-free follicular phase. The women with greater degrees of premenstrual distress possessed higher SNS activity and lower PNS activity in the late luteal phase than the women with less symptomatology. The ANS activity in the follicular phase did not differ among the subjects regardless of their premenstrual symptoms. Although causes and consequences continue to elude, the present study provides additional intriguing evidence that the altered functioning of ANS in the late luteal phase could be associated with diverse psychosomatic or behavioral symptoms appearing premenstrually.

We investigated the effect of workload and the use of pedal straps on the spatial distribution of neuromuscular activation within the rectus femoris (RF) muscle during pedaling movements.Eleven healthy men performed submaximal pedaling exercises on an electrically braked ergometer at different workloads and with or without pedal straps. During these tasks, surface electromyograms (SEMGs) were recorded from the RF using 36 electrode pairs, and central locus activation (CLA) was calculated along the longitudinal line of the muscle.CLA moved markedly, indicating changes in spatial distribution of SEMG within the muscle, during a crank cycle under all conditions (P 0.05). There were significant differences in CLA among different workloads and between those with and without pedal straps (P 0.05).These results suggest that neuromuscular activation within the RF is regulated regionally by changes in workload and the use of pedal straps during pedaling.

Inflammatory pseudotumor is a generic term used to designate a heterogeneous group of inflammatory mass-forming lesions histologically characterized by myofibroblastic proliferation with chronic inflammatory infiltrate. Inflammatory pseudotumor is multifactorial in etiology and generally benign, but it is often mistaken for malignancy given its aggressive appearance. It can occur throughout the body and is seen in all age groups. Inflammatory pseudotumor has been described in the literature by many organ-specific names, resulting in confusion. Recently within this generic category of inflammatory pseudotumor, inflammatory myofibroblastic tumor has emerged as a distinct entity and is now recognized as a fibroblastic/myofibroblastic neoplasm with intermediate biological potential and occurring mostly in children. We present interesting pediatric cases of inflammatory myofibroblastic tumors given this entity’s tendency to occur in children. Familiarity and knowledge of the imaging features of inflammatory pseudotumor can help in making an accurate diagnosis, thereby avoiding unnecessary radical surgery.

Magnetic resonance imaging with phased-array coils was performed in patients with prostate carcinoma before and after hormonal therapy, radiation therapy or radical prostatectomy to evaluate therapeutic effect and recurrence. After hormonal therapy, the prostate gland, seminal vesicle and primary site of tumor usually decrease in size with variable T2 hypointensity. Recurrent or residual tumors after hormonal therapy usually represent T2 hyperintense lesions compared to the hypointensity of the surrounding tissues. Changes of metastatic sites after therapy were also demonstrated.

Objective: (1) To detect diffuse axonal injury (DAI) lesions by diffusion-weighted imaging (DWI), as compared with fluid-attenuated inversion recovery (FLAIR) imaging and (2) to evaluate hemorrhagic DAI lesions by b0 images obtained from DWI, as compared with gradient-echo (GRE) imaging. Methods: We reviewed MR images of 36 patients with a diagnosis of DAI. MR imaging was performed 20 h to 14 days (mean, 3.7 days) after traumatic brain injury. We evaluated: (1) conspicuity of lesions on DWI and FLAIR and (2) conspicuity of hemorrhage in DAI lesions on b0 images and GRE imaging. Results: DWI clearly depicted high-signal DAI lesions. The sensitivity of DWI to lesional conspicuity in DAI lesions was almost equal to that of FLAIR. The sensitivity of b0 images to identification of hemorrhagic DAI lesions was inferior to that of GRE. Conclusion: DWI is as useful as FLAIR in detecting DAI lesions. GRE imaging is still the superior tool for the evaluation of hemorrhagic DAI.

This paper summarizes my Basmajian keynote presentation at the 2004 International Society of Electrophysiology and Kinesiology Conference. I dedicate this paper to Dr. Herbert A. deVries, the mentor of my research career. The following topics will be covered from the standpoint of Electrophysiology and Kinesiology for health and disease: (1) electromechanical manifestations of neuromuscular fatigue and muscle soreness, (2) cardiac depolarization-repolarization characteristics of normal and patients, (3) etiology of obesity and diabetes and autonomic nervous system, and (4) functional electrical stimulation for health and disease, respectively.

