Search

We report a 41-year-old man with meningoencephalitis associated with herpes simplex virus type 1 (HSV-1). The patient developed fever, headache and dysuria followed by generalized convulsion and neck stiffness, and the CSF showed pleocytosis. The titers of enzyme-linked immunosorbent assay against HSV measured 6 days after onset showed a significant rise; IgG antibody 4.89 (

The rate model regarding the development of movement disorders of basal ganglia origin suggests that hyperkinetic and hypokinetic disorders occur as a result of changes in the firing rates in the GPi and SNr, which in turn suppress thalamocortical output. Dopamine depletion in Parkinson's disease increases basal ganglia output, then decreases thalamocortical output, leading to bradykinesia. This model, however, cannot explain a lack of deterioration of parkinsonian signs following thalamic coagulation surgery. Instead of the rate model, the beta oscillation hypothesis has been proposed, explaining that synchronized oscillation in the beta frequency in the basal ganglia disturbs initiation of voluntary movement. We observed that effective high-frequency STN stimulation in parkinsonian monkeys was associated with increase in the firing rate and the pattern shift from irregular burst firing to regular high-frequency firing in the projecting sites. High-frequency neural activation by deep brain stimulation is supposed to cancel lower frequency oscillation including beta oscillation, leading to improvement of bradykinesia. Our observation supports the significance of the neural activity pattern, rather than the tonic activity level, in the development of movement disorders. The rate model cannot explain the improvement of ballismus and chorea by pallidotomy because pallidotomy increases the disinhibition of the thalamocortical projection, which should increase the movements. We observed repetitive bursts or pauses of neuronal firing of the globus pallidus synchronized to ballistic movements in patients with hemiballism or chorea, suggesting that phasic neuronal driving in the basal ganglia is important as their pathophysiology.

Integrated Coal Gasification Combined Cycle (IGCC) is attracting considerable attention as clean coal technology for several reasons, including rising natural gas price, escalating environmental scrutiny and fuel diversification. Mitsubishi Heavy Industries, Ltd. (MHI) has developed an air-blown two stage entrained bed coal gasifier, which realizes the highest net plant efficiency by using a smaller ASU (Air Separation Unit), dry coal feed, and excellent reliability with a membrane water wall structure. A 250 MW demonstration plant is currently under construction in Japan and scheduled to start operation in 2007. This plant will validate MHI Air Blown technology under dispatching conditions. In the mean time, responding to increasing interest on this technology around the world, MHI is expediting the design of a 500MW IGCC plant to be operated with G class gas turbines. The MHI air blown gasifier concept is particularly attractive to the US market, not only because of the higher efficiency, when compared with oxygen blown designs, but because of its capability to handle a wide variety of coals including PRB. This paper will discuss what kind of IGCC will soon be commercially available and how it will fit practical needs in the US market showing the time schedule of realization of commercial plants and economical evaluation in addition to the technical integrity. MHI believes that IGCC is one of the most important clean coal technologies to contribute to worldwide energy security and environmental needs.Copyright © 2007 by ASME

A case report.To report the first myotonic dystrophy case in which cervical kyphosis had been surgically corrected.Myotonic dystrophy is an autosomal dominant disease that shows myotonia, progressive muscle atrophy, and other various symptoms. Instability of the neck is expected to cause disorders of the cervical spine; however, there are no detailed reports on deformity of cervical spine associated with this disease.A 43-year-old man with cervical kyphosis due to myotonic dystrophy had undergone an occiput-T2 fusion with autogenous iliac bone using spinal instrumentation.The activity of daily life of the patient had improved markedly, and the good results continued to be preserved for 5 years. There were not any major perioperative complications.Surgical correction of cervical spine is not necessarily a contraindication for myotonic dystrophy.

