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Biomedical subjects

I Akiguchi

Publications and source records attributed to I Akiguchi.

At least 19 recordsLinked to original sources
PubMed2005

The relationship between 24-hour blood pressure readings, subcortical ischemic lesions and vascular dementia.

BACKGROUND: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). METHODS: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP - nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0-0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. RESULTS: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20-9.34), advanced PVH (OR 14.42; 95% CI 5.62-36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37-115.95; reverse dipper: OR 11.95; 95% CI 1.27-112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38-11.17), high daytime (OR 2.06; 95% CI 1.03-4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13-5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03-7.05; reverse dipper: OR 3.78; 95% CI 1.38-10.34) were significantly associated with PVH. CONCLUSIONS: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

Aged↗
PubMed2005

CD16+CD57- natural killer cells in multifocal motor neuropathy.

We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.

Adult↗
PubMed2005

Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis.

Accumulating evidences indicate that ceramide is closely involved in apoptotic cell death in neurodegenerative disorders and aging. We examined ceramide levels in the cerebrospinal fluid (CSF) or brain tissues from patients with neurodegenerative disorders and the mechanism of how intra- and extracellular ceramide was regulated during neuronal apoptosis. We screened the ceramide levels in the CSF of patients with neurodegenerative disorders, and found that ceramide was significantly increased in patients with Alzheimer's disease (AD) than in patients with age-matched amyotrophic lateral sclerosis (ALS) and other neurological controls. With immunohistochemistry in AD brains, ceramide was aberrantly expressed in astroglia in the frontal cortices, but not detected in ALS and control brains. To explore for the regulation of ceramide in astroglia in Alzheimer's disease brains, we examined the metabolism of ceramide during neuronal apoptosis. In retinoic acid (RA)-induced neuronal apoptosis, RA slightly increased de novo synthesis of ceramide, but interestingly, RA dramatically inhibited conversion of [14C] ceramide to glucosylceramide (GlcCer), suggesting that the increase of ceramide mass is mainly due to inhibition of the ceramide-metabolizing enzyme GlcCer synthase. In addition, a significant increase of the [14C] ceramide level in the culture medium was detected by chasing and turnover experiments without alteration of extracellular [14C] sphingomyelin levels. A 2.5-fold increase of ceramide mass in the supernatant was also detected after 48 h of treatment with RA. These results suggest a regulatory mechanism of intracellular ceramide through inhibition of GlcCer synthase and a possible role of ceramide as an extracellular/intercellular mediator for neuronal apoptosis. The increased ceramide level in the CSF from AD patients, which may be derived from astroglia, raises a possibility of neuronal apoptosis by the response to intercellular ceramide in AD.

Aged↗
PubMed2003

Chronic cerebral hypoperfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat.

Cerebrovascular white matter lesions represent an age-related neurodegenerative condition that appears as a hyperintense signal on magnetic resonance images. These lesions are frequently observed in aging, hypertension and cerebrovascular disease, and are responsible for cognitive decline and gait disorders in the elderly population. In humans, cerebrovascular white matter lesions are accompanied by apoptosis of oligodendroglia, and have been thought to be caused by chronic cerebral ischemia. In the present study, we tested whether chronic cerebral hypoperfusion induces white matter lesions and apoptosis of oligodendroglia in the rat. Doppler flow meter analysis revealed an immediate reduction of cerebral blood flow ranging from 30% to 40% of that before operation; this remained at 52-64% between 7 and 30 days after operation. Transferrin-immunoreactive oligodendroglia decreased in number and the myelin became degenerated in the medial corpus callosum at 7 days and thereafter. Using the TUNEL method, the number of cells showing DNA fragmentation increased three- to eightfold between 3 and 30 days post-surgery compared to sham-operated animals. Double labeling with TUNEL and immunohistochemistry for markers of either astroglia or oligodendroglia showed that DNA fragmentation occurred in both of these glia. Messenger RNA for caspase-3 increased approximately twofold versus the sham-operated rats between 1 and 30 days post-surgery. Immunohistochemistry revealed up-regulation of caspase-3 in the oligodendroglia of the white matter, and also in the astroglia and neurons of the gray matter. Molecules involved in apoptotic signaling such as TNF-alpha and Bax were also up-regulated in glial cells. These results indicate that chronic cerebral hypoperfusion induces white matter degeneration in association with DNA fragmentation in oligodendroglia.

