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Kyoon Huh

Publications and source records attributed to Kyoon Huh.

At least 19 recordsLinked to original sources
PubMed2007

IFN-gamma-induced BACE1 expression is mediated by activation of JAK2 and ERK1/2 signaling pathways and direct binding of STAT1 to BACE1 promoter in astrocytes.

Beta-site APP cleaving enzyme 1 (BACE1) is an essential enzyme for the production of beta amyloid. Since we found that injection of interferon-gamma (IFN-gamma) into young mouse brains increased BACE1 expression in astrocytes, we investigated molecular mechanisms underlying this process by cloning a putative BACE1 promoter. BACE1 promoter activity was differentially regulated by IFN-gamma in a region specific manner and down-regulated by an inhibitor of Janus kinase 2 (JAK2). A dominant negative mutant of signal transducer and activator of transcription 1 (STAT1) expression suppressed BACE1 promoter activity, and this was rescued by transfecting wild type STAT1. Electrophoretic mobility shift assay and promoter activity assays indicated that STAT1 binds directly to the putative STAT1 binding sequence of BACE1 promoter. Because IFN-gamma treatment induced STAT1 phosphorylation, we examined whether the expression of a suppressor of cytokine signaling (SOCS), negative regulator of JAK2, suppresses BACE1 promoter activity. The results show that SOCS1 or SOCS3 expression suppressed BACE1 promoter by blocking phosphorylation of Tyr701 residue in STAT1. Also, because IFN-gamma treatment specifically potentiated extracellular signal regulated MAP kinase (ERK) 1/2 activation, pretreatment of mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, PD98059, significantly attenuated IFN-gamma-induced BACE1 promoter activity and protein expression through blocking phosphorylation of Ser727 residue in STAT1, suggesting that ERK1/2 is associated with IFN-gamma-induced STAT1 signaling cascade. Taken together, our results suggest that IFN-gamma activates JAK2 and ERK1/2 and then phosphorylated STAT1 binds to the putative STAT1 binding sequences in BACE1 promoter region to modulate BACE1 protein expression in astrocytes.

Alzheimer Disease↗
PubMed2006

Effect of ischemic neuronal insults on amyloid precursor protein processing.

The nature of the association between ischemic stroke and Alzheimer's disease (AD) at the cellular and molecular level is still unknown. We evaluated the effect of ischemic neuronal insults on the regulation of amyloid precursor protein (APP) processing. We used an in vitro model of cerebral ischemia (oxygen-glucose deprivation) to evaluate the effect of ischemic neuronal insults on the amyloidogenic and non-amyloidogenic pathways using human neuroblastoma cell line and primary cultured cells of transgenic mice which expressed human APP (Tg2576). Ischemic neuronal insults increased the production of Abeta in Tg2576 primary culture cells compared to controls. A disintegrin and metalloprotease 10 (ADAM 10) was markedly increased in early stage of ischemic insults, which was followed by decreased level of ADAM 10 expression in later stage. The protein and mRNA expression of beta-site cleavage enzyme (BACE) and BACE activity was not significantly different between the group of ischemic insults and control. By contrast, the activity of gamma-secretase was significantly increased after 4 h of ischemic insults, as compared to controls. The present study showed that the ischemic neuronal insults increased the production of Abeta by influencing APP metabolism, which may link the role of ischemic insults to the pathogenesis of AD.

Amino Acid Sequence↗
PubMed2006

Cardiac 123I-MIBG scintigraphy in patients with essential tremor.

In some cases, it is difficult to differentiate essential tremor (ET) from Parkinson's disease (PD), especially in the early stages of the disease. We investigated cardiac sympathetic dysfunction using (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 22 patients with ET, in comparison with early PD and tremor-dominant PD (TDPD). The mean ratio of (123)I-MIBG uptake in the region of interest in the heart to that in the mediastinum (H/M ratio) was significantly greater in patients with ET (1.99 +/- 0.21) than in those with either TDPD (1.28 +/- 0.11) or early PD (1.28 +/- 0.17; each P < 0.001). The H/M ratio in all patients with ET was greater than two standard deviations above the range of the ratio in the patients with early PD or TDPD.

