International experience in stroke registries: Korean Stroke Registry.
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Aged↗
Biomedical subjects
Byung-Chul Lee
Publications and source records attributed to Byung-Chul Lee.
Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females.
An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. We investigated the association of polymorphisms in klotho with ischemic stroke. We searched for sequence variants in promoter and exons of klotho gene. For the association study, selected variants were genotyped in control subjects and in patients with ischemic stroke and vascular dementia. The association with ischemic stroke was further investigated with its subtypes classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No significant association was observed for both G-395A and C1818T with ischemic stroke and vascular dementia (P>0.05). The analysis with subtypes of ischemic stroke revealed the associations that the A allele of G-395A increased the risk of cardioembolic stroke (CE, OR=2.60; P=0.006), and subjects carrying the A allele were susceptible to CE in both of dominant (AA+GA versus GG; OR=2.50; P=0.046) and recessive (AA versus GA+GG; OR=6.52; P=0.007) models. Further analysis of data partitioned by gender showed that the associations of G-395A with CE only existed in women (A versus G; OR=4.33; P=0.002), AA+GA versus GG; OR=5.68; P=0.014, and AA versus GA+GG; OR=9.07; P=0.012), but the significance disappeared in men (P>0.05). The sequence variant of G-395A in klotho might be a genetic risk factor for CE in females.
Acute Disease↗
Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for vascular dementia.
Sequence variants of angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) T235M, angiotensin II type 1 receptor (AT1R) A1166C, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G were analyzed to see their genetic associations with vascular dementia as its candidate genetic risk factors involving renin-angiotensin and fibrin systems. While the ACE I/D, AT1R A1166C, and PAI-1 4G/5G did not contribute to the genetic susceptibility to vascular dementia (P>0.05), a significant association with vascular dementia was shown in the T235M polymorphism of AGT. The frequency of the M allele in patients was higher than in controls with the odds ratio (OR) estimate of 1.51 (P<0.05). In a dominant model, the TM+MM genotypes increased the risk of vascular dementia compared to the TT genotype (OR=2.01; P<0.001). The current results suggested that AGT T235M polymorphism might be a risk factor of vascular dementia.
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Prediction of protein secondary structure content using amino acid composition and evolutionary information.
Knowing protein structure and inferring its function from the structure are one of the main issues of computational structural biology, and often the first step is studying protein secondary structure. There have been many attempts to predict protein secondary structure contents. Previous attempts assumed that the content of protein secondary structure can be predicted successfully using the information on the amino acid composition of a protein. Recent methods achieved remarkable prediction accuracy by using the expanded composition information. The overall average error of the most successful method is 3.4%. Here, we demonstrate that even if we only use the simple amino acid composition information alone, it is possible to improve the prediction accuracy significantly if the evolutionary information is included. The idea is motivated by the observation that evolutionarily related proteins share the similar structure. After calculating the homolog-averaged amino acid composition of a protein, which can be easily obtained from the multiple sequence alignment by running PSI-BLAST, those 20 numbers are learned by a multiple linear regression, an artificial neural network and a support vector regression. The overall average error of method by a support vector regression is 3.3%. It is remarkable that we obtain the comparable accuracy without utilizing the expanded composition information such as pair-coupled amino acid composition. This work again demonstrates that the amino acid composition is a fundamental characteristic of a protein. It is anticipated that our novel idea can be applied to many areas of protein bioinformatics where the amino acid composition information is utilized, such as subcellular localization prediction, enzyme subclass prediction, domain boundary prediction, signal sequence prediction, and prediction of unfolded segment in a protein sequence, to name a few.
Amino Acid Sequence↗
The Hallym Stroke Registry: a web-based stroke data bank with an analysis of 1,654 consecutive patients with acute stroke.
