[Acute motor neuropathy].
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Acute Disease↗
Biomedical subjects
G Sobue
Publications and source records attributed to G Sobue.
[Acute sensory neuropathy].
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Acute Disease↗
[Subacute idiopathic demyelinating polyradiculoneuropathy (SIDP)].
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Acute Disease↗
[A sporadic case of Charcot-Marie-Tooth disease type 1 A associated with a duplication in chromosome 17 p11.2-p12].
Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant demyelinating peripheral neuropathy. Most patients with CMT1A including sporadic cases have been found to have a 1.5 megabase tandem DNA duplication in chromosome 17 p11.2-p12 (CMT1A duplication). We reported a 7-year-old girl with sporadic CMT 1 associated with the CMT1A duplication. The diagnosis of CMT 1 was based on the symmetrical distal muscle weakness, per cavus deformity, reduced motor and sensory nerve conduction velocities, and segmental de- and remyelinatin on sural nerve biopsy. To detect the CMT 1A duplication, peripheral myelin protein 22 (PMP-22) cDNA and a polymorphic marker in this region, VAW409 R3, were employed as probes for Southern blot analysis. Sporadic cases of autosomal dominant-CMT type 1 can not be clinically differentiated from recessive-CMT1. Testing for the CMT1A duplication is an important first step even in the molecular diagnosis of sporadic CMT1.
Charcot-Marie-Tooth Disease↗
[Diagnostic utility of positron emission tomography for parkinsonism after chronic manganese exposure].
Positron emission tomography (PET) with [18F] 6-fluoro-L-dopa (18F-FDOPA) was performed in three South Korean patients with parkinsonism who developed after chronic manganese exposure. A 51-year-old man (patient 1) suffered from masked face, marked postural tremor of hands, dystonia in the neck and the upper extremities, severe retropulsion and lateropulsion which were typical for chronic manganese intoxication. 18F-FDOPA scan was normal. Other two patients, a 46-year-old man (patient 2) and a 47-year-old man (patient 3), showed tremor at rest and rigidity predominantly on the right side, bradykinesia, stooped posture and postural instability; all of these were typical for Parkinson's disease (PD). There was reduced uptake of 18F-FDOPA in the striatum, particularly in the posterior putamen predominant on the left side, in both patient 2 and 3. From these results, patient 1 was diagnosed as pure manganism, while patient 2 and 3 were primarily as PD, because loss of nigrostriatal fibers was obvious with asymmetry of affection in the putamen. PET with 18F-FDOPA provides valuable information for differentiation between PD and manganism, although it is not clear whether development of parkinsonian symptoms in patient 2 and 3 was modified by excessive manganese exposure.
Diagnosis, Differential↗
[An adult patient of Reye's syndrome--the possible background mechanism of lesions in claustrum, striatum and limbic system and limbic dementia].
We reported a 35-year-old male patient with Reye's syndrome, who showed temporarily lesions of claustrum, striatum, hippocampus and amygdala on CT, MRI and PET scan. He was previously healthy and affected upper respiratory infection. After taking 4 tablets of aspirin (335 mg x 4), he developed severe headache and status epileptics. The cerebrospinal fluid showed normal cell count and protein. The serum GOT and GPT elevated to 499 IU/l and 221 IU/l respectively. The parainfluenza virus type I titer was 32 times on admission and increased up to 128 times two weeks later. In spite of the anticonvulsant, status epileptics lasted for about one month and he needed mechanical ventilation. On 13-18 days of illness, abnormal lesions appeared in bilateral claustrum and striatum on CT and MRI. On 49 days of illness, abnormal lesions appeared in bilateral hippocampus and amygdala. All these lesions changed into normal on MRI on 111 days of illness. The 18F-FDG PET study on 80 days of illness revealed high uptake on striatum, hippocampus and amygdala bilaterally and changed into normal on 130 days of illness. He has improved markedly but showed long-standing abnormal signs of limbic dementia. We suggested this patient could be suffered from post infectious encephalitis in limbic system after Reye's syndrome.
