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We report a 7-month-old boy with Menkes disease who presented West syndrome. Magnetic resonance imaging (MRI) revealed atrophy of the frontal and parietal lobes, subdural hematoma on the right side, and left temporal lobe lesion (low intensity in T1-weighted imaging (T1-WI), high intensity in T2-weighted imaging (T2-WI) and low intensity in diffusion-weighted imaging (DW-I)) at 7 months of age. The apparent diffusion coefficient (ADC) was 1.68×10(-3)mm(2)/s in the left temporal lobe lesion and 1.15×10(-3)mm(2)/s on the contralateral side. (1)H-magnetic resonance spectroscopy ((1)H-MRS) revealed a decrease in N-acetylaspartate/(creatine+phosphocreatine) (NAA/Cr) (0.71) and a lactate peak in the left temporal lobe lesion. At 8 months of age, the left temporal lobe lesion disappeared, the ADC of this lesion was within the normal range (1.10×10(-3)mm(2)/s), and (1)H-MRS revealed a slight increase in NAA/Cr (1.12) and disappearance of the lactate peak. We suspected that the transient temporal lobe lesion in Menkes disease was mainly vasogenic edema. Electroencephalography (EEG) revealed left hemisphere dominant hypsarrhythmia and slowing in the left hemisphere. Ictal EEG revealed generalized slow wave burst with P3, T3 spike antecedence and the antecedent spike was consistent with left temporal lobe lesion. After disappearance of the left temporal lobe lesion, tonic spasms disappeared and EEG findings improved. In this case, the clinical course and ictal EEG suggested that epileptic activity from the left temporal lobe lesion may have given rise to tonic spasms., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Prompted by our neuroimaging findings in 60 normal people, we examined whether focal damage to the hand section of precentral motor regions impairs hand kinesthesia in a patient, and investigated brain regions related to recovery of kinesthetic function. The damage impaired contralateral kinesthesia. The peri-lesional cerebral motor region, together with the ipsilateral intermediate cerebellum, participated in the recovered kinesthetic processing. The study confirmed the importance of precentral motor regions in human kinesthesia, and indicated a contribution of the peri-lesional cerebral region in recovered kinesthesia after precentral damage, which conceptually fits with cases of recovery of motor function.

Procedural motor learning includes a period when no substantial gain in performance improvement is obtained even with repeated, daily practice. Prompted by the potential benefit of high-frequency transcutaneous electrical stimulation, we examined if the stimulation to the hand reduces redundant motor activity that likely exists in an acquired hand motor skill, so as to further upgrade stable motor performance. Healthy participants were trained until their motor performance of continuously rotating two balls in the palm of their right hand became stable. In the series of experiments, they repeated a trial performing this cyclic rotation as many times as possible in 15 s. In trials where we applied the stimulation to the relaxed thumb before they initiated the task, most reported that their movements became smoother and they could perform the movements at a higher cycle compared to the control trials. This was not possible when the dorsal side of the wrist was stimulated. The performance improvement was associated with reduction of amplitude of finger displacement, which was consistently observed irrespective of the task demands. Importantly, this kinematic change occurred without being noticed by the participants, and their intentional changes of motor strategies (reducing amplitude of finger displacement) never improved the performance. Moreover, the performance never spontaneously improved during one-week training without stimulation, whereas the improvement in association with stimulation was consistently observed across days during training on another week combined with the stimulation. The improved effect obtained in stimulation trials on one day partially carried over to the next day, thereby promoting daily improvement of plateaued performance, which could not be unlocked by the first-week intensive training. This study demonstrated the possibility of effectively improving a plateaued motor skill, and pre-movement somatic stimulation driving this behavioral change.

Sasa veitchii or "kumazasa" has been used for the preservation of food, or preventing bacterial activity. However, the antiviral activity of kumazasa is poorly understood. In the present study, the antiviral activity of kumazasa extract (KE) was assessed by the plaque reduction assay for the pseudorabies virus (PRV). KE reduced 99% of the plaque formation of PRV at concentrations of 1.2%, showing that KE inhibited PRV adsorption to cells and IE180 expression. The polysaccharide fraction of KE showed a concentration dependent inhibition of PRV plaque formation. We conclude that KE possesses potent anti PRV activity, and the candidate responsible for the antiviral property was the polysaccharide fraction.

Background: Little is known regarding annual changes of respiratory functions among patients with asthma after asthma symptoms enter remission., Objective: Annual changes of respiratory function and influence of patient characteristics and treatment variables on these changes were assessed in patients with adult asthma., Methods: Respiratory function (pre- and postbronchodilator forced expiratory volume in one second [FEV₁] and reversibility by short-acting β₂-agonist) and their changes were retrospectively investigated and relationships between these changes, after symptomatic remission, and patient characteristics and treatments were analyzed in adult outpatients with asthma who had undergone spirometry (including a reversibility test) ≥5 times in >5 years., Results: In patients ≥40 years old, or with disease duration ≥10 years or receiving treatment for severe asthma (steps 4-5, high-dose inhaled glucocorticosteroids, or addition of other medications), both pre- and postbronchodilator FEV₁ values were significantly lower (p < .05). Mean annual change of prebronchodilator FEV₁ (Δpre-FEV₁), annual change of postbronchodilator FEV₁ (Δpost-FEV₁), and annual change of reversibility (Δ reversibility) were -13.8 ± 59.7 ml/year, -25.9 ± 51.0 ml/year, and -0.56% ± 1.89%/year, respectively. Multivariate analysis after stepwise selection for variables in patient characteristics or treatments showed that disease duration ≥10 years contributed to annual improvement of respiratory functions (Δpre-FEV₁: odds ratio [OR] 1.57, 95% confidence interval [CI] 1.01-2.46; Δpost-FEV₁: OR 2.13, 95% CI 1.25-3.66), treatment with long-acting β₂-agonists (LABAs) contributed to annual improvement of respiratory function (Δpre-FEV₁: OR 2.05, 95% CI 1.23-3.16; Δpost-FEV₁: OR 1.78, 95% CI 1.11-2.87), and poor compliance contributed to annual worsening of respiratory functions (Δpre-FEV₁: OR 0.43, 95% CI 0.24-0.76; Δpost-FEV₁: OR 0.39, 95% CI 0.22-0.70). In addition, duration of disease ≥10 years and severe treatment (steps 4-5) from the beginning contributed to decreasing Δreversibility (OR 0.55, 95% CI 0.34-0.87 and OR 0.50, 95% CI 0.29-0.83, respectively)., Conclusions: Long-term treatments for asthma are expected to normalize respiratory dysfunction, which cannot be repaired in the short term. Treatment with LABAs and patient compliance may be the most important factors associated with annual improvement of respiratory functions.