OBJECTIVES: In Korea, stroke ranks as one of the leading causes of death along with cancer and ischemic heart disease. The purpose of this study was to better understand clinical characteristics, risk factors and subtypes of acute stroke among Korean people. METHOD: 1,654 acute stroke patients within 7 days of onset were consecutively enrolled in the Hallym Stroke Registry (HSR). The study was a prospective hospital-based registry aided with a web-based, computerized data bank system. The project began in January 1996 and the data obtained until September 2002 were analyzed. The analysis was basically carried out regarding demographic features, risk factors, time elapsed before coming to the hospitals after the symptom onset, duration of hospitalization, and 30-day mortality rate. RESULTS: 1,567 patients had ischemic stroke and 87 patients had hemorrhagic stroke. The mean age of the patients was 63.6 +/- 11.8 years, and 815 patients (56.8%) were men. The estimated time interval between stroke onset and hospital visit was 1.3 days on average and the mean duration of hospital stay was 12.1 days. Only a small fraction (12%) of patients reached the hospital within 3 h after the symptom onset. As for the risk factors, hypertension topped for both ischemic and hemorrhagic strokes followed by smoking and prior history of stroke, diabetes, hyperlipidemia and cardioembolism. With respect to subtype classification of ischemic stroke, large-artery atherosclerosis was most frequent (42.0%), followed by small-vessel occlusion (31.0%), cardioembolism (8.7%), other determined etiology (1.9%), and undetermined etiology (16.4%). The 30-day mortality rate was 7.2%. CONCLUSION: In the HSR, demographic features were essentially comparable with other major registries. However, the data analysis varies from registry to registry. This may in part be due to a different study design, racial-ethnic differences and patient selection methods.
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The clinico-radiologic properties of deep small basal ganglia infarction: lacune or small striatocapsular infarction?
OBJECTIVE: Deep small basal ganglia infarction (DSBI) cannot be clearly classified as either lacune or striatocapsular infarction by their sizes only. We tried to elucidate clinical and other properties of DSBI to understand better in pathophysiology of ischemic lesion of basal ganglia. METHODS: We analyzed 36 patients with acute ischemic lesion of basal ganglia with the size varying from 1.5 to 3 cm in maximal diameters. We assessed clinical features, laboratory data, risk factors of stroke, and radiologic findings such as MRI and MR angiography. RESULTS: Patients with DSBI could be largely divided into two distinctive groups, small infarction with cortical sign (SICS) and lacunar syndrome (LS) according to their presence of cortical manifestations. Total of 11 patients were in SICS group and they showed cortical manifestations such as eyeball deviation, visual field defect, aphasia and neglect. They also showed severer non-cortical neurologic deficit compared with LS group. Whereas LS group showed various MRA patterns, 7 patients of SICS group (63.6%) showed proximal MCA stenosis in MRA. CONCLUSIONS: We found that many patients with DSBI could have the features of either lacune or striatocapsular infarction. Although they have similar morphologic characteristics but they are presumed to have different pathophysiologic mechanism.
Adult↗
Significance of silent infarcts in acute ischemic stroke patients aged 80 years and older.
BACKGROUND: The significance of silent infarcts (SIs) is unknown in very elderly patients with first-ever acute ischemic stroke. METHODS: Fifty patients aged 80 years and older with first-ever acute ischemic stroke were studied. The conventional risk factors for stroke, the scores of age-related white matter changes, and the findings on echocardiography were compared between patients with and without SIs. RESULTS: Thirty-eight patients (76%) had one or more SIs. The patients without SIs frequently had atrial fibrillation (50% vs. 13.2%, p = 0.014) or spontaneous echo contrast or thrombi on echocardiography (57.1% vs. 0%, p = 0.026) and showed lower scores on age-related white matter changes (0.5 +/- 0.67 vs. 1.13 +/- 0.58, p = 0.002) than did patients with SIs. There were no differences in other risk factors for stroke between the two groups. CONCLUSION: In patients aged 80 years and older, the absence of SIs with a first-ever acute ischemic stroke may suggest the presence of cardiac embolic sources or atrial fibrillation.
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Fold recognition by combining profile-profile alignment and support vector machine.
MOTIVATION: Currently, the most accurate fold-recognition method is to perform profile-profile alignments and estimate the statistical significances of those alignments by calculating Z-score or E-value. Although this scheme is reliable in recognizing relatively close homologs related at the family level, it has difficulty in finding the remote homologs that are related at the superfamily or fold level. RESULTS: In this paper, we present an alternative method to estimate the significance of the alignments. The alignment between a query protein and a template of length n in the fold library is transformed into a feature vector of length n + 1, which is then evaluated by support vector machine (SVM). The output from SVM is converted to a posterior probability that a query sequence is related to a template, given SVM output. Results show that a new method shows significantly better performance than PSI-BLAST and profile-profile alignment with Z-score scheme. While PSI-BLAST and Z-score scheme detect 16 and 20% of superfamily-related proteins, respectively, at 90% specificity, a new method detects 46% of these proteins, resulting in more than 2-fold increase in sensitivity. More significantly, at the fold level, a new method can detect 14% of remotely related proteins at 90% specificity, a remarkable result considering the fact that the other methods can detect almost none at the same level of specificity.
