Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease caused by mutations in the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The spectrum of clinical manifestations is broad, ranging from asymptomatic to typical ischemic stroke, and mainly depends on the location of the mutations. We describe the case of a 76-year-old female without apparent neurological deficits. However, brain magnetic resonance imaging revealed confluent lesions in the white matter. Direct sequencing of the NOTCH3 gene revealed a novel pathogenic mutation, c.811T>A, which results in a mild phenotype. Therefore, this report will expand the current knowledge in regards to the mutations that can cause CADASIL.

BACKGROUND: The angiotensin converting enzyme(ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cadiovascular diseases. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction. The insertion/deletion(I/D) polymorphism of the ACE detected by PCR analysis appears to be associated with hypertension in Koreans and its nucleotide was subcloned into T-vector and its nucleotide sequences were determined. We also examined an association between hypertension and genetic variance of ACE. METHODS AND RESULTS: We identified the angiotensin I-converting enzyme genotype in 127 hypertensive and 189 normotensive Korean subjects. The distribution of ACE genotype II, ID, DD were 39.2%, 40.2%, 20.6% respectively and the frequency for ACE alleles I and D were 0.593 and 0.407, respecively in all subjects. The frequency of D allele in Korean males is higher than that of Korean females(male; 0.438 : female; 0.267), and the frequency of I allele in Korean females is higher than that of Korean males(female; 0.733 : male; 0.562). Genotype distributions of angiotensin I-converting enzyme genes in Korean normal adult population were different from that of Caucasians(P<0.001). There were no significant differences in genotype frequency between the hypertensive control group(n=127) and the normotensive group(n=189). CONCLUSIONS: We observed significant differences of ACE genotype distribution between the male group and the female group in total(P=0.001) and in hypertensive Korean subjects(P=0.013).
Adult ; Alleles ; Angiotensins* ; Base Sequence ; Female ; Gene Frequency* ; Genotype* ; Humans ; Hypertension ; Male ; Myocardial Infarction ; Peptidyl-Dipeptidase A* ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Renin-Angiotensin System ; Risk Factors

BACKGROUND: The rising prevalence of asthma worldwide may be associated with the rising prevalence of obesity in developed nations. Although several studies have suggested a relationship between asthma and obesity, controversy still remains. The aim of this study was to examine the relationship between obesity and asthmatic factors such as atopy, eosinophilia, serum total Ig E and bronchial hyperresponsiveness in chronic cough patients. METHODS: This study was a retrospective, observational study in two centers done between January 2007 and June 2008. The subjects included individuals who had a chronic cough. We examined body mass index (BMI) to measure obesity and pulmonary function. We did a metacholine provocation test for airway hyperresponsiveness (AHR), a skin prick test for atopy, and tests for blood eosinophils and serum IgE. RESULTS: A total of 1022 subjects were included. Airway hyperresponsiveness was not related with obesity (p=0.06), and atopy incidence was significant higher in non obese patients (p=0.00). There was no significant difference in serum IgE and blood eosinophil counts between obese and non obese patients. Forced expiratory volue in one second (FEV1)/forced vital capacity (FVC) was significantly reduced in obese patients (p=0.03), but FEV1 and FVC were no significant difference between obese and non obese patients. CONCLUSION: There is no relationship between obesity and bronchial hyperresponsiveness. The nonobese group appears to have more atopy. The relationship between obesity and bronchial hyperresponsiveness and atopy need further investigation.
Asthma ; Body Mass Index ; Cough ; Dermatitis, Atopic ; Developed Countries ; Eosinophilia ; Eosinophils ; Humans ; Immunoglobulin E ; Incidence ; Obesity ; Prevalence ; Retrospective Studies ; Skin ; Vital Capacity

Interruption of the aortic arch is an uncommon congenital cardiovascular malformation invariably accompanied by other cardiovascular anomalies. This carries a 76% mortality rate in the first month of life. We recently experienced a case of interruption of the aortic arch with patent ductus arteriosus in a 21-year-old man with systolic murmur. he did not showed any other symptoms or signs. Cardiac catheterization with angiography showed interruption of the aortic arch with many systemic arterial collaterals and patent ductus arteriosus.
Angiography ; Aorta* ; Aorta, Thoracic ; Cardiac Catheterization ; Cardiac Catheters ; Ductus Arteriosus, Patent* ; Humans ; Mortality ; Systolic Murmurs ; Young Adult