Background The T allele of the C825T polymorphism of the G protein β3 subunit gene ( GNB3 ) is reported to be associated with increased intracellular signal transduction and the prevalence of essential hypertension. Because the two major receptors in the autonomic nervous system (ANS), the adrenergic and muscarinic acetylcholine receptors, are G protein-coupled receptors, it was expected that the GNB3 C825T polymorphism was associated with ANS function. In the present study, we have investigated the association of this polymorphism with ANS in young, healthy Japanese male individuals. Methods A total of 94 young, healthy subjects underwent the genotyping for the GNB3 C825T polymorphism and electrocardiogram R-R interval power spectral analysis in supine rest and standing positions. Results There were no significant differences among genotypes in any of the characteristics investigated (body mass index, blood pressure, plasma glucose, insulin, lipids, and family history of hypertension, diabetes, or obesity). However, in power spectral analysis of heart rate variability, the very-low-frequency component when standing was higher in TT carriers than in CC carriers, and TT and CT carriers had a significantly higher sympathetic nervous system (SNS) index and lower parasympathetic nervous system (PNS) index when standing than CC carriers. In addition, we found that TT carriers showed no chronological variations in either SNS or PNS index after postural change. Conclusions These observations suggested that GNB3 C825T polymorphism is associated with ANS in youth. These findings raise the possibility that individuals who are T allele carriers are at increased risk for developing hypertension in relation to ANS function.

The purpose of this study is to examine whether or not the application of independent component analysis (ICA) is useful for separation of motor unit action potential trains (MUAPTs) from the multi-channel surface EMG (sEMG) signals. In this study, the eight-channel sEMG signals were recorded from tibialis anterior muscles during isometric dorsi-flexions at 5%, 10%, 15% and 20% maximal voluntary contraction. Recording MUAP waveforms with little time delay mounted between the channels were obtained by vertical sEMG channel arrangements to muscle fibers. The independent components estimated by FastICA were compared with the sEMG signals and the principal components calculated by principal component analysis (PCA). From our results, it was shown that FastICA could separate groups of similar MUAP waveforms of the sEMG signals separated into each independent component while PCA could not sufficiently separate the groups into the principal components. A greater reduction of interferences between different MUAP waveforms was demonstrated by the use of FastICA. Therefore, it is suggested that FastICA could provide much better discrimination of the properties of MUAPTs for sEMG signal decomposition, i.e. waveforms, discharge intervals, etc., than not only PCA but also the original sEMG signals.

This pictorial essay illustrates the usefulness of diffusion-weighted imaging (DWI) on various vasculitis or vasculopathies, including systemic lupus erythematosus (SLE), Behcet's disease, Churg-Strauss disease, primary angitis of the central nervous system (PACNS), giant cell arteritis, infectious vasculitis, sickle cell disease, drug-induced vasculopathy and hypertensive vasculopathy. DWI proves to detect small and active ischemic changes not visible on conventional MRI, and it clearly discriminates cytotoxic from vasogenic edema in patients with cerebral vasculitis or vasculopathy. DWI seems useful in assessing the treatment and patient outcome.

This paper demonstrates usual and unusual findings on MR imaging (MRI) including fluid-attenuated inversion recovery (FLAIR), diffusion- and perfusion-weighted image and MR angiography (MRA) in 30 patients with sickle cell cerebrovascular disease. This paper also illustrates the underlying pathophysiology of sickle cell cerebrovascular disease by using the cases with usual and unusual MR findings, including long-time follow-up cases during transfusion therapy. MRI and MRA are useful in defining the basis for stroke and assessing the effects of chronic transfusion therapy.

Our objective was to investigate the effect of a long-term moderate exercise program on cardiac autonomic nervous system (ANS) activity in healthy children. Three hundred and five children aged 6–11 years participated in a 12-month school-based exercise training program (130–140 bpm, 20 min/day, 5 days/week). Cardiac ANS activities were measured using heart rate variability (HRV) power spectral analysis in resting conditions. Following the first measurement, 100 children from the lowest total power (TP) HRV were chosen as experimental samples and the same number of age-, height-, and weight-matched controls (CG) was randomly selected from the remaining children. In the low group (LG), all the frequency components of the HRV were significantly increased after the training period, whereas only low-frequency power was augmented in the control group (CG). Our data suggest that the 12-month moderate exercise training has a positive effect on cardiac ANS activity in the children who initially had low HRV.

