The severity of periodontitis and metabolic syndrome in Korean population: The Dong-gu study.

OBJECTIVES: We assessed the association between periodontal disease status and metabolic syndrome (MetS) and its individual components in Korean adults over 50 years old. MATERIAL AND METHODS: In the Dong-gu study, 5078 men and women aged over 50 years were included. They underwent a questionnaire survey, physical assessment, biochemical assessment and periodontal assessment. The percentages of sites with periodontal probing depth ≥4 mm, and clinical attachment loss ≥4 mm were recorded for each participant. Periodontal disease was also classified by the Centers for Disease Control and Prevention/American Academy of Periodontology definition of periodontitis and the American Academy of Periodontology definition (1999). MetS was defined by the 2009 guidelines of the International Diabetes Federation. This study used multivariate negative binominal regression analysis to assess the association between the severity of periodontitis and MetS, after age, smoking habits, alcohol consumption and physical activity related factors were adjusted for. RESULTS: Prevalence of MetS was 32.3%, 36.2% and 45.9% among men with no or mild, moderate and severe periodontitis, respectively. The severity of periodontitis was positively associated with the prevalent MetS in men but not in women. In men, severe periodontitis showed a higher risk of MetS than those with no or mild periodontitis (relative risk 1.43, 95% confidence interval 1.17-1.73) after adjusting for confounders. Periodontal probing depth was positively associated with the prevalence of MetS in both genders. In the analysis separated by individual MetS components, periodontitis severity was positively associated with hypertriglyceridemia and low high-density lipoprotein cholesterol in men, while positively associated with low high-density lipoprotein cholesterol and abdominal obesity in women. CONCLUSION: Increasing the severity of periodontitis was associated with the risk of prevalent MetS in Korean adults. This result confirmed that periodontal inflammation might be a contributive factor of MetS.

Association between eNOS polymorphisms and risk of coronary artery disease in a Korean population: a meta-analysis.

Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk.

Neuropilin-2 gene expression correlates with malignant progression in cutaneous melanoma.

BACKGROUND: It is currently not possible to predict the metastatic potential of early-stage melanoma lesions by histological examination alone; however, a significant number of thin melanomas will progress over time to advanced disease. Molecular biomarkers that could identify patients with melanoma at high risk at the time of original diagnosis would contribute significantly to improved patient outcomes and increased survival. Neuropilin-2 (NRP2), a cell surface receptor involved in tumour-associated angiogenesis and lymphangiogenesis, has recently been shown to be expressed in melanoma. OBJECTIVES: To evaluate the potential value of NRP2 gene transcript levels as biomarkers for malignant melanoma progression. METHODS: We measured NRP2 gene expression in a panel of formalin-fixed paraffin-embedded tissue specimens consisting of naevi, primary melanomas and metastatic melanomas using quantitative reverse transcriptase-polymerase chain reaction technique. RESULTS: NRP2 levels are clearly segregated among the groups of naevi, primary and metastatic melanoma samples with a statistical trend towards increasing NRP2 gene expression correlating with disease progression. Logistic regression analysis reveals that the probability of malignant progression increases with elevated levels of NRP2 (odds ratio of 2·60 with confidence interval 1·29-5·21). Within the group of primary melanomas, there is a positive correlation (r = 0·823) between NRP2 expression and Breslow depth. This correlation was validated in an independent sample set of patients with melanoma. CONCLUSIONS: This preliminary study strongly supports the significance of NRP2 as a useful biomarker for malignant progression of melanoma, which may be useful for early identification of patients with melanoma at high risk.

Plasma total homocysteine and the methylenetetrahydrofolate reductase 677C>T polymorphism do not contribute to the distribution of cervico-cerebral atherosclerosis in ischaemic stroke patients.

