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Biomedical subjects

K Huh

Publications and source records attributed to K Huh.

At least 19 recordsLinked to original sources

The plasma alpha-synuclein levels in patients with Parkinson's disease and multiple system atrophy.

alpha-Synuclein, a synaptic protein of unknown function, is a major component of Lewy bodies and may play a role in the pathophysiological process of Parkinson's disease (PD). In this study, we measured the plasma alpha-synuclein levels in 105 patients with PD, 38 patients with multiple system atrophy (MSA), and 51 age-matched controls. The alpha-synuclein level was significantly elevated in patients with PD (79.9 +/- 4.0 pg/ml, p < 0.001) and in those with MSA (78.1 +/- 3.5 pg/ml, p = 0.019) compared with the level in controls (76.1 +/- 3.9 pg/ml). The alpha-synuclein level was higher in patients with PD than in those with MSA (79.9 +/- 4.0 vs 78.1 +/- 3.5, p = 0.016). Our study demonstrated that the alpha-synuclein level in plasma is elevated in patients with PD and MSA.

Adult↗

Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism.

Cardiac sympathetic dysfunction was investigated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 20 patients with drug induced parkinsonism (DIP). The mean heart to mediastinum ratio was significantly greater in patients with DIP than in those with Parkinson's disease (mean (SD): 2.07 (0.39) v 1.28 (0.15), p<0.001). MIBG uptake was not different between the DIP patients and controls. Two DIP patients whose MIBG uptake was significantly reduced showed persistent parkinsonism and responded dramatically to levodopa.

Adult↗

Association of the metabolic syndrome with intracranial atherosclerotic stroke.

To investigate the impact of metabolic syndrome (MetSD) on the development of intracranial atherosclerotic stroke, the authors evaluated the components of the MetSD in 512 patients with stroke. The MetSD was observed most frequently in patients with intracranial atherosclerosis (p = 0.007). In multiple regression analysis, the MetSD, but not conventional risk factors, was independently associated with intracranial atherosclerosis (p = 0.005). The results suggest that treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerosis.

Aged↗

Circulating beta amyloid protein is elevated in patients with acute ischemic stroke.

Recent clinical and experimental studies suggest that ischemic strokes may play an important role in the pathogenesis of Alzheimer's disease (AD). Beta amyloid (Abeta), a major component of senile plaque in AD, is known to be derived from ischemic brain or activated platelets. We prospectively enrolled 62 patients with acute ischemic stroke and 27 age-matched controls. The serum Abeta and P-selectin levels were determined using the Sandwich-ELISA. We divided ischemic strokes into subgroups according to the clinical syndrome, pathogenesis, and infarct size, and compared the Abeta level between each subgroup. The Abeta1-40 level was markedly elevated in ischemic stroke patients, as compared to controls (140.2 +/- 54.0 vs 88.44 +/- 34.96 pg/ml, p<0.001). Cardioembolic and larger artery atherosclerotic infarcts had higher Abeta1-40 level than small vessel disease (p = 0.001). Both infarct size and the initial NIHSS score had significantly positive correlations with the serum level of Abeta1-40 (r = 0.539, p<0.001 and r = 0.425, p = 0.001, respectively). However, the P-selectin level was not significantly correlated with serum Abeta1-40. Our data suggest that elevated circulating Abeta1-40 in ischemic stroke patients may be derived from brain as a consequence of ischemic insults.

Acute Disease↗

Parkinsonism as an initial manifestation of dural arteriovenous fistula.

Parkinsonism associated with dural arteriovenous fistula (DAVF) has been described rarely; however, isolated parkinsonism as the presenting symptom of DAVF has not been reported. Here, we describe a patient with DAVF showing reversible isolated parkinsonism after embolization, which was well correlated with perfusion status of basal ganglia, suggesting that a perfusion defect was responsible for the pathogenesis of the parkinsonism in our DAVF patient.

Brain↗

Inflammatory markers, rather than conventional risk factors, are different between carotid and MCA atherosclerosis.