3-Iodobenzylguanidine↗
PubMed2005

Correlation of midbrain diameter and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Although gait disturbance is an important feature of idiopathic normal pressure hydrocephalus (NPH), only tentative theories have been offered to explain its pathophysiology. It has been suggested that the mesencephalic locomotor region is the anatomical substrate for the development of the hypokinetic NPH gait. To investigate this possibility, we evaluated the correlation between gait disturbance and midbrain diameter. METHODS: We enrolled 21 patients with NPH and 20 age-matched control subjects for the study. The maximal diameter of the midbrain and pons, and the width of the lateral and third ventricles were measured using midsagittal T1-weighted MRI and axial T2-weighted MRI, respectively. Gait disturbance, cognitive dysfunction, and incontinence were semiquantified. RESULTS: The maximal midbrain diameter was significantly smaller in the NPH group than in the controls (14.8 +/- 0.9 vs. 17.1 +/- 0.7 mm, p < 0.001). There were inverse correlations between the midbrain diameter and the widths of the two ventricles (r = -0.562, p = 0.008 for the third ventricle, and r = -0.510, p = 0.018 for the lateral ventricle). The severity of gait disturbance was negatively correlated with the midbrain diameter (r = -0.598, p = 0.004), but the degree of cognitive dysfunction and incontinence showed no significant correlation with midbrain diameter or ventricular width. CONCLUSIONS: This study suggests that midbrain atrophy is significantly associated with gait disturbance in NPH.

Aged↗
PubMed2005

Antiepileptic drug withdrawal after successful surgery for intractable temporal lobe epilepsy.

PURPOSE: To investigate the prognosis related to antiepileptic drug (AED) discontinuation after successful surgery for intractable temporal lobe epilepsy. METHODS: The clinical courses after temporal lobectomies (TLs) were retrospectively analyzed in 88 consecutive patients. All the patients had TLs as the only surgical procedure, and they had been followed up for longer than 3 years. AED discontinuation was attempted if the patient had been seizure free without aura for >or=1 year during the follow-up period. RESULTS: Sixty-six (75%) patients achieved complete seizure freedom for >or=1 year; 28 patients were seizure free immediately after surgery (immediate success); and 38 patients became seizure free after some period of recurrent seizures (delayed success). AED discontinuation was attempted in 60 (91%) of 66 patients with a successful outcome. In 13 (22%) patients, seizure relapse developed during AED reduction (n=60), and in seven (12%) patients after discontinuation of AEDs (n=38). The seizure recurrence rate was not different between the immediate-and delayed-success groups. Among 20 patients with seizure relapse related to AED tapering, nine (45%) of them regained seizure freedom after reinstitution of AED treatment, and AEDs were eventually discontinued in six of them. Seizures that recurred after complete AED discontinuation had a better prognosis than did the seizures that recurred during AED reduction (seizure freedom in 86% vs. 23%). At the final assessment, 54 (61%) patients had been seizure free >or=1 year; 37 without AEDs and 17 with AEDs. The successful discontinuation of AEDs was more frequent for patients with a younger age at the time of surgery and for those patients with shorter disease duration. CONCLUSIONS: Our results suggest that seizure freedom without aura at >or=1 year is a reasonable indication for the attempt at AED discontinuation. The subsequent control of recurrent seizures was excellent, especially if seizures relapsed after the complete discontinuation of AEDs. Younger age at the time of surgery and a shorter disease duration seem to affect successful AED discontinuation for a long-term period.

Adolescent↗
PubMed2004

Repetitive involuntary leg movements in patients with brainstem lesions involving the pontine tegmentum: evidence for a pontine inhibitory region in humans.

Repetitive involuntary limbs movements have been mostly reported in patients with extensive brainstem pathologies, but the region responsible is unknown. We describe two patients with progressive basilar artery infarcts who showed automatic stepping and one patient with an osmotic demyelination disorder who showed periodic involuntary leg movements. By subtracting diffusion-weighted images before and after the development of repetitive involuntary leg movements, the brainstem lesion responsible for the involuntary movements was distinctively located in the vicinity of the pontine tegmentum, which is known as the pontine inhibitory region in animal studies.

Adult↗
PubMed2004

Global aphasia without hemiparesis: lesion analysis and its mechanism in 11 Korean patients.

