Association of angiopoietin-like protein 3 with hepatic triglyceride lipase and lipoprotein lipase activities in human plasma.

BACKGROUND: The relationship between plasma angiopoietin-like protein 3 (ANGPTL3), and lipoprotein lipase (LPL) activity and hepatic triglyceride lipase (HTGL) activity has not been investigated in the metabolism of remnant lipoproteins (RLPs) and high-density lipoprotein (HDL) in human plasma. METHODS: ANGPTL3, LPL activity, HTGL activity, RLP-C and RLP-TG and small, dense LDL-cholesterol (sd LDL-C) were measured in 20 overweight and obese subjects in the fasting and postprandial states. RESULTS: Plasma TG, RLP-C, RLP-TG and sd LDL-C were inversely correlated with LPL activity both in the fasting and postprandial states, but not correlated with HTGL activity and ANGPTL3. However, plasma HDL-C was positively correlated with LPL activity both in the fasting and postprandial states, while inversely correlated with HTGL activity. ANGPTL3 was inversely correlated with HTGL activity both in the fasting and postprandial states, but not correlated with LPL activity. CONCLUSION: HTGL plays a major role in HDL metabolism, but not RLP metabolism. These findings suggest that ANGPTL3 is strongly associated with the inhibition of HTGL activity and regulates HDL metabolism, but not associated with the inhibition of LPL activity for the metabolism of RLPs in human plasma.

Analysis on the co-localization of asbestos bodies and Fas or CD163 expression in asbestos lung tissue by in-air micro-pixe.

To prevent and control disease caused by exposure to various agents, it is necessary to determine the harmful level of intervention and to establish a method for measuring that level. In-air microparticle-induced X-ray emission (in-air micro-PIXE) analysis is based on irradiation of specimens with a proton ion microbeam, and has been modified for biological application. Two-dimensional analysis and quantitative analysis using the system confirmed that asbestos induced apoptosis by upregulating Fas expression and also revealed the accumulation of CD163-expressing macrophages in the lungs of patients with asbestosis. By quantitative comparison of the area of Fas or CD163 expression and the Fas- or CD163-negative area in asbestos lung tissue, the harmful levels which caused the expression of Fas or CD163 could be estimated on Silica, Ferrous iron, and Magnesium (the components of asbestos) deposition. These results indicate that the system could be useful for investigating the pathogenesis of inhaled particle-induced immune reactions and for determining harmful levels of exogenous agents.

In-air micro-particle induced X-ray emission analysis of asbestos and metals in lung tissue.

Inhalation of asbestos increases the risk of lung cancer and pulmonary fibrosis. It is difficult to directly assess the distribution and content of inhaled particles in lung tissue sections. The purpose of this study is to employ an in-air micro particle induced X-ray emission (in-air micro-PIXE) system for assessment of the spatial distribution and content of asbestos and other metals in lung tissue. A proton ion-microbeam from this system was applied to irradiate lung tissue of patients with or without asbestosis, tumor tissue from both groups, and asbestos fibers (in vitro). The content of each element composing asbestos and those of other metals were calculated and their distribution was assessed from the characteristic X-ray pattern for each element obtained after irradiation. This in-air micro-PIXE system could identify the location of asbestos bodies composed of Si, Mg, and Fe in lung tissue sections. Macrophage and lymphocytes accumulated in that area. This new system also revealed deposits of titanium, nickel, and cobalt in the lung tissues, in addition to asbestos bodies. The Si and Fe content were higher in lungs with asbestosis than in lungs without asbestosis or in tumor tissue. Analysis of asbestos fibers composed of chrysotile, crocidolite, and amosite showed that the ratios of Si, Fe, and Mg corresponded with those for the chemical structures. In-air micro-PIXE analysis is useful for assessing the distribution and quantities of asbestos bodies and also other metals in lung tissue comparing to immune-related cell localizations, and is also useful for analysis of standard asbestos fibers.

Intracellular changes of metal elements by fucoidan extracted from brown seaweed (Cladosiphon okamuranus).