BACKGROUND: The apparent differences in risk factors for intra- and extracranial atherosclerosis are unclear and the mechanisms that underlie strokes in patients with intracranial atherosclerosis are not well known. We investigated the conventional vascular risk factors as well as other factors in stroke patients with large artery atherosclerosis. METHODS: Using diffusion weighted imaging (DWI) and vascular and cardiologic studies, we selected patients with acute non-cardioembolic cerebral infarcts within the middle cerebral artery (MCA) territory. Patients were divided into two groups: those with atherosclerotic lesions on the carotid sinus (n = 112) and those with isolated lesions on the proximal MCA (n = 160). Clinical features, risk factors, and DWI patterns were compared between groups. RESULTS: There were no differences in conventional risk factors, but markers for inflammation were significantly higher in patients with carotid atherosclerosis than in those with isolated MCA atherosclerosis (p < 0.01 for both). After adjustments for age/sex and the severity of stroke, an inverse correlation was observed between C-reactive protein levels and MCA atherosclerosis (odds ratio 0.57 per 1 mg/dl increase; 95% confidence interval 0.35 to 0.92; p = 0.02). Internal borderzone infarcts suggestive of haemodynamic causes were the most frequent DWI pattern in patients with MCA occlusion, whereas territorial infarcts suggesting plaque ruptures were most common in those with carotid occlusion. CONCLUSIONS: Our results indicate that inflammatory markers, rather than conventional risk factors, reveal clinical and radiological differences between patients with carotid and MCA atherosclerosis. Plaques associated with MCA atherosclerosis may be more stable than those associated with carotid atherosclerosis.

Acute Disease↗

Pathogenesis of deep white matter medullary infarcts: a diffusion weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The pathogenesis of deep white matter medullary (WMM) artery infarcts remains controversial. To address this question, we analysed the stroke patterns of WMM infarcts using diffusion weighted magnetic resonance imaging (DWI) to detect embolic signals and investigate stroke subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications. METHODS: We identified WMM infarcts on DWI using templates to determine the subcortical vascular territories. We classified WMM infarcts into those with small artery disease (SAD), large artery disease (LAD), cardioembolism (CE), two or more aetiologies, or undetermined aetiology. Clinical course, risk factors, and cortical spotty lesions were compared. RESULTS: Of the 1420 consecutive patients, 103 (7.3%) met the criteria for WMM infarcts. The stroke subtypes were as follows: 65 (63.1%) patients with LAD, 18 (17.5%) with SAD, 12 (11.7%) with CE, four (3.9%) with two or more aetiologies, three (2.1%) with undetermined aetiology, and one (1.0%) with other determined aetiology. LAD (87.7%) or CE (83.3%) was significantly accompanied by cortical embolic signals as compared to SAD (0%, p<0.001). The LAD infarcts were larger and tended to be chain-like in shape. Ischaemic stroke recurrence was more common in strokes with cortical embolic signals than in those without embolic signals (18.9% v 0%, p = 0.009). CONCLUSIONS: In present study, the most common pathogenesis of WMM infarcts was LAD. Our study indicates that WMM infarcts accompanying cortical embolic signals warrant evaluation of the underlying embolic sources in the large artery or the heart.

Aged↗

Infarct patterns in atherosclerotic middle cerebral artery versus internal carotid artery disease.

