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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
PubMed1997

Age-related changes in the brain transfer of blood-borne horseradish peroxidase in the hippocampus of senescence-accelerated mouse.

Age-related changes in the brain transfer of blood-borne horseradish peroxidase (HRP) were examined by light microscopy in senescence-accelerated prone mice (SAMP8) and senescence-accelerated resistant mice (SAMR1). The intracerebral HRP transferred from the blood stream was reacted with tetramethyl benzidine (TMB) and the area showing the presence of HRP-TMB reaction products was morphometrically evaluated. Areas containing HRP reaction products in the medial CA1 region and medial dentate gyrus of the hippocampus were observed in 3- and 13-month-old SAMP8 and SAMR1. The mean percentage of the positive area for the HRP to the area of interest was significantly higher in the rostral portion of the hippocampus in 13-month-old than in 3-month-old SAMP8. On the other hand, age-related changes in the area positive for HRP-TMB reaction products in the cortices and the caudal portion of the hippocampus in SAMP8 were not observed. In addition, positive staining reaction for HRP was also observed in the dorsal portion of the thalamus of 13-month-old SAMP8. There were no significant age-related changes in the area positive for HRP-TMB reaction products in rostral and caudal portions of the cortices and the hippocampus of SAMR1. These findings suggest that blood-borne macromolecules have access to the medial and rostral portion of the hippocampus, that this phenomenon becomes more pronounced during the process of senescence in the SAMP8 brain and, moreover, that intravascular macromolecules have access to the dorsal portion (periventricular area) of the thalamus of 13-month-old SAMP8.

Aging↗
PubMed1997

Comparative study of ubiquitin immunoreactivity of hippocampal granular cells in amyotrophic lateral sclerosis with dementia, Guamanian amyotrophic lateral sclerosis and Guamanian parkinsonism-dementia complex.

This report concerns an investigation on ubiquitin immunoreactivity in the neuronal perikarya of hippocampal granular cells in Guamanian amyotrophic lateral sclerosis (G-ALS) and Guamanian parkinsonism-dementia complex (G-PDC). Specimens from two non-Guamanian cases of ALS with dementia (ALS-D) were included for comparison. Histologically normal hippocampi from five adults served as controls. Antibodies to ubiquitin and tau protein were used throughout. Most Guamanian patients examined had granular cells with perikaryal ubiquitin immunoreactivity in the dentate gyrus, but in comparison to ALS-D, the frequency of ubiquitin-positive neurons was significantly lower. Tau-positive granular cells were detected in most Guamanian patients, but not in ALS-D. There was a relationship between the numbers of ubiquitin-positive and tau-positive neurons in the dentate granular cell layer of G-ALS and G-PDC patients. This was verified on sections double immunostained for tau protein and ubiquitin. The present findings suggest that the ubiquitin-positive materials observed in the perikarya of the dentate granular cells of patients with G-ALS or with G-PDC seem to be Alzheimer's neurofibrillary tangles rather than the typical ubiquitin-positive intracytoplasmic neuronal inclusions, characteristics of ALS-D. Our data would indicate that different mechanisms are involved in the geneses of cortical neuronal degeneration and decline in cognitive function in ALS-D, G-ALS and G-PDC.

Adult↗
PubMed1997

Expression of interleukin-1 receptor antagonist protein in post-mortem human brain tissues of Alzheimer's disease and control cases.

The immunohistochemical localization of interleukin-1 receptor antagonist protein (Il-1ra) was examined in brain tissues of neurologically normal controls as well as in cases of Alzheimer's disease (AD) and Pick's disease. In all control cases, immunoreactivity was observed in some normal-appearing neurons in the neocortex and hippocampus. In AD, there appeared to be increased numbers of positively staining neurons, and the staining of individual neurons was somewhat more intense. Il-1ra was additionally expressed in globular deposits in senile plaques and, weakly, in some extracellular neurofibrillary tangles. In Pick's disease, there was similar staining of normal-appearing neurons and intense staining in some degenerating neurons. Using reverse transcriptase-polymerase chain reaction techniques, the mRNA for IL-1ra was detected in cultured IMR-32 human neuroblastoma cells following differentiation with dibutyryl cAMP and bromodeoxyuridine. Taken together, these data suggest that IL-1ra is a product of normal neurons which may be upregulated in some pathological circumstances.