Humans can judge whether an object is graspable or not by merely glancing at it. This judgment is possible because of the brain's pragmatic function that links action with perception, i.e., the spatial property of the object is immediately associated with the motor capability of hands. In this study, we investigated the neural correlates of this cognitive-motor process by conducting an event-related functional magnetic resonance imaging experiment. Healthy right-handed participants were made to judge whether they could grasp visually presented objects with their right hand without generating any actual movements [motor evaluation (ME) task]. Objects of various sizes were presented to the participants in front of their hands; they judged the graspability of the object as soon as possible. For the control, the participants simply compared the size of the presented object and the static size of their fists [size comparison (SC) task]. Thus, only in the former task, the participants had to evaluate their motor capability by briefly simulating their range of hand motion. Rostral parts of the dorsal premotor cortices (prePMd) were activated bilaterally only during the ME task, and the activities were positively correlated with the duration of the evaluation. The prePMd participates in the judgment of graspability for external objects by evaluating hand motor capability. This function may assure a basic premise for the selection of an appropriate motor option when our hands interact with a variety of external objects., (Copyright 2009 Elsevier B.V. All rights reserved.)

Introduction: Semi-solid nutrition with high viscosity has the advantage of reducing gastroesophageal reflux and diarrhea and shortens the duration of administration compared with liquid nutrition. This is the first report describing the administration of semi-solid nutrition with high viscosity via a nasogastric tube, which achieved a remarkable improvement in the patient's nutritional state., Case Presentation: A 67-year-old man (mongoloid race, Japanese) with tuberculosis, a pressure ulcer and malnutrition was admitted to our hospital. He also had right hemiplegia, dysphagia and aphasia as sequelae of a cerebral hemorrhage. Before his admission, he had been treated at another hospital with 600 kcal/day of liquid nutrition via a nasogastric tube, which was insufficient and induced severe malnutrition. After he was admitted to our hospital, we increased the quantity of his liquid nutrition without success because of complications, specifically diarrhea and gastroesophageal reflux. As it was difficult to confirm whether or not he would accept gastrostomy feeding, we administered semi-solid nutrition with high viscosity (20,000 mPa x s) via a large-bore nasogastric tube (18 French). Soon after he was started on semi-solid nutrition, his pressure ulcer and malnutrition improved without diarrhea or complications accompanying the large-bore nasogastric tube., Conclusion: When patients have problems with liquid nutrition, such as diarrhea or gastroesophageal reflux, semi-solid nutrition via a nasogastric tube is a useful method of achieving improvements in nutritional state in a short period of time.

We examined whether visual information on the dynamic aspect of the actions performed by an individual can influence an observer's action. Sixteen participants cyclically generated an isometric precision grip force with their right thumb and index finger in synchronization with the contraction (in-phase) or relaxation phase of an experimenter's hand, foot, and mouth movements presented in videos. Visual information of the hand action significantly enhanced the observer's grip force, and this enhancement exclusively occurred during the in-phase condition. These results suggest that the effector matching between the observed and the performed actions and the temporal coincidence in the movement phase are the key factors when visual information on the dynamics of the action of an individual influences the observer's action.

We previously reported that Kluyveromyces marxianus YIT 8292 exhibited more potent hypocholesterolemic activity than other yeasts containing Saccharomyces cerevisiae . To clarify the reason for the higher hypocholesterolemic activity, we examined the side-chain structure of cell surface polysaccharide, mannan, of K. marxianus YIT 8292. The result shows that K. marxianus YIT 8292 had shorter alpha-(1,2)-linked oligomannosyl side chains and lower phosphate content in mannan than S. cerevisiae. The association between its structural features and hypocholesterolemic activity was investigated by comparing the hypocholesterolemic activities of S. cerevisiae mannan mutants in rats fed a high-cholesterol diet. S. cerevisiae mnn5 mutant with deficiencies in the phosphorylation and elongation of mannan side chains showed higher hypocholesterolemic activity than the wild-type strain. These results show that the side-chain length and phosphate contents of mannan affect hypocholesterolemic activity.

Near-infrared spectroscopy (NIRS) has recently been used to measure human motor-cortical activation, enabling the classification of the content of a sensory-motor event such as whether the left or right hand was used. Here, we advance this NIRS application by demonstrating quantitative estimates of multiple sensory-motor events from single-trial NIRS signals. It is known that different degrees of sensory-motor activation are required to generate various hand/finger force levels. Thus, using a sparse linear regression method, we examined whether the temporal changes in different force levels could be reconstructed from NIRS signals. We measured the relative changes in oxyhemoglobin concentrations in the bilateral sensory-motor cortices while participants performed an isometric finger-pinch force production with their thumb and index finger by repeatedly exerting one of three target forces (25, 50, or 75% of the maximum voluntary contraction) for 12 s. To reconstruct the generated forces, we determined the regression parameters from the training datasets and applied these parameters to new test datasets to validate the parameters in the single-trial reconstruction. The temporal changes in the three different levels of generated forces, as well as the baseline resting state, could be reconstructed, even for the test datasets. The best reconstruction was achieved when using only the selected NIRS channels dominantly located in the contralateral sensory-motor cortex, and with a four second hemodynamic delay. These data demonstrate the potential for reconstructing different levels of external loads (forces) from those of the internal loads (activation) in the human brain using NIRS.

