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The forkhead box G1 (FOXG1) gene encodes a brain-specific transcription factor and is associated with a congenital variant of atypical Rett syndrome (RTT); several FOXG1 mutations have been identified. The congenital variant of RTT shows a hypoplastic corpus callosum, delayed myelination, and frontal and temporal atrophy. Although no report has described a hippocampal abnormality in humans, the current study suggests that FOXG1 also regulates neurogenesis in the postnatal hippocampus. In the present case, severe developmental delay was observed in a patient with a congenital variant of RTT from about 4months, in conjunction with acquired microcephaly, hypotonia, limited motor function, absent purposeful hand use, and repetitive jerky movements of the upper limbs. A novel missense mutation was identified in FOXG1 on gene analysis (c. 569T>A, p. Ile190Asn). The patient showed not only the typical cerebral abnormalities of a congenital variant of RTT, but also a hypoplastic hippocampus. This novel mutation and cerebral findings may provide new insights into the pathophysiology of the congenital variant of RTT.

The aim of this study was to evaluate the hypothesis that cerebral hemoglobin (Hb) oxygenation is related to phosphorylation potential during primary and secondary cerebral energy failure in newborn infants who have experienced birth asphyxia. We subjected newborn piglets to severe transient cerebral hypoxic-ischemia followed by resuscitation and examined cerebral energy metabolism by 31P-magnetic resonance spectroscopy and evaluated changes in cerebral Hb oxygen saturation (ScO2) using full-spectrum near-infrared spectroscopy before, during, and up to 54 h after the hypoxic-ischemic insult. ScO2 was significantly decreased during the hypoxic-ischemic insult compared with baseline values. During secondary energy failure, piglets were separated based on the relationship between the ratio of phosphocreatine to inorganic phosphate and ScO2; those with a negative correlation were less injured than those with a positive correlation. These results indicate that changes in ScO2 as measured by near-infrared spectroscopy are related to phosphorylation potential during secondary energy failure in asphyxiated infants.

Using optical topography, changes in the cerebral oxygenation were compared in the parieto-temporal lobe of preterm and term infants of equal postconceptional age in response to verbal stimulation. Eight preterm infants of gestational age 23-34 weeks were studied at postconceptional term age (38-46 weeks). Ten term infants were studied at 2-11 days after birth. Twenty-four-channel near-infrared optical topography (NIOT) was used to measure changes in concentration of oxyhemoglobin ([oxyHb]), deoxyhemoglobin ([deoxyHb]) and total hemoglobin ([totalHb]) in the bilateral temporal cortices. Verbal stimulation was provided by a recording of a Japanese fairy tale. The latency in response to verbal stimulation was significantly shorter in the preterm infants than in the term infants. This time is thought to reflect brain development, particularly the development of the neuro-vascular coupling mechanisms in the cerebral cortex. The present results indicate that the number of days after birth is more closely related to development of auditory system and neuro-vascular coupling than is postconceptional age. Thus, this suggests that early extrauterine environment affects the cortical responses to verbal stimulation in preterm infants.

Purpose: While many patients with childhood-onset epilepsy go into remission before reaching adulthood, a significant number of patients continue to suffer from refractory epilepsy. The purpose of this study was to clarify the long-term outcome of childhood-onset epilepsies.Subjects and Methods: We retrospectively studied 445 adult patients with childhood-onset epilepsies who were still being treated at the Department of Child Neurology, Okayama University Hospital.Results: Age at onset of epilepsy was < 7 years in 66% of the patients; 7 to 14 years in 30%; and 15 to 19 years in 5%. We classified the subjects into three groups: Group PE (289 patients) with partial epilepsy; Group GE (60 patients) with generalized epilepsy; Group RE (70 patients) consisting of patients with a history of West syndrome, Lennox-Gastaut syndrome, Doose syndrome and related epileptic syndromes; and 26 other unclassified cases. At follow-up, frequent seizures (≥ per month) were observed in 26%, 13% and 63% of patients in Groups PE, GE and RE, respectively. Of 168 patients in remission across these three groups, AEDs were discontinued or being reduced in 21% each, while 36% had experienced relapse of seizures, mainly caused by AED withdrawal.Discussion: This study indicated that these adult patients could be classified into two types: patients who still have frequent seizures even after reaching adulthood, and patients in remission or with rare seizures. For long-term management of these patients, an efficient system with cooperation between medical and comedical staff, and a comprehensive care system are essential.