Aged↗
PubMed1997

Ubiquitin-related cytoskeletal abnormality in frontotemporal dementia: immunohistochemical and immunoelectron microscope studies.

Although reports of dementia lacking the distinctive non-Alzheimer-type histopathology have been increasing, the concept is still far from clear. It has become apparent that this population shows neuropathological heterogeneity, and some recent reports have proposed a classification or criteria for these disease conditions. Of the reported cases, frontotemporal dementia (FTD) of motor neuron disease is unique in that the neurons of the hippocampus and entorhinal cortex have ubiquitin-related abnormalities. Recently, a new ubiquitin-related abnormality, characterized by ubiquitinated inclusions in the neurites, has been found in some FTD cases. Using immunoelectron microscopy with immunogold particles, we have found that in these two disease conditions ubiquitinated inclusions consist of abnormal filaments of 10-15 nm in diameter. Our results support the speculation that there is a close relationship between ubiquitin and abnormal filaments in these two types of FTD, indicating that cytoskeletal-related disorders may underlie certain types of FTD.

Aged↗
PubMed1997

Regressive changes of astroglia in white matter lesions in cerebrovascular disease and Alzheimer's disease patients.

The pathogenesis of white matter lesions, which are frequently found in ischemic cerebrovascular disease and Alzheimer's disease, remains unclear. Using light and electron microscopic immunohistochemistry for glial fibrillary acidic protein (GFAP) as a marker, the present study focused on the role of astroglia which show characteristic morphological alterations. Of 29 brains of patients with cerebrovascular disease and Alzheimer's disease, 4 brains showed extensive swelling and vacuolation of white matter astroglia with their processes disintegrated and beaded (termed clasmatodendrosis). No such cells were observed in 6 control patients. Clasmatodendritic astroglia were not intensely eosinophilic using hematoxylin and eosin staining and included large lipophilic granules in their perikarya. These astroglia were immunoreactive for serum proteins such as immunoglobulins, fibrinogen and complement C3, C1q and C3d, as well as for proteins which are known to increase in reactive astroglia, such as vimentin, alpha-B crystallin, apolipoprotein-E and laminin. Double labeling for GFAP and microglial cell markers indicated that these cells were of astroglial lineage. Immunoelectron microscopy for GFAP revealed that clasmatodendritic astroglia had condensed chromatin, lysosomes and large membrane-bound osmiophilic cytoplasmic inclusions, which corresponded to the lipophilic granules observed with light microscopy. These cytochemical features collectively suggest that clasmatodendritic astroglia incorporate edema fluid and phagocytose cellular debris, and eventually degenerate as a result of cerebral edema.

Aged↗
PubMed1997

p35nck5a and cyclin-dependent kinase 5 colocalize in Lewy bodies of brains with Parkinson's disease.

We examined the immunohistochemical localization of p35nck5a, the regulatory subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from patients with Parkinson's disease (PD) and controls. We found p35nck5a immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and neocortex of brains from patients with PD. In addition, p35nck5a was colocalized with cdk5 immunoreactivity in LB. Cdk5 is the kinase most likely to be responsible for the phosphorylation of neurofilament proteins of LB, which is a crucial step for the formation of the insoluble LB fibrils. Since p35nck5a regulates the catalytic activity of cdk5 by forming a heterodimer with cdk5, the present results strongly support the hypothesis that a cdk5-p35nck5a complex is involved in the formation of LB fibrils.

Aged↗
PubMed1997

Amnesia following infarction in the right retrosplenial region.