We used functional magnetic resonance imaging (fMRI) to identify brain areas involved in auditory rhythm perception. Participants listened to three rhythm sequences that varied in temporal predictability. The most predictable sequence was an isochronous rhythm sequence of a single interval (ISO). The other two sequences had nine intervals with unequal durations. One of these had interval durations of integer ratios relative to the shortest interval (METRIC). The other had interval durations of non-integer ratios relative to the shortest interval (NON-METRIC), and was thus perceptually more complex than the other two. In addition, we presented unpredictable sequences with randomly distributed intervals (RAN). We tested two hypotheses. Firstly, that areas involved in motor timing control would also process the temporal predictability of sensory cues. Therefore, there was no active task included in the experiment that could influence the participant perception or induce motor preparation. We found that dorsal premotor cortex (PMD), SMA, preSMA, and lateral cerebellum were more active when participants listen to rhythm sequences compared to random sequences. The activity pattern in supplementary motor area (SMA) and preSMA suggested a modulation dependent on sequence predictability, strongly suggesting a role in temporal sensory prediction. Secondly, we hypothesized that the more complex the rhythm sequence, the more it would engage short-term memory processes of the prefrontal cortex. We found that the superior prefrontal cortex was more active when listening to METRIC and NON-METRIC compared to ISO. We argue that the complexity of rhythm sequences is an important factor in modulating activity in many of the rhythm areas. However, the difference in complexity of our stimuli should be regarded as continuous.

Across cultures, social relationships are often thought of, described, and acted out in terms of physical space (e.g. "close friends" "high lord"). Does this cognitive mapping of social concepts arise from shared brain resources for processing social and physical relationships? Using fMRI, we found that the tasks of evaluating social compatibility and of evaluating physical distances engage a common brain substrate in the parietal cortex. The present study shows the possibility of an analytic brain mechanism to process and represent complex networks of social relationships. Given parietal cortex's known role in constructing egocentric maps of physical space, our present findings may help to explain the linguistic, psychological and behavioural links between social and physical space.

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (tau), quantitative trait locus (QTL) analysis was performed using F(2) mice obtained from an F(1) cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For tau, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

Combination of visual and kinesthetic information is essential to perceive bodily movements. We conducted behavioral and functional magnetic resonance imaging experiments to investigate the neuronal correlates of visuokinesthetic combination in perception of hand movement. Participants experienced illusory flexion movement of their hand elicited by tendon vibration while they viewed video-recorded flexion (congruent: CONG) or extension (incongruent: INCONG) motions of their hand. The amount of illusory experience was graded by the visual velocities only when visual information regarding hand motion was concordant with kinesthetic information (CONG). The left posterolateral cerebellum was specifically recruited under the CONG, and this left cerebellar activation was consistent for both left and right hands. The left cerebellar activity reflected the participants' intensity of illusory hand movement under the CONG, and we further showed that coupling of activity between the left cerebellum and the "right" parietal cortex emerges during this visuokinesthetic combination/perception. The "left" cerebellum, working with the anatomically connected high-order bodily region of the "right" parietal cortex, participates in online combination of exteroceptive (vision) and interoceptive (kinesthesia) information to perceive hand movement. The cerebro-cerebellar interaction may underlie updating of one's "body image," when perceiving bodily movement from visual and kinesthetic information.

The introduction of tandem mass spectrometry (MS/MS) has made it possible to screen for very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. To confirm the diagnosis in cases with an abnormal profile of blood acylcarnitines, we developed a new enzymatic assay method for determining dehydrogenase activity toward palmitoyl-CoA (C16:0) in lymphocytes. Using this method, the production of 2-hexadecenoyl-CoA (C16:1) by crude cell lysates can be directly quantified using high performance liquid chromatography (HPLC). We applied the assay to 7 myopathic patients, 7 hypoglycemic patients, and 2 presymptomatic newborns with elevated levels of tetradecenoylcarnitine (C14:1 AC) in blood, and found impaired VLCAD activity in all of the 7 myopathic patients and both of the 2 newborns. All of the 7 hypoglycemic patients had normal level of the enzyme activity. Results of the ACADVL gene analysis were in consistent with the enzymatic diagnosis. These results suggest that MS/MS-based screening for VLCAD deficiency using blood C14:1 AC as the indicator may show a considerably high false-positive rate in selective screening of symptomatic patients. Our practical enzymatic assay can be a useful test for the accurate diagnosis of VLCAD deficiency cases screened by MS/MS.

Lactate-utilizing butyrate-producers were isolated from human feces and identified based on the sequences of 16S rRNA gene. Anaerostipes caccae strain L2, one of the seven human fecal isolates, was administered to rats with galacto-oligosaccharides (GOS) as bifidogenic carbohydrates for stimulating lactate formation in the hindgut. Ingestion of GOS alone increased concentrations of cecal lactate and butyrate compared with control rats (P<0.05). Additional administration of strain L2 on GOS tended to enhance the promoting effect of GOS on cecal butyrate formation (P=0.06) and lowered the mean value of cecal lactate concentration (P=0.32). Consequently, cecal and fecal butyrate concentrations in rats administered with both strain L2 and GOS were significantly higher than those in the control rats (P<0.01 and P<0.05, respectively). Significant changes were observed in the other fermentation acids, such as succinate, acetate, and propionate, depending on the ingestion of strain L2. Administered strain L2 was retrieved from the cecal content of a rat based on randomly amplified polymorphic DNA analysis. The results suggest that synbiotic ingestion of lactate-utilizing butyrate-producers and GOS alters the microbial fermentation and promotes the formation of beneficial fermentation acids, including butyrate, in the gut.