OBJECTIVE: To compare clinical and radiologic characteristics of atherosclerotic middle cerebral artery (MCA) vs internal carotid artery (ICA) disease. METHODS: The authors defined atherosclerotic MCA and ICA disease as >50% symptomatic stenosis or occlusion without significant ICA and MCA stenosis on MR angiography. Patients with potential cardiac sources of embolism were excluded. The authors analyzed clinical, laboratory, and neuroradiologic data of the two groups. RESULTS: Among the 920 consecutive patients with acute ischemic strokes, 112 met the criteria for atherosclerotic MCA and 71 met the criteria for ICA disease. Clinically, the MCA group more frequently presented with lacunar syndrome (p = 0.001), whereas the ICA group more often presented with total anterior circulation infarct and had higher initial NIH Stroke Scale scores than the MCA group (all p < 0.001). Whereas deep perforator and internal border-zone infarcts were associated with MCA disease (p < 0.001 and 0.012), territorial infarcts and superficial perforator infarcts were associated with ICA disease (p < 0.001 and p = 0.009). The topographic patterns with respect to the degree of stenosis were also significantly different between the two groups. CONCLUSIONS: The clinical and radiologic stroke patterns were distinctively different between atherosclerotic MCA and ICA disease, suggesting different underlying pathogeneses.

Acute Disease↗

Isolated middle cerebral artery disease: clinical and neuroradiological features depending on the pathogenesis.

BACKGROUND: Isolated atherosclerotic middle cerebral artery (MCA) disease is often difficult to differentiate from cardioembolic disease if intracranial atherosclerosis coexists with cardiac disease. OBJECTIVES: To evaluate whether clinical and neuroradiological features of isolated MCA disease differ according to the underlying aetiology. METHODS: Isolated MCA disease was defined as a unilateral angiographically occlusive lesion of the MCA on the symptomatic side without lesions of other intracranial or extracranial vessels. Patients with isolated MCA disease were divided into atherosclerotic and potentially cardioembolic, and the clinical, laboratory, and neuroradiological data analysed. RESULTS: Among the 850 consecutive patients with acute ischaemic stroke or transient ischaemic attack, 107 (12.6%) met the criteria for isolated MCA disease (76 with atherosclerotic disease and 31 with a potential source of cardiac embolism). Total anterior circulation infarcts were more common and baseline NIHSS score was higher in potentially embolic occlusions than in atherosclerotic disease (each p<0.001). While cortical infarcts and territorial infarcts were more common in the potential embolism group (p = 0.028 and p<0.001, respectively), subcortical border zone infarcts were more common in the atherosclerotic group (p<0.001). Multiple regression analysis showed that border zone infarcts and mild stroke were independently associated with atherosclerotic MCA disease, while territorial and cortical infarcts were associated with potential cardiac embolic disease. CONCLUSIONS: Clinical and neuroradiological characteristics can differentiate isolated atherosclerotic MCA disease from MCA disease associated with potential sources of cardiac embolism, and may reflect the differences in underlying pathogenesis.

Acute Disease↗

Pontine atrophy precedes cerebellar degeneration in spinocerebellar ataxia 7: MRI-based volumetric analysis.

BACKGROUND AND OBJECTIVE: Spinocerebellar ataxia 7 (SCA7) is characterised by cerebellar ataxia and visual loss. The aim of the present study was to elucidate the magnetic resonance imaging (MRI) findings characteristic of patients with SCA7. METHODS: Twenty patients with SCA (eight SCA3, three SCA6, and nine SCA7) and 20 control subjects underwent an MRI-based volumetric analysis. RESULTS: The pontine volume in patients with SCA7 was decreased by a greater amount than in patients with other types of SCA (p<0.01), whereas the cerebellar volume was not different from that in other types of SCA (p>0.05). Pontine atrophy was a consistent finding in all patients with SCA7 regardless of the degree of cerebellar atrophy or the severity or duration of illness. In contrast, cerebellar atrophy was not found in those with a short duration of illness or mild ataxia, but became prominent as the severity and duration of illness progressed. CONCLUSIONS: Our study suggests that neurodegeneration is ongoing during the life of individuals with SCA7, and that the primary pathology in these individuals involves the brainstem rather than the cerebellum. In addition, pontine atrophy is a prominent, consistent finding in SCA7, and may help in establishing the clinical diagnosis of SCA7.

Adult↗

Dynamics of population code for working memory in the prefrontal cortex.