Animals↗
PubMed2002

Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct.

BACKGROUND AND PURPOSE: A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events. METHODS: One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis. RESULTS: Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient-years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events. CONCLUSIONS: Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events.

Aged↗
PubMed2001

Acidic fibroblast growth factor (FGF-1) in the anterior horn cells of ALS and control cases.

The expression and localization of acidic fibroblast growth factor (aFGF; FGF-1) were examined in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) and controls by reverse transcription-polymerase chain reaction (RT-PCR) method and immunohistochemistry. The RT-PCR experiments demonstrated that aFGF amplification products were clearly detected in all control cases but could be scarcely seen in ALS patients. aFGF immunoreactivity was detected in the anterior horn cells of the spinal cord. Double immunostaining for aFGF and choline acetyltransferase revealed that the majority (95.9%) of cholinergic neurons expressed aFGF. In ALS cases, the number and the staining intensity of aFGF-positive neurons were markedly decreased. These results suggest that aFGF is involved in ALS pathology.

Acetylcholine↗
PubMed2001

Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Postoperative brain dysfunction, such as delirium, is a common complication of anesthesia and is sometimes prolonged, especially in patients with cerebrovascular disease. In the present study we investigated the effect of hypocapnia during anesthesia on neuronal damage using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced by clipping the bilateral common carotid arteries in male Wistar rats. Fourteen days after the operation, these animals were mechanically ventilated for 2 hours and then kept in suitable conditions for an additional 14 days. Twenty-four rats were assigned to 4 groups: those with chronic cerebral hypoperfusion with either hypocapnia or normocapnia during anesthesia, and those given sham operation with either hypocapnia or normocapnia. White matter lesions in the brain sections were evaluated with Klüver-Barrera staining. Proliferation of glial cells was estimated with the use of immunohistochemistry of glial fibrillary acidic protein, a marker for astroglia, and CD11b, a marker for microglia. Computer-assisted morphometry was applied to the immunohistochemical results of microtubule-associated protein 2 to evaluate the loss of neurons. RESULTS: The histological damage was localized almost exclusively in the white matter in the rats subjected to chronic cerebral hypoperfusion but without hypocapnia. Neuronal damage and astroglial proliferation occurred with aggravated white matter lesions in the caudoputamen in the rats with chronic cerebral hypoperfusion and hypocapnia. No lesions were observed in sham-operated rats with either hypocapnia or normocapnia. CONCLUSIONS: These results indicate that hypocapnia during anesthesia causes tissue damage in the caudoputamen, which may be responsible for long-lasting postoperative delirium in patients with stroke and/or dementia.

Anesthesia↗
PubMed2001

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3.

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

Aged↗
PubMed2001

White matter lesions and alteration of vascular cell composition in the brain of spontaneously hypertensive rats.

There have been few studies on the white matter lesions of spontaneously hypertensive rats (SHR). From the point of view of hypertension and arteriosclerosis, white matter lesions were examined in SHR and stroke-prone SHR (SHRSP), and were then compared with Wistar-Kyoto (WKY) rats. The vasculopathy was analyzed by morphometric immunohistochemistry for collagen and smooth muscle actin. Both SHR and SHRSP had hypertension at > or = 12 weeks of age, and the latter developed severe white matter lesions at 20 weeks. Immuno- histochemistry revealed proliferation of microglia in the white matter and an increase in smooth muscle actin in the vessels of SHRSP compared with the WKY rats and SHR, but there were no changes in the collagen. These results indicate a role of hypertension in the pathogenesis of white matter lesions. However, genetic difference may also be responsible since SHR and SHRSP showed similar hypertension.

Actins↗
PubMed2001

Ultrastructural and permeability features of microvessels in the periventricular area of senescence-accelerated mice (SAM).

