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Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor β-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.

Moss phlox, Phlox subulata L., commonly known as ‘Shiba zakura’ (turf cherry), is one of the most important ornamental plants in Japan. Since 1956, thousands of visitors have gathered each spring in different prefectures to enjoy the beauty of this Phlox as part of a traditional festival. Recently, foliage dieback symptoms were observed in Phlox from many parks in the Chubu area of Japan, causing significant commercial losses (Fig. 1A-C). Dieback is a common symptom caused by Ditylenchus dipsaci (Kuhn) Filipjev (Hooper, 1972), which primarily infects onion and garlic but can also occur in many flowering plants, including Phlox, and is a quarantine species (Jones et al., 2013). The occurrence of this nematode in Japan is well documented on onion, narcissus, lily, tulip and hyacinth (Inagaki, 1985; Katsunori, 1987), but has never been documented on Phlox, although D. dipsaci was reported in 1993 by the Hokkaido Plant Protection Office (unpubl.). Herein, we report the first confirmed occurrence of D. dipsaci on Phlox from the Chubu area of Japan, the nematode identity being confirmed through morphological, molecular and phylogenetic methods. This finding is of quarantine importance for other areas of Japan.

Neuromuscular disorders associated with hyperthyroidism have several variations in their clinical phenotype, such as ophthalmopathy, periodic paralysis, and thyrotoxic myopathy. We herein report an unusual case of thyrotoxic myopathy presenting as unilateral drop foot. Histopathological examinations of the left tibialis anterior muscle showed marked variation in the fiber size, mild inflammatory cell infiltration, and necrotic and regenerated muscle fibers with predominantly type 1 fiber atrophy. Medical treatment with propylthiouracil resulted in complete improvement of the left drop foot. This case expands the phenotype of thyrotoxicosis and suggests that thyrotoxicosis be considered as a possible cause of unilateral drop foot.

A 56-year-old man, who presented with 6 years history of difficulty in walking, was diagnosed as having vascular parkinsonism on the basis of the clinical findings of parkinsonism, pyramidal sign and the brain MRI findings of multiple lacunar infarction. Although he did not have hypertension, he had hyperhomocysteinemia and homozygous methylenetetrahydrofolate reductase (MTHFR) gene variant (C677T) as risk factors for ischemic stroke. Recent studies have shown that hyperhomocysteinemia and MTHFR gene variant are associated with small-vessel disease, suggesting that these risk factors may underlie vascular parkinsonism, particularly in patients lacking hypertension and in those with a relatively younger age at onset of this disease.

The prognosis of carcinomatous meningitis is very poor, although epidermal growth factor receptor-tyrosine kinase inhibitors have recently improved it. A 56-year-old woman was diagnosed with adenocarcinoma of the lung and underwent left lobectomy. Four years after the operation, she was diagnosed with carcinomatous meningitis. There was no recurrence of lung cancer at the time of initial carcinomatous meningitis diagnosis. Epidermal growth factor receptor-tyrosine kinase inhibitors were not used for this patient, because epidermal growth factor receptor mutations were not detected. She was treated by whole-brain radiation therapy and intrathecal chemotherapy, resulting in a very long-term survival of 889 days (29.6 months) from diagnosis of carcinomatous meningitis. We can expect long-term survival in patients with carcinomatous meningitis from non-small cell lung cancer, especially in patients without the primary tumor recurrence at the time of diagnosis, even without treatment with epidermal growth factor receptor-tyrosine kinase inhibitors.

A 49-year-old man presented with fever and pain, redness, swelling, and difficulty in walking. The serum C-reactive protein (CRP), creatin kinase (CK), and endotoxin levels were elevated. A blood culture revealed Edwardsiella tarda(E. tarda). Computed tomography (CT) showed subfascial and subcutaneous low-density areas in the lower legs, suggesting focal abscesses and edema. The patient was likely to have necrotizing fasciitis or cellulitis. He was successfully treated with several antibiotics and discharged after 43 days. Because E. tarda causes sepsis and fulminating necrotizing fasciitis with a high mortality rate in patients with an underlying illness, it should be considered a potentially important pathogen. The lack of an underlying illness may be a factor for a good outcome in this case.