This study was undertaken to elucidate the intracellular changes of metal elements after the administration of fucoidan extracted from Cladosiphon okamuranus. TRL1215 cells (normal rat liver cell line) were treated with 0, 0.1, or 1.0 mg/ml fucoidan and incubated in 5% CO2 at 37 degrees C. The cellular levels of Mg, Al, Fe, and Zn were significantly increased in the 1.0 mg/ml fucoidan-treated cells compared to those of the 0.1 mg/ml fucoidan-treated cells and the control. Next, TRL1215 cells were cultured on Mylar film overnight. At 24 h after 5-bromo-2'-deoxyuridine dosing, 0, 0.1, or 1.0 mg/ml fucoidan was treated for 9 h. The cellular distribution of elements was analyzed using in-air micro-micro-particle induced X-ray emission. The X-ray spectra showed that yields of Al, Mg, and Zn were high in order of the 1.0 mg/ml fucoidan-treated sample, the 0.1 mg/ml fucoidan-treated sample, and the control. Fe yield was mildly increased by fucoidan administration. In fucoidan-treated cells, the focal accumulation of Br was correlated spatially with phosphorous-rich region, suggesting that Br was localized within the nucleus. Al distribution provided a spatial association with Br map. These data suggest that fucoidan increases the accumulations of Al, Mg, Fe, and Zn in normal rat hepatocytes, and fucoidan-binding Al is postulated to be transferred into the nucleus.

Usefulness of MEG magnetometer for spike detection in patients with mesial temporal epileptic focus.

The present study investigated the sensitivity of magnetoencephalography (MEG) for spikes depending on sensor type in patients with mesial temporal epileptic focus. We recorded MEG in 6 patients with mesial temporal epileptic focus using two sensor types (magnetometer and gradiometer) simultaneously. The number of spikes detected and the corresponding equivalent current dipole (ECD) parameters (distance from the coordinated head center (radius), and dipole moment) were evaluated with respect to sensor type. Among 426 MEG 'consensus spikes' determined by 3 reviewers, 378 spikes satisfied the predetermined criteria for source localization. Comparing ECD parameters, spikes detected by magnetometer alone displayed a smaller radius and larger dipole moment than those detected by gradiometer alone. Spikes estimated in the mesial temporal area were more frequently detected by magnetometer alone (38.5%) than by gradiometer alone (11.5%), whereas spikes in the lateral temporal area were detected less by magnetometer alone (3.7%) than by gradiometer alone (53.9%). The present results suggest that a magnetometer is advantageous for spike detection in patients with mesial temporal epileptic focus. This also implies the higher sensitivity of magnetometer for deep sources.

Analysis of tissue cadmium distribution in chronic cadmium-exposed mice using in-air micro-PIXE.

This study undertook the analysis of tissue cadmium (Cd) distribution using in-air micro-particle-induced X-ray emission (PIXE) and the examination of the involvement of metal ions in parenteral Cd toxicity. A mouse was injected intraperitoneally with 3 mg/kg body weight of CdCl2 thrice weekly. After 27 wk, the liver and kidney were excised and fixed in 10% formalin solution for 4 h and then embedded in paraffin. Thin paraffin sections were used to analyze trace elements with in-air micro-PIXE and to examine metallothionein protein and histological changes. Cd distribution was determined by micro-PIXE in the liver and renal cortex of the Cd-exposed mouse, and the net Cd count was higher in the liver than in the renal cortex. The net iron (Fe) count was higher in the liver of the Cd-exposed mouse compared to the control, and an opposite tendency was observed in the renal cortex. Wide cellular Cd distribution was demonstrated in the liver and renal cortex of the chronic Cd-exposed mouse compared to the control. Metallothionein staining was increased by chronic exposure to Cd both in the liver and kidney, and nephrotoxicity was more apparent than hepatotoxicity. The modification of tissue Fe and calcium distribution by an intraperitoneal injection of Cd might be involved in Cd-induced toxicity.

A recovery from enhancement of activation in auditory cortex of patients with idiopathic sudden sensorineural hearing loss.