Adult↗
[The cerebral peduncle lesion in multiple system atrophy].
Atrophy of the cerebral peduncle and the pons can be seen on radiologic examination in patients of multiple system atrophy. This radiologic finding is one of the landmarks for the diagnosis of multiple system atrophy, but its detailed pathological background has not been thoroughly assessed. To clarify the pathological features of the cerebral peduncle lesion, samples from 28 autopsied cases (male 16, female 12; age 50-76 yr) were semiquantitatively examined after staining by HE, KB, Holzer, GFAP, Bodian and Gallyas methods. Atrophy of the cerebral peduncle was symmetric in most cases and resulted from the loss of small-sized nerve fibers. The glial cytoplasmic inclusion (GCI) in the cerebral peduncle increased significantly in severe atrophic cases compared with mild atrophic cases. However, in the most severe atrophic cases, in which this tissue was severely damaged, the GCI was decreased. The atrophy of the cerebral peduncle correlated significantly with the degree of degeneration in the olivo-ponto-cerebellar system and tended to correlate with a decrease in brain weight. The duration of disease is significantly longer in severe atrophic cases compared with mild atrophic cases.
Aged↗
[Direct Gram staining of blood culture sample enabled the early diagnosis of brain abscess due to Listeria monocytogenes].
A 58 year old woman had a long history of immunocompromised state. Since age 28 she had multiple endocrine neoplasm type 2A: her thyroid gland and bilateral adrenal glands were removed because of pheochromocytoma and thyroid medullary carcinoma. Corticosteroid and levothyroxine were supplemented. At age 57 she was afflicted with systemic lupus erythematodes and nephrotic syndrome. Prednisolone therapy was started. Two months later she developed fever, lethergy, headache and left hemiparesis. MRI revealed multiple ring-enhancing lesions in the right cerebrum. CSF was negative for microorganisms. Blood culture hemolysed after 24 hours. Direct gram staining of the blood culture sample revealed gram-positive short rods without spore, suggested listeria. This enabled prompt initiation of high dose penicillin therapy before the official report of listseria infection. Neurological abnormality including left hemiparesis disappeared completely within one month. Enhancement of abscess wall decreased every month, but it persisted for five months despite continuous intravenous penicillin therapy. Listeria monocytogenes is well-recognized as an opportunistic pathogen. It requires prolonged therapy with antibiotics, since it is the intracellular organism. Monitoring of the brain abscess wall by the enhanced MRI is useful to determine the completion of therapy. Since listerial contamination is common among raw meat and unpasteurized milk, immunocompromised patients should be alarmed not to eat uncooked food products.
Bacteriological Techniques↗
[Pathogenesis and treatment of neuropathy--recent advances].
Wide variety of underlying mechanisms are present for pathogenesis and pathophysiology of neuropaties, some of the which are being elucidated recently. Remarkable recent advances are discovery of causative gene mutations of various hereditary neuropathies and elucidation of pathogenic mechanism of inflammatory demyelinating neuropathy. Particularly, causative gene mutations for Charcot-Marie-Tooth (CMT) disease and pathogenic role of glycolipid antigens for Guillain-Barré syndrome have recently been documented. Moreover, efficacious treatment based on the background pathophysiology have also been developed, such as intravenous immunoglobulin infusion and plasmapheresis for inflammatory demyelinating neuropathy, and liver transplantation for familial amyloid polyneuropathy. These advances on the understanding of pathogenic mechanisms and development of treatment have changed the clinical approach to peripheral neuropathies. In this review, I overviewed the recent advances on three neuropathies, familial amyloid polyneuropathy, chronic inflammatory demyelinating polyneuropathy, and Charcot-Marie-Tooth disease with special reference to pathogenic mechanism and treatment.
Female↗
Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.
The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.
Adult↗
Zep: A novel zinc finger protein containing a large proline-rich domain.