Some neurons (delay cells) in the prefrontal cortex elevate their activities throughout the time period during which the animal is required to remember past events and prepare future behavior, suggesting that working memory is mediated by continuous neural activity. It is unknown, however, how working memory is represented within a population of prefrontal cortical neurons. We recorded from neuronal ensembles in the prefrontal cortex as rats learned a new delayed alternation task. Ensemble activities changed in parallel with behavioral learning so that they increasingly allowed correct decoding of previous and future goal choices. In well-trained rats, considerable decoding was possible based on only a few neurons and after removing continuously active delay cells. These results show that neural activity in the prefrontal cortex changes dynamically during new task learning so that working memory is robustly represented and that working memory can be mediated by sequential activation of different neural populations.

Action Potentials↗

Cholinergic modulation of synaptic physiology in deep layer entorhinal cortex of the rat.

We have recently shown that cholinergic effects on synaptic transmission and plasticity in the superficial (II/III) layers of the rat medial entorhinal cortex (EC) are similar, but not identical, to those in the hippocampus (Yun et al. [2000] Neuroscience 97:671-676). Because the superficial and deep layers of the EC preferentially convey afferent and efferent hippocampal projections, respectively, it is of interest to compare cholinergic effects between the two regions. We therefore investigated the physiological effects of cholinergic agents in the layer V of medial EC slices under experimental conditions identical to those in the previous study. Bath application of carbachol (0.5 microM) induced transient depression of field potential responses in all cases tested (30 of 30; 18.5% +/- 2.3%) and rarely induced long-lasting potentiation (only 3 of 30; 20.4% +/- 3.2% in successful cases). At 5 microM, carbachol induced transient depression only (20 of 20, 48.9% +/- 2.8%), which was blocked by atropine (10 microM). Paired-pulse facilitation was enhanced during carbachol-induced depression, suggesting presynaptic action of carbachol. Long-term potentiation (LTP) could be induced in the presence of 10 microM atropine by theta burst stimulation, but its magnitude was significantly lower (9.1% +/- 4.7%, n = 15) compared to LTP in control slices (22.4% +/- 3.9%, n = 20). These results, combined with our previous findings, demonstrate remarkably similar cholinergic modulation of synaptic transmission and plasticity across the superficial and deep layers of EC.

Acetylcholine↗

Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells.

Although estrogen is known to exert beneficial effects on Alzheimer's disease, its underlying cellular mechanisms have not been clear. In this study we investigated whether or not neuroprotective effects of estrogen are mediated by estrogen receptors (ERs). Treatment of estrogen (1.8 nM) reduced beta-amyloid (Abeta)-induced death of ER-expressing W4 cells. This effect of estrogen was blocked by a specific ER blocker ICI 182,780. When estrogen was treated to HT22 cells, which lack functional ERs, Abeta-induced cell death was not affected. Transfection of HT22 cells with human ERalpha, but not ERbeta, restored protective action of estrogen against Abeta. Hoechst staining revealed that estrogen protected ERalpha-expressing cells by blocking Abeta-induced apoptosis. These results indicate that estrogen blocks Abeta-induced cell death via ERalpha-dependent pathways.

Amyloid beta-Peptides↗

Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice.

We investigated the cognition enhancing effects of ginsenoside Rb1 and Rg1. Mice were trained in a Morris water maze following injection (i.p.) of Rb1 (1 mg/kg) or Rg1 (1 mg/kg) for 4 days. Both Rb1- and Rg1-injected mice showed enhanced spatial learning compared to control animals. The hippocampus, but not the frontal cortex, of treated mice contained higher density of a synaptic marker protein, synaptophysin, compared to control mice. Electrophysiological recordings in hippocampal slices revealed that Rb1 or Rg1 injection did not change the magnitude of paired-pulse facilitation or long-term potentiation. Our results suggest that Rb1 and Rg1 enhance spatial learning ability by increasing hippocampal synaptic density without changing plasticity of individual synapses.

Animals↗

Blockade of PKC epsilon activation attenuates phorbol ester-induced increase of alpha-secretase-derived secreted form of amyloid precursor protein.