Background: Spinocerebellar ataxia type 15 (SCA15) is a progressive neurodegenerative disorder characterized by pure cerebellar ataxia, very slow progression, and distinct cerebellar atrophy. The locus for SCA15 was first mapped to 3p24.2-3pter in an Australian family. We have subsequently mapped two Japanese families presenting with ataxia and postural tremor of the head, arm, or trunk to the SCA15 locus. Recently, partial deletions involving both the type 1 inositol 1,4,5-triphosphate receptor (ITPR1) and sulfatase modifying factor 1 (SUMF1) genes have been identified in Australian and British families with SCA15. Methods: We conducted fine haplotype analysis on the region including ITPR1. To identify the deletion, we conducted gene dosage analysis and array-based comparative genomic hybridization (aCGH) analysis. Gene expression analysis was performed using quantitative real-time reverse transcription PCR. Mutational analyses of ITPR1 and SUMF1 were also performed. Results: We have identified a 414-kb deletion including the entire ITPR1 and exon 1 of SUMF1 in patients in family A. The expression levels of ITPR1 and SUMF1 mRNAs of the patient were half those of the normal control. Furthermore, in family B, we have identified a C-to-T substitution at position 8581 of ITPR1, resulting in the amino acid substitution of leucine for proline at codon 1059, which is highly conserved among species. Conclusions: Our results strongly confirm that ITPR1 is the causative gene for SCA15 and suggest that we need to investigate the point mutation in ITPR1 in the patients with autosomal dominant cerebellar ataxia and tremor.

To investigate the clinical range of spinocerebellar ataxia type 6 (SCA6), we screened CAG repeat expansion in the voltage-dependent alpha 1A calcium channel gene (CACNL1A4) in 71 ataxic patients in 60 families; 54 patients in 43 families with hereditary ataxia and 17 sporadic patients. Thirteen patients with SCA6 were detected to have elongated CAG in CACNL1A4. Of these, 7 patients had been diagnosed as having hereditary cerebellar cortical atrophy, and 6 patients had been found to have sporadic occurrence. One patient showed distinct pontine atrophy with prominent horizontal or oblique gaze nystagmus which is an unusual feature in sporadic olivopontocerebellar atrophy. For the efficient screening of SCA6, we would propose testing CAG repeat expansion in CACNL1A4, in patients with one of two markers: (1) horizontal or oblique gaze nystagmus without other eye movement disorders, (2) pure cerebellar atrophy, even if occurrence is sporadic. We should note that the pontine atrophy could also be caused by CAG repeat expansion in CACNL1A4.

We have previously shown that a cortical stab wound induces the proliferation of microglia and astrocytes in situ, but no evidence was obtained for proliferation of cells of the oligodendrocyte lineage (Amat et al., 1996). To study further the properties of cells involved in repair following brain injury, groups of adult rats received either sham operations or bilateral stab wounds. Proliferating cells were labeled in vivo 3 days later with [ 3 H]-thymidine (Thy) and sacrificed the same day. Oligodendrocyte-enriched preparations were isolated, cultured, and analyzed. The fate and antigenic phenotype of the proliferating cells was analyzed using three-color immunofluorescence combined with autoradiography at 1, 2, 3, 5, and 10 days in vitro (DIV). Cells were immunostained for ganglioside GD3 (glial stem cells), 04 antigen (cells of the oligodendrocyte lineage), galactosyl ceramide (GC, differentiated oligodendrocytes), and GFAP (astrocytes). Thymidine-labeled O4+/GC- cells were found only in cultures from wounded animals and most of them differentiated in vitro as mature oligodendrocytes, but no Thy+/O4+/GC+ oligodendrocytes were seen at 1, 2, or 3 DIV. There was also a marked increase in the number of Thy+/GD3+ cells in the experimental cultures. In both experimental and control groups the total number of Thy+ and Thy- GD3+ cells declined with time in culture concomitant with an increase in total number of both Thy+ and Thy- GFAP+ astrocytes, and without any significant change in the Thy+ cell fraction of O4+ oligodendrocytes in the experimental cultures. Therefore most of the GD3+/O4- cells apparently differentiated as GFAP+ astrocytes, not as oligodendrocytes. We conclude that O4+/GC- oligodendrocyte precursor cells, but not differentiated oligodendrocytes, proliferate in response to brain injury. These cells proliferate slowly or not at all in normal adult animals and constitute a phenotypically and kinetically distinct group from the GD3+ glial precursors. This result is consistent with the existence within the adult CNS of a quiescent premyelinating oligodendrocyte. We propose that these immature committed oligodendrocytes are induced to proliferate at the wound site and serve as a source of new oligodendrocytes.