BACKGROUND: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome. This study localized the lesion and examined the pathogenic mechanism in Korean patients with GAWH, and investigated whether areas of extensive hypoperfusion existed outside the diffusion-weighted imaging (DWI) lesions seen in these patients. MATERIAL AND METHODS: Eleven patients were diagnosed with aphasia using the Western Aphasia Battery. To identify decreased perfusion, which might be functionally relevant to aphasia but not detected by DWI, single photon emission tomography (SPECT) was performed in five patients. To uncover the possible pathogenic mechanisms of ischemic stroke, vascular and cardiologic work-ups were performed in all of the patients. RESULTS: The lesions seen on DWI varied, and included both inferior frontal and superior temporal (three), isolated inferior frontal (four) or superior temporal (one), subcortical (two), and even parieto-occipital (one) lesions. Brain SPECT did not reveal an extensive lesion of the peri-sylvian area outside the DWI lesion in any of the patients, except one with the subcortical lesions. CONCLUSION: Our results indicate that a single lesion in different locations may be sufficient to produce GAWH, and the lesion profile and stroke mechanism in GAWH are heterogeneous, suggesting that lesions to an area of complex functional anatomy result in aphasia.

Adult↗
PubMed2004

The course of patients with lacunar infarcts and a parent arterial lesion: similarities to large artery vs small artery disease.

BACKGROUND: The significance of occlusive lesions of the parent artery in patients with lacunar syndrome (LS) and small deep infarcts (SDIs) on diffusion-weighted imaging remains unclear. OBJECTIVE: To compare the recurrence of stroke in patients with LS and SDIs between those with vs without a parent arterial lesion. DESIGN: Analysis of data from a prospective acute stroke registry. SETTING: University hospital. PATIENTS: Using clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 173 patients into 3 groups: (1) parent arterial disease occluding deep perforators (PAD), LS with SDIs, and a parent arterial lesion (n = 32); (2) small artery disease (SAD) (n = 70); and (3) large artery disease (LAD) (n = 71). MAIN OUTCOME MEASURES: Recurrent strokes and the prognosis were registered for 1 year, and the outcome of the PAD group was compared with that of the SAD and LAD groups. RESULTS: During follow-up, there were 9 deaths (6 vascular) and 18 recurrent strokes. The recurrence rate in the PAD group (16%) was significantly higher than that in the SAD group (1%) (P =.01) but similar to that in the LAD group (17%) (P =.87). The presence of the parent arterial lesion was the only independent predictor of stroke recurrence in patients with LS and SDIs (odds ratio, 13.8; 95% confidence interval, 1.5-123.9; P =.02). CONCLUSIONS: Although LS on examination, SDIs on diffusion-weighted imaging, and a stable hospital course suggest lacunar stroke of benign course, our results indicate that the PAD group represents an intracranial type of LAD.

Adult↗
PubMed2004

Neuroprotective effect of genistein against beta amyloid-induced neurotoxicity.

Estrogen is beneficial to patients with Alzheimer's disease (AD) but has a limited clinical use due to its proliferative and oncogenic effects on non-neuronal cells responsive to estrogen. In an attempt to find an estrogen substitute that retains the beneficial effects of estrogen with minimal side effects, we compared the neuroprotective and proliferative effects of genistein, a selective estrogen receptor (ER) beta-agonist, with those of estrogen. Genistein and 17beta-estradiol showed comparable levels of protection against Abeta-induced deaths of cultured SH-SY5Y human neuroblastoma cells, which were blocked by an estrogen receptor antagonist, ICI 182,780. On the other hand, 17beta-estradiol, but not genistein, induced proliferation of uterine endometrial cells. Our results suggest that genistein is a potential alternative to estrogen in the treatment of Alzheimer's disease.

Amyloid beta-Peptides↗
PubMed2004

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness.

Charcot-Marie-Tooth disease with deafness is a clinically distinct entity and is associated with mutations or deletions in several genes including PMP22 gene. Here, we report a large family showing characteristic phenotypes of Charcot-Marie-Tooth type 1A along with deafness in an autosomal dominant fashion. We detected a sequence variation (c.68C>G) co-segregating with the disease phenotype and leading to a T23R missense mutation in PMP22.