The present study examined, whether or not mechanomyogram (MMG) amplitude and frequency component could reflect the contractile properties of the triceps surae muscles, composed of relatively slow soleus (SOL) and fast medial gastrocnemius (MG), during experimentally induced hypothermia condition. In eight male subjects, lying in prone position, supramaximal single twitch and repetitive electrical stimulations at 10 Hz were applied at the intramuscular temperatures of control (34 degrees C), 15, 20, and 25 degrees C, respectively. The hypothermia induced substantial reduction in muscle contractile properties, e.g. prolonged twitch contraction and half relaxation times, resulted in a highly significant reduction in the fluctuation of force signal during the repetitive stimulations. These changes were almost mirrored by the similar and significant reductions in the MMG amplitude in both SOL and MG. Power spectrum analysis revealed that peak frequency components of MMG and fluctuation of force were almost matched with the applied stimulation frequencies, independent of the temperature condition. These results strongly suggest that MMG analysis could be employed to study muscle contractile properties varying across different physiological conditions.

Posterior reversible leukoencephalopathy syndrome is characterized by reversible white matter lesions. However, ischemic injury with irreversible damage may occur. This pictorial essay illustrates MR features associated with posterior reversible leukoencephalopathy syndrome. We will emphasize the role of diffusion-weighted imaging for the discrimination of irreversible ischemic injury from reversible vasogenic edema.

Epidermal nevus syndrome (ENS) is a sporadic neurocutaneous disorder characterized by the combination of epidermal nevi with significant central nervous system, eye, and skeletal abnormalities. Hemimegalencephaly and related brain abnormalities are the dominant neuropathologic abnormalities in ENS. Magnetic resonance imaging features of the case reported here revealed enlargement of both cerebral hemispheres and malformed basal ganglia, with incomplete separation of the caudate nucleus and putamen. In addition, the right cerebellar hemisphere was enlarged, with disorganized folia. None of these findings have been reported previously in this disorder.

There is considerable evidence to suggest that electrical stimulation (ES) activates glucose uptake in rodent skeletal muscle. It is, however, unknown whether ES can lead to similar metabolic enhancement in humans. We employed low-frequency ES through surface electrodes placed over motor points of quadriceps femoris muscles. In male subjects lying in the supine position, the highest oxygen uptake was obtained by a stimulation pattern with 0.2-ms biphasic square pulses at 20 Hz and a 1-s on-off duty cycle. Oxygen uptake was increased by approximately twofold throughout the 20-min stimulation period and returned to baseline immediately after stimulation. Concurrent elevation of the respiratory exchange ratio and blood lactate concentration indicated anaerobic glycogen breakdown and utilization during ES. Whole body glucose uptake determined by the glucose disposal rate during euglycemic clamp was acutely increased by 2.5 mg · kg−1 · min−1in response to ES and, moreover, remained elevated by 3–4 mg · kg−1 · min−1for at least 90 min after cessation of stimulation. Thus the stimulatory effect of ES on whole body glucose uptake persisted not only during, but also after, stimulation. Low-frequency ES may become a useful therapeutic approach to activate energy and glucose metabolism in humans.

Reductions in tonic vagal controls of the heart and depressed baroreflex sensitivity (BRS) have been associated with a postural fall in blood pressure (BP) and the incidence of cardiac events among older people. We examined the hypothesis that BP regulation during orthostatic challenge as well as heart rate variability (HRV) at rest can be better maintained in long-term exercise-trained, healthy, older men (aged 60-70 years). Subjects were classified into two groups; long-term exercise-trained (LTET, n=14) and sedentary (SED, n=10) according to their history of physical activity. Prior to the dynamic BRS assessment, supine resting autonomic cardiac modulation was assessed by means of time domain HRV [standard deviation of ECG R-R interval (RRISD) and the coefficient of variation (CV)]. The BRS was assessed during 60 degrees head-up tilting by simultaneously measuring beat-by-beat systolic blood pressure (SBP) and ECG R-R interval changes. The BRS gain was determined by the regression slope coefficient based on the extent of the SBP fall and the corresponding ECG R-R shortening during the orthostatic challenge. The results indicated that the LTET group manifested greater ECG R-R interval fluctuations with significantly higher resting RRISD and CV, compared with the SED group [59.5 (10.4) versus 27.7 (7.8) ms, p0.05; 5.5 (0.8) versus 2.8 (0.7)%, p0.05], respectively. Using dynamic BRS testing during the acute orthostatic challenge, the LTET group showed a significantly higher BRS gain than the SED [6.4 (0.8) versus 3.8 (0.6) ms x mmHg(-1), p0.017] group. These results indicate that CV and BRS are well maintained in healthy, LTET older individuals when compared with their sedentary peers. Our data suggest that this augmented autonomic cardiac modulation reflects better parasympathetic responsiveness in LTET individuals. Data provide further support for long-term exercise training as another possible cardioprotective factor that might decrease susceptibility to ventricular fibrillation as well as assist arterial BP at the onset of an orthostatic challenge in older men.