Algorithms↗
Enzymatic properties of the Caenorhabditis elegans Dna2 endonuclease/helicase and a species-specific interaction between RPA and Dna2.
In both budding and fission yeasts, a null mutation of the DNA2 gene is lethal. In contrast, a null mutation of Caenorhabditis elegans dna2+ causes a delayed lethality, allowing survival of some mutant C.elegans adults to F2 generation. In order to understand reasons for this difference in requirement of Dna2 between these organisms, we examined the enzymatic properties of the recombinant C.elegans Dna2 (CeDna2) and its interaction with replication-protein A (RPA) from various sources. Like budding yeast Dna2, CeDna2 possesses DNA-dependent ATPase, helicase and endonuclease activities. The specific activities of both ATPase and endonuclease activities of the CeDna2 were considerably higher than the yeast Dna2 (approximately 10- and 20-fold, respectively). CeDna2 endonuclease efficiently degraded a short 5' single-stranded DNA tail (<10 nt) that was hardly cleaved by ScDna2. Both endonuclease and helicase activities of CeDna2 were stimulated by CeRPA, but not by human or yeast RPA, demonstrating a species-specific interaction between Dna2 and RPA. These and other enzymatic properties of CeDna2 described in this paper may shed light on the observation that C.elegans is less stringently dependent on Dna2 for its viability than Saccharomyces cerevisiae. We propose that flaps generated by DNA polymerase delta-mediated displacement DNA synthesis are mostly short in C.elegans eukaryotes, and hence less dependent on Dna2 for viability.
Adenosine Triphosphatases↗
Analysis of cellular fatty acids in Orientia tsutsugamushi as taxonomic markers.
Six Orientia strains including 3 prototype strains such as Gilliam, Karp, and Kato, and 3 strains (Boryong, Pajoo, and Yongworl) isolated in Korea, were studied for the profiles of their cellular fatty acids. All tested strains contained octadecenoic acid C (18: 1) omega 9 c(57.3 +/- 3.5%), octadecanoic acid C (18: 0) (15.3 +/- 1.5%), and hexadecanoic acid C (16: 0) (12.7 +/- 1.7%) as major components; however, interestingly, eicosenoic acid C (20: 1) omega 9 c(2.6 +/- 0.6%) was found in all strains except the Yongworl strain. Furthermore none of the strains contained 3-hydroxy fatty acids. The ratios of total saturated fatty acid (SFA) to total unsaturated fatty acid (UFA) were within the range of 0.34 to 0.54. These results showed that the cellular fatty acid profile should provide more reliable information for the identification of these bacteria.
Biomarkers↗
Dominant ipsilateral posterior cerebral artery on magnetic resonance angiography in acute ischemic stroke.
BACKGROUND: In acute infarction involving the anterior circulation, the ipsilateral posterior cerebral artery (PCA) often appears to be longer than the contralateral PCA on magnetic resonance angiography. We described this finding as dominant ipsilateral PCA (DIPCA). We sought to find the frequency of DIPCA and its predictors. METHODS: We recruited 164 consecutive individuals with acute infarct involving the anterior circulation, and analyzed their radiological and clinical features. RESULTS: DIPCA was noted in 27 patients (16.5%). It was more frequent in patients with than in patients without steno-occlusive disease of the ipsilateral anterior circulation (30.5 vs. 2.4%, p < 0.001). Multivariate analysis revealed a significant relationship between the severity of arterial lesions in the ipsilateral anterior circulation and DIPCA (p = 0.039). CONCLUSIONS: DIPCA may reflect increased leptomeningeal collateral flow via the ipsilateral PCA, and its development may be dependent on the stenotic anterior circulation.
Acute Disease↗
Cdk5/p35 expression in the mouse ovary.