Adult↗
PubMed2003

Subcortical white matter infarcts: comparison of superficial perforating artery and internal border-zone infarcts using diffusion-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: Because of difficulty in distinguishing between superficial perforator (SP) and internal border-zone (IB) infarcts, some studies lumped SP and IB infarcts together as so-called subcortical white matter infarcts, which might complicate the classification of infarct type and its pathogenesis. Using diffusion-weighted MRI (DWI), we made comparative analyses of clinical and neuroradiological characteristics between IB and SP infarcts to clarify the difference in underlying pathogenesis. METHODS: We selected SP and IB infarcts on DWI using templates for the identification of subcortical vascular territories. Sex, age, neurological symptoms, clinical course, risk factors, concomitant cortical spotty lesions, and degree and location of arterial occlusive disease were compared between the 2 groups. RESULTS: Among the 720 consecutive patients, 54 and 29 patients met the criteria for SP and IB infarcts, respectively. The SP group had lower initial National Institutes of Health Stroke Scale scores (2.4+/-2.1 versus 4.4+/-3.1; P=0.001), favorable clinical outcomes (P=0.001), and more frequent potential cardioembolic sources (14.8% versus 0%; P=0.046) than the IB group. Cortical spotty lesions were more frequently accompanied by SP than IB infarcts (72.2% versus 24.1%; P<0.001). IB infarcts were larger (24.2+/-10.2 versus 11.4+/-8.5 mm; P<0.001), appeared in a chainlike fashion (72.4% versus 33.3%; P=0.001), and had a higher degree of stenosis or occlusion (86.2% versus 46.3%; P=0.001) compared with SP infarcts. CONCLUSIONS: Our present study suggests that embolic pathogenesis makes a greater contribution to SP infarcts than IB infarcts. This finding may explain the difference in clinical and neuroradiological characteristics between the 2 groups.

Acute Disease↗
PubMed2003

Important link between dementia subtype and apolipoprotein E: a meta-analysis.

To evaluate the differential diagnostic role of apolipoprotein E (apoE) genotype in dementia, we carried out a meta- analysis of 78 case-control series, including our own new data. The dementia subjects were grouped into Alzheimer's disease (AD) and non-AD. AD patients were subgrouped according to their subtypes, and non-AD patients into vascular dementia (VD), mixed dementia (MD), and non-AD non-VD dementia (NAVD). The apoE allele frequencies and apoE genotype-specific odds ratio (OR) of each group were estimated. The (4 allele frequency was higher in all of the dementia subgroups than in the elderly controls, and the associations with (4 allele were lower in the non-AD (OR 1.8) patients than in the AD (OR 4.2) patients. However, the apoE-related risk alsovaried as a function of the subgroup, in both the AD and non-AD groups; for AD, it was dependent on the subtype of AD (OR 2.3 - 11.3), and higher in late- onset and familial cases than in early-onset and sporadic cases, respectively; among non-AD patients, it was higher in MD (OR 2.6) than in VD (OR 1.3), and intermediate in NAVD (OR 1.9), in which a significant difference was also found between Lewy body dementia (LBD) type (OR 5.1) and non-LBD type (OR 1.3). In conclusion, variability in the apoE-related risk was found in both the AD and non-AD cases, depending on the subgroup. Therefore, precise subgrouping of both AD and non-AD patients should be performed, and this information should taken into consideration when interpreting the results of apoE genotyping.

Aged↗
PubMed2003

Clinical and neuroradiological features of patients with spinocerebellar ataxias from Korean kindreds.