We present a case of retrosplenial amnesia following an infarction in the right retrosplenial region. A 62-year-old male showed mild weakness of the left hand, dizziness and gait disturbance. He also noticed that he could not perceive objects that he saw as real, but could perceive an object as real only by touching it. Magnetic resonance imaging (MRI) showed an infarction in the splenium of the corpus callosum and retrosplenial region on the right side. There was no aphasia or apraxia, but mild topographic disturbance was present. Intelligence was normal, but amnesia was noted. Both verbal and visual memory were disturbed equally. This case suggests that memory plays a role in the right retrosplenial region.

Amnesia↗
PubMed1997

Myofibrillar myopathy. III. Abnormal expression of cyclin-dependent kinases and nuclear proteins.

The pathological process in myofibrillar myopathy (MFM) (previously also referred to as "desmin storage" or "intermediate filament myopathy") results in dissolution of myofibrils, accumulation of products of the degradative process, and abnormal ectopic expression of desmin, dystrophin, gelsolin, NCAM, and N-terminal components of beta-amyloid precursor protein. We now demonstrate that the abnormal fiber regions in MFM immunoreact strongly for (a) CDC2 kinase, the mitotic kinase that phosphorylates and disassembles intermediate filaments; (b) cyclin-dependent kinases CDK2, CDK4, and CDK7, which are involved in regulation of the cell cycle; (c) lamin B, which normally supports the inner nuclear membrane; and (d) the nuclear matrix associated protein. The normal muscle fiber lies in a terminally differentiated state and is refractory to reentry into the cell cycle. The abnormal expression of multiple cyclin-dependent kinases in the terminally differentiated muscle fiber implies inappropriate activation of positive regulators of mitosis and may signal a mitotic catastrophe. The dissolution of myofibrils may be due to hyperphosphorylation occurring during this event.

Adult↗
PubMed1997

Alterations in glia and axons in the brains of Binswanger's disease patients.

BACKGROUND AND PURPOSE: Although increasing attention is being paid to Binswanger's disease, a form of vascular dementia characterized by diffuse white matter lesions, only limited information is available on the pathological changes that occur in the glia and axons in the white matter. We therefore investigated the brains of patients with Binswanger's disease to gain further insight into its pathophysiology. METHODS: Autopsied brains from patients with Binswanger's disease (group 3; n = 17) were compared with those of nonneurological controls (group 1; n = 5) and controls with large cortical infarcts but without significant white matter lesions (group 2; n = 5). Glial fibrillary acidic protein (GFAP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR was used as a marker for activated microglia. Axonal damage was assessed by the accumulation of proteins, which are transported by fast axonal flow, amyloid protein precursor (APP), synaptophysin, and chromogranin A. RESULTS: Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia were observed in 7 of 17 patients with Binswanger's disease. LCA-immunoreactive microglia were 1.7 times more numerous in Binswanger's disease than in group 1 (P < .05). HLA-DR-immunoreactive-activated microglia were 3.4 times and 2.1 times more numerous in Binswanger's disease as compared with group 1 (P < .01) and group 2 (P < .05), respectively. There was frequent perivascular lymphocyte cuffing, and clusters of macrophages with a decreased number of oligodendroglia were observed in the rarefied white matter. The grading scores for the number of axons immunoreactive for either APP, synaptophysin, or chromogranin A were significantly higher in Binswanger's disease than in group 1 or 2. CONCLUSIONS: The pathological alterations in Binswanger's diseased brains include regressive changes in the astroglia and activation of the microglia with a decrease in the oligodendroglia, which were associated with the degradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, mediated by chronic ischemia, may play an important role in the pathophysiology of Binswanger's disease.

Aged↗
PubMed1997

Cyclin-dependent kinase 5 in Lewy body-like inclusions in anterior horn cells of a patient with sporadic amyotrophic lateral sclerosis.

Lewy body-like inclusion (LI) is a cytoplasmic inclusion body deposited in anterior horn cells of patients with amyotrophic lateral sclerosis (ALS), in which there are phosphorylated neurofilament proteins (NFP). Since phosphorylation of NFP occurs normally in the axon, aberrant phosphorylation of NFP should take place in these cell bodies. To clarify the mechanism of LI formation it is crucial to identify the kinase responsible for the phosphorylation. We found cyclin-dependent kinase 5 (cdk5) immunoreactivity in most of LI in an ALS patient. Since cdk5 phosphorylates NFP, cdk5 is a candidate kinase for NFP in LI and might be involved in the cytoskeletal disorganization in LI-containing neurons.

