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Biomedical subjects

I Akiguchi

Publications and source records attributed to I Akiguchi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Adverse effect of nighttime blood pressure on the outcome of lacunar infarct patients.

BACKGROUND AND PURPOSE: Antihypertensive therapy has dramatically reduced the incidence of stroke recurrence; however, recent studies have suggested that the excessive lowering of blood pressure (BP) could cause ischemic cerebral lesions. We conducted a prospective study using MRI and ambulatory blood pressure monitoring to elucidate the appropriate BP control level for the prevention of silent and symptomatic cerebral infarction. METHODS: We studied 105 patients with symptomatic lacunar infarcts who underWent repeated MRI and 24-hour BP monitoring in the period between the two MRI examinations. The patients were divided into five groups according to their outcome as follows: group 1, those who showed neither symptomatic episodes nor the development of new silent lesions detected by repeated MRI; group 2, those who only showed the development of silent lacunae; group 3, those who showed development of diffuse white matter lesions only; group 4, those who showed the development of both silent lacunae and diffuse white matter lesions; and group 5, those who showed symptomatic cerebrovascular disease. Groups 2 through 5 were then compared with group 1 with respect to the ambulatory BP values. RESULTS: The average follow-up period was 3.2 +/- 2.6 years (mean +/- SD). In all patients in group 4 and group 5, nighttime systolic BPs were significantly higher than in group 1 (both P<.01), and the magnitude of the nocturnal systolic BP dip and diastolic BP dip in group 4 and group 5 were significantly smaller than in group 1 (all P<.01). In patients who took antihypertensive agents, the 24-hour systolic and diastolic BPs and nighttime systolic and diastolic BPs in group 4 were significantly higher than in group 1 (P<.01, P<.01, P<.001, P<.01, respectively). The magnitude of the nocturnal systolic and diastolic BP dip in group 5 was significantly smaller than in group 1 (both P<.01). CONCLUSIONS: A high average ambulatory BP, especially nighttime BP, and a reduced nocturnal BP dip may have an adverse effect on the development of silent ischemic lesions and symptomatic stroke attack in patients with lacunar infarcts.

Aged↗
PubMed1998

Mechanisms of tissue injury in vasculitic neuropathies.

We studied the expression of candidate molecules for tissue injury in vasculitic neuropathies immunohistochemically, using samples obtained by nerve biopsy from seven patients with necrotizing angitis. In the involved vessels of all samples, numerous infiltrating cells were positive for perforin, nitric oxide synthase (m-NOS), cyclooxygenase-2 (COX-2), or matrix metalloproteinase-1 (MMP-1). Cell-mediated cytotoxicity may be involved in the pathogenesis of small vessel injury in vasculitic neuropathies. In the endoneurium following axonal degeneration, scattered and phagocytosing macrophages showed immunostaining for m-NOS and MMP-1, but COX-2 was all but restricted to phagocytosing macrophages. This suggests a role for prostaglandins in nerve damage.

Adolescent↗
PubMed1998

Repeated injections of nicergoline increase the nerve growth factor level in the aged rat brain.

We studied whether nicergoline, clinically active in chronic cerebrovascular insufficiency, influences nerve growth factor (NGF) levels in the rat brain. In young Fischer rats, repeated intraperitoneal injections of nicergoline (0.3 and 1.0 mg/kg body weight) did not show any effects on frontal NGF contents determined by a highly sensitive enzyme immunoassay. In aged rats, 22-month-old, however, repeated injections of nicergoline (1.0 mg/kg body weight) induced a significant increase in the NGF level in the frontal region.

Aging↗
PubMed1998

[Ictal 99mTC-HMPAO-SPECT in a case of paroxysmal kinesigenic choreoathetosis].

A case of paroxysmal kinesigenic choreoathetosis (PKC) was described. The patient had attacks of paroxysmal choreoathetotic movements lasting 20-30 seconds. The attacks were regularly precipitated by sudden and unintentional movements. There were no metabolic abnormalities. EEG showed no epileptiform discharges. The attacks were subsided after administration of carbamazepine. We studied this patient with single photon emission computed tomography (SPECT) using 99mTc-HMPAO. Ictal SPECT revealed decrease of cerebral blood flow in the basal ganglia on the contralateral side of choreothetotic movements. Although the pathophysiology of PKC is still uncertain, it is hypothesized that motor activities are influenced by the direct pathway (positive feedback) and the indirect pathway (negative feedback) from the basal ganglia to the motor cortecis. Dysfunction of negative feedback is considered to be common underlying mechanisms of hyperkinetic disorders. Our findings support this hypothesis. Dysfunction of basal ganglia is likely relevant to the genesis of choreoathetosis.

Adolescent↗
PubMed1997

Unusual sensory disturbance in the thoracic region after stroke: relationship to cheiro-oral and cheiro-oral-pedal syndrome.

Three patients with unusual unilateral sensory disturbances in the thorax, in addition to hand and mouth, hand and foot, and hand, mouth and foot regions, respectively, after stroke, are described. Magnetic resonance imaging (MRI) showed a causative lesion in the ventral posteromedial and ventral posterolateral nucleus of the contralateral thalamus in two patients and the contralateral thalamocortical projections in one patient. Symptoms in three patients were due to infarction. Objective sensory loss was not found, but subjective paresthesia was observed in the thorax, in addition to the hand and mouth, hand and foot, and hand, mouth and foot regions, respectively. Paresthesia recovery time was evaluated in these three patients in addition to seven patients with cheiro-oral syndrome and eight patients with cheiro-oral-pedal syndrome. All thirteen patients who demonstrated recovery showed regional improvement of paresthesia in the following sequences: thorax, foot, mouth and then hand, which suggests that the detection threshold, from highest to lowest, occurs in the following sequences: thorax>foot>mouth>hand. These three cases with thoracic sensory disturbance form the explanatory links between the cheiro-oral syndrome and the cheiro-oral-pedal syndrome; cases with sensory disturbance in the hand, mouth, foot or thorax could be regarded as cases of sensory hemisyndrome in which the subjective experience of symptoms was restricted to the hand, mouth, foot or thorax. These symptoms may possibly be attributable to differential detection thresholds.

Aged↗
PubMed1997

Encephalitogenic peptide (EP) in human cerebrovascular white matter lesions.

The expression of encephalitogenic peptide (EP), a 68-86 amino acid sequence of guinea pig myelin basic protein (MBP), was investigated in autopsied brains with focal cerebral damage or with diffuse white matter (WM) lesions. EP immunoreactive fibers were distributed in parallel with fibers immunoreactive for amyloid protein precursor (APP), an indicator of WM damages. EP was expressed in the periphery of cerebral infarctions and hematoma in the acute and subacute stages, but was also distributed in diffuse WM lesions due to heterogeneous causes. These data indicate that EP epitopes are exposed specifically in ongoing WM damages, and that the destruction of myelin occurs sporadically in diffuse WM lesions of varying intensity.

Aged↗
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↗