A family with dystonia associated with dyschromatosis symmetrica hereditaria (DSH), mental deterioration, and tissue calcification is described. The proband possessed an adenosine deaminase acting on the RNA 1 gene (ADAR1) mutation Gly1007Arg. This ADAR1 mutation could disturb RNA editing at Q/R sites of glutamate receptor in the brain and increase Ca2+ influx into neurons, which is thought to induce dystonia and mental deterioration. The observations in our family raise the possibility that the ADAR1 mutation might be a direct cause or a predisposing factor for heredodegenerative dystonia. Further investigation of ADAR1 mutations will shed light on the genotype–phenotype correlation in DSH. © 2006 Movement Disorder Society

Both folate and betaine, a choline metabolite, play essential roles in the remethylation of homocysteine to methionine. We have studied the effects of folate and choline deficiency on the plasma kinetics of methionine, especially remethylation of homocysteine to methionine, by means of stable isotope methodology. After a bolus intravenous administration of [(2)H(7)]methionine (5 mg/kg body weight) into the rats fed with folate-, choline-, folate + choline-deficient or control diets, the plasma concentrations of [(2)H(7)]methionine, demethylated [(2)H(4)]homocysteine, and remethylated [(2)H(4)]methionine were determined simultaneously with endogenous methionine and homocysteine by gas chromatography-mass spectrometry-selected ion monitoring. The total plasma clearance of [(2)H(7)]methionine was not significantly different among groups, suggesting that the formation of [(2)H(4)]homocysteine from [(2)H(7)]methionine was not influenced by deficiencies of folate and choline. The area under concentration-time curve of [(2)H(4)]homocysteine significantly increased in the folate- and folate + choline-deficient group as compared with the control, but not in the choline-deficient group. The time profile of plasma concentrations of [(2)H(4)]methionine in the folate-deficient group was the same as the control group, whereas the appearance of [(2)H(4)]methionine in plasma was delayed in the choline- and folate + choline-deficient group. These results suggested plasma levels of remethylated methionine were influenced by choline deficiency rather than folate deficiency.

Thalamic stimulation alleviated coarse action tremor in a patient with spinocerebellar degeneration (SCD) and led to substantial improvement in daily functioning, though disability from ataxia remained. Intraoperative microrecording revealed a significant correlation between neuronal activity of the ventral intermediate nucleus (Vim) and tremor electromyograms. The tremor-correlated activities of Vim neurons and abolition of the tremor by Vim stimulation suggest that Vim may be related to the generation of action tremor in SCD. Thalamic stimulation can be a useful treatment option for SCD patients with disabling tremor.

The stereoselective kinetics of methionine enantiomers in rats was investigated to evaluate the fraction that converted from D-methionine to the L-enantiomer using a stable isotope methodology. After bolus i.v. administration of D -o rL-( 2 H3)methionine, their plasma concentrations and that of endogenous L-methionine were determined by a stereoselective GC-MS method. L-( 2 H3)Methionine appeared rapidly after administration of D-( 2 H3)methionine, whereas D-( 2 H3)methionine was not detected after administration of L-( 2 H3)methionine. The fraction of conversion of D-( 2 H3)methionine into L-( 2 H3)methionine was estimated using the area under the plasma concentration vs. time curve of L-( 2 H3)methionine on D-( 2 H3)methionine administration and total clearance of L-( 2 H3)methionine on L-( 2 H3)methionine administration, and that fraction was 90%. This result demonstrates that almost all i.v. administered D-methionine is converted into the L-enantiomer in vivo. J. Nutr. 135: 2001-2005

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was resistant to corticosteroids and immunosuppressants, but after administration of rituximab, clinical symptoms improved and the patient remained in a stable state for approximately 10 months. Rituximab may be a potent therapeutic option for refractory cases of CIDP irrespective of detectable M-protein in either serum or urine.

High frequency (>100Hz) electrical stimulation in both the external (GPe) and internal (GPi) segments of the globus pallidus was effective in improving parkinsonian motor signs. Improvement generally occurred at short latency (

We describe a patient with type I hereditary angioedema presenting recurrent episodes of skin swelling and abdominal pain. Laboratory examination showed reduced levels of CH50 and C4 with a normal C3 level. The C1 inhibitor was decreased to 7.0 mg/dl (normal, 10-25 mg/dl) with a remarkably reduced activity (

We compared postural sway parameters during a 1-minute quiet stance in 28 patients with idiopathic Parkinson's disease (PD) in off phase with those in 17 age-matched normal subjects and investigated differences in the sway parameters before and after unilateral pallidotomy in 16 PD patients. The PD patients showed larger sway area (SA) and longer total sway path length (SPL) compared with normal subjects. Total SPL after subtraction of tremor effect did not differ from that in normal subjects. The shift of the mean center of foot pressure (CFP) position from the first 30 seconds to the last 30 seconds showed that the CFP tended to move forward in PD patients compared with normal subjects and to move laterally more in PD patients than normal subjects, especially in those with less severity (Unified Parkinson's Disease Rating Scale, motor score < 40). After the operation, there was little change in either SA or lateral movement of CFP, but forward movement of CFP and total SPL tended to be normalized, along with an improvement of major parkinsonian symptoms. From these results, it is concluded that SPL elongation significantly involves tremor effect, forward movement of CFP in PD derives from basal ganglia dysfunction, and SA enlargement and large lateral movement of CFP may be caused partly by compensatory movements or by dysfunction outside the basal ganglia circuitry.