Brain transfer of intravenously injected horseradish peroxidase (HRP) and the ultrastructural features of the vessels were examined in periventricular areas in senescence-accelerated mice (SAMP8), which show age-related deficits in learning and memory, and senescence-accelerated resistant mice (SAMR1), which do not show age-related deficits. In all mice examined with light microscopy, staining reaction for HRP was seen in the periventricular area adjacent to the medial side of the lateral ventricle. Electron microscopic examination in the periventricular area of young and old mice of both strains showed that the staining reaction for HRP appeared in the vesicular profiles of the endothelial cytoplasm, the cytoplasm of the perivascular cells, the basal lamina, and the adjoining extracellular spaces of the white matter, suggesting an incomplete blood-brain barrier (BBB) in the periventricular white matter. In addition, irregularly thickened endothelial cell cytoplasm, membranous inclusions within the basal lamina, and electron-dense endothelial cell cytoplasm were occasionally seen in aged SAMP8 mice. These findings were not observed in 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. Perivascular collagen deposits were also frequently seen in aged SAMP8 mice. These findings indicate that the endothelial cells and pericytes in the periventricular white matter in aged SAMP8 mice have an ultrastructure with damaged BBB function. Intravascular substances can easily penetrate the periventricular white matter and the BBB of the vessels in the area can be deteriorated with aging in SAMP8 mice.

Aging↗
PubMed2001

Inclusion body myositis: expression of extracellular signal-regulated kinase and its substrate.

OBJECTIVE: To assess abnormal intracellular signal transduction in inclusion body myositis (IBM). BACKGROUND: Mitogen-activated protein kinases (MAPKs) play pivotal roles in intracellular signal transduction and regulate cell growth and differentiation. Upon their activation, MAPKs translocate from the cytoplasm into the nucleus. DESIGN/METHODS: The authors investigated the localization of several forms of the MAPK family-extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 MAPK (p38)-in 10 patients with sporadic IBM and in 52 control subjects. The relationship between the localization of immunopositive deposits and nuclei was tested with bis-benzimide. RESULTS: Vacuolated fibers in IBM displayed very strong focal immunoreactivity of ERK, but not of JNK or p38. The ERK-positive deposits in these vacuolated fibers colocalized with the nuclear substrate of ERK, Elk-1. ERK- and Elk-1-positive deposits were located frequently on the surface of the nuclei in vacuolated fibers in IBM. Similar findings to those of sporadic IBM were observed in three patients with distal myopathy with rimmed vacuoles, but not in eight normal or the other 41 disease controls. CONCLUSION: There is evidence for impaired molecular transport to the nucleus from the cytoplasm in the vacuolated fibers in IBM. This could be due to cytoplasmic aggregation of ERK and Elk-1 or to abnormal nuclear pore machinery involved in the transport of ERK and its substrate upon ERK activation.

Adult↗
PubMed2001

The coagulation-fibrinolysis system in patients with leukoaraiosis and Binswanger disease.

BACKGROUND: Hypercoagulability is observed in vascular dementia, including Binswanger disease. However, the correlation between hypercoagulability, leukoaraiosis, and dementia remains unclear. OBJECTIVE: To examine how activation of the coagulation fibrinolysis correlates with leukoaraiosis and dementia. PATIENTS AND METHODS: Thrombin-antithrombin complex (TAT), prothrombin fragment(1 + 2) (F1 + 2) and cross-linked D-dimer (XDP) were measured consecutively in 18 subjects without dementia and with leukoaraiosis, and in 29 subjects with subcortical vascular dementia and severe leukoaraiosis (Binswanger disease) at either stable or deteriorating stages. They were compared with 19 patients with old lacunar infarctions and 24 patients with other neurological diseases. We also examined the indices of cognitive impairment and brain atrophy. In each group, the ventricular area-cranial space area ratio was measured by an image analyzer. RESULTS: Patients with Binswanger disease who were exclusively at deteriorating stages showed increased TAT and XDP levels and an increased ventricular area-cranial space area ratio, as compared with the patients with other neurological diseases (P<.001). The index of cognitive impairment in patients at a deteriorating stage showed a decreasing trend vs that of patients in the stable stage. Among the variables that were significantly associated with a hypercoagulable condition (ie, age, scores on Mini-Mental State Examination or the Hasegawa Dementia Rating Scale, Revised [MMSE/HDRS], white matter lesions, ventricular area-cranial space area ratio, and C-reactive protein), age (odds ratio [OR], 2.82) and MMSE/HDSR scores (OR, 0.43) survived as predictors for coagulation activation, and C-reactive protein survived for fibrinolysis activation (OR, 4.63) in multivariate analysis. CONCLUSION: Hypercoagulability in a subgroup of patients with Binswanger disease and with more severe cognitive impairment and brain atrophy does not support a triggering role for a coagulation-fibrinolysis system, although it may contribute to worsening of neurological deficits.