We report 2 patients of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and consider the pathophysiology of stroke-like lesions, using magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) on MRI, perfusion imaging on MRI, and 1H magnetic resonance spectroscopy (1H-MRS). In Patient 1, T2-weighted imaging (T2-WI) on MRI at onset and even at 44 days after onset of the stroke-like episode showed high intensity in left parietal, temporal, and occipital lobe lesions. In the temporal lobe lesion, the apparent diffusion coefficient (ADC) at 44 days after onset was higher (average: 1.219x10(-3)mm2/s) than that in a normal region (average: 0.796x10(-3)mm2/s). (1)H-MRS of the left parietal lobe lesion at the same day showed a decrease in N-acetylaspartate/(creatine+phosphocreatine) (NAA/Cr) (0.43) and a peak in lactate. 1H-MRS of the contralateral side at the same day showed NAA/Cr (1.57) and no peak in lactate. Thereafter, ADC gradually decreased and NAA/Cr gradually increased, and the peak in lactate disappeared in the lesion. In Patient 2, T2-WI at onset showed high intensity in bilateral occipital lobe lesions. In the left occipital lobe lesion, ADC at the same day was higher (1.082x10(-3)mm2/s) than that in a normal region (average: 0.841x10(-3)mm2/s). (1)H-MRS of the left occipital lobe lesion at the same day showed a decrease of NAA (3.0mM) and a peak in lactate (13.1mM) (measured by LCModel). In 1H-MRS of the normal left parietooccipital lobe at 4 months before onset, NAA was 7.6mM and there was no peak in lactate (0mM). Perfusion imaging at onset showed high intensity in bilateral occipital lobes, which indicated hyperperfusion in stroke-like lesions. Thereafter, ADC gradually decreased and the peak in lactate partially decreased, and the low concentration of NAA persisted (regardless of the partial recovery) in the lesion. These results suggest that the stroke-like episodes is related to vasogenic edema, hyperperfusion, and neuronal damage. Acute oxidative phosphorylation defect may have a crucial role in the pathophysiology of stroke-like episodes.

In mammals, the suprachiasmatic nucleus (SCN), the circadian pacemaker, receives light information via the retina and functions in the entrainment of circadian rhythms and in phasing the seasonal responses of behavioral and physiological functions. To better understand photoperiod-related alterations in the SCN physiology, we analyzed the clock gene expression in the mouse SCN by performing in situ hybridization and real-time monitoring of the mPer1::luc bioluminescence. Under long photoperiod (LP) conditions, the expression rhythms of mPer1 and Bmal1 in the caudal SCN phase-led those in the rostral SCN; further, within the middle SCN, the rhythms in the ventrolateral (VL)-like subdivision advanced compared with those in the dorsomedial (DM)-like subdivision. The mPer1::luc rhythms in the entire coronal slice obtained from the middle SCN exhibited 2 peaks with a wide peak width under LP conditions. Imaging analysis of the mPer1::luc rhythms in several subdivisions of the rostral, middle, caudal, and horizontal SCN revealed wide regional variations in the peak time in the rostral half of the SCN under LP conditions. These variations were not due to alterations in the waveform of a single SCN neuronal rhythm. Our results indicate that LP conditions induce phase changes in the rhythms in multiple regions in the rostral half of the SCN; this leads to different circadian waveforms in the entire SCN, coding for day length.

The question of how the brain represents the spatial relationship between the own body and external objects is fundamental. Here we investigate the neural correlates of the somatic perception of bimanual interaction with an external object. A novel bodily illusion was used in conjunction with functional magnetic resonance imaging (fMRI). During fMRI scanning, seven blindfolded right-handed participants held a cylinder between the palms of the two hands while the tendon of the right wrist extensor muscle was vibrated. This elicited a kinesthetic illusion that the right hand was flexing and that the hand-held cylinder was shrinking from the right side. As controls, we vibrated the skin surface over the nearby bone beside the tendon or vibrated the tendon when the hands were not holding the object. Neither control condition elicited this illusion. The significance of the illusion was also confirmed in supplementary experiments outside the scanner on another 16 participants. The "bimanual shrinking-object illusion" activated anterior parts of the superior parietal lobule (SPL) bilaterally. This region has never been activated in previous studies on unimanual hand or hand-object illusion. The illusion also activated left-hemispheric brain structures including area 2 and inferior parietal lobule, an area related to illusory unimanual hand-object interaction between a vibrated hand and a touched object in our previous study. The anterior SPL seems to be involved in the somatic perception of bimanual interaction with an external object probably by computing the spatial relationship between the two hands and a hand-held object.

Sensing movements of the upper and lower extremities is important in controlling whole-body movements. We have shown that kinesthetic illusory hand movements activate motor areas and right-sided fronto-parietal cortices. We investigated whether illusions for the upper and lower extremities, i.e. right or left hand or foot, activate the somatotopical sections of motor areas, and if an illusion for each limb engages the right-sided cortices. We scanned the brain activity of 19 blindfolded right-handed participants using functional magnetic resonance imaging (fMRI) while they experienced an illusion for each limb elicited by vibrating its tendon at 110 Hz (ILLUSION). As a control, we applied identical stimuli to the skin over a nearby bone, which does not elicit illusions (VIBRATION). The illusory movement (ILLUSION vs. VIBRATION) of each immobile limb activated limb-specific sections of the contralateral motor cortex (along with somatosensory area 3a), dorsal premotor cortex (PMD), supplementary motor area (SMA), cingulate motor area (CMA), and the ipsilateral cerebellum, which normally participate in execution of movements of the corresponding limb. We found complex non-limb-specific representations in rostral parts of the bilateral SMA and CMA, and illusions for all limbs consistently engaged concentrated regions in right-sided fronto-parietal cortices and basal ganglia. This study demonstrated complete sets of brain representations related to kinesthetic processing of single-joint movements of the four human extremities. The kinesthetic function of motor areas suggests their importance in somatic perception of limb movement, and the non-limb-specific representations indicate high-order kinesthetic processing related to human somatic perception of one's own body.

The hypocholesterolemic effects of Kluyveromyces marxianus YIT 8292 crude cell wall (KM-CW) were examined. In pilot studies, KM-CW tablets were administered to mildly hypercholesterolemic subjects at doses of 8.0, 4.0, 2.0, or 1.0 g/d for 4 weeks. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) decreased at doses above 2.0 and 4.0 g/d, respectively. Further, we examined the effect of intake of yogurt containing 3.0 or 4.0 g of KM-CW/d for 8 weeks in normal and hypercholesterolemic subjects in a double-blind placebo-controlled study. The intake of either of the KM-CW-containing yogurts was associated with significantly improved TC and LDL-C in hypercholesterolemic subjects, but had no effect on these levels in normal subjects. TC was significantly lower at week 8 in the hypercholesterolemic subjects who ingested yogurt containing 3.0 or 4.0 g of KM-CW than in those who consumed placebo yogurt. Intake of KM-CW might contribute to the prevention of hypercholesterolemia.