Background: The light-emitting diode is used as one of the new light sources for phototherapy. NeoBLUE (Atom Medical, Tokyo, Japan) incorporates blue light-emitting diodes for the treatment of neonatal hyperbilirubinemia. The authors compared the in vitro efficacy of neoBLUE with conventional phototherapy devices. Methods: The three light devices used included neoBLUE and two conventional phototherapy devices with six blue–white (BW) or six green (GR) fluorescent tubes. A bilirubin/human serum albumin solution (15 mg/dL) in 200 × 300 mm elliptical bag was irradiated with each three light device. The average light intensity of neoBLUE, BW and GR was 22.5, 10.2 and 2.6 μW/cm2 per nm, respectively, for the irradiated area. Bilirubin photoisomers and native bilirubin were measured by high-performance liquid chromatography. Results: In neoBLUE, BW and GR, the respective production rate of cyclobilirubin was 6.0, 3.7 and 3.9 × 10−2 mg/dL/min, and the respective (4Z, 15E)-bilirubin/(4Z, 15Z)-bilirubin ratio after irradiation was 0.44, 0.33 and 0.12; the (4Z, 15Z)-bilirubin reduction rate at 20 min after irradiation was 60, 68 and 82%, respectively. The reduction rate of (4Z, 15Z)-bilirubin correlated with the (4Z, 15E)-bilirubin/(4Z, 15Z)-bilirubin ratio. Conclusion: Phototherapy using the neoBLUE under high level may be clinically more effective than therapy using the conventional light source from the results of the production rate of cyclobilirubin.

Summary Background: Estimation of hemodynamics is important for critically ill infants. Pulse dye densitometry (PDD) using indocyanine green (ICG), which enables measurements of circulating blood volume at the bedside, has recently been developed for adults. Methods: We conducted a basic investigation to determine whether this method can be applied to infants and measured circulating blood volume in 25 infants whose gestational ages ranged from 24 to 40 weeks (median, 32 weeks). At first, to validate the accuracy of measurements, arterial ICG concentrations determined by blood sample measurements were compared using a spectrophotometer ([ICG blood]) and by noninvasive measurement using PDD ([ICG pdd]) in seven infants. Next, blood volumes in 25 infants were estimated by the PDD method. Results: There was a positive relationships between [ICG blood] and [ICG pdd] (r = 0.913, P

Background: The clinical effect of phototherapy for neonatal hyperbilirubinemia is based on the production and elimination of cyclobilirubin. Generally, the clinical effect of light sources is estimated by the reduction in the total serum bilirubin level. One procedure with less invasiveness than blood collecting is urine collection. Whether the effectiveness of light sources used for phototherapy could be assessed using measurements of bilirubin photoisomers in urine was studied. Methods: This study was a retrospective analysis of 38 term infants with hyperbilirubinemia who underwent phototherapy. Bilirubin fractions in serum and urine before and 24 h after the phototherapy were measured by high-performance liquid chromatography. The light sources used for the phototherapy were blue-white light (n = 11), Biliblanket plus high output (n = 13) or green light (n = 14). The relationships between serum and urine bilirubin photoisomers after phototherapy and whether the levels of urine bilirubin photoisomer are affected by the light sources with different wavelength characteristic were analyzed. Results: There was no correlation between serum (ZE)-bilirubin and urine configurational isomers, but a weak positive correlation between serum (EZ)-cyclobilirubin and urine structural isomers after phototherapy. Although serum (ZE)-bilirubin levels depended on the wavelength characteristic of each light source during phototherapy, the urine configurational isomer levels did not depend on it. The increase in serum (EZ)-cyclobilirubin levels and the urine structural isomer levels were mostly in agreement. Conclusions: The urine bilirubin structural isomers may be used to estimate the serum (EZ)-cyclobilirubin levels and to evaluate the clinical effects of light sources.

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation‐specific brain structures, thereby providing useful information on structure‐function relationships in both normal and disease states. We used multichannel near‐infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications. Hum. Brain Mapping 22:124–134, 2004. © 2004 Wiley‐Liss, Inc.