Adult↗
PubMed1997

[Relapsing polychondritis with mental disorders: a case report].

A 60-year-old man developed disorientation, euphoria, hyperactive behavior, mental confusion, and a moderate decrease of cognition during the course of relapsing polychondritis with bilateral auricular chondritis, sensorineural hearing loss, episcleritis and nasal chondritis. An electroencephalogram showed diffuse slow wave abnormality. The CSF analysis revealed pleocytosis and increased protein. MRI with contrast showed enhancement and edema in bilateral medial temporal regions. These abnormal findings improved markedly with the treatment of corticosteroids. This is the first Japanese case report of relapsing polychondritis presenting as mental disorders.

Anti-Inflammatory Agents↗
PubMed1997

[White matter lesions after occlusion of the bilateral carotid arteries in the rat--temporal profile of cerebral blood flow (CBF), oligodendroglia and myelin].

In the present investigation, we examined cerebral blood flow (CBF), numerical density of oligodendroglia and extent of white matter lesions after bilateral ligation of common carotid arteries in Wistar rats. Doppler flow-meter revealed a reduction of CBF to 30-40% of that before operation after 1 and 3 days, however recovered to 50-60% after 7 and 14 days. Semiquantitative evaluation with immunohistochemistry for transferrin showed a numerical decrease of oligodendroglia in the medial corpus callosum after 14 and 30 days. Tissue rare-faction promptly occurred in the optic nerve and optic tract after 3 days, whereas it was delayed to 7 days after operation and increased in intensity gradually in the other white matter regions. These results indicate that bilateral occlusion of common carotid arteries in Wistar rats elicits a chronic cerebral hypoperfusion, which cumulatively leads to delayed appearance of white matter lesions.

Animals↗
PubMed1997

[Bilateral vertebral artery occlusion].

We studied 9 patients with bilateral vertebral artery occlusion (BVAO). BVAO was confirmed using angiography in order to clarify its clinical feature, mechanism, and long term prognosis. Three patients showed bilateral intra-cranial occlusion, 3 bilateral extra-cranial occlusion, and 3 intra and extra-cranial occlusion. The basilar artery was fed by the posterior communicating artery in 8 out of 9 patients. In one of the 8, reconstitution of the thyrocervical artery was seen. We divided the patients into 4 groups according to MRI findings, as follows: Group 1 with no abnormal finding on MRI (N = 2); Group 2 with deep pontine infarcts and non-territorial small cerebellar infarcts (N = 2); Group 3 with extended pontine infarcts (N = 3); and Group 4 with cerebellar cortical artery infarcts, deep pontine infarcts, and non-territorial small cerebellar infarcts (N = 2). Transient episodes were seen in all patients, 8 patients out of 9 had vertigo/dizziness, 3 tinnitus, 2 diplopia, 2 headache, 2 numbness, and 1 hearing disturbance. These episodes preceded a final attack or complete stroke 2 days to 5 months, and those who had a longer period of episodes in the preceding term tended to have less severe deficits. Six of the patients had vertebro-basiler symptoms after being in the upright position, including all the patients in Groups 2 and 4, which had cerebellar border zone/terminal zone infarcts. These results indicate that the hemodynamic mechanism plays an important role in BVAO. The prognosis was not always grave. Four of the patients could walk independently, 2 could walk with a cane, and 3 were bed ridden (2 of which died). Long-term follow-up data (a mean of 5 years) were obtained in all patients. In the patients who could walk, one had asymptomatic cerebellar infarcts, and one had TIAs frequently. Patients with BVAO often also have TIAs and/or preceding episode and show cerebellar border zone/terminal zone infarcts. This research strongly suggests that hemodynamic mechanism might play an important role in BVAO, and that paying attention to border zone infarction in MRI and transient episodes can lead to earlier diagnosis and treatment.