Using the mPer1::luc real-time monitoring technique, the authors observed the bimodal patterns of mPer1 bioluminescence on each side of the SCN, in parallel with maintaining synchronization between the left and right sides of the SCN under an artificial light:dark:light:dark (LDLD) 7:5:7:5 condition. In situ hybridization analysis of mPer1 and mBmal1 mRNA distribution in the SCN showed that in 1 photophase (morning photophase; M) of LDLD, the mPer1 level in the ventrolateral-like (VL-like) subdivision of the SCN was higher than that in the dorsomedial-like (DM-like) subdivision, and this regional distribution pattern was reversed in another photophase (evening photophase; E). In contrast, the mBmal1 level was higher in the DM-like subdivision than in the VL-like subdivision in the M phase, and this distribution changed in the E phase. The prokineticin 2 (PK2) mRNA that encodes an SCN output molecule that is thought to transmit the circadian locomotor rhythms was reduced in both the DM-like and VL-like SCN and did not clearly correlate with the activity under the LDLD condition. The expression of mPer1 and mPer2 in the liver was clearly bimodal, whereas the expressions of other clock genes were not synchronized to the LDLD condition. These results may provide important insights into the mechanism underlying the splitting or bimodal rhythms that may in turn facilitate the understanding of the ability to measure the seasonal day length in mammals.

We investigated how the human sensory-motor system elicits a somatosensory aftereffect. Tendon vibration of a limb excites the muscle spindle afferents that contribute to eliciting illusory movements of the limb. After the cessation of vibration, a transient sensation in which the vibrated limb returns towards its original position (kinesthetic aftereffect) is often experienced, even in the absence of the afferent inputs recruited by the vibration. We vibrated the tendon of either the right wrist extensor or flexor muscle that elicited an illusory flexion or extension movement, which was followed by its corresponding extension or flexion aftereffect. First, we psychophysically investigated how the preceding illusory movement affects the aftereffect. Second, we examined the cortico-spinal excitability during the aftereffect to evaluate its changes from the time during the illusion. We measured the amplitude of the motor-evoked potential that is evoked by a single-pulse transcranial magnetic stimulation to the hand section of the contralateral motor cortex (M1). All 19 subjects experienced the aftereffect, and the amount of aftereffect was approximately 70% of the preceding illusion. During the illusion, the cortico-spinal excitability increased more in non-vibrated than in vibrated muscle, so as to reflect the illusory directions. During the aftereffect, the excitability was significantly reduced only in the non-vibrated muscle, with no change in the vibrated muscle, which, in turn, caused an opposite pattern in the unbalanced excitability between the two muscles, and the degree of unbalanced excitability was correlated with the sensation of aftereffect. The kinesthetic aftereffect seems to be elicited by a sensory process that is determined by the preceding illusory movements. Motor-cortical processing of the unbalanced sensory information from the stimulated and non-stimulated muscles may contribute to the elicitation of kinesthetic aftereffect.

A short tandem repeat (STR) in the intron 1a of paternally imprinted gene, KCNQ1, is evaluated as a new probe for use in parentally imprinting allele (PIA) typing. This typing can determine the inheritance of one allele from father by the methylation difference. Allelic and genotypic frequencies of the STR were determined using samples from 175 unrelated Japanese and 170 unrelated Germans. The polymorphism information contents were 0.652 and 0.634 for the Japanese and the Germans, respectively, indicating usefulness in individual identification. This method was applied to five Japanese families consisting of 19 individuals. Genomic DNA was digested by methylation-sensitive restriction endonucleases, HhaI and HapII, followed by PCR amplification using two-step sandwich primer sets and the products were analyzed on polyacrylamide gel electrophoresis. For all of the families, each child's paternal allele given by PIA typing corresponded to one of the two alleles from father, not the two from mother, that were determined by the STR genotyping. The results demonstrate that this STR probe is feasible for use in PIA typing and that its typing method can contribute to paternity testing.

The perception of the size and shape of one's body (body image) is a fundamental aspect of how we experience ourselves. We studied the neural correlates underlying perceived changes in the relative size of body parts by using a perceptual illusion in which participants felt that their waist was shrinking. We scanned the brains of the participants using functional magnetic resonance imaging. We found that activity in the cortices lining the left postcentral sulcus and the anterior part of the intraparietal sulcus reflected the illusion of waist shrinking, and that this activity was correlated with the reported degree of shrinking. These results suggest that the perceived changes in the size and shape of body parts are mediated by hierarchically higher-order somatosensory areas in the parietal cortex. Based on this finding we suggest that relative size of body parts is computed by the integration of more elementary somatic signals from different body segments.

We developed a simple and sensitive stable-isotope dilution method for the quantification of 3-hydroxyglutaric acid (3HGA) and glutaric acid (GA) in body fluids. In our method, tert-butyldimethylsilyl (tBDMS) derivatives of 3HGA and GA were measured with a conventional electron-impact ionization (EI) mode in gas chromatography-mass spectrometry (GC-MS). The control values for 3HGA in nmol/ml were 0.15+/-0.08 (serum; n=10) and 0.07+/-0.03 (CSF; n=10). In addition, glutarylcarnitine and free carnitine were quantified by electrospray tandem mass spectrometry. Using these methods, we monitored 3HGA, GA, and glutarylcarnitine in the body fluids of three patients with glutaric aciduria type 1 found during newborn screening. None of the patients had experienced neurological strokes, which are possibly caused by the accumulation of 3HGA, at 15-24 months of age under a disease-specific treatment, including carnitine supplementation. Our data showed that 3HGA levels were relatively high in some serum samples with lower glutarylcarnitine and carnitine levels, suggesting that carnitine supplementation may play a role in preventing the accumulation of 3HGA in patients with this disease.

We studied six infants with thiamine-responsive congenital lactic acidosis and normal pyruvate dehydrogenase complex activity in vitro, through clinical and biochemical analysis. In addition to elevated lactate and pyruvate levels, the data revealed increased urinary excretion of alpha-ketoglutarate, alpha-ketoadipate, and branched chain ketoacids, indicating functional impairment of thiamine-requiring enzymes, such as pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, alpha-ketoadipate dehydrogenase, and branched chain amino acid dehydrogenase. The metabolism of thiamine has not been investigated in patients with thiamine-responsive congenital lactic acidosis. We evaluated two specific transport systems, THTR-1 (SLC19A2) and THTR-2 (SLC19A3), and a pyrophosphorylating enzyme of thiamine, thiamine pyrophosphokinase (hTPK 1), in addition to pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex activity; no abnormality was found. Although the clinical features of thiamine-responsive congenital lactic acidosis are heterogeneous and clinical responses to thiamine administration vary, we emphasize the importance of early diagnosis and initiation of thiamine therapy before the occurrence of permanent brain damage. Careful monitoring of lactate and pyruvate would be useful in determining thiamine dosage.