The growth inhibitor factor (GIF) is a new member of the metallothionein family that is downregulated in Alzheimer's disease brain. Using a confocal laser scan microscope with polyclonal and monoclonal antibodies to GIF, and monoclonal antibodies to glial fibrillary acidic protein (GFAP) and MAP-2, we demonstrated that GIF immunoreactivity was expressed primarily in astrocytes and much less in neurons. In astrocytes of normal rat brain GIF immunoreactivity was detected mainly in the cell bodies, while GFAP immunoreactivity was detected mainly in the processes. GIF immunoreactivity was more strongly expressed in reactive astrocytes. These findings were confirmed with both polyclonal and monoclonal antibodies. Following stab wounds, a number of GIF-positive reactive astrocytes were detected around the wounds at 3 days postoperation. After 7 days GIF immunoreactivity was detected in cell bodies and processes of reactive astrocytes. The number of GIF-positive astrocytes and the intensity of the immunoreactivity remained elevated over the control levels at least through 28 days. These immunocytochemical findings correlated well with changes in GIF protein and mRNA levels. Not only changes in GIF protein and mRNA levels but also intracellular localization of GIF in normal rat brain and after stab wounds in rat brain were different from those of GFAP. These results support the concept that GIF plays an important role in the processing of reconstruction after brain damage.

Brain injury induces reactive gliosis, characterized by increased expression of glial fibrillary acidic protein (GFAP), astrocyte hypertrophy, and hyperplasia of astrocytes and microglia. One hypothesis tested in this study was whether ganglioside GD3+ glial precursor cells would contribute to macroglial proliferation following injury. Adult rats received a cortical stab wound. Proliferating cells were identified by immunostaining for proliferating cell nuclear antigen (PCNA) and by [3H]-thymidine autoradiography, and cell phenotypes by immunocytochemical staining for GD3, GFAP, ED1 (for reactive microglia) and for Bandeiraea Simplicifolia isolectin-B4 binding (all microglia). Animals were labeled with thymidine at 1,2,3, and 4 days postlesion (dpl) and sacrificed at various times thereafter. Proliferating cells of each phenotype were quantified. A dramatic upregulation of GD3 on ramified microglia was seen in the ipsilateral hemisphere by 2 dpl. Proliferating cells consisted of microglia and fewer astrocytes. Microglia proliferated maximally at 2-3 dpl and one third to one half were GD3+. Astrocytes proliferated maximally at 3-4 dpl, and some were also GD3+. Both ramified and ameboid forms of microglia proliferated and by 4 dpl all GD3+ microglia were ED1+ and vice versa. In the contralateral cortex microglia expressed neither GD3 nor ED1. Thus they acquired these antigens when activated. Neither microglia nor astrocytes that were thymidine-labeled at 2, 3, or 4 dpl changed in number in subsequent days. Most thymidine+ astrocytes were large GFAP+ reactive cells that clearly arose from pre-existing astrocytes, not from GD3+ glial precursors. In this model of injury microglia proliferate earlier and to a much greater extent than astrocytes, they can divide when in ramified form, and GD3 is up-regulated in most reactive microglia and in a subset of reactive astrocytes. We also conclude that microglial proliferation precedes proliferation of invading blood-borne macrophages.