Near-infrared spectroscopy (NIRS) has been used for measurement of changes in cerebral hemoglobin concentrations in neonates to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved reflectance spectroscopy (TRS) were performed in a piglet model with various degrees of cerebral oxygenation to estimate the differential pathlength factor (DPF). A portable three-wavelength TRS system (TRS-10, Hamamatsu Photonics K.K.) with a probe attached to the head of a piglet was used. Eleven newborn piglets were anesthetized and respired by a ventilator to induce stepwise hypoxia loading. The DPF showed positive linear relationship with arterial hemoglobin (Hb) oxygen saturation and sagittal sinus venous Hb oxygen saturation at 761 and 795 nm. The DPF at 835 nm also showed very slight positive linear relationship with arterial hemoglobin oxygen saturation. The DPF values obtained in this study should contribute to a better understanding of noninvasive measurements by NIRS in neonates.

This is the first report on the use of near-infrared topography (NIRT) for functional imaging of the visual cortex of newborn infants during photic stimulation (PS) under the condition of natural sleep. Measurements were conducted in four healthy term neonates within 1 week after birth. NIRT was performed on the occipital region of the head using a device consisting of 16 optical fibers, 8 for transmission and 8 for detection, and 24-measuring points were determined. Baseline data were collected over a period of 10 s. PS was produced by flashing lights (laser-emitting diodes) at 8 Hz and lasting for 15 s, followed by a 45-s rest period. Data were collected every 0.1 s, averaged over 10 cycles, and smoothed. As control data, hemodynamic changes in all neonates without stimulation were measured by the same method. PS caused marked increases from the baseline values in oxyhemoglobin ([HbO2]) and total hemoglobin ([T-Hb]) and a decrease in deoxyhemoglobin ([Hb]) in the primary visual areas of all neonates. We conclude that our method is useful for imaging and evaluating the primary visual area function in response to PS even in newborn infants during natural sleep.

We demonstrated spatiotemporal changes in hemoglobin concentrations in the sensorimotor cortex of a neonate during passive motor stimulation using multichannel near-infrared spectroscopy. This study was carried out on a healthy term neonate without neurological problems under the condition of sedative sleep. We employed a 24-channel near-infrared topography device with two wavelengths (780 and 830 nm), each with an interoptode distance of 2 cm, in this study. The probes were placed in the parietotemporal region over the sensorimotor cortex. An examiner flexed and extended the infant's leg and arm at the knee and elbow joints at a frequency of approximately 0.7 Hz. This passive motor stimulation consisted of 8–10 repetitions of the movement, each lasting for 15 s, followed by a 30-s rest period. Contralateral knee movement caused marked increases in oxyhemoglobin concentration ([HbO2]) and totalhemoglobin concentration ([T-Hb]) from the baseline values at almost all locations in the primary sensorimotor area and a decrease in local deoxyhemoglobin concentration ([Hb]). On the other hand, contralateral elbow movement caused marked increases in [HbO2] and [T-Hb] in more restricted regions than did knee movement. The results show that sensorimotor area function in response to passive motor stimulation can be imaged and evaluated even in newborn infants during sedative sleep.

A young male with Marfan syndrome, diagnosed at the age of 10 years, presented with conspicuous elongation and tortuosity of the internal carotid, middle cerebral, vertebral and basilar arteries on cranial magnetic resonance and computed tomography angiography. There is a little mention of cerebral blood vessel examinations in the guidelines of the American Academy of Pediatrics for Marfan syndrome. Guidelines may be provided for the evaluation of cerebrovascular system for the patients with Marfan syndrome who have family history of Marfan syndrome as well as a family history of death from subarachinoid hemorrhage.

Tsubame-Sanjo (hereafter called Tsubame) is one of the world's top class precise metalworking cluster located in Nigata prefecture Japan. Tsubame cluster has 400 years history and changed the major products or processing objects from time to time at least seven different products for adapting to the domestic or global market needs through various type of innovations. During 1980s Tsubame was the world's top position as table ware manufacturing center. After losing the competitiveness toward Asian tableware manufacturers, Tsubame has created the new type of the cluster with wide diversification and sub-clusters which have mutual net workings. Some companies have world top class precise metal processing capabilities which were used for manufacturing one hundred millions of iPod cases. Silicon Valley on the other hand boasts 100 years of history and has formed the strongest industrial cluster in the world while implementing substantial changes in its core industries. The results of a historical comparison of the core industries of Silicon Valley and Japan's Tsubame cluster show that both are characterized by a different style of cluster transformation. Silicon Valley promotes cumulative change through product innovation, whereas the Tsubame cluster embraces changes in process technology.