The parentally imprinted allele (PIA) typing that we have recently developed determines parental alleles at a VNTR locus in the differentially methylated region upstream of the human H19 gene. The usefulness of this typing was demonstrated by its application to blood samples in paternity cases. However, its applicability to other tissue DNA remains to be tested. DNA samples from fifteen different postmortem tissues such as cerebrum, skeletal muscle and skin were examined, all of which were obtained from three autopsy cases 2-11h after death. DNA was digested with a methylation-sensitive HhaI enzyme and diluted solutions of the digests were subjected to the first PCR amplification, providing amplification of only the paternal H19 methylated allele. Subsequent VNTR typing was carried out for the amplified products to determine which allele was of paternal origin. No tissue-dependent difference was observed and all the samples examined, though degraded, were successfully used for determining the paternal allele. These results substantiate the usefulness of PIA typing in forensic examinations. Its application to two identity cases, a burned male body and a male body with adipocere formation, was also shown.

Electrophysiological studies have shown that cortico-spinal excitability increases during the motor preparation period in reaction time (RT) paradigms. However, there is a line of contradictory evidence with transcranial magnetic stimulation (TMS) showing that its excitability is reduced during the preparation period. In these studies, the subjects can predict the TMS timings. Thus we investigated how the predictability of TMS timing affects cortico-spinal excitability. A single-pulse TMS was delivered to the hand section of the left motor cortex while seven right-handed subjects relaxed their hands in a flexed position. We prepared three conditions: (i) in the semi-PREDICTABLE condition, two visual stimuli at 500 ms interval were presented and the TMS was delivered either 0, 125, 250, 375, or 500 ms after the first stimulus; (ii) in the PREDICTABLE condition, the TMS was provided only at 500 ms after the first stimulus; (iii) in the UNPREDICTABLE condition, no visual cue preceded the TMS. We recorded motor evoked potentials (MEPs) from the wrist flexor and extensor muscles. We found a significant reduction of MEP amplitude in the flexor muscles in both the PREDICTABLE and semi-PREDICTABLE conditions, but not in the UNPREDICTABLE condition. These results showed that the predictability of TMS per se, without the preparation of motor outputs, can reduce cortico-spinal excitability.

The cellular components involved in the hypocholesterolemic activity of Kluyveromyces marxianus YIT 8292 were examined in rats fed on a high-cholesterol diet. Whole cells (KM) were heated at 115 degrees C for 10 minutes and fractionated into water-soluble extract 1 and the insoluble residue (KM-CW). After mechanical disruption by glass beads, KM-CW was separated into the cell wall (KM-W) and water-soluble extract 2. Plasma total cholesterol was decreased by feeding KM-CW or KM-W, but was not changed by feeding extract 1 or extract 2. Feeding KM-CW and KM-W increased the fecal sterol excretion and concentration of short-chain fatty acids (SCFA) in the cecum. The hypocholesterolemic activity of KM-CW was completely abolished by the enzymatic degradation of alpha-mannan and beta-glucan. These results suggest that alpha-mannan and beta-glucan were the major active components of KM, and that its hypocholesterolemic activity may be attributable to the increasing fecal sterol excretion and/or production of SCFA.

We have previously shown that motor areas are engaged when subjects experience illusory limb movements elicited by tendon vibration. However, traditionally cytoarchitectonic area 2 is held responsible for kinesthesia. Here we use functional magnetic resonance imaging and cytoarchitectural mapping to examine whether area 2 is engaged in kinesthesia, whether it is engaged bilaterally because area 2 in non-human primates has strong callosal connections, which other areas are active members of the network for kinesthesia, and if there is a dominance for the right hemisphere in kinesthesia as has been suggested. Ten right-handed blindfolded healthy subjects participated. The tendon of the extensor carpi ulnaris muscles of the right or left hand was vibrated at 80 Hz, which elicited illusory palmar flexion in an immobile hand (illusion). As control we applied identical stimuli to the skin over the processus styloideus ulnae, which did not elicit any illusions (vibration). We found robust activations in cortical motor areas [areas 4a, 4p, 6; dorsal premotor cortex (PMD) and bilateral supplementary motor area (SMA)] and ipsilateral cerebellum during kinesthetic illusions (illusion-vibration). The illusions also activated contralateral area 2 and right area 2 was active in common irrespective of illusions of right or left hand. Right areas 44, 45, anterior part of intraparietal region (IP1) and caudo-lateral part of parietal opercular region (OP1), cortex rostral to PMD, anterior insula and superior temporal gyrus were also activated in common during illusions of right or left hand. These right-sided areas were significantly more activated than the corresponding areas in the left hemisphere. The present data, together with our previous results, suggest that human kinesthesia is associated with a network of active brain areas that consists of motor areas, cerebellum, and the right fronto-parietal areas including high-order somatosensory areas. Furthermore, our results provide evidence for a right hemisphere dominance for perception of limb movement.

A single-pulse TMS to the human motor cortex (M1) influences reaction time (RT). We may summarize from previous studies where different groups of subjects participated in various types of RT tasks that TMS above motor threshold (MT) delays RT, whereas TMS below MT shortens RT and that these RT changes depends on TMS timings during RT period. However, these effects have never been systematically investigated in a single study where an identical group of subjects participated. The purpose of this study is to test previous TMS effects in a study of simple RT task. Seven subjects isometrically abducted their right index fingers as quickly as possible when a visual stimulus appeared. A single-pulse TMS was randomly delivered over the left M1 at various timings during RT period in a single trial (at 0, 40, 60, 80 or 100 ms after the visual stimulus). Motor-evoked potential (MEP) and EMG activity for response were recorded from the right finger muscles. Only the TMS above MT delivered at 80 or 100 ms, which increased MEP amplitude, significantly delayed RT and increased the size of response EMG activities that may reflect contents of central motor commands. The TMS below MT at these timings, which occasionally evoked MEP, exclusively shortened RT despite the fact that the response EMG size was unchanged. A single-pulse TMS has different effects on the ongoing neuronal processes in M1 during the pre-movement period: TMS above MT may temporally retard the processes and also affect contents of central motor commands, whereas TMS below MT may simply facilitate its processes without affecting motor commands.