OBJECTIVE: We previously reported enhanced activation of auditory cortex in patients with bilateral chronic inner-ear hearing loss. To determine whether this enhancement can exhibit a short-term alteration, we measured auditory evoked magnetic fields (AEFs) in patients with idiopathic sudden sensorineural hearing loss (ISSHL) in the acute phase (AP) and recovery phases (RPs). METHODS: We recorded AEFs in two unilateral ISSHL patients at three time points (AP, RP1, and RP2) using a whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally to the affected and healthy ear at four different intensities (40-70 dB HL). RESULTS: Both patients showed the enhancement of N100 m moment at AP and not at RPs in response to the affected ear stimulation, and stronger N100 m moment in ipsilateral than contralateral hemisphere in response to the healthy ear stimulation at AP. CONCLUSIONS: Enhancement of N100 m amplitude occurs in ISSHL patients and disappears on the scale of days. Enhancement of activity in the auditory cortex derived from inner-ear hearing loss can thus exhibit short-term change. SIGNIFICANCE: The results of this study provide first evidence for a recovery from enhancement of activation in the auditory cortex following injury of peripheral hearing organ.

Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy.

We compared the cognitive functions and interictal cerebral glucose metabolism of 11 patients with mesial temporal lobe epilepsy (MTLE) with frequent seizures to those of 10 patients with MTLE with rare seizures; the groups were matched for age, sex, education, IQ, and focus side. The frequent-seizure group had more set-shifting impairment that correlated with glucose hypometabolism in the prefrontal cortices. Our results suggest that frequent seizures in MTLE are associated with hypofunction of the prefrontal cortex.

Dominance of ipsilateral corticospinal pathway in congenital mirror movements.

OBJECTIVE: To clarify the mechanism of congenital mirror movements. DESIGN: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. RESULTS: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. CONCLUSIONS: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.

Intracarotid propofol test for speech and memory dominance in man.

OBJECTIVE: To evaluate the usefulness of propofol as an alternative drug to amobarbital for the Wada test. METHODS: The authors analyzed 67 right-handed patients out of 123 patients who were candidates for neurosurgical therapy and thus underwent the Wada test as a preoperative evaluation. Twelve were tested with propofol and 55 were tested with amobarbital. Test conditions of the Wada test, recovery time of muscle power to manual muscle testing (MMT) Grade 3 (T3/5) and Grade 5 (T5/5), onset time of the first verbal response (Tverb) after injection and that of the first nonverbal response (Tnon-verb), were compared between the two groups. Power spectrum analysis of EEG background activity during the Wada test was performed and the time and spatial distribution of polymorphic slow activities were also compared in three cases. RESULTS: With propofol injection, lateralities of language and memory function were identified in 12 and 9 of 12 patients in comparison to amobarbital (52 and 41 of 55 patients detection in language and memory function). No complications with direct intracarotid injection of propofol were observed. T3/5 and T5/5 with propofol injection were shorter while Tverb and Tnon-verb were longer compared to amobarbital. Absolute power of polymorphic slow EEG waves gradually increased and then rapidly decreased with propofol, which was in contrast to amobarbital injection. CONCLUSIONS: With direct intracarotid propofol injection, the Wada test was satisfactorily performed in all 12 patients and 2 more patients with left-handedness or with different injection dose for each side without any complications. Clinical usefulness of propofol as an alternative drug to amobarbital for the Wada test was indicated.

Subregions of human MT complex revealed by comparative MEG and direct electrocorticographic recordings.

OBJECTIVE: To locate the visual motion complex (MT+) and study its response properties in an epilepsy surgery patient. METHODS: A 17-year-old epilepsy patient underwent invasive monitoring with subdural electrodes in the right temporo-parieto-occipital area. MT+ was investigated by cortical electric stimulation and by epicortical visual evoked potentials time-locked to motion onset of sinusoidal gratings (motion VEP). Motion-related visual evoked magnetic field (motion VEF) was also recorded before the electrode implantation to complement the invasive recording. RESULTS: Motion VEPs revealed two subregions within MT+, generating early and late potentials respectively. The early activity with a peak around 130 ms was localized at a single electrode situated immediately caudal to the initial portion of the ascending limb of the superior temporal sulcus (AL-STS). The late activity, peaking at 242-274 ms, was located ventro-rostrally over three electrodes. Among the four electrodes with motion VEPs, cortical stimulation at the most caudal pair elicited motion-in-depth perception involving the whole visual field. In addition to two subregions revealed on the gyral crown, magnetoencephalography (MEG) demonstrated another subregion with a late motion VEF in AL-STS immediately rostral to the electrode with the early motion VEP. CONCLUSIONS: In combination with MEG recording, the present invasive exploration demonstrated human MT+ in a focal area of the temporo-parieto-occipital junction and delineated possible three subregions as indicated by the different latencies and distributions of the motion VEP/VEFs. SIGNIFICANCE: Comparative MEG and direct electrocorticographic recordings delineated possible subregions within the human MT complex.