Carbonyl stress compounds such as glyoxal and methylglyoxal have been recently attracting much attention because of their possible clinical significance in chronic and age-related diseases. A high-performance liquid chromatographic procedure has been developed for the simultaneous quantitation of glyoxal and methylglyoxal in human urine. The assay is based on the reaction of these compounds with 1,2-diamino-4,5-dimethoxybenzene to form fluorescent adducts, which are separated by reversed-phase high-performance liquid chromatography in a total run time of 45 minutes and quantitated fluorometrically using 2,3-pentanedione as an internal standard. Derivatization is performed for diluted urine (100-120 mOsm/kg H2O) under acidic conditions (pH 4.5) at 60 degrees C over a prolonged time (15 h) to maximize the yields. The assay is specific and sensitive enough to analyze urinary levels of glyoxal and methylglyoxal with the within- and between-day relative standard deviations of less than 5%. Urinary levels (mean +/- standard deviation, n = 16) of glyoxal and methylglyoxal in healthy subjects were 4.7 +/- 1.35 microg/mg creatinine, 2.2 +/- 0.65 microg/mg creatinine, respectively, the former being 2 to 3 times more than the latter in every subject. The glyoxal and methylglyoxal levels positively correlated with each other, which may suggest that the levels reflect the individual activity of glyoxalase by which both compounds are detoxified.

To investigate clinical aspects of the neutropenia induced by high-dose intravenous immunoglobulin therapy (IVIG) we performed serial hematology, including differentiation of white blood cells (WBC), before and after 22 instances of IVIG in 16 patients with neuroimmunologic disorders. WBC and neutrophils showed a significant decrease with a nadir 2 days after IVIG, but returned to previous values by 14 days with no treatment except in 2 cases. No patient showed any infectious complication. Both WBC and neutrophils were significantly decreased in cases without corticosteroid therapy but not in those with medication. In nine instances (4 with and 5 without corticosteroid treatment), CD11b and CD16 on neutrophils were investigated using flow cytometry. In 3 of 5 instances without corticosteroid treatment the expression of CD11b was decreased after IVIG, while no change was detected in CD16. There was no difference in either CD11b or CD16 between before and after IVIG in instances with corticosteroid therapy. Neutropenia commonly and transiently develops just after IVIG, and can be prevented by corticosteroid pretreatment. Circulating neutrophils might bind to the vascular wall mainly with the involvement of CD11b and migrate into a storage pool, resulting in an apparent neutropenia after IVIG.

Stargardt-like macular dystrophy (STGD3) is an autosomal dominant form of early onset macular degeneration. The disease causing gene ELOVL4 encodes a protein that belongs to a family of proteins functioning in elongation of long chain fatty acids. The purpose of this study is to characterize cross-species conservation of ELOVL4 and investigate its mRNA distribution in the developing mouse eye.Bovine and porcine orthologs of the human ELOVL4 gene were cloned using RT-PCR method. EST and HTGS databases were searched for orthologs of ELOVL4. Cross-species alignments were performed using ClustalW. In situ hybridizations using murine Elovl4 probes were performed on frozen sections of mouse eyes.Elovl4 orthologs from mammalian to invertebrate species share strong sequence homology with human ELOVL4 at the amino acid level, suggesting functional conservation of Elovl4 during evolution. Expression of Elovl4 in mouse retina begins at E15 during embryogenesis and persists in postnatal stages. However, Elovl4 is predominantly expressed in the retinal ganglion cells at P1-P3, followed by predominant expression in the outer nuclear layer at P7, with its final expression enriched in inner segments of photoreceptors.Elovl4 expression in developing retina follows a dynamic pattern. It switches from predominant ganglion cell expression in embryonic and early postnatal development to predominant expression in the photoreceptor inner segments in later stages. Phylogenetic analysis reveals strong conservation of Elovl4 among different species throughout the vertebrate subphylum consistent with our hypothesis that ELOVL4 performs a fundamentally important function.