The adult form of Sandhoff disease with the motor neuron disease phenotype is a rare neurodegenerative disorder caused by mutations in HEXB encoding the β-subunit of β-hexosaminidase, yet the properties of mutant β-subunits of the disease have not been fully determined. We identified a novel mutation (H235Y) in the β-sheet of the (β/α)8-barrel domain, in addition to the previously reported P417L mutation that causes aberrant splicing, in a Japanese patient with the motor neuron disease phenotype. Enzyme assays, gel filtration studies and immunoprecipitation studies with HEK293 cells transiently expressing mutant β-subunits demonstrated that the H235Y mutation abolished both α–β and β–β dimer formation without increasing β-hexosaminidase activity, whereas other reported mutant β-subunits (Y456S, P504S or R533H) associated with the motor neuron disease phenotype formed dimers. Structural analysis suggested that the H235Y mutation in the β-sheet of the (β/α)8-barrel domain changed the conformation of the β-subunit by causing a clash with the E288 side chain. In summary, H235Y is the first mutation in the β-sheet of the (β/α)8-barrel domain of the β-subunit that abolishes α–β and β–β dimer formation; the presented patient is the second patient to exhibit the motor neuron disease phenotype with P417L and a non-functional allele of HEXB.

The chemical vapor deposition of a thin layer of silica on alumina is shown to improve the thermal stability of alumina with respect to sintering and to reduce the loss of surface area of alumina during heating. Benzaldehyde-ammonia titration showed that samples with high stability were almost completely covered by silica. These observations suggest that an ultrathin silica layer, probably a monolayer, thermally stabilizes the surface. Bronsted acidity was observed even after calcination at 1493 K: it was initially diminished by this calcination, but readily recovered on exposure to a humid atmosphere, whereas conventional solid-acid catalysts are irreversibly deactivated by complete sintering.

The growth inhibitory factor (GIF) is a new metallothionein (MT)-like protein that is downregulated in Alzheimer's disease (AD) brain. The biological function of GIF has not been fully clarified yet. We have raised an antibody to the synthetic polypeptide that is specific for rat GIF. The purified antibody reacted to recombinant GIF and native rat GIF but not to MT or maltose-binding protein. Using the antibody and GIF cDNA probe, we investigated changes of GIF and GIF mRNA by Western and Northern blotting techniques in rat brains after stab wounds. The levels of GIF and GIF mRNA began to increase 4 days postoperation, reached a maximum at 14-21 days and sustained the increased level at least through 28 days. While both glial fibrillary acidic protein (GFAP) and GIF were recognized in astrocytes, the increases of these 2 proteins after stab wounds showed different patterns. The results indicated that GIF could play an important role in the repair after brain damage and also produce new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP.

A 21-year-old man complained of severe pain and muscle twitching localized in his right arm. Neurological examination showed muscle fasciculations in his right forearm but no myokymia or myotonia. Needle electromyography revealed fibrillation potentials in his biceps brachii muscle and extensor carpi radialis muscle at rest but no myokymic discharges. His serum anti-voltage-gated potassium channel (VGKC)-complex antibody level was significantly high (194.2pM; controls

The developmental changes in localization of myelin-associated glycoprotein (MAG) isoforms in the mouse brain were demonstrated by an immunohistochemical method using antisera specific to two MAG isoforms. The antiserum to the large isoform of MAG (L-MAG) stained the myelin sheaths and the cytoplasm of oligodendroglia in the active myelinating stage in the mouse central nervous system. However, the antiserum to the small isoform of MAG (S-MAG) stained only myelin sheaths in the adult stage. These findings suggest that L-MAG plays an important role in active myelination.