The role of PKC epsilon in amyloid precursor protein (APP) processing was investigated using APP-overexpressing B103 cells. As reported previously, a PKC activator, phorbol-12,13-dibutyrate (PDBu), enhanced secretion of APP alpha, and this effect was blocked by a PKC inhibitor, GF109203X in this system. Selective inhibition of PKC epsilon by overexpressing the PKC epsilon V1 region, which binds specifically to the receptor for activated C-kinase (RACK), blocked PDBu-induced enhancement of APP alpha secretion as well as PDBu-induced decrease in beta-secretase-derived APP C-terminal fragment production. On the other hand, the level of PKC epsilon, but not that of PKC alpha or PKC gamma, was substantially lower in the brains of Alzheimer's disease patients compared to age-matched controls. These results add to a growing body of evidence that PKC epsilon plays an important role in modulating APP processing, and suggest that reduced PKC epsilon activity may contribute to the development of Alzheimer's disease.

Alzheimer Disease↗

Toxicology of Kalopanax pictus extract and hematological effect of the isolated anti-rheumatoidal kalopanaxsaponin A on the Freunds complete adjuvant reagent-treated rat.

We have reported that kalopanaxsaponin A (KPS-A) isolated from Kalopanax pictus have anti-rheumatoidal activity in the rat treated with Freunds complete adjuvant (FCA) reagent. In addition, it has been also reported that KPS-A is a potent antioxidant in the rheumatoidal rat. This research was undertaken to examine whether the saponins of KPS-A and -I could adjust the abnormal lipid metabolisms and hematological changes in immunological diseases. KPS-A significantly inhibited the increases in both triglycerides and total proteins in addition to the decrease in total cholesterol induced by FCA reagent treatment. KPS-A treatment decreased the number of leucocytes elevated by FCA reagent treatment. Excess dose of the methanol extract produced no severe toxicity on the body weight, wet organ weights and hepatic functions. Since LD50 value of K. pictus methanol extract was shown to be 4,033 mg/kg, it could be estimated to be a safe agent for anti-rheumatoidal herbal medicines.

Animals↗

Partial cDNA sequence analysis of the boar proacrosin-binding protein.

A partial cDNA sequence of the boar 28, 29-kDa proacrosin-binding protein was determined. The desired sequence was amplified and obtained by RT-PCR followed by nested PCR. The oligonucleotide primers for RT-PCR were designed by deduction from the internal amino acid sequence of the boar proacrosin-binding protein. An approximately 1-kbp DNA fragment was analysed by agarose gel electrophoresis, in which the boar testicular total RNA or poly(A)+ RNA was used as a template for RT-PCR followed by nested PCR. This PCR product was inserted into a TA vector. The DNA sequence of the inserted PCR product was then determined by the chain termination method.

Amino Acid Sequence↗

In vitro effects of hydroxybenzaldehydes from Gastrodia elata and their analogues on GABAergic neurotransmission, and a structure-activity correlation.

The present study was designed to characterize the modulatory effects of the constituents of Gastrodia elata and their analogues on the GABAergic neurotransmission. 4-Hydroxybenzaldehyde (1) and 4-hydroxy-3-methoxybenzaldehyde (4) inhibited potently the activity of GABA transaminase (IC(50) = 4.1 and 5.4 microg/ml, respectively), while the activity of another constituent, 4-hydroxybenzyl alcohol (2), was very weak. Further investigation with 10 analogues revealed a structure-activity correlation, suggesting that the aldehyde group and the hydroxy group at C-4 are necessary for the inhibitory effect on the enzyme activity. Some potent enzyme inhibitors were examined for the effect on the radioligands to the GABA(A) receptor complexes of rat cerebral cortices. Among them, the component 4 dose-dependently increased (20 - 30 %) the binding of [(3)H]flunitrazepam in the presence of GABA.

4-Aminobutyrate Transaminase↗