We describe a patient with cutaneous polyarteritis nodosa (CPN) and a patient with nonsystemic vasculitic neuropathy (NSVN), both presenting mononeuritis multiplex. Patient 1 was a 50 year-old woman. She developed livedo reticularis, palpable purpura, and sensory disturbance of lower extremities. Laboratory examinations showed no abnormal findings except for slight elevation of ESR, CRP, and anti-nuclear antibody. Skin biopsy revealed vasculitis of small to medium sized arterioles in dermis and subcutaneous adipose tissue. Sural nerve biopsy revealed axonal degeneration of myelinated fibers and infiltration of polymorphonuclear cells and mononuclear cells around feeding arteries. From these findings, she was diagnosed as having CPN. She was treated with intravenous injections of methylprednisolone (1,000 mg/day) followed by oral prednisolone (40 mg/day), which had a limited effect. Addition of an immunosuppressive agent (azathioprine 50 mg/day) produced marked improvement in her clinical symptoms. However, azathioprine was discontinued because of liver injury. Then, we added cyclophosphamide which was as effective as azathioprine. Patient 2 was a 57 year-old man. He developed weakness of legs and sensory disturbance of lower extremities and trunk. Laboratory examinations showed no abnormal findings except for slight elevation of CRP and anti-nuclear antibody. Sural nerve biopsy revealed infiltration of inflammatory cells mainly consisting of mononuclear cells around small sized arterioles in the epineurium and severe loss of myelinated fibers. From these findings, he was diagnosed as having NSVN. Treatment with oral prednisolone (60 mg/day) and azathioprine (50 mg/day) improved his clinical symptoms. CPN is differentiated from NSVN by the existence of skin lesions and the type of inflammatory cells involved. However, these two diseases share common clinical features such as mononeuritis multiplex, absence of systemic organ involvement, no specific abnormal laboratory data, effectiveness of immunosuppressive therapy, and relatively good prognosis. We suggest that CPN and NSVN are included in the same category of nonsystemic vasculitis that can involve peripheral nerves and/or skin.

To evaluate the therapeutic efficacy of liver transplantation in patients with ATTR Val30Met familial amyloid polyneuropathy (FAP), were repeatedly examined the neurophysiological function of peripheral nerves in nine patients. The maximal motor and sensory conduction velocities (MCV and SCV) of the ulnar and tibial nerves, size of compound muscle action potential (CMAP), terminal latency of CMAP, skin temperature of extremities, CVR-R, blood pressure, heart rate, and Schellong's test were examined before and every 6 months after the operation. Although there were no changes in CVR-R, blood pressure, or heart rate, the skin temperature of foot and hand increased soon after surgery and did not decrease during the period of observation. The temperature-adjusted MCV of tibial nerve gradually increased, but the MCV of ulnar nerve showed no change. The temperature-adjusted tibial nerve SCV worsened slightly soon after transplantation and remained at that level in the distal part. The ulnar nerve SCV worsened and subsequently improved. Liver transplantation is very effective for halting the progression of this type of FAP, but the recovery of peripheral nerve function in patients seems to be very slow and limited, especially the function of large diameter myelinated fibers.

We report the results of a collaborative study on malignant syndrome (MS) that developed in patients being treated with levodopa and other anti-parkinsonian drugs. We analyzed clinical features, laboratory findings, precipitating events, and risk factors for poor outcome. The study was conducted in five centers in Japan. Patients who developed MS between January 1991 and December 1997 were included. The enrollment criteria used were the same as those for neuroleptic MS proposed by Levenson et al. (1985).A total of 99 episodes were encountered in 93 patients (72 with Parkinson's disease and 21 with secondary parkinsonism); one patient had four recurrences of MS and three patients had two recurrences. High fever was the most frequent clinical manifestation of MS followed by worsening of parkinsonism, and then altered levels of consciousness. Serum creatine kinase was abnormally elevated in all the patients studied. Life-threatening complications were rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. The most frequent precipitating event was discontinuation or dose reduction of anti-parkinsonian drugs, particularly levodopa. No drug was the exception in the precipitation of MS. Intercurrent infection was the next most common precipitating event. MS developed without drug withdrawal or infection in some patients. In five patients, severe "wearing off" phenomenon was the only event preceding the onset of MS. Hot weather and dehydration appeared to be the cause in three patients. Among the total of 99 episodes, patients recovered to the pre-MS state following 68 episodes (68.7%); in the remaining 31.3%, patients failed to recover to their previous state. Older age, higher Hoehn and Yahr stage during the symptomatic phase of MS, higher akinesia score, and the absence of wearing off phenomenon prior to developing MS were associated with poor outcome. The most frequently used treatments of MS were intravenous fluid, levodopa, dantrolene sodium, and intragastric bromocriptine. Early introduction of treatment is important. Any elevation of body temperature during the course of anti-parkinsonian drug treatment should be considered as MS until proved otherwise.