BACKGROUND: Comparative studies of clinical and magnetic resonance imaging findings in patients with spinocerebellar ataxias (SCAs) have been seldom reported. OBJECTIVE: To investigate clinical, genetic, and neuroradiological characteristics of SCAs in Korean kindreds. SETTING: University hospital. PATIENTS AND METHODS: Molecular analysis of SCA types 1, 2, 3, 6, and 7 and dentatorubral pallidoluysian atrophy and magnetic resonance imaging were performed in 67 patients with ataxia. RESULTS: The overall prevalence of 6 types of SCAs was 54% (36 of 67 patients), irrespective of patients' family histories. The most frequent type was SCA7 (11 patients, 16%), followed by SCA3 and SCA6 (10 patients, 15% for both). Certain clinical features suggested specific gene defects, although overlap among the 6 SCA subtypes was broad: visual disturbance was noted in patients with SCA3 and SCA6, dystonia in 1 patient with SCA6, and sporadic ataxia without pigmentary retinopathy in 1 patient with SCA7. Compared with the control subjects, patients with SCAs and multisystem atrophy had a significant enlargement of the fourth ventricle and atrophy of the cerebellum (P<.01). An inverse correlation between the pontine area and the degree of cerebellar atrophy was found in patients with multisystem atrophy (r = -0.73) but not in patients with SCAs. Magnetic resonance imaging revealed significant differences in pattern of morphological alterations among patients with different SCA gene mutations. A similar finding was observed in SCA patients with atypical phenotype. CONCLUSION: The clinical and neuroradiological characteristics of Korean patients with SCAs might be helpful in detecting underlying gene mutations.

Age of Onset↗
PubMed2003

Frequency and mechanisms of stroke recurrence after cryptogenic stroke.

The purpose of this study was to better understand the frequency and mechanisms of stroke recurrence after the stroke with no determined cause (NC). We prospectively studied consecutive patients with acute cerebral infarcts. We divided the patients into five groups (large artery disease [LAD], cardioembolism [CE], small artery disease [SAD], two or more causes [TMC], and NC) and registered recurrent strokes and prognosis for 1 year. Those in the NC group were compared with other subtypes. A total of 204 patients were included; 56 LAD, 22 CE, 62 SAD, 27 TMC, and 37 NC. During follow-up, there were 7 deaths and 31 first recurrent strokes. Patients of the NC group showed a significantly higher rate (30%) of recurrent stroke than those of other subtypes (LAD 16%; CE 14%; SAD 2%), and it was associated with the existence of mild stenosis (</=50%) on relevant artery or the stenosis of greater than 50% on nonrelevant artery. Occlusive lesions other than significant stenosis of relevant artery may play an important role in the development of stroke recurrence in patients of the NC group. Therefore, from the therapeutic and prognostic point of view, the detection of such occlusive lesions in patients with cryptogenic stroke may be needed.

Aged↗
PubMed2003

Subtraction brain SPECT imaging in a patient with gait ignition failure.

The precise anatomical location and pathophysiology of gait ignition failure (GIF) is poorly understood. We investigated the cerebral perfusion patterns using subtraction brain single photon emission computed tomography (SPECT) in a patient with GIF. Subtraction brain SPECT imaging revealed an increased activity in the region of right ventrolateral midbrain and ventral medulla.

Atrophy↗
PubMed2003

The role of transcranial Doppler in symptomatic striatocapsular small deep infarction.

BACKGROUND AND PURPOSE: The transcranial Doppler (TCD) findings in symptomatic small deep infarction are not well known. The aim of this study was to evaluate the role of TCD in striatocapsular small deep infarctions (SSDIs). METHODS: The cerebral angiography and TCD findings were analyzed on 100 patients with symptomatic cerebral infarcts on the middle cerebral artery (MCA) territory. The sensitivity, specificity, and accuracy of TCD in detecting the MCA lesions were compared between lacunar group (the patients with lacunar syndrome and SSDIs on magnetic resonance image) and nonlacunar group. RESULTS: Thirty-eight patients were classified as the lacunar group, whereas 62 patients as the nonlacunar group. On angiography, occlusive lesion of MCA was found in 18 of the lacunar group and 24 patients of the nonlacunar group. The degree of MCA stenosis was higher in the nonlacunar group (80.8% +/- 21.2%) than the lacunar group (60.4% +/- 21.6%). The accuracy of TCD for the detection of MCA stenosis was not different between the groups. However, the sensitivity of TCD in the lacunar group was lower (72%) than in the nonlacunar group (88%), and it might have been due to the difference in the degree of MCA stenosis among the groups. CONCLUSION: Occlusive lesions of the MCA should be considered as a potential cause of SSDIs. In this respect, TCD may be used for screening candidates for conventional angiography in those patients. High rate of mild-degree stenosis of MCA in patients with SSDIs, however, caused a risk for missing such stenosis on TCD.

Adult↗