Zep, a novel 49 kDa zinc finger protein, was found in the brain of day-13 mouse embryos and cloned. Zep contains two C2H2-type zinc finger motifs close to the N-terminal region. The majority of the molecule is composed of a proline-rich domain showing similarity to proline-rich domains in transcription factors and a salivary proline-rich protein. In addition to the proline-rich domain, Zep has an acidic domain and a serine/threonine-rich domain, all of which are frequently found in many transcription factors. The overall organization of Zep shows no similarity to any other proteins. There is a nuclear localization signal in Zep, and the Zep-GFP (green fluorescent protein) fusion protein is located predominantly in the nucleus. In the day-13 mouse embryo, Zep is strongly expressed in the nervous system, i.e. brain, spinal cord, and dorsal root ganglia, with strong to weak expression observed in other regions. Zep continues to be strongly expressed in the neonatal brain; however, its expression is weak in the brain and spinal cord of adult mice. In situ hybridization reveals strong signals for Zep mRNA in the cerebellum and olfactory bulb with moderate signals detected in the hippocampus and cortex. Strong Zep expression is observed in adult thymus, lung, spleen, testis, and ovary. Zep may be involved in the formation and remodeling of various tissues including nervous tissue, probably through transcriptional regulation.
Amino Acid Sequence↗
Caspase-3 cleaves the expanded androgen receptor protein of spinal and bulbar muscular atrophy in a polyglutamine repeat length-dependent manner.
Spinal and bulbar muscular atrophy (SBMA) is one of a group of human inherited neurodegenerative diseases caused by polyglutamine expansion. There is increasing evidence that generation of truncated proteins containing an expanded polyglutamine tract may be an important step in the pathogenesis of these disorders. We have previously demonstrated that the SBMA gene product, the androgen receptor (AR) protein, is toxic when truncated. We now report that in vitro translated full-length AR proteins containing different sized polyglutamine repeats (24, 65 and 97 repeats, respectively) are specifically cleaved by recombinant caspase-3, liberating a polyglutamine containing fragment, and that the susceptibility to cleavage is polyglutamine repeat length-dependent. These findings suggest that AR protein is one of the "death substrates" cleaved by caspase-3 and that caspase-3 might be involved in the pathogenesis of SBMA.
Bulbar Palsy, Progressive↗
Differential signaling cascade of MAP kinase and S6 kinase depends on 3',5'-monophosphate concentration in schwann cells: correlation to cellular differentiation and proliferation.
Schwann cells produce myelin in the peripheral nervous system (PNS) and play an important role in the maintenance of the normal function of PNS. Our previous studies have shown that derivatives of adenosine 3',5'-monophosphate (cAMP) can regulate the cell-fate (i.e., proliferation and differentiation into cell surface galactocerebroside-positive cells) depending on its concentration in vitro. Higher concentration of cAMP can induce the expression of cell surface galactocerebroside, while proliferation can be induced by lower concentration of cAMP. However, the detailed molecular mechanism of how the same second messenger yields different phenotypes of Schwann cells depending on its concentration remains to be elucidated. Here we show that low concentration of 8-bromo cAMP, a cell-permeable derivative of cAMP, activates S6 kinase activity with a short-lived activation of mitogen-activated protein kinase (MAPK), whereas high dose of the reagent activates S6 kinase much less than that of low dose with a small and prolonged activation of MAPK in Schwann cells. These data clearly demonstrated that a rise in the intracellular cAMP uses the MAPK-S6 kinase pathway as an intracellular sinaling cascade and different magnitude and duration of the activation of this pathway might underlie the different cellular fate depending on the intensity of the stimulation.
8-Bromo Cyclic Adenosine Monophosphate↗
Expression of glial cell line-derived neurotrophic factor and GDNFR-alpha mRNAs in human peripheral neuropathies.
The steady-state mRNA levels of glial cell line-derived neurotrophic factor (GDNF), GDNFR-alpha and RET were examined in various human peripheral neuropathies to determine the relationship with myelinated fiber pathology, and T cell and macrophage invasions in the diseased nerves. GDNF and GDNFR-alpha mRNA levels were elevated to variable extent in the diseased nerves, although they were not specific to the type of diseases. The increase of GDNFR-alpha mRNA levels was correlated with the extent of the nerves with axonal pathology, and was proportional to the extent of invasion of the nerves by T cells and macrophages. The GDNF mRNA levels were not related to axonal, demyelinating pathology, or inflammatory cell invasions. RET mRNA expression was not detected in normal nor diseased nerves. The GDNF and GDNFR-alpha expression in the diseased human nerves is regulated by an underlying pathology-related process, and could play a role in peripheral nerve repair.
Axons↗
Accelerated formation of N epsilon-(carboxymethyl) lysine, an advanced glycation end product, by glyoxal and 3-deoxyglucosone in cultured rat sensory neurons.
The formation of advanced glycation end products (AGEs) is associated with pathophysiological changes with aging and disease processes. In the neurodegeneration in Alzheimer's disease and other neurodegenerative diseases. AGEs are speculated to play a role in their pathogenesis. We provide the first evidence for the induction of AGEs in cultured neuronal cells. Glyoxal and 3-deoxyglucosone (3-DG), AGE precursors, induced N epsilon-(carboxymethyl) lysine (CML), a well characterized and major AGE structure, in cultured rat sensory neurons in a time- and dose-dependent manner. CML formation was prevented by addition of aminoguanidine, an inhibitor of AGE formation. This culture system provides a useful model to analyze the role of the glycoxidation reaction in neuronal aging and neurodegenerative disorder.
Animals↗
NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule: in vitro study of adult rat sympathetic ganglion explants.
The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.
Analysis of Variance↗
Differential temporal expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha and gp130) in injured peripheral nerves.
The mRNA expression of the neuropoietic cytokines, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptor components (CNTFRalpha, LIFRbeta, IL-6Ralpha and gp130) was examined in peripheral nerves after two different types of injury, crush and transection. The CNTF mRNA expression levels decreased after injury and remained low in the transected model, but recovered in 4 weeks in the crushed model. The LIF mRNA rapidly increased after damage and returned gradually to control levels. The IL-6 mRNA expression increased rapidly within 1 day after injury but dramatically decreased soon after. The CNTFRalpha mRNA levels gradually increased after nerve injury. LIFRbeta was expressed in the intact nerve and decreased slightly after injury. The IL-6Ralpha expression was observed faintly in the intact nerve and increased significantly soon after injury. There was also an increase in the expression of gp130. Although the temporal expression of these neuropoietic cytokines and receptors was extremely different, their pattern was similar between the crushed and transected models, except for CNTF. These results suggest that the expression of the ligands and receptors are differentially regulated after peripheral nerve injury, implying that each cytokine and signal transduction system has entirely distinctive functions in neuronal regeneration and repair.
Animals↗
Mismatched nucleotides may facilitate expansion of trinucleotide repeats in genetic diseases.
We have studied the contribution of mismatch sequences to the trinucleotide repeat expansion that causes hereditary diseases. Using an oligonucleotide duplex, (CAG)5/(CTG)5, as a template-primer, DNA synthesis was carried out using either Escherichia coli DNA polymerase I (Klenow fragment) or human immunodeficiency virus type I reverse transcriptase (HIV-RT). Both enzymes expanded the repeat sequence longer than 27 nucleotides (nt), beyond the maximum length expected from the template size. The expansion was observed under conditions in which extension occurs either in both strands or in one strand. In contrast, with another template-primer that contains a non-repetitive flanking sequence 5'-upstream of the repetitive sequence, the reaction products were not extended beyond the template size (45 nt) by these DNA polymerases. We then used mismatched template-primers, in which either 1, 2 or 6 non-complementary nucleotides were introduced to the repeat sequence that is flanked by a non-repetitive sequence. In this case, primers were efficiently expanded over the expected length of 45 nt, in a mismatch-dependent manner. One of the primers with six mismatches extended as long as 72 nt. These results imply that the misincorporation of non-complementary deoxyribonucleoside monophosphates (dNMPs) into the repeat sequence makes double-stranded DNA unstable and triggers the slippage and expansion of trinucleotide repeats by forming loops or hairpin structures during DNA synthesis.
Base Sequence↗