The rapid growth of Chinese major information appliances maker's to the global enterprises is often explained as "compression of time" effect by enjoyment of latecomer advantages. On the other hand, as to core technologies, there are NEW TYPE of latecomer disadvantages coming from (1) complexity and acceleration of technology developments, (2) higher licensing fee, and (3) technology protection by strict IP (intellectual property) or "Black Boxes" which hide proprietary/ unique/specific technologies not to be copied. This paper analyzes how have the three major Chinese information appliances makers (Haier, Changhong and TCL) overcome the above mentioned NEW TYPE of latecomer disadvantages. Then common factors will be extracted to clarify the innovation process to become the global enterprises.

Nowadays many Japanese companies are becoming "global niche top companies" with unique products or technologies originating, in many cases, in traditional or commonly-used technologies. These companies contribute, as parts or materials, to high-tech or high quality final products in the global market. A "global niche top company" is defined as a company holding the leading position in a specific niche market at the global level. Analyzing these companies from the viewpoint of innovation creation, and extracting common factors, is very meaningful for companies aiming for the global niche top position. In this paper, three companies are analyzed from the innovation viewpoint through the case study method, including interviews with top management, and then the common factors are extracted. The "two-step innovation process" is observed as the common factor among these three companies. The two-step innovation process is composed of, first, a small innovation and then, second, a major innovation. The first small innovation is created through combining the accumulated skills of traditional technologies or commonly-used technologies with modern technologies. Following that, the major innovation occurs as a result of the further skills which have been accumulated through the usage of the first innovation.

We report herein the case of a 38-year-old woman in whom a large tumor, 15 cm in diameter, was detected in the right lower quadrant of the abdomen. The tumor was removed and histological examination indicated that it was an inflammatory pseudotumor (IPT). IPT is not completely understood, but according to the few documented cases of IPT of the abdomen, its clinical behavior is benign and no recurrence has ever been reported. Thus, local resection is the most effective treatment.

Near-infrared spectroscopy has been used for measurement of changes in cerebral Hb concentrations in infants to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved spectroscopy (TRS) were performed in 22 neonates to estimate the values of light absorption coefficient and reduced scattering coefficient (mu'(s)), cerebral Hb oxygen saturation (SCO2), cerebral blood volume (CBV), and differential pathlength factor (DPF), and the relationships between postconceptional age and mu'(s), SCO2, CBV, and DPF were investigated. A portable three-wavelength TRS system with a probe attached to the head of the neonate was used. The mean mu'(s) values at 761, 795, and 835 nm in neonates were estimated to be (mean +/- SD) 6.46 +/- 1.21, 5.90 +/- 1.15 and 6.40 +/- 1.16/cm, respectively. There was a significant positive relationship between postconceptional age and mu'(s) at those three wavelengths. The mean SCO2 value was calculated to be 70.0 +/- 4.6%, and postconceptional age and SCO2 showed a negative linear relationship. The mean value of CBV was 2.31 +/- 0.56 mL/100 g. There was a significant positive relationship between postconceptional age and CBV. The mean DPF values at 761, 795, and 835 nm were estimated to be 4.58 +/- 0.41, 4.64 +/- 0.46, and 4.31 +/- 0.42, respectively. There was no relationship between postconceptional age and DPF at those three wavelengths. The results demonstrated that our near-infrared TRS method can be used to monitor mu'(s), SCO2, CBV, and DPF in the neonatal brain at the bedside in an intensive care unit.