Activities of Daily Living↗
PubMed1997

[Detection of mit DNA point mutations by mutation-specific PCR].

Growing understanding in recent years about the prevalence and diversity of mitochondrial DNA mutations in human diseases has prompted a need for a simple screening method. We designed multiplex mutation-specific PCR, in which mutant DNAs were selectively amplified, for the 3243 (A to G) and 8344 (A to G) mutations. This method was simple and sensitive. We detected bands corresponding to the mutations in 1 and 2% mixtures of the 3243 and 8344 mutations respectively. Mutation-specific PCR is useful for detecting mutant mitochondrial DNA in peripheral blood, where its ratio to wild type DNA is sometimes too small to be detected by conventional assay, and for large scale screening to uncover a hitherto unknown relationship between mitochondrial DNA mutations and certain diseases.

DNA Mutational Analysis↗
PubMed1997

[Bilateral caudate head infarcts].

We reported a 67-year-old woman with bilateral caudate head infarcts. She developed sudden mutism followed by abulia. She was admitted to our hospital 2 months after ictus for further examination. She showed prominent abulia and was inactive, slow and apathetic. Spontaneous activity and speech, immediate response to queries, spontaneous word recall and attention and persistence to complex programs were disturbed. Apparent motor disturbance, gait disturbance, motor aphasia, apraxia and remote memory disturbance were not identified. She seemed to be depressed but not sad. Brain CT and MRI revealed bilateral caudate head hemorrhagic infarcts including bilateral anterior internal capsules, in which the left lesion was more extensive than right one and involved the part of the left putamen. These infarct locations were thought to be supplied by the area around the medial striate artery including Heubner's arteries and the A1 perforator. Digital subtraction angiography showed asymptomatic right internal carotid artery occlusion. She bad had hypertension, diabetes mellitus and atrial fibrillation and also had a left atrium with a large diameter. The infarcts were thought to be caused by cardioembolic occlusion to the distal portion of the left internal carotid artery. Although some variations of vasculature at the anterior communicating artery might contribute to bilateral medial striate artery infarcts, we could not demonstrate such abnormalities by angiography. Bilateral caudate head infarcts involving the anterior internal capsule may cause prominent abulia. The patient did not improve by drug and rehabilitation therapy and died suddenly a year after discharge.

Aged↗
PubMed1996

Pancreastatin-like immunoreactivity in globular dystrophic neurites of senile plaques in brains of patients with Alzheimer's disease.

The immunohistochemical localization of pancreastatin (PST) was examined in brains of Alzheimer's disease (AD) and control cases using three different antisera to PST, and was compared with the staining for chromogranin A (CgA), the precursor of PST. In control brains, CgA-like immunoreactivity was observed in the cytoplasm and fibers of certain neuronal populations, which were not immunostained with any of the PST antisera. In AD brains, dystrophic neurites of globular shape located in senile plaques were immunostained with each of the PST antisera, as well as with the CgA antibody. PST-positive and CgA-positive dystrophic neurites showed similar profiles. The present study indicates that CgA is probably cleaved to produce PST in some globular dystrophic neurites in senile plaques.

Aged↗
PubMed1996

Midkine-like immunoreactivity in extracellular neurofibrillary tangles in brains of patients with parkinsonism-dementia complex of Guam.

Midkine (MK) has been shown to be present in amyloid deposits in Alzheimer's disease (AD). In the present study, expression of midkine was examined immunohistochemically in brains of patients with the parkinsonism-dementia complex of Guam, lytico bodig disease (LB), using an affinity purified antibody to midkine. Positive staining was identified on some extracellular neurofibrillary tangles. The relative prevalence was somewhat less than for beta-amyloid protein (Abeta)-positive extracellular tangles. The results demonstrate that expression of MK and Abeta is not an exclusive feature of amyloid deposits in Alzheimer brain, but is also found in LB brain.

Antibody Specificity↗