Cyclin-dependent kinase 5 (Cdk5) is primarily associated with brain development but it is also implicated in lens and muscle differentiation. We found that Cdk5 is also expressed in mouse ovary, and explored the possibility that it plays a role in that tissue. We show by Western blotting and immunohistochemistry that the known Cdk5 activator, p35, is also present in the mouse ovary. Cdk5 and p35 were detected in oocytes at all stages of the follicle. While Cdk5 was present in the cytoplasm and nucleus of the oocyte, p35 was observed only in the cytoplasm. Both proteins were detected in the cytoplasm of luteinized cells in the corpus luteum. Immunoprecipitation and histone H1 kinase assays revealed that they form an ovarian complex with considerable kinase activity. Phosphorylation assays showed that several ovarian proteins are substrates for Cdk5/p35 in vitro. Together our findings suggest that p35-associated Cdk5 activity plays an important role in the ovary, where it may regulate cell differentiation and apoptosis as it does in the brain.
Animals↗
[Differences of cesarean section rates according to San-Yin-Jiao(SP6) acupressure for women in labor].
PURPOSE: The purpose of this study was to explain differences of cesarean section rates according to San-Yin-Jiao(SP6) acupressure for women in labor. METHOD: A nonequivalent control group pre test--post test design was used to explain differences of cesarean section rates according to SP6 acupressure. The participants were 209 women who were assigned to one of three groups SP6 acupressure(n=86), SP6 touch(n=47), and control group(n=76). For 30 minutes, the SP6 acupressure group received SP6 acupressure,and the SP6 touch group received SP6 touch for the duration of each uterine contraction. The Control group was encouraged to deep breath and relax for the duration of each uterine contraction for 30 minutes. RESULT: The rates of cesarean section were 12.8%, 29.8%, and 22.4% for the SP6 acupressure group, SP6 touch group, and control group respectively. There was a significant difference among groups (p=0.049). Cesarean section rates were significantly different between the SP6 acupressure and non-SP6 acupressure group(p=0.035). CONCLUSION: This finding shows that 30 minutes of SP6 acupressure was effective in decreasing the cesarean section rate. Therefore, SP6 acupressure during labor could be applied as an effective nursing intervention.
Acupressure↗
Outer dense fibers serve as a functional target for Cdk5.p35 in the developing sperm tail.
Cdk5 is ubiquitously expressed in all tissues, but its activators, p35 and p39, are principally found in brain, and Cdk5 activity has mostly been associated with brain development, particularly neuronal differentiation and migration. Here we show that the p35 transcript and protein are also present in the testis, and an active Cdk5.p35 complex exists in this tissue as well. Cdk5 and p35 are prominently observed in elongating spermatid tails, particularly over the tail outer dense fibers (ODF). The appearance of Cdk5.p35 proceeds from the proximal to the distal end of elongating spermatids, coinciding with the proximal to distal assembly of ODF along the length of the tail axoneme. Incidentally, increased Cdk5.p35 activity is observed in isolated elongating spermatids and at a time when elongating spermatids appear in the developing testis, suggesting a role for Cdk5.p35 in spermiogenesis. The presence of Cdk5 and p35 in ODF isolated from rat sperm tails implies a strong association among these proteins. In vitro ODF phosphorylation by Cdk5.p35 and decreased in vivo sperm tail ODF phosphorylation in p35-deficient mice indicate that Cdk5.p35 is an integral component of ODF and that ODF is a functional Cdk5.p35 target in the testis. Our results demonstrate for the first time that Cdk5.p35 may participate in the regulation of sperm tail development via a mechanism involving ODF phosphorylation. Apparently, as in brain development, Cdk5.p35 plays a part in testis development.
Animals↗
Immunohistochemistry of voltage-gated calcium channel alpha1B subunit in mouse cerebellum.
Secretion of neurotransmitters is initiated by voltage-gated calcium influx through presynaptic, voltage- gated N-type calcium channels. However, little is known about their cellular distribution in the mouse cerebellum. In the cerebellum, alpha1B immunoreactivity is found mainly on the cell bodies of all Purkinje cells. In addition, the immunoreactivity was detected on a subset of Purkinje cell dendrites, clustered to form a parasagittal array of bands. In the anterior lobe vermis, immunoreactive Purkinje cell dendrites form narrow stripes separated by broad bands of unstained dendrites. Moving caudally through the vermis, these stripes become thicker as a larger fraction of the Purkinje cell dendrites become immunoreactive. This localization study of the alpha1B pore-forming subunits in mouse cerebellum may guide future investigations of the role of calcium channels in neurological pathways.
Animals↗