The receptor tyrosine kinase Flk1 is known to mediate signals of vascular endothelial growth factor (VEGF) during vasculogenesis and hematopoiesis. We demonstrate by in situ hybridization that in addition to endothelial cells, chick Flk1 mRNA is also expressed in the notochord and in the neural epithelial cells of the ventral diencephalon, hindbrain, and spinal cord. During the development of the avascular chick retina, Flk1 mRNA is detected in the proliferative zone of the neural epithelium, whereas the VEGF ligand is expressed by differentiated retinal ganglion cells. Moreover, expression patterns of Flk1 in the retina are conserved among chick, quail and mouse, thus suggesting a distinct role of Flk1 and VEGF in the development of the vertebrate central nervous system.

We reported 2 patients with pseudogout manifested by severe posterior neck pain. Patient 1 was a 78-year-old woman. She had experienced attacks of posterior neck pain several times for 4 years. On July 3, 2001, she developed severe pain in the posterior neck and left acromioclavicular joint, and was admitted to our hospital. On examination, her body temperature was 38.1 degrees C, ESR 140 mm/hr and CRP 14.7 mg/dl. Linear calcifications in meniscus of the right knee and left acromioclavicular joint were observed in roentgenograms. The CT of the cervical spines revealed multiple nodular calcifications in the ligamenta flava at the level of C3-C7. She was treated with NSAIDs, and her symptoms and inflammatory reactions rapidly subsided. Patient 2 was was a 76-year-old man. His clinical courses and laboratory findings were very similar to those of patient 1. Both patients presented here were older than 70, and shared such common clinical findings as back neck pain, fever, elevations of serum ESR and CRP level, and effiveness of NSAIDs. We could not detect any findings that could explain the neck pain and fever in cervical spinal roentgenograms and MRIs. Cerebrospinal fluid examinations showed no abnormalities. We diagnosed them as having cervical arthritis caused by calcium pyrophosphate dihydrate deposition (pseudogout) based on the cervical CT examinations, which showed multiple nodular calcifications in the ligamenta flava. Calcium pyrophosphate dihydrate deposition on cervical spine is very rare, and only 50 patients with this condition have been reported to date. In the literatures, the mean age of patients with cervical spine pseudogout is old (72.3 years old) and 84% of them are females. The ligamenta flava at the level of C3-C6 and transverse ligament of the atlas are most commonly involved. Pseudogout of the cervical spine should be considered as a differential diagnosis when we examine the elderly patients with back neck pain. Cervical spinal CT is the most sensitive and useful examination to diagnose this disease.

This report concerns two patients with fulminant meningoencephalitis presenting in status epilepticus with periodic lateralised epileptiform discharges (PLEDs) observed on electroencephalogram. The titer of herpes simplex virus type 1 antibody was not elevated in either serum or cerebrospinal fluid, and acyclovir was not effective for either patient. Corticosteroid therapy was dramatically effective, however, suggesting that autoimmune inflammatory diseases were the underlying systemic disorders. PLEDs can thus be associated with steroid-responsive inflammatory meningoencephalitis.