Two polypeptide isoforms of myelin-associated glycoprotein (MAG) with molecular masses of 72 and 67 kDa are produced by alternative splicing of the exon 12 portion. Our previous work has demonstrated that in the quaking mouse brain this alternative splicing is lacking and that the mRNA coding the large MAG isoform (L-MAG) is scarcely expressed, whereas that of small MAG isoform (S-MAG) is overexpressed. In the present study, we prepared antisera specific to the S-MAG and L-MAG amino acid residues, respectively. Immunoblots showed that the L-MAG band was scarcely detectable in the quaking mouse brain, whereas the S-MAG band had an apparently higher molecular mass than in the normal control. Our immunohistochemical study also showed that L-MAG was scarcely stained in the quaking mouse brain. These results seemed to reflect a reduction in content of L-MAG mRNA and abnormal glycosylation in the quaking mouse brain.

Dysferlinopathies exhibit marked heterogeneity in the initial distribution of muscle involvement at the onset of the disease. We describe a Japanese patient with dysferlinopathy who exhibited distal anterior compartment myopathy (DACM) with early contractures of the ankle, whose pedigree included patients with two other types of dysferlinopathy. The existence of three phenotypes of dysferlinopathy in one pedigree is reported, indicating the involvement of molecules other than dysferlin in the pathogenesis.

Here, we report a Japanese man with adult Sandhoff disease who presented with a motor neuron disease phenotype with slow progression. At the age of 42, he noticed weakness in his legs. At the age of 46, he was admitted to our hospital. Neurological examination revealed muscle weakness and atrophy of the upper and lower extremities, and hyperreflexia of the upper extremities. Magnetic resonance imaging showed very mild cerebellar atrophy. We diagnosed him as having atypical amyotrophic lateral sclerosis. Because of the atypical course of motor neuron disease, hexosaminidase activity in peripheral leukocytes was indicated. Asseys of hexosaminidase A and hexosaminidase B showed low activities, and we found a membranous cytoplasmic body in the submucosal nerve, leading to the diagnosis of Sandhoff disease. This is the second case of a Japanese adult with Sandhoff disease presenting with a motor neuron disease phenotype, and to our knowledge, this is the latest age of onset in Japan.

高齢者においてはビタミンB12 (以下VitB12) の組織内欠乏は明らかでも血清VitB12の低下を示さないことがあるといわれている. 症例は71歳男性, 亜急性の歩行障害で発症, 血清VitB12値正常であったが, 脊髄MRIにて頸髄～上部胸髄, 下部胸髄, 腰髄の後索, 両側索に高信号域を認め, 血清, 尿中メチルマロン酸値上昇にてVitB12組織内欠乏による亜急性脊髄連合変性症 (subacute combined degeneration : SCD) と診断した. VitB12投与により症状は軽快し, 杖歩行が可能となった.

A 50-year-old woman lost about 10 kg of body weight within two months. Thereafter, she developed dysphagia and dysphonia. She visited our hospital and presented with a weak elevation of the soft palate, fasciculation of the tongue, hoarseness of voice, muscle weakness of the neck and extremities, and a decrement in vital capacity. She was admitted with a provisional diagnosis of motor neuron disease. The results of laboratory examinations showed an elevation in serum lysozyme and liquor protein levels, and pleocytosis in the liquor. Needle electromyography showed neurogenic changes, and bilateral hilar lymphadenopathy was revealed by computerized tomography. A biopsy specimen was excised from lymph nodes near the right anterior scalene muscle, which showed noncaseating granulomas consistent with sarcoidosis. All her symptoms improved after steroid administration. Such patients can be treatable with steroids. Moreover, the differential diagnosis from motor neuron disease is important.