Enhanced activation of the auditory cortex in patients with inner-ear hearing impairment: a magnetoencephalographic study.

OBJECTIVE: Injury of peripheral auditory organ often induces abnormality of loudness sensation such as loudness recruitment. However, objective evaluation of this phenomenon has rarely been performed. To elucidate this abnormal loudness sensation, cortical mechanisms were investigated by recording auditory evoked magnetic fields (AEFs). METHODS: We recorded AEFs in 8 patients suffering from inner-ear hearing impairment with loudness recruitment and in 14 healthy hearing controls using a 122-channel whole-head neuromagnetometer. Tone bursts of 1 kHz were presented monaurally at 4 different intensities (40, 50, 60, 70 dB HL) with a constant interstimulus interval of 1 s. RESULTS: In both groups, the 100 ms response (N100m) increased in amplitude and decreased in latency as a function of stimulus intensity in both hemispheres. Concerning the source strength, increment of dipole moment of N100m was more rapid according to the stimulus intensity in patients compared with that in healthy subjects. Source strength of N100m was enhanced at high stimulus intensity in patients, and its ratio to healthy subjects was 1.08 at 50 dB, 1.69 at 60 dB and 2.04 at 70 dB. CONCLUSIONS: In patients with inner-ear hearing impairment, enhanced activation of the auditory cortex was observed, and may help explain loudness recruitment.

Maturational change of parallel auditory processing in school-aged children revealed by simultaneous recording of magnetic and electric cortical responses.

OBJECTIVES: To elucidate the maturational change of cortical auditory processing, we analyzed simultaneously recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs) in school-aged children. METHODS: Simultaneous recording of AEP and AEF were performed in 32 healthy children of age ranging from 6 to 14 years and 10 adults. Tone bursts of 1 kHz were presented to the left and right ears alternately with 3 different within-ear stimulus onset asynchronies (SOAs) (1.6, 3.0 and 5.0 s for each ear) under attention-distracted condition. RESULTS: All subjects showed clear N100 and N100m peaks under the longest SOA condition (5.0 s). Under the shortest SOA condition (1.6 s), 4 out of 19 subjects under 12 years (21%) failed to show the N100m component. By contrast, N250 and N250m were observed in the majority of children (29/32: 91%) while those were detected in only 4 out of 10 adults (40%). The spatial distribution of N100 in children under 9 years differed from that in older subjects, whereas the dipole orientation of N100m was constant among age groups, suggesting that radially oriented sources might make additional contribution to the generation of N100 in early childhood. N250 was significantly larger in children than in adults. The strength of N250 was suppressed with longer SOAs, whereas that of N100 was enhanced. The dipole of N250m was located around Heschl's gyrus on the superior temporal plane which was significantly medial, anterior and inferior to that of N100m. CONCLUSIONS: Dissociation of maturational change between the tangential and radial components of N100 suggests that auditory processing at around 100 ms consists of multiple parallel pathways which mature independently. Furthermore, a negative peak at around 250 ms specifically seen in children has different generators from N100 and might represent a special auditory processing which takes an active part until acquisition of the efficient cortical networks of the adult brain.

Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp: an fMRI study.