The neural retina is a critical component of the visual system, which provides the majority of sensory input in humans. Various retinal degenerative diseases can result in the permanent loss of retinal neurons, especially the light-sensing photoreceptors and the centrally projecting retinal ganglion cells (RGCs). The replenishment of lost RGCs and the repair of optic nerve damage are particularly challenging, as both RGC specification and their subsequent axonal growth and projection involve complex and precise regulation. To explore the developmental potential of pluripotent stem cell-derived neural progenitors, we have established mouse iPS cells that allow cell lineage tracing of progenitors that have expressed Atoh7/Math5, a bHLH transcription factor required for RGC production. These Atoh7 lineage reporter iPS cells encode Cre to replace one copy of the endogenous Atoh7 gene and a Cre-dependent YFP reporter in the ROSA locus. In addition, they express pluripotent markers and are capable of generating teratomas in vivo. Under anterior neural induction and neurogenic conditions in vitro, the Atoh7-Cre/ROSA-YFP iPS cells differentiate into neurons that co-express various RGC markers and YFP, indicating that these neurons are derived from Atoh7-expressing progenitors. Consistent with previous in vivo cell lineage studies, the Atoh7-Cre/ROSA-YFP iPS cells also give rise to a subset of Crx-positive photoreceptor precursors. Furthermore, inhibition of Notch signaling in the iPSC cultures results in a significant increase of YFP-positive RGCs and photoreceptor precursors. Together, these results show that Atoh7-Cre/ROSA-YFP iPS cells can be used to monitor the development and survival of RGCs and photoreceptors from pluripotent stem cells.

Background: An increasing number of elderly patients present with intracranial aneurysms. In addition to female gender, an older age is associated with a higher risk of developing a subarachnoid hemorrhage (SAH), and these patients often fare poorly in terms of long-term outcome. It is often thought that elderly patients would especially benefit from endovascular aneurysm treatment. We assessed the clinical outcomes in elderly patients with ruptured intracranial aneurysms (RIAs) who were treated by endovascular procedures. Methods: We performed a retrospective review of a prospective database of elderly patients treated with coil embolization for RIAs. The clinical outcomes were assessed using the modified Glasgow Outcome Scale. The rates of procedural complications and adverse events were also recorded. Results: During a period of 5 years, 162 patients with 183 intracranial aneurysms were treated in our hospital by means of an endovascular approach. Among them, 51 patients (31.5%) with a ruptured aneurysm were aged 70 years or older. These patients aged 70-91 years (mean age, 74 years) were treated by coil embolization for RIAs. Among them, seven had a Hunt and Hess (HH) grade of I or II, 42 had an HH grade of III or IV, and 2 had an HH grade of V. Endovascular treatment resulted in 32 complete occlusions (62.7%), 15 neck remnants (22%), and 4 body fillings (7.9%). Procedural complications occurred in five patients (9.8%). The outcomes were good or excellent in 17 patients (33.3%). Three patients (5.8%) who died had an HH grade of IV or V. Rebleeding occurred during follow-up in one patient (1.9%). Conclusions: Coil embolization of intracranial aneurysms is safe and effective in the elderly. However, the morbidity and mortality rates are higher in patients with high HH grades. This finding suggests that the timing of treatment should be based on the patient's initial clinical status.

Pallidotomy was performed in a patient with hemichorea caused by lacunar infarction in the striatum. Chorea in the lower limb was reduced after a neurosurgical lesion in the medial portion of the sensorimotor territory of the internal segment of the globus pallidus, and chorea in the upper limb disappeared after an additional lesion in the lateral portion of that same area. Intraoperative neuronal recording revealed that mean firing rates were low, and that firing was irregular in the globus pallidus compared with off-state parkinsonian patients. These results suggest that chorea with striatal infarction is driven by phasic neuronal activity with a low firing rate in the globus pallidus and that the neural pathway of chorea has a functional somatotopical organization in the globus pallidus.

A gas chromatographic–mass spectrometric method for the simultaneous determination of methionine and total homocysteine in human plasma is described. dl-[2H4]Methionine and dl-[2H8]homocystine were used as internal standards. The method involved reduction of the disulfide bond with dithiothreitol, purification by cation-exchange chromatography using a BondElut SCX cartridge and derivatization with isobutyl chlorocarbonate in water–ethanol–pyridine. Quantitation was performed by selected-ion monitoring of the quasi-molecular ions of N(O,S)-isobutyloxycarbonyl ethyl ester (IBC-OEt) derivatives for methionine and [2H4]methionine, respectively, and the fragment ions ([M+H–COOisoBu–COOEt]+) for IBC-OEt derivatives for homocysteine and [2H4]homocysteine, respectively. The sensitivity, specificity, accuracy and precision of the method were demonstrated to be satisfactory for measuring concentrations of methionine and total homocysteine in human plasma.