We describe the case of a patient with cavernous angioma (CA). A 44-year-old woman complained of numbness on the left side of the body as an initial symptom of the disease. The initial magnetic resonance (MR) imaging revealed a cystic mass with a fluid-fluid level without perifocal edema in the right thalamus on the T 2-weighted image (T 2WI) and T2*-weighted image (T2*WI). Her symptoms were self-controllable; therefore we decided to observe her natural course only with serial MR imaging. The cystic mass was not enhanced by gadolinium on T1-weighted images, although, we suspected the tumor was complicated by vascular malformation. Therefore, we performed cranial angiography to eliminate the possibility of bleeding from the vascular malformation. Angiography did not demonstrate tumor staining nor vascular malformation. Longitudinally, the tumor demonstrated mosaic signal intensities on each sequence with perifocal edema. Moreover, the tumor exhibited hypointensities on T2* WIs without perifocal edema. The natural history of the tumor on MR imaging exhibited a typical case of CA. Some previous reports described cystic CA with perifocal edema and vascular malformation. In our present case, we clinically diagnosed CA on the basis of the final MR imaging together with previous reports. An intra-axial fluid-fluid level is a very rare finding of MR imaging. Here, we report the case of a patient with cystic CA accompanied by a fluid-fluid level. This finding is not a pathognomonic sign of CA; although, we consider that it is very important to follow up carefully the natural history of such cases.

We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.

The use of intravenous immunoglobulin (IVIG) has become an accepted treatment for patients with Guillain-Barré syndrome. Few patients develop adverse reactions to IVIG such as flushing, urticaria, eczema, chest tightness, wheezing, diaphoresis and hypotension. We report three patients who each received a five day course of IVIG at the standard dose of 0.4 g/kg/day. Two patients had Guillain-Barré syndrome, and the other had Miller Fisher syndrome. All developed eczematous reactions after 4 days from the start day of therapy to 5 days from the last day of therapy. One patient with GBS had widespread eczematous eruption with severe pompholyx lesions on the palms, fingers and soles, and spread over a period of 2 to 3 weeks to become generalized. That persisted for 4 weeks but gradually settled with desquamation by the use of topical steroids. None of our patients subsequently developed long-term or chronic eczema after the resolution of the initial cutaneous reaction. Eczematous reactions of our patients were similar to those reported in the literature and clinically typical as pompholyx. Although pompholyx has been recognized as a clinical entity, its cause remains obscure. Cutaneous reactions after IVIG infusion are recognized to be rare, but actually they may occur more frequently than our recognition, and its knowledge is essential to make the right clinical decision.

A 76-year-old man with supranuclear palsy, developed consciousness disturbance followed by the treatment of decubitus ulcer in the sacral region using iodoform-gauze. He was semicoma and tachycardia. His pupils were miotic and light reflexes were absent. EEG demonstrated diffuse and random slow activities. Plasma concentration of free iodine was high (151 micrograms/dl), but the other laboratory findings including thyroid functions were normal. He was diagnosed as suffering from iodoform poisoning. The symptoms and laboratory abnormalities of the patient recovered soon after the removal of iodoform-gauze. Although iodoform has been widely used for the treatment of wounds, there are few case reports of its side effects, such as consciousness disturbance, delirium, headache and tachycardia.

Study Objectives: Recent CSF and postmortem brain hypocretin measurements in human narcolepsy suggest that hypocretin deficiency is involved in the pathophysiology of the disease. In this study, we measured CSF hypocretin-1 levels in various age ranges from infants to elder people to investigate the age-dependent change of hypocretin concentrations. Design: CSF hypocretin levels were compared by age groups and gender. ANOVA was used to examine the influences of these two parameters on CSF hypocretin levels. Setting: University-based sleep and biology laboratory. Patients or Participants: Two hundred seventy two patients were included in this study, with 157 males and 115 females (0-79 years old). Interventions: CSF samples were obtained by lumber punctures with informed consents. Measurements and Results: Hypocretin-1 levels are not different in respect to gender or age, although our samples constitute a heterogeneous group with various disease conditions,. CSF hypocretin-1 levels in infants under 4 months are similar to those in adults. Conclusions: Early maturation of hypocretin transmission is suggested. No age- or gender-dependent changes in CSF hypocretin is observed.