Background Phototherapy has been a standard treatment for neonatal hyperbilirubinemia for more than 40 years, but it has remained sub-optimal. Aims To clarify the developmental changes in parameters of (4 E , 15 Z )-cyclobilirubin (( EZ )-C) elimination in order to obtain basic data for establishing optimal phototherapy. Study design Blood samples were taken at regular intervals after stopping phototherapy, and bilirubin fractions were analyzed by high-performance liquid chromatography. Subjects and methods The subjects were 46 infants with hyperbilirubinemia who underwent phototherapy. The gestational age and birth weight of the subjects ranged from 25.0 to 41.0 weeks and from 656 to 3810 g, respectively, and the age at cessation of phototherapy was a median of 5 days. A kinetic model of ( EZ )-C elimination was established, and the serum half-life of ( EZ )-C was calculated on the basis of the determined model. Relationships of the half-life of ( EZ )-C with birth weight and gestational age were investigated. Results Serum ( EZ )-C elimination followed a first-order kinetic model in 43 infants and a zero-order kinetic model in three extremely low birth weight infants. The half-life of ( EZ )-C calculated on the basis of a first-order elimination model in serum ranged from 68 to 274 min and showed weak negative correlations with birth weight and gestational age. Conclusions Serum ( EZ )-C excretion followed a first-order kinetic model in most of the neonates. The half-life of ( EZ )-C becomes more prolonged in the very low birth weight infant and early gestational age.

The aim of this study was to determine the validity of the hypothesis that excitatory amino acids are related to phosphorylation potential during primary and secondary cerebral energy failure observed in asphyxiated infants. We report here the results of experiments using newborn piglets subjected to severe transient cerebral hypoxia-ischemia followed by resuscitation. We examined cerebral energy metabolism by phosphorus nuclear magnetic resonance spectroscopy and changes in levels of amino acid neurotransmitters in the cortex by microdialysis before, during, and up to 24 h after the hypoxic-ischemic insult. The concentrations of aspartate, glutamate, taurine, and gamma-aminobutyric acid were significantly elevated during the hypoxic-ischemic insult compared with prebaseline values. Shortly after resuscitation, glutamate, taurine, and gamma-aminobutyric acid concentrations decreased but then began to increase again. These secondary elevations were greater than the primary elevations. A negative linear correlation was found between primary interstitial levels of glutamate and taurine and minimum values of phosphocreatine/inorganic phosphate during the secondary energy failure. The cerebral energy state depended on the time course of changes in excitatory amino acids, suggesting that amino acids play distinct roles during the early and delayed phases of injury.

Hypoxic ischemic encephalopathy (HIE) in newborn infants is one of the causes of later serious brain damage. In recent years, hypothermia therapy has attracted attention as an effective means of for preventing HIE-induced brain damage and has been used clinically 1, 2,3. However, the problem of which newborn infants should be selected for hypothermia therapy remains unsolved. Currently, selection is based on results of various tests such as neurological tests, blood biochemical tests and electroencephalography (EEG) 4. However, there is no definitive evaluation method.

Near-infrared spectroscopy (NIRS) has been used for measurement of cerebral hemoglobin (Hb) concentrations in neonates to study cerebral oxygenation and hemodynamics. We perform measurements by portable three-wavelength NIR time-resolved spectroscopy (TRS) in a piglet hypoxia model with various degrees of oxygenation to estimate the absorption coefficient (mu(a)) and reduced scattering coefficient (mu(s)') of the head. Measurements of absolute values of mu(a) at three wavelengths enable estimation of Hb concentration and Hb oxygen saturation in the head (SO2). However, there is a problem concerning which background absorption should be used to estimate Hb concentration in the head derived from mu(a) at three wavelengths because it is different from a simple in vitro model. Therefore, we use two different background absorption values with the assumption that background absorption is due only to 85% (by volume) water or that background absorption is equal to absorption of the piglet head with blood exchange transfusion by fluorocarbon (FC), and we compared SO2 measured by TRS with arterial Hb oxygen saturation (SaO2) and sagittal sinus venous Hb oxygen saturation (SvO2) measured by a co-oximeter at several inspired fractional O2(FI(O2)) concentrations. We find that SO2 values using the absorption (abs) of the piglet head with blood exchange transfusion (BET) by FC are not significantly different from SO2 values using the water-only background at FI(O2) in the range of 15 to 100%, but that the values using abs of the head with BET by FC are lower than the values using the water-only background at FI(O2) in the range of 12 to 4%. The SO2 values calculated from the water-only background are higher than those of SaO2 at FI(O2) in the range of 10 to 4%. However, SO2 values using the abs of the head with BET by FC are between those of SaO2 and SvO2 over the whole range of FI(O2). Therefore, abs of the head with BET by FC is more useful for estimation of the absolute values of oxyHb and deoxyHb of the piglet head.