Several polymorphisms of genes involved in autonomic nervous system (ANS) function have been reported to affect metabolic regulation. We have investigated the association of an alpha(2B)-adrenergic receptor (alpha(2B)AR) three-amino acid deletion polymorphism with ANS activity in young healthy subjects by means of electrocardiogram R-R interval power spectral analysis. Three hundred eighty-one young healthy Japanese males (mean +/- SE, 20.6 +/- 0.1 yr) were studied. One hundred sixty-eight (44.1%) were homozygotes of Long allele (Long/Long), 162 (42.5%) were heterozygotes (Long/Short), and 51 (13.4%) were homozygotes of Short allele (Short/Short). The allele frequency of Short allele was 0.35. No significant differences were observed in any of the characteristics investigated: body mass index, plasma glucose, plasma insulin, or family history of diabetes and obesity. In R-R spectral analysis of heart rate variability, carriers of Short/Short had significantly greater low frequency and very low frequency than Long/Long, as well as a higher sympathetic nervous system index. These findings suggest that the alpha(2B)AR deletion polymorphism might result in metabolic disorder by altering ANS function.

NAGAI, NARUMI, TAMAKI MATSUMOTO, HIROKO KITA, AND TOSHIO MORITANI. Autonomic nervous system activity and the state and development of obesity in Japanese school children. Obes Res. 2003;11:25–32. Objective: The autonomic nervous system (ANS) plays an important role in regulating energy expenditure and body fat content; however, the extent to which the ANS contributes to pediatric obesity remains inconclusive. The aim of this study was to evaluate whether sympathetic and/or the parasympathetic nerve activities were altered in an obese pediatric population. We further examined a physiological association between the duration of obesity and the sympatho-vagal activities to scrutinize the nature of ANS alteration as a possible etiologic factor of childhood obesity. Research Methods and Procedures: Forty-two obese and 42 non-obese healthy sedentary school children were carefully selected from 1080 participants initially recruited to this study. The two groups were matched in age, gender, and height. The clinical records of physical characteristics and development of the obese children were retrospectively reviewed to investigate the onset and progression of obesity. The ANS activities were assessed during a resting condition by means of heart rate variability power spectral analysis, which enables us to identify separate frequency components, i.e., total power (TP), low-frequency (LF) power, and high-frequency (HF) power. The spectral powers were then logarithmically transformed for statistical testing. Results: The obese children demonstrated a significantly lower TP (6.77 0.12 vs. 7.11 0.04 ln ms 2 , p 0.05), LF power (6.16 0.12 vs. 6.42 0.05 ln ms 2 , p 0.05), and HF power (5.84 0.15 vs. 6.34 0.07 ln ms 2 , p 0.01) compared with the non-obese children. A partial correlation analysis revealed that the LF and HF powers among 42 obese children were negatively associated with the duration of obesity independent of age (LF: partial r 0.55, p 0.001; HF: partial r 0.40, p 0.01). The obese children were further subdivided into two groups based on the length of their obesity. All three spectral powers were significantly reduced in the obese group with obesity of 3 years (n 18) compared to the group with obesity of 3 years. Discussion: Our data indicate that obese children possess reduced sympathetic as well as parasympathetic nerve activities. Such autonomic depression, which is associated with the duration of obesity, could be a physiological factor promoting the state and development of obesity. These findings further imply that preventing and treating obesity beginning in the childhood years could be an urgent and crucial pediatric public health issue.

Leptin is an adipocyte-derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho-vagal activities in age- and height-matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 +/- 5.89 vs. 11.2 +/- 1.10 ng. ml(-1), P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 +/- 1.39 vs. 37.8 +/- 8.1 ms(2). ml. ng(-1), P < 0.01; SNS index per leptin: 0.04 +/- 0.008 vs. 0.33 +/- 0.01 ml c. ng(-1), P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r(2) = 0.57, P < 0.01; SNS index per leptin r(2) = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced.

We report a 53-year-old woman with a rare ruptured lumbar intraspinal epidermoid cyst causing chemical meningitis evaluated with MRI (including diffusion-weighted imaging), with histopathologic correlation.