Objective: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones., Design: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined., Measurements: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays., Results: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood., Conclusions: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.

Does viewing someone's actions activate a viewer's somatosensory cortex? We tested if visual information of limb movements activated limb sections in somatosensory areas that are normally engaged in kinesthetic processing of the limb. We showed, with functional magnetic resonance imaging in 17 right-handed healthy subjects, that passive observation of flexion-extension movements of an experimenter's right hand activated the observer's contralateral hand section of area 2 which is involved in kinesthetic processing of right hand movements. This could be interpreted as a pragmatic function of the brain that permits visual information to reach the somatosensory area, and suggests human area 2 has an association function between kinesthesia and vision.

The twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance., (Copyright 2004 Wiley-Liss, Inc.)

To depict neural substrates of implicit motor learning, regional cerebral blood flow was measured using positron emission tomography (PET) in 13 volunteers in the rest condition and during performance of a unimanual two-ball rotation task. Subjects rotated two balls in a single hand; a slow rotation (0.5 Hz) was followed by two sessions requiring as rapid rotation as possible. The process was repeated four times by a single hand (Block 1) and then by the opposite hand (Block 2). One group of volunteers began with the right hand (n = 7), and the other with the left (n = 6). Performance was assessed by both quickness and efficiency of movements. The former was assessed with the maximum number of rotation per unit time, and the latter with the electromyographic activity under constant speed of the movement. Both showed learning transfer from the right hand to the left hand. Activation of cerebrum and cerebellum varied according to hand. Activation common to both hands occurred in the bilateral dorsal premotor cortex and parasagittal cerebellum, right inferior frontal gyms, left lateral cerebellum and thalamus, supplementary motor area, and cerebellar vermis. The left lateral cerebellum showed the most prominent activation on the first trial of the novel task, and hence may be related the early phase of learning, or "what to do" learning. Left parasagittal cerebellum activity diminished with training both in first and second blocks, correlating inversely with task performance. This region may therefore be involved in later learning or "how to do" learning. The activity of these regions was less prominent with prior training than without it. Thus the left cerebellar hemisphere may be related to learning transfer across hands., (Copyright 2004 Elsevier Inc.)

A 1-year-old boy with methylmalonic acidemia had symmetrical lesions of the bilateral basal ganglia, which suggested Leigh encephalopathy. The findings on brain magnetic resonance imaging (MRI) and his physical condition greatly improved by the intravenous administration of vitamin B1. We hypothesized that in this case, clinical Leigh encephalopathy was caused by a impairment of the activity of pyruvate carboxylase induced by the accumulation of methylmalonyl CoA and an impairment of energy production due to a lack of vitamin B1, especially impairment of the activity of pyruvate dehydrogenase complex during an acute worsening of methylmalonic acidemia. Thus, in the treatment of methylmalonic acidemia, attention should be paid to vitamin B1 deficiency. During an acute worsening, vitamin B1 should be administered by intravenous drip injection.

Dynamic facial expressions of emotion constitute natural and powerful media of communication between individuals. However, little is known about the neural substrate underlying the processing of dynamic facial expressions of emotion. We depicted the brain areas by using fMRI with 22 right-handed healthy subjects. The facial expressions are dynamically morphed from neutral to fearful or happy expressions. Two types of control stimuli were presented: (i) static facial expressions, which provided sustained fearful or happy expressions, and (ii) dynamic mosaic images, which provided dynamic information with no facial features. Subjects passively viewed these stimuli. The left amygdala was highly activated in response to dynamic facial expressions relative to both control stimuli in the case of fearful expressions, but not in the case of happy expressions. The broad region of the occipital and temporal cortices, especially in the right hemisphere, which included the activation foci of the inferior occipital gyri, middle temporal gyri, and fusiform gyri, showed higher activation during viewing of the dynamic facial expressions than it did during the viewing of either control stimulus, common to both expressions. In the same manner, the right ventral premotor cortex was also activated. These results identify the neural substrate for enhanced emotional, perceptual/cognitive, and motor processing of dynamic facial expressions of emotion., (Copyright 2004 Elsevier B.V.)

We can precisely control only what we can sense. Sensing limb position or limb movement is essential when we precisely control our limb movements. It has been generally believed that somatic perception takes place in the neuronal network of somatosensory areas. Recent neuroimaging techniques (PET, fMRI, transcranial magnetic stimulation) have revealed in human brains that motor areas participate in somatic perception of limb movements during kinesthetic illusion in the absence of actual limb movement. In particular, the primary motor cortex, which is an executive locus of voluntary limb movements, is primarily responsible for kinesthetic perception of limb movements. This probably forms the most efficient circuits for voluntary limb movements between the controlled muscles and the motor areas.

The effects of cytochrome P450 (P450, CYP) ligands and permeabilization of microsomes on 3-hydroxybenzo(a)pyrene [3-OH-B(a)P] glucuronidation mediated by rat hepatic microsomes were studied. While the UDP-glucuronosyltransferase (UGT) activity with non-permeabilized microsomes from 3-methylcholanthrene (MC)-treated rats was markedly reduced by alpha-naphthoflavone (NF), this inhibitor had hardly any effect when permeabilized microsomes were used in which the inhibitor was expected to have easy access to UGT. Kinetic analysis indicated that the inhibitory effect of alpha-NF is competitive. These results suggest that a UGT isoform(s) involved in 3-OH-B(a)P glucuronidation is interfered by a CYP1A inhibitor via a mechanism dependent on the intact nature of microsomal membranes in MC-treated rats. It is likely that P450 functions as a substrate transporter for some isoforms of UGT via possible interactions between UGT and P450.