[Objective] It makes a through study on the popularization and usefulness plan of Moxa Combustion, therefore popularizing practical use of that.
[Methods] It was based on the established treatises and books, in order to studying about the literature of Moxa Combustion.
[Results & Conclusions] It makes a through study on the whole of Moxa Combustion, the results as follows.
1. We explained (illustrated) the origin, history, classification and mechanism (effect) of Moxa Combustion.
2. The study of standardization plan of Moxa Combustion for popularization.
The thermal stimulation of Moxa Combustion was decided the characteristic pattern of combustion temperature by moxa burning and that makes a measure to grasp the effective action of Moxa Combustion upon human body. Thereupon it is necessary to continue further studies by analyzing the characteristic pattern of combustion temperature by moxa burning and there clinical effects in practice.
3. The usefulness of Moxa Combustion.
The therapeutic effect of Moxa Combustion are hematopoiesis (increase the blood), analgesic function, increase the immunity, antioxidant activity, diuretic action, control of hormone (endocrine gland), suppression of carcinogenesis, increase the self involution (natural healing), decrease of GOT/GPT, glucose, cholesterol level.

In this work, GLUTs phosphorylations by a downstream effector of PI3-kinase, PKC- zeta, were studied, and GLUT4 phosphorylation was compared with GLUT2 phosphorylation in relation to the translocation mechanism. Prior to phosphorylation experiment, PKC- zeta kinase activity was determined as 20.76+/-4.09 pmoles Pi/min/25 ng enzymes. GLUT4 was phosphorylated by PKC- zeta and the phosphorylation was increased on the vesicles immunoadsorpted from LDM and on GLUT4 immunoprecipitated from GLUT4-contianing vesicles of adipocytes treated with insulin. However, GLUT2 in hepatocytes was neither phosphorylated by PKC- zeta nor changed in response to insulin treatment. It was confirmed by measuring the subcellular distribution of GLUT2 based on GLUT2 immunoblot density among the four membrane fractions before and after insulin treatment. Total GLUT2 distributions at PM, LYSO, HDM and LDM were 37.7+/-12.0%, 42.4+/-12.1%, 19.2+/-5.0% and 0.7+/-1.2% in the absence of insulin. Total GLUT2 distribution in the presence of insulin was almost same as that in the absence of insulin. Present data with previous findings suggest that GLUT4 translocation may be attributed to GLUT4 phosphorylation by PKC- zeta but GLUT2 does not translocate because GLUT2 is not phosphorylated by the kinase. Therefore, GLUT phosphorylation may be required in GLUT translocation mechanism.
Adipocytes ; Hepatocytes ; Insulin ; Membranes ; Phosphatidylinositol 3-Kinases ; Phosphorylation* ; Phosphotransferases

Insulin stimulates glucose transport in muscle and fat cells by promoting the translocation of glucose transporter (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3-kinase) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt and PKC- zeta, those are known as the downstream target of PI3-kinase in regulation of GLUT4 translocation, is not known yet. An interesting possibility is that these protein kinases phosphorylate GLUT4 directly in this process. In the present study, PKB- alpha and PKC- zeta were added exogenously to GLUT4-containing vesicles purified from low density microsome (LDM) of the rat adipocytes by immunoadsorption and immunoprecipitation for direct phosphorylation of GLUT4. Interestingly GLUT4 was phosphorylated by PKC- zeta and its phosphorylation was increased in insulin stimulated state but GLUT4 was not phosphorylated by PKB- alpha. However, the GST-fusion proteins, GLUT4 C-terminal cytoplasmic domain (GLUT4C) and the entire major GLUT4 cytoplasmic domain corresponding to N-terminus, central loop and C-terminus in tandem (GLUT4NLC) were phosphorylated by both PKB- alpha and PKC- zeta. The immunoblots of PKC- zeta and PKB- alpha antibodies with GLUT4-containing vesicles preparation showed that PKC- zeta was co-localized with the vesicles but not PKB- alpha. From the above results, it is clear that PKC- zeta interacts with GLUT4-containing vesicles and it phosphorylates GLUT4 protein directly but PKB- alpha does not interact with GLUT4, suggesting that insulin-elicited signals that pass through PI3-kinase subsequently diverge into two independent pathways, an Akt pathway and a PKC- zeta pathway, and that later pathway contributes, at least in part, insulin stimulation of GLUT4 translocation in adipocytes via a direct GLUT4 phosphorylation.
Adipocytes* ; Animals ; Antibodies ; Cytoplasm ; Glucose ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 4 ; Immunoprecipitation ; Insulin ; Microsomes ; Phosphatidylinositol 3-Kinases ; Phosphorylation* ; Protein Kinases ; Proto-Oncogene Proteins c-akt ; Rats*