Aged↗
PubMed2001

Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene.

We report a case of familial frontotemporal dementia and parkinsonism characterized by early onset with mental retardation. The patient died at the age of 54; neuronal loss was severe in the frontal and temporal cortices, globus pallidus, substantia nigra, red nucleus and dentate nucleus. Anti-tau-positive fibrillary changes were observed in neurons and glia in these regions. Although the patient had 2 novel point mutations of the tau gene, P301P (CCG to CCA) and an intron 10+11-splice site (T to C), exon trapping analysis indicated that the latter was pathogenic.

Brain↗
PubMed2001

P39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple system atrophy.

Glial cytoplasmic inclusions (GCIs) characteristically occur in the oligodendrocytes of patients with multiple system atrophy (MSA). Cyclin-dependent kinase 5 (Cdk5) regulates cytoskeletal dynamism through phosphorylation of cytoskeletal proteins such as neurofilament proteins, tau and microtubule-associated protein 2. We examined the immunohistochemical localization of p39, a Cdk5 activator, in human brain specimens obtained post mortem from controls and patients with MSA. Among control specimens, p39 immunoreactivity was found in some neuronal somata and axons. Similar immunoreactivity was detected in MSA neuronal cell bodies and axons, but a number of inclusions were heavily labeled. These results suggest that p39 and Cdk5 are up-regulated in oligodendrocytes and may be involved in the formation of GCIs through phosphorylation of cytoskeletal proteins in oligodendrocytes in MSA.

Aged↗
PubMed2001

Up-regulation of cyclooxygenase-2 in inflammatory demyelinating neuropathy.

To clarify the role of prostaglandins in peripheral nerve demyelination, we examined the expression of cyclooxygenase-2 (COX-2) using selected nerve specimens from patients with chronic inflammatory demyelinating polyneuropathy. COX-2 protein was up-regulated in macrophages causing active demyelination. In situ hybridization revealed that COX-2 mRNA signals were strongly expressed on macrophages adhering to the demyelinating nerve fibers at the endoneurium. This observation may provide a rationale for application of neuroprotective strategies employing COX-2 inhibitors in inflammatory demyelinating neuropathies.

Adolescent↗
PubMed2001

Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter.

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2-expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

Animals↗
PubMed2001

Twenty-four-hour blood pressure changes in the course of lacunar disease.

BACKGROUND: Changes in blood pressure (BP) over time have not been considered in investigations on the relationship between BP and cerebrovascular disease (CVD). OBJECTIVE: To investigate BP changes throughout a 24-hour period in lacunar infarct patients with different outcomes. METHODS: Twelve control subjects (group 1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct patients were divided into three groups: group 2, 25 patients with a fair outcome without any cerebrovascular attack or progressive dementia (mean follow-up period: 4.4 years); group 3, 14 patients with worsening of clinical dementia rating and silent lesions, which included lacunae and diffuse white matter lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on two separate occasions. No patient was treated with antihypertensive agents during the course of the study. RESULTS: In group 2, the second measurements were significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP, 24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p < 0.05). In group 3, the second measurements were significantly lower than the first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for all). In group 4, the second measurements were significantly lower than the first for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse rate became positive for group 2 in second measurements, but was not positive for groups 3 and 4. CONCLUSIONS: BP tended to elevate over time in patients with a fair outcome. In contrast, BP tended to decrease in those who developed dementia and symptomatic infarct. Autonomic functions including sympathetic activity might play a role in changes in BP in lacunar infarct patients during the course of disease.

Aged↗