The stereoselective acyl migration of diastereomeric 1beta-O-acyl glucuronides of (R)- and (S)-2-phenylpropionic acid [(R)-1PG and (S)-IPG, respectively] in phosphate buffer (pH 7.4) at 310K was investigated using HPLC. The disappearance of (R)-1PG was faster than that of (S)-1PG according to pseudo first-order kinetics. A kinetic model describing the degradation reactions was constructed. The rate constant for acyl migration from the 1beta-O-isomer to the 2-O-acyl isomer (k12) was about one order magnitude larger than that for hydrolysis from 1beta-O-acyl isomer to aglycone (k10). The k12 of (R)-IPG (0.377 +/- 0.005 h(-1)) was about two times larger than that of (S)-IPG (0.184 +/- 0.003 h(-1)). The results indicated that the stereoselectivity in the degradation of 1PG was apparently governed by the acyl migration from 1-isomer to 2-isomer. The kinetic parameters for acyl migration from 1-isomer to 2-isomer were estimated from temperature-dependent experiments using the transition state theory. The value of the free energy of activation at 310 K for (R)-1PG (99.67 kJ/mol) was smaller than that of (S)-IPG (101.60kJ/mol), suggesting that (R)-IPG showed thermodynamically higher reactivity in acyl migration than (S)-1PG.

Pallidotomy was performed in a parkinsonian patient with off-period foot dystonia. Dystonia appeared at the beginning of surgery and disappeared after the first microelectrode penetration of the globus pallidus, perhaps a micropallidotomy effect. Neuronal recording during dystonia revealed that the mean firing rates were low in both the internal and external segments of the globus pallidus, and that firing was irregular in the internal segment of the globus pallidus, compared with firing patterns in off-state parkinsonian patients without dystonia. These firing patterns immediately changed into those of nondystonic, off-state parkinsonism after relief of dystonia. These results suggest that off-period dystonia results from the same physiological change in the basal ganglia as that in primary dystonia.

This article describes a 13C-labelling and nuclear magnetic resonance approach for hippuric acid test which is potentially useful for evaluating liver reserve. In this approach, urine samples collected after ingestion of 13C-labelled benzoic acid were directly analysed by 13C nuclear magnetic resonance spectroscopy, and the excreted 13C-labelled hippuric acid formed from the administered benzoic acid was quantitated. The amount of labelled hippuric acid excreted in a specified time can be a useful index of liver reserve. In this study, the feasibility of the nuclear magnetic resonance approach has been investigated in several healthy subjects. This approach is simple and convenient compared with conventional analytical procedures, because no chromatographic separation is required. The approach could give new insights into the liver reserve, because the benzoic acid conversion to hippuric acid intimately relates to the hepatic energy metabolism. This measurement can be conducted at a wide range of dosages without interference from endogenous hippuric acid.

Decreased neuronal activity and altered firing patterns in the globus pallidus have been commonly observed in primary dystonia. Intraoperative neuronal recording in a patient with off-period dystonia revealed that the mean firing rates were considerably low in both the internal and external segments of the globus pallidus and that firing was irregular in the internal segment of the globus pallidus when dystonia developed, as compared with firing patterns in off-state parkinsonian patients without dystonia. These altered firing patterns were immediately reversed to those of off-state parkinsonism after relief of dystonia. These results suggest that primary dystonia and off-period dystonia result from the same physiological change in the basal ganglia. Ablation and stimulation of the internal segment of the globus pallidus can abolish both types of dystonia by blocking the abnormal activity of pallidal neurons.

During the screening test of the animal crude drug "Chan su" (Chinese name, toad-cake), the venom of Bufo bufo gargorizans CANTOR (Bufonidae), on blood coagulation, platelet aggregation, fibrinolysis system and cytotoxicity, the ethyl acetate extract showed promotive action on platelet aggregation and remarkable cytotoxic activity on HeLa-S3 cells. Nine kinds of bufadienolides were isolated from the ethyl acetate extract by bioactivity-guided fractionation and were identified by chemical and spectral analysis.

We report a Rathke's cleft cyst which presented as pituitary apoplexy, a rare presentation. A 46-year-old woman suffered sudden headache and visual loss. T1-weighted MRI 3 weeks after this apoplectic episode demonstrated a cystic lesion between the anterior and posterior lobes of the pituitary, with some high-signal material layering in it. The mass showed spontaneous regression on an image 3 weeks later. Trans-sphenoidal surgery confirmed the diagnosis of a Rathke's cleft cyst with a haematoma within it.

Evaluation of the amount of overall animal movement is important for investigations of motor control mechanisms in the central nervous system. We describe a new method to quantify overall free movements of an animal without any markers using a video camera and a personal computer equipped with a video-capture board. The operating principle is that the amount of overall movement of an object can be expressed by the difference in total area occupied by the object in two consecutive picture frames. The software for this application operates in real-time. Using this method and with proper setting for the cage and recording view, we can estimate three-dimensional movements of animals. The major advantages are low cost, easy operation and high sensitivity. The experimental results indicate that this method can be applied to various fields of motion analysis.

The combination of hemiballism, hyperglycemia and hyperintensity of the striatum on T1-weighted MRI constitutes a unique syndrome. We report the follow-up of a patient with this disorder whose hemiballism was sustained for over 5 years. High density on CT of the right striatum turned into normodensity in 4 months, and hyperintensity on T1-weighted MRI and hypointensity on T2-weighted MRI of the lesion were resolved in 18 months. A decreased perfusion of the lesion by SPECT remained 37 months after onset. There was no volume change of the lesion during the course of the illness. The radiological features support the possible pathology of either or both petechial hemorrhage and astrocytosis with high protein concentration after ischemic insult. The hemiballism may result from selective damage of GABA/enkephalin-containing neurons in the striatum and can persist without the primary histological changes causing the striatal T1-hyperintensity in this disorder.

Object. The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy. Methods. Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by “form fitting” the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies. Conclusions. These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

A 28-year-old Japanese woman with Balo's concentric sclerosis developed a rapidly progressive form of encephalopathy. Magnetic resonance imaging (MRI) showed multiple concentric lesions in the central white matter and the cerebellum. The administration of corticosteroid regimen resulted in little benefit Immunoadsorption plasmapheresis led to a remission within 1 month of onset Serial MRI study was described here for the first time, which allowed us to observe the development of concentric stuctures. The observation indicated that initially, a central core, a round demyelinated area, and surrounding edema appeared around a vessel. Subsequently, concentric demyelineated bands formed simultaneously, not centrifugally, with diminution of the edema. Analysis of cerebrospinal fluid showed elevated levels of interleukin-6 and tumor necrosis factor-α. The success of immunoadsorption plasmapheresis therapy in this patient suggests that both humoral demyelinating factors and cell-mediated immunity may be involved in the pathogenesis of this disorder.

Background: Chronic subdural hematoma (CSDH) is generally treated by burr hole irrigation. However, sometimes repeated recurrence is observed, and treatment may consequently become difficult. We examined the efficacy of embolization of the middle meningeal artery (MMA) for such cases. Methods: We considered embolization of the MMA for three patients who had refractory CSDH with repeated recurrence and two CSDH patients who were at risk of recurrence and showed signs of recurrence after surgery. A microcatheter was advanced through the MMA as peripherally as possible, and embolization was performed with 15-20% n-butyl-2-cyanoacrylate or 200 μm polyvinyl alcohol particles. Results: Embolization was performed in the three patients who had refractory CSDH with repeated recurrence: The procedure was performed after burr hole irrigation of the hematoma in two patients and before the irrigation in one patient. In the two CSDH patients at risk of recurrence, embolization was performed when signs of recurrence appeared. The timing of embolization differed for each patient. However, in all the patients, the hematoma tended to decrease in size, and no recurrence was observed. Conclusion: Embolization of the MMA is effective for refractory CSDH or CSDH patients with a risk of recurrence, and is considered an effective therapeutic method to stop hematoma enlargement and promote resolution.

Inhibition by antipsychotic drugs of voltage-gated L-type Ca2+ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 microM) inhibited Ba2+ current permeating through Ca2+ channels. Fluspirilene and pimozide the Ba2+ current at lower concentrations (fluspirilene, 0.1 pM to 1 nM; pimozide 10 pM to 1 microM). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 microM), an antagonist to dopamine D2 receptors, and SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine; 1 and 10 microM), an antagonist to dopamine D1 receptors, also inhibited the Ba2+ current. As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 microM) as well as calmidazolium (10 nM to 1 microM) reduced the Ba2+ current. The inhibition by haloperidol or fluspirilene of the Ba2+ current was not affected when GTP in intracellular solution was replaced with GDP beta S. These properties of the Ca2+ channel inhibition are discussed by comparing with those of the K+ channel inhibition and in relation to therapeutic relevance.