The developmental maximum expression of the large myelin-associated glycoprotein isoform (L-MAG) protein prior to that of the small myelin-associated glycoprotein isoform (S-MAG) in both the central and peripheral nervous systems (CNS, PNS) in mice was shown by immunoblotting techniques using specific antibodies to the L-MAG protein and the S-MAG protein. Both the L-MAG protein and the S-MAG protein were expressed earlier in the PNS than in the CNS, which reflects earlier myelination in the PNS. The peak of the L-MAG protein concentration was 8 days in the sciatic nerve and 15 days in the brainstem. The concentration of the S-MAG protein in the sciatic nerve reached a peak at 15 days, whereas in the brainstem it increased rapidly between 15 and 20 days and gradually thereafter. Thus, the preceding maximum expression of the L-MAG during active myelination in the PNS demonstrated here as well as in the CNS strongly suggests an important role for L-MAG in myelin formation.

Immunohistochemical study on growth inhibitory factor (GIF) in rat brain has revealed that a glial cell layer on the surface of cerebral cortex and the cells surrounding Purkinje cells has been reported. In addition, neurons in gray matter were weakly immunostained for GIF. In situ hybridization using digoxigenin-labeled single-strand RNA probes also demonstrated that most of the neurons and small round cells, which were presumably astrocytes, expressed GIF mRNA in the cerebral cortex of rat brain. These findings indicate that GIF is produced in neurons as well as in astrocytes. The most prominent findings in this study are, a very strong reaction of GIF and GIF mRNA in the reactive astrocytes around the site of injury induced by stab wound or kainic acid injection. These results raised the possibility that GIF may act as an acute-phase protein in reactive astrocytes and have a role in tissue repair.

It is reported that cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) concentrations in patients with narcolepsy are significantly low. Human narcolepsy is also known to be closely associated with a specific human histocompatibility leukocyte antigen (HLA), suggesting that autoimmunity is involved in the pathophysiology of the disease. Thus, it is important to know whether hypocretin changes are found in definite neuroimmunological diseases such as multiple sclerosis and Guillain-Barré syndrome (GBS). The results of the present study indicate that some patients with GBS have lower levels of CSF hypocretin-1.

The large myelin-associated glycoprotein isoform (L-MAG) protein and small myelin-associated glycoprotein isoform (S-MAG) protein were demonstrated after sciatic nerve crush injury in mice by an immunoblotting technique using specific antibodies to the L-MAG protein and the S-MAG protein, respectively. Immunoblots indicated a rapid decrease in expression of both isoform proteins in the crushed sciatic nerves to

The mouse myelin-associated glycoprotein gene was isolated from a mouse gene library. This gene was split into 13 exons distributed about 15 kb in length. Each extracellular immunoglobulin-related domain was encoded by a single exon, and RNA splicing between those exons occurred between the first and second nucleotides of the junctional codon, the features of which are conserved in most of the genes of the immunoglobulin superfamily. The sequence of the 5'-flanking region appeared to have some regions homologous to other myelin proteins, which suggested that they were possible cis-elements for specific expression of oligodendrocytes.

Two forms of myelin-associated glycoprotein (MAG) mRNA are produced by alternative splicing of the exon 12 portion. Expression of the two forms of MAG mRNA was studied here in experimentally introduced demyelination and remyelination by Cuprizone intoxication. During the demyelinating stage, both forms of MAG mRNA decreased markedly. When feeding with Cuprizone was stopped, MAG mRNA began to increase. One form of MAG mRNA without the exon 12 portion, which appears in normal development at the period of active myelination, was characteristically induced during the remyelinating stage. The other form containing the exon 12 portion was also induced but recovered only to the level in normal development.

We report siblings, a 21-year-old woman (proband) and her 26-year-old brother, with dentatorubral-pallidolysian atrophy (DRPLA). There was no family history of DRPLA and no clinical abnormalities in their parents, who were both above the age of 50. Analysis of the DRPLA gene of leukocytes showed CAG repeat sizes to be 64/17 in the proband, 58/20 in her brother, and 56/8 in their mother. Sporadic cases of DRPLA can occur with maternal as well as paternal transmission.

CSF hypocretin-1 was measured in 28 Guillain-Barre syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (