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Biomedical subjects

I Akiguchi

Publications and source records attributed to I Akiguchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neuregulin is associated with nerve regeneration in axonal neuropathies.

Neuregulins (NRG), the only trophic factors known to support Schwann cell survival, have a potential for use in treatment of patients with chronic neuropathies. Expression of one NRG isoform, NRG-beta1, was increased in axons in the early phase of axonal degeneration in nerve biopsy specimens from patients with neuropathy. Regenerating nerve fibers contained abundant NRG-beta1 in axons, but nerves from patients with chronic axonal neuropathy showed less. NRG-beta1 may act as an axonally derived signal having a trophic effect on denervated Schwann cells, facilitating their supportive role in axonal regeneration.

Axons↗
PubMed2000

Immunohistochemical localization of glial cell line-derived neurotrophic factor family receptor alpha-1 in the rat brain: confirmation of expression in various neuronal systems.

The localization of glial cell line-derived neurotrophic factor (GDNF) family receptor alpha-1 (GFRalpha-1) was investigated in rat brain by immunohistochemistry using a polyclonal antibody against a specific sequence of the rat protein. For raising the antisera in rabbits, we synthesized the oligopeptide SDVFQQVEHISKGN that corresponds to residues 139 to 152 of rat GFRalpha-1. On immunospot assay, 0.5 microg/ml of an affinity-purified antibody was capable of detecting 7.8 pmol of the rat GFRalpha-1 oligopeptides. When rat brain homogenates were examined by Western blots, the antibody revealed two main bands with molecular weights of approximately 47 kDa and 53 kDa, corresponding to the known sizes of GFRalpha-1. Immunohistochemistry in rat brain demonstrated that GFRalpha-1-like immunoreactivity was present in neurons but not in glial cells. The localization of GFRalpha-1-like immunoreactivity was largely consistent with that of the corresponding GFRalpha-1 mRNA. Positive neurons were distributed widely in various brain regions, but were particularly abundant in such regions as the olfactory bulb, diagonal band, substantia innominata, zona incerta, substantia nigra, cerebellar cortex, nuclei of the cranial nerves including auditory system and spinal motoneurons. The present study showed that GFRalpha-1 in the normal central nervous system is expressed preferentially in certain multiple neuronal systems that include cholinergic system as well as dopaminergic system and motor neurons. As GFRalpha-1 protein was found in numerous brain structures, GDNF family ligands may have therapeutic application not only in degenerative diseases affecting in specific nervous systems, such as Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy, but in diffusely damaging diseases like cerebrovascular diseases.

Animals↗
PubMed2000

Implication of sensorimotor integration in the generation of periodic dystonic myoclonus in subacute sclerosing panencephalitis (SSPE).

To clarify the mechanism of periodic dystonic myoclonus in subacute sclerosing panencephalitis (SSPE), a 22-year-old patient with a clinical diagnosis of SSPE was electrophysiologically investigated. Involuntary movements consisted of generalized dystonic posturing which occurred quasiperiodically once every 4 to 8 seconds. Effects of sensory stimuli and voluntary movements were studied by means of polygraphic recording of surface electromyogram (EMG), scalp electroencephalogram (EEG), and magnetoencephalogram (MEG). EEG showed quasi-periodic, generalized, transient complexes synchronous to each dystonic myoclonus, which were preceded by a slow negative EEG shift at the parietal region by approximately 5 seconds. Neither external stimuli nor self-paced movements alone influenced the periodicity of dystonic myoclonus or EEG complexes. In the reaction time task, however, the external stimuli given as an imperative cue to execute a motor task elicited dystonic myoclonus and generalized EEG complexes only if they were presented in the latter segment of the interval between the two successive EEG complexes while the slow negative EEG shift appeared. These findings suggest that EEG complexes and periodic movements spontaneously occur when cortical excitability reaches a certain critical level, but both phenomena are elicited even before if the sensory stimuli as an imperative signal requiring motor execution are presented. This finding most likely implies involvement of the sensorimotor integration mechanism in these periodic phenomena.

Adult↗
PubMed2000

Cyclooxygenase-2 is induced in microglia during chronic cerebral ischemia in humans.

Cyclooxygenase-2 (COX-2) is known to be up-regulated in ischemic rodent brains, but only little information is available for the human brain. Using immunohistochemistry for COX-2, we investigated brains from control subjects and from patients with cerebrovascular diseases. COX-2 was markedly up-regulated in the neurons and endothelial cells in acute cerebral infarction, but was detected sparsely at chronic stages in these cellular compartments. In contrast, COX-2 immunoreactivity in glial cells was localized to the perinuclear region even in control brains. This immunolabeling was more intense and occurred also in the glial cytoplasm in the brains with chronic cerebral ischemia such as Binswanger's disease. Double-labeling immunohistochemistry confirmed that COX-2-immunoreactive glia were mostly microglia. These results indicate that prostanoid synthesis is up-regulated in microglia during chronic cerebral ischemia, and that these cells may be involved in tissue repair or inflammation-mediated cell responses.

Aged↗
PubMed2000

Apoptosis of perineurial cells in sensory perineuritis.

A 71-year-old man presented a 6-month history of progressive paresthesia of all four limbs. Sural nerve biopsy specimens showed dense mononuclear infiltrates in the perineurium and subperineurium, indicating sensory perineuritis. One section revealed disruption of the perineurial barrier. Perforin and granzyme B were present in the infiltrates, and apoptosis of perineurial cells was indicated by a terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. These findings suggest T cell-mediated apoptosis of the perineurium and nerve injury caused by perineurial damage.

Aged↗
PubMed2000

Glial cell line-derived neurotrophic factor-like immunoreactivity in the cerebella of normal subjects and patients with multiple system atrophy.

Glial cell line-derived neurotrophic factor (GDNF) has a trophic effect on various types of neurons, including cerebellar Purkinje cells. To investigate the role of GDNF in the human cerebellum, we examined the cerebella of eight control cases and eight patients with multiple system atrophy (MSA) immunohistochemically using a polyclonal anti-GDNF antibody. The antibody recognized a single band of approximately 34 kDa on Western blot analysis of human cerebellar homogenates. In the cerebella from normal subjects, the neuronal somata and dendrites of the Purkinje cells were immunostained intensely, as were some axons, including torpedoes, immunolabeled in the granular layer. Many axons and a few oligodendrocytes were also immunopositive in the white matter, and weak immunoreactivity was detected in the granule cells and neurons in the cerebellar nuclei. In the cerebella from patients with MSA, the general immunostaining pattern was similar to that observed in the normal subjects. Most of the remaining Purkinje cells showed strong immunoreactivity, and abundant GDNF-positive granular structures or dense arborizations of GDNF-positive dendrites were found in some areas of the molecular layer. These data suggest that GDNF may be mainly produced and localized in the Purkinje cells of the human cerebellum, even in patients with MSA, and that the functional impairment of the Purkinje cells of MSA patients might cause a focal accumulation of GDNF in the dendrites of some of the surviving Purkinje cells.

Aged↗
PubMed2000

Blood-brain barrier permeability in the periventricular areas of the normal mouse brain.

The main objective of this study was to assess the blood-brain barrier (BBB) permeability in periventricular areas of the normal mouse brain to test the hypothesis that the fragility of the BBB in periventricular areas may play a role in periventricular white matter lesions. Vascular permeability to intravenously injected horseradish peroxidase (HRP) was examined in the periventricular areas of adult mouse brain using light and electron microscopy. Staining for HRP appeared in the periventricular area adjacent to medial side of the lateral ventricle as well as in BBB-free areas, in the lateral septal nucleus, in the medial portion of the hippocampus and in the dorsal portion of the thalamus. In addition, the staining for HRP appeared in ependymal cell layer located near the choroid plexus and was found early after HRP injection in the wall of some vessels located at medial side of the optic tract. Ultrastructural examination of the vessel wall revealed that staining for HRP in the perfusion-fixed mice after circulation of the tracer for 5 min appeared in the perivascular space, in the basal lamina, in several vesicular profiles of the endothelial cell cytoplasm including abluminal pits, in vesicular profiles of perivascular cells and in the adjacent extracellular space. In the mice perfusion-fixed after HRP circulation for 90 min, staining for HRP in the vessels at medial side of the optic tract appeared in the cytoplasm of the perivascular cells, in vesicular structures of the endothelial cell cytoplasm such as plasmalemmal vesicles, endosomes and multivesicular bodies and occasionally in the vascular basal lamina. No clear staining reaction for HRP was found in the periventricular areas adjacent to lateral side of the lateral ventricles. These findings indicate that the BBB in the periventricular area adjacent to medial side of the lateral ventricle near the root of the choroid plexus is not so tight as it is in the cortex or in the lateral periventricular areas, and suggest that the perivascular cells play a scavenger role in the periventricular area as a component of the BBB. In addition, they indicate that blood-borne macromolecules can also invade the areas adjacent to the ventricles such as the lateral septal nucleus, the medial portion of the hippocampus and the dorsal portion of the thalamus.

Animals↗
PubMed2000

Magnetic resonance imaging distinguishes progressive supranuclear palsy from multiple system atrophy.

To establish diagnostic magnetic resonance imaging (MRI) criteria for differentiating progressive supranuclear palsy (PSP) from multiple system atrophy (MSA), magnetic resonance images from eight patients with probable PSP, 30 with probable MSA (nine striatonigral degeneration (MSA-P) and 21 olivopontocerebellar atrophy (MSA-C)), and ten age-matched controls were retrospectively studied. Anteroposterior diameters in the midline sagittal T1-weighted image of the rostral (RMT) and caudal midbrain tegmentum (CMT), caudal pons and medulla were measured. Divergence of the red nuclei (RN) in the axial T2-weighted image was judged. All PSP images had a smaller RMT diameter than the lower limit of the normal range, showed RN divergence, and had a pontine diameter within the normal range. All MSA images had a CMT diameter within the normal range; no MSA images showed divergence of RN. Forty-four percent (4/9) of MSA-P and 76% (16/21) of MSA-C images had a pontine diameter smaller than the lower limit of the normal range. On basis of the results, we propose MRI diagnostic criteria for differentiating PSP from MSA.

Age of Onset↗
PubMed2000

Immunohistochemical localization of glial cell line-derived neurotrophic factor in the human central nervous system.

Glial cell line-derived neurotrophic factor, initially purified from the rat glial cell line B49, has the ability to promote the survival and differentiation of various types of neurons in the central and peripheral nervous systems. In the present study, to evaluate the physiological role of glial cell line-derived neurotrophic factor in the central nervous system, we investigated the cellular and regional distribution of glial cell line-derived neurotrophic factor immunoreactivity in autopsied control human brains and spinal cords using a polyclonal glial cell line-derived neurotrophic factor-specific antibody. On western blot analysis, the antibody reacted with recombinant human glial cell line-derived neurotrophic factor, and recognized a single band at a molecular weight of approximately 34,000 in human brain homogenates. Glial cell line-derived neurotrophic factor immunoreactivity was observed mainly in the neuronal somata, dendrites and axons. In the telencephalon, diencephalon and brainstem, the cell bodies and proximal processes of several neuronal subtypes were immunostained with punctate dots. Furthermore, immunopositive nerve fibers were also observed, and numerous axons were intensely immunolabeled in the internal segment of the globus pallidus and the pars reticulata of the substantia nigra. In the cerebellum, the most conspicuous immunostaining was found in the Purkinje cells, in which the somata and dendrites were strongly immunolabeled. Intense immunoreactivity was also detected in the posterior horn of the spinal cord. In addition to the neuronal elements, immunopositive glial cell bodies and processes were observed in various regions. Our results suggest that glial cell line-derived neurotrophic factor is widely localized, but can be found selectively in certain neuronal subpopulations of the human central nervous system. Glial cell line-derived neurotrophic factor may regulate the maintenance of neuronal functions under normal circumstances.

Aged↗
PubMed2000

Membranous lipodystrophy presenting with palilalia: a PET study of cerebral glucose metabolism.

A case of membranous lipodystrophy (Nasu-Hakola disease; NHD) associated with palilalia was reported. A 38-year-old Japanese woman developed walking difficulty in her twenties. At age 35 she manifested neuropsychiatric symptoms characterized by euphoria, palilalia and dementia. A bone marrow biopsy showed periodic acid Schiff-positive membranous cystic lesions in the adipose tissue. Positron emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose disclosed that regional cerebral glucose metabolism was decreased in the bilateral frontal white matter with mild hypometabolism in the thalamus and basal ganglia; all predominantly on the right. Taken together with the previous postmortem findings, it is postulated that frontal lobe hypofunction, predominantly in the right hemisphere, produced the unique neuropsychiatric symptoms in this patient.

Adult↗
PubMed2000

Neuropathology of amyotrophic lateral sclerosis with extra-motor system degeneration: characteristics and differences in the molecular pathology between ALS with dementia and Guamanian ALS.

Amyotrophic lateral sclerosis (ALS) is classified into distinct subtypes mainly based on clinicopathological features, in addition to epidemiologic and genetic backgrounds. In addition to sporadic ALS with classical pathology, characteristics in the clinical features, in the histological findings and their topographical distribution, and in the molecular pathology, especially the intracytoplasmic neuronal inclusions, enable us to identify the following subtypes: ALS with dementia (ALS-D), ALS in the Western Pacific, ALS with multi-system degeneration, familial ALS, and superoxide dismutase 1-linked ALS. These subtypes not infrequently exhibit various types of extra-motor system degeneration, and even multi-system pathology. Some of the subtypes (for instance ALS-D or familial ALS) can be deduced, to a certain extent, from characteristic neuronal inclusions such as ALS-type ubiquitinated inclusions, Lewy body-like hyaline inclusions (LBHIs), or ubiquitinated intracytoplasmic neuronal inclusions as typically seen in the dentate fascia. The purpose of this article is to clarify the molecular pathogenesis of the cerebral cortex in ALS-D and Guamanian ALS and parkinsonism-dementia complex (PDC), in order to elucidate the relationship and distinction between these two subtypes. As indicated previously, investigations on ubiquitin-immunoreactivity in the hippocampus further support the view that the pathology of G-ALS/PDC may be that of a tau-related tangle disorder, whilst ALS-D has a feature of the motor neuron disease type-frontotemporal dementia.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Vascular cell components of the medullary arteries in Binswanger's disease brains: a morphometric and immunoelectron microscopic study.

BACKGROUND AND PURPOSE: It has been hypothesized that fibrohyalinosis of the medullary arteries may cause white matter lesions in Binswanger's disease (BD). However, previous reports have been inconsistent on the pathological alterations of the cellular components, which may vary in terms of vessel sizes. We therefore quantitatively examined vasculopathy in the medullary arteries of a defined caliber in BD brains with a quantitative technique. METHODS: A total of 20 brains were examined: 10 from patients with BD and 10 from age-matched nonneurological control patients. The alterations in the vascular cell components were examined with quantitative immunohistochemistry and immunoelectron microscopy for collagen and smooth muscle actin. RESULTS: The nonneurological control patients showed no white matter lesions. In contrast, the patients with BD invariably had marked white matter lesions, as well as fibrohyalinosis of the medullary arteries. The ratio of the area immunolabeled for collagen type I and type IV to the cross-sectional area was 2-fold higher in the BD patients than in the control patients, regardless of the vessel caliber (P<0.005). Although the ratio for smooth muscle actin in the BD brains was increased in arteries of <100 microm (P<0.0001), there was no corresponding increase in the arteries of >100 microm. However, in the ultrastructure of these vessels, the cell bodies immunolabeled for smooth muscle actin were hypertrophic and segregated from each other by proliferated fibrils. The basal lamina appeared multilayered, and the endothelial cells were swollen. Collagen type I and type IV immunoreactive fibrils also proliferated in the pericapillary space of the BD brains. CONCLUSIONS: The proliferation of collagen fibrils in the media and adventitia of the blood vessels in BD brains was not specific to small arteries and arterioles but also occurred in the pericapillary spaces. Pericapillary sclerosis, smooth muscle cell proliferation in the terminal arterioles, and their morphological transformation in the proximal arteries may alter the shear rates and thus cause profound microcirculatory disturbances in BD brains.

Actins↗
PubMed2000

Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects.

OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.

Aged↗
PubMed2000

Effects of an antithrombin drug in patients with subacute exacerbations of Binswanger disease.

The blood coagulation system has been shown to be activated in subacute exacerbations of Binswanger disease (BD). In our previous study, the antithrombin drug argatroban t ameliorated the neurological exacerbations in a BD patient with antiphospholipid antibody syndrome. We have further examined the therapeutic efficacy of argatroban in 3 BD patients with subacute exacerbations, but without any immune-mediated prothrombotic complications. In 1 out of these 4 patients, treatment with sodium ozagrel, an antiplatelet drug was applied, but was ineffective. In all patients, argatroban treatment reduced the levels of the hemostatic markers, with a corresponding improvement in cognitive dysfunction and gait disorders. These results suggest that the antithrombin effect is true also for BD patients not compromised by the immune-mediated prothrombotic condition.

Acute Disease↗
PubMed2000

Hemizygous mutation of the peripheral myelin protein 22 gene associated with Charcot-Marie-Tooth disease type 1.

We studied a female patient who presented with autosomal recessive or sporadic Charcot-Marie-Tooth disease type 1 (CMT1). We found that she had a 1.5-megabase deletion in chromosome 17p11.2-p12 containing the peripheral myelin protein 22 gene (PMP22) and an Arg157Gly mutation of PMP22. Hemizygous mutation of PMP22 should be considered in patients with autosomal recessive CMT1 or with severe hereditary neuropathy with liability to pressure palsy.

Charcot-Marie-Tooth Disease↗