Enlargement of the lateral ventricles and atrophy of the brain were documented ultrasonographically in utero at as early as 28th week of gestation in a female patient with lactic acidosis due to deficiency of the pyruvate dehydrogenase E1alpha subunit, demonstrating that the changes characteristic of this disease can occur antenatally. The mechanism of infantile spasms in this disease may be linked to mosaicism of the brain cells involving the normal enzyme and the mutant enzyme.

We investigate whether imagery of voluntary movements of different body parts activates somatotopical sections of the human motor cortices. We used functional magnetic resonance imaging to detect the cortical activity when 7 healthy subjects imagine performing repetitive (0.5-Hz) flexion/extension movements of the right fingers or right toes, or horizontal movements of the tongue. We also collected functional images when the subjects actually executed these movements and used these data to define somatotopical representations in the motor areas. In this study, we relate the functional activation maps to cytoarchitectural population maps of areas 4a, 4p, and 6 in the same standard anatomical space. The important novel findings are 1). that imagery of hand movements specifically activates the hand sections of the contralateral primary motor cortex (area 4a) and the contralateral dorsal premotor cortex (area 6) and a hand representation located in the caudal cingulate motor area and the most ventral part of the supplementary motor area; 2). that when imagining making foot movements, the foot zones of the posterior part of the contralateral supplementary motor area (area 6) and the contralateral primary motor cortex (area 4a) are active; and 3). that imagery of tongue movements activates the tongue region of the primary motor cortex and the premotor cortex bilaterally (areas 4a, 4p, and 6). These results demonstrate that imagery of action engages the somatotopically organized sections of the primary motor cortex in a systematic manner as well as activating some body-part-specific representations in the nonprimary motor areas. Thus the content of the mental motor image, in this case the body part, is reflected in the pattern of motor cortical activation.

Conventional PCR-based genotyping is useful for forensic testing but cannot be used to determine parental origins of alleles in DNA specimens. Here we describe a novel method of combined conventional genotyping and PIA typing (parentally imprinted allele typing) at a minisatellite region upstream from the H19 locus. The PIA typing uses two sets of primers and DNA digested with methylation-sensitive Hha I enzyme. The first amplification produces only the methylated fragment of paternal H19 allele, and the second detects polymorphism in the minisatellite. Hence, this distinguishes paternal and maternal alleles by difference in the DNA methylation. Furthermore, the polymorphism in this polymorphic locus was examined using 199 unrelated Japanese and 171 unrelated Germans, their polymorphism information content being 0.671 and 0.705, respectively. Feasibility of this typing is demonstrated for six families, and the usefulness is shown by application to paternity testing.

To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8). The plasma ghrelin concentrations in cord blood ranged from 110.6-446.1 pmol/liter (median, 206.7 pmol/liter), which were equal to or higher than those in normal weight adults. These values were inversely correlated with birth weight (r = -0.40; P = 0.002), birth length (r = -0.36; P = 0.007), placental weight (r = -0.35; P = 0.01), and IGF-I concentration (r = -0.49; P = 0.0002), but were not significantly correlated with the GH concentration (r = 0.22; P = 0.12). The ghrelin concentrations in small for gestational age newborn were significantly higher than those in appropriate for gestational age newborns (P = 0.0008). The ghrelin concentrations in the vein were significantly higher than those in the artery in 8 cord blood samples (P = 0.01), which suggests that the placenta is an important source of fetal ghrelin. In neonates, the ghrelin concentrations ranged from 133.0-481.7 pmol/liter (median, 268.3 pmol/liter), which were significantly higher than those in cord blood (P < 0.0001). These results suggest that ghrelin may contribute to fetal and neonatal growth.

When two cylinders are passively moved in-phase on the volar surface of the right second and third fingers, human subjects estimate the stimuli to originate from one object, whereas two separate objects are estimated for out-of-phase stimuli. While five blindfolded subjects performed this estimation task, brain activity was measured by fMRI. The in-phase stimuli activated the left intraparietal and inferior parietal areas significantly more than did out-of-phase stimuli. These parietal regions may play important roles in the integration of moving tactile stimuli that are independently provided on plural fingers, from which subjects internally construct a single object.

The functions of the cortical and subcortical motor areas have been regarded as the execution and control of limb movements. We introduce recent neuroimaging evidence in humans that somatic sensation elicited by afferent inputs that signal limb movement also engage the motor areas. It is generally understood that somatic sensation can only be experienced once movement has been executed. Here we provide evidence that somatic sensation of limb movement can be internally simulated before the movement gets started by recruiting the motor areas. It is suggested that the sensory experiences that are expected when movements are actually executed can be internally simulated in the network of the motor areas during motor imagery.

The primary motor cortex (MI) is regarded as the site for motor control. Occasional reports that MI neurons react to sensory stimuli have either been ignored or attributed to guidance of voluntary movements. Here, we show that MI activation is necessary for the somatic perception of movement of our limbs. We made use of an illusion: when the wrist tendon of one hand is vibrated, it is perceived as the hand moving. If the vibrated hand has skin contact with the other hand, it is perceived as both hands bending. Using fMRI and TMS, we show that the activation in MI controlling the nonvibrated hand is compulsory for the somatic perception of the hand movement. This novel function of MI contrasts with its traditional role as the executive locus of voluntary limb movement.

The human pyruvate dehydrogenase complex (PDHC) catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment is very effective for some patients with PDHC deficiency. Among these patients, five mutations of the pyruvate dehydrogenase (E1)alpha subunit have been reported previously: H44R, R88S, G89S, R263G, and V389fs. All five mutations are in a region outside the thiamine pyrophosphate (TPP)-binding region of the E1alpha subunit. We report the biochemical and molecular analysis of two patients with clinically thiamine-responsive lactic acidemia. The PDHC activity was assayed using two different concentrations of TPP. These two patients displayed very low PDHC activity in the presence of a low (1 x 10(-4) mM) TPP concentration, but their PDHC activity significantly increased at a high (0.4 mM) TPP concentration. Therefore, the PDHC deficiency in these two patients was due to a decreased affinity of PDHC for TPP. Treatment of both patients with thiamine resulted in a reduction in the serum lactate concentration and clinical improvement, suggesting that these two patients have a thiamine-responsive PDHC deficiency. The DNA sequence of these two male patients' X-linked E1alpha subunit revealed a point mutation (F205L and L216F) within the TPP-binding region in exon 7.