Zonisamide (ZNS) has been proven as a safe, effective, and well-tolerated antiepileptic drug. We report an epilepsy patient who had a severe, dose-dependent, memory deficit after ZNS administration. A 65-year-old man visited our epilepsy clinic due to the occurrence of nocturnal convulsions. Despite the absence of seizures, he developed a severe impairment of verbal and visual memory functions after the increment of ZNS dosage from 200 mg/day to 300 mg/day. We substituted 1,000 mg/day valproic acid for ZNS. His cognitive performances were returned to original levels.
Aged ; Epilepsy ; Humans ; Isoxazoles ; Memory ; Memory Disorders ; Seizures ; Valproic Acid

STATs (signal transducers and activators of transcription) are proteins with dual functions: signal transducers in the cytoplasm and transcriptional activators in the nucleus. STAT proteins act as transcription factors activated by phosphorylation on its tyrosine residues upon stimulation by various cytokines. The phosphorylated STAT molecules then form homo- or heterodimers through SH2-mediated interaction and translocate into the nucleus to activate the transcription of various target genes. STAT5 recognizes the interferon-gamma activated site TTCNNNGAA (GAS sequence) in the promoter region of the beta-casein gene. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5a activation in various systems are not clear. Here we showed that STAT5a was phosphorylated 10 min after desferrioxamine (DFO) treatment, and reached a maximum induction at 4 h in mammary epithelial cells (HC11) and transfected COS-7 cells. Under hypoxic conditions (2% O2), a maximal phosphorylation of STAT5a was observed within 6 h. EMSA (electrophoretic mobility shift assay) showed that DFO or hypoxia enhanced the binding activities of STAT5a DNA to beta-casein gene promoter in mammary epithelial cells (HC11) and transfected COS-7 cells. These results showed that DFO or hypoxia induces tyrosine phosphorylation of STAT5a and also increases the binding activity of STAT5a DNA in mammary epithelial cells. Our data suggest that the STAT5 may act as a mediator in hypoxia-mediated gene expression.
Animals ; Anoxia/*genetics/*metabolism ; Caseins/genetics ; Cell Line ; DNA/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Deferoxamine/pharmacology ; Epithelial Cells/drug effects/*metabolism ; Gene Expression Regulation ; Mammary Glands, Animal/cytology/*metabolism ; Mice ; Phosphorylation/drug effects ; Phosphotyrosine/metabolism ; Promoter Regions (Genetics)/genetics ; Protein Binding ; Response Elements/*genetics ; Support, Non-U.S. Gov't ; Trans-Activators/*metabolism

BACKGROUND AND PURPOSE: We investigated the cognitive change of patients with juvenile myoclonic epilepsy (JME) after a long-term antiepileptic drug(s) (AED) administration to clarify the cause of cognitive impairment. METHODS: Thirty-three patients with JME who were newly diagnosed or did not take any AED for at least 6 months prior to the beginning of the study were included. We conducted neuropsychological tests at baseline and after at least 12 months of AEDs trial. Forty healthy controls were acquired according to age- and education-match to patients with JME. We compared the differences of neuropsychological outcomes among them. We tried to identify the determinants for cognitive performances after AEDs trial. RESULTS: Twenty-seven patients completed the second neuropsychological tests. Seizure frequency and EEG abnormality were significantly decreased after AEDs intake. The Number of epileptiform discharges (EDs) on EEG tended to be decreased at last visit. However, cognitive performances between baseline and follow-up period were not different. Cognitive measures of baseline and follow-up period were worse than those of controls in list learning, forward digit span, backward digit span, Trail Making Test, and verbal fluency. Cognitive performances of follow-up period in the JME group were not correlated with age at seizure onset, duration of epilepsy, seizure recurrence, EEG abnormality, and type of AEDs. CONCLUSIONS: Cognitive performances of JME were not recovered to the level of healthy controls despite the control of seizures and EDs by AEDs. Therefore, cognitive impairment of JME may be due to irreversible, disease-related characteristics.
Cognition ; Electroencephalography ; Epilepsy ; Follow-Up Studies ; Humans ; Learning ; Myoclonic Epilepsy, Juvenile ; Neuropsychological Tests ; Recurrence ; Seizures ; Trail Making Test