Although it is hypothesized that there is abnormal motor inhibition in patients with dystonia, the question remains as to whether the mechanism related to motor inhibition is specifically impaired. The objective of the present study was to clarify the possible abnormalities of the mechanisms underlying voluntary muscle relaxation during motor preparation and execution in patients with writer's cramp, using event-related functional MRI. Eight patients with writer's cramp and 12 age-matched control subjects participated in the study. Two motor tasks were employed as an experimental paradigm. In the relaxation task, subjects were asked to hold their right wrist in the horizontal plane by maintaining moderate contraction of wrist extensor muscles in the premotor phase; they relaxed those muscles voluntarily just once during each fMRI scanning session. In the contraction task, subjects extended the right wrist voluntarily from the same premotor state as for the relaxation task. Five axial images covering the primary sensorimotor cortex (SMC) and supplementary motor area (SMA) were obtained once every second. Activated volumes in the left SMC and the SMA were significantly reduced in patients for both muscle relaxation and contraction tasks. These data suggest that there is impaired activation in both SMC and SMA in voluntary muscle relaxation and contraction in patients with writer's cramp. This implies that abnormalities of both inhibitory and excitatory mechanisms in motor cortices might play a role in the pathophysiology of focal dystonia.

Mapping quantitative trait loci controlling seed longevity in rice ( Oryza sativa L.).

Quantitative trait loci (QTLs) controlling seed longevity in rice were identified using 98 backcross inbred lines (BILs) derived from a cross between a japonica variety Nipponbare and an indica variety Kasalath. Seeds of each BIL were kept for 12 months at 30 degrees C in dry conditions to promote loss of viability. To measure seed longevity, we performed an additional aging-processing treatment for 2 months at 30 degrees C maintaining seeds at 15% moisture content. We measured the germination percent of these treated seeds at 25 degrees C for 7 days as the degree of seed longevity. The germination of BILs ranged from 0 to 100% with continuous variation. Three putative QTLs for seed longevity, qLG-2, qLG-4 and qLG-9, were detected on chromosome 2, 4 and 9, respectively. Kasalath alleles increased the seed longevity at these QTLs. The QTL with the largest effect, qLG-9, explained 59.5% of total phenotypic variation in BILs. The other two QTLs, qLG-2 and qLG-4, explained 13.4 and 11.6% of the total phenotypic variation, respectively. We also verified the effect of the Kasalath allele of qLG-9 using chromosome segment substitution lines. Furthermore, QTLs for seed dormancy were identified on chromosomes 1, 3, 5, 7 and 11. Based on the comparison of the chromosomal location of QTLs for seed longevity and seed dormancy, these traits seem to be controlled by different genetic factors.

Identification of new low-molecular-weight glutenin subunit genes in wheat.

To clarify the composition of low-molecular-weight glutenin subunits (LMW-GSs) in a soft wheat cultivar, we cloned and characterized LMW-GS genes from a cDNA library and genomic DNA in Norin 61. Based on alignment of the conserved N- and C- terminal domains of the deduced amino-acid sequences, these genes are classified into 12 groups. One of these groups (group 5), the corresponding gene of which has not been reported previously, contains two additional hydrophobic amino-acid clusters interrupting the N-terminal repetitive domain. Other groups (groups 11 and 12), which were not identified in other cultivars as a protein product, showed all eight cysteines in the C-terminal conserved domain. With specific primer sets for these groups it was revealed that Glu-D3 and Glu-A3 encoded the former and the latter, respectively. Both groups of genes were expressed in immature seeds. The presence of these groups of LMW-GSs may affect the dough strength of soft wheat.

Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine.

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.

Parametric modeling of somatosensory evoked potentials using discrete cosine transform.

This paper introduces a parametric method for identifying the somatosensory evoked potentials (SEPs). The identification was carried out by using pole-zero modeling of the SEPs in the discrete cosine transform (DCT) domain. It was found that the DCT coefficients of a monophasic signal can be sufficiently approximated by a second-order transfer function with a conjugate pole pair. The averaged SEP signal was modeled by the sum of several second-order transfer functions with appropriate zeros and poles estimated using the least square method in the DCT domain. Results of the estimation demonstrated that the model output was in an excellent agreement with the raw SEPs both qualitatively and quantitatively. Comparing with the common autoregressive model with exogenous input modeling in the time domain, the DCT domain modeling achieves a high goodness of fitting with a very low model order. Applications of the proposed method are possible in clinical practice for feature extraction, noise cancellation and individual component decomposition of the SEPs as well as other evoked potentials.