OBJECTIVE: To evaluate the effects of plasma total homocysteine (tHcyt) and the MTHFR 677C>T polymorphism on determining the intracranial- (IC) and extracranial (EC) locations of atherosclerosis. METHODS: Brain MR angiography was performed on 463 patients with symptomatic ischaemic stroke to detect significant atherosclerosis (more than 50% stenosis of vessel diameter) in the IC- and EC arteries. Relationships between IC- or EC atherosclerosis and plasma tHcyt level and/or MTHFR 677C>T genotypes were analyzed after adjusting for vascular risk factors. RESULTS: The odd ratios (ORs) of plasma tHcyt were not significantly higher in patients with either IC- or EC atherosclerosis than in patients with no atherosclerosis. When the study subjects were stratified into three subgroups according to their plasma tHcyt levels, neither the crude ORs nor adjusted ORs of each IC- and EC atherosclerosis in highest and middle plasma tHcyt tertile were significantly different from those in lowest plasma tHcyt tertile. The ORs of the MTHFR 677TT genotype in IC- and EC atherosclerosis were not significantly different from those in no atherosclerosis. There was no dose-dependent effect of MTHFR 677T allele on either IC- or EC atherosclerosis. CONCLUSION: Plasma tHcyt level and the MTHFR 677C>T polymorphism do not contribute to the distribution of cervico-cerebral atherosclerosis in ischaemic stroke patients.

Cerebellopontine angle epidermoid tumour presenting with bilateral gaze nystagmus.

Vestibular symptoms have been rarely described in cerebellopontine angle epidermoid tumours. We report a case of CPA epidermoid tumour presenting with subacute onset of vestibular symptoms such as vertigo, gait ataxia, and nystagmus masquerading as acute vestibular neuritis or central vertigo. The vestibular symptoms disappeared after excision of the tumour.

Bilateral cerebral hemispheric infarction associated with sildenafil citrate (Viagra) use.

Sildenafil citrate (Viagra) is one of the frequently prescribed drugs for men with erectile dysfunction. We describe a 52-year-old man with bilateral middle cerebral artery (MCA) territory infarction after sildenafil use. He ingested 100 mg of sildenafil and about 1 h later, he complained of chest discomfort, palpitation and dizziness followed by mental obtundation, global aphasia and left hemiparesis. Brain magnetic resonance imaging documented acute bilateral hemispheric infarction, and cerebral angiography showed occluded bilateral MCA. Despite significant bilateral MCA stenosis and cerebral infarction, systemic hypotension persisted for a day. We presume that cerebral infarction was caused by cardioembolism with sildenafil use.

ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction.

OBJECTIVES: Angiotensin-converting enzyme (ACE) polymorphism may play a role in stroke and silent brain infarction (SBI) susceptibility, but the results among the populations studied to date have not been consistent. Thus, we investigated the association between ACE genotypes and ischemic stroke and SBI in Korean patients. SUBJECTS AND METHODS: DNA samples from 237 stroke patients, 264 SBI patients and 234 age-matched controls were amplified using polymerase chain reaction to detect the ACE ins/del (I/D) polymorphism. Genotype was determined by the presence of a 490-bp band (I allele) or a 190-bp band (D allele) in agarose gel electrophoresis. RESULTS: Odds ratios of the I/D and D/D genotypes and the overall (I/D + D/D) for the I/I genotype were significantly different between stroke patients and normal controls. However, there was no significant difference between patients with SBI and controls. CONCLUSIONS: This study is the first report of a significant association between ACE polymorphism and ischemic stroke in the Asian population. Although no consistent associations have been found between ACE polymorphism and stroke in the populations studied to date, the ACE polymorphism may be a genetic determinant of ischemic stroke, at least in Korean patients.

Elective stenting for symptomatic middle cerebral artery stenosis presenting as transient ischaemic deficits or stroke attacks: short term arteriographical and clinical outcome.

BACKGROUND: Although stent assisted angioplasty is an effective treatment for coronary and peripheral arterial disease, its efficacy in intracranial arteriosclerotic disease has not been verified. OBJECTIVES: To assess the radiographic and clinical outcome of stent assisted angioplasty for symptomatic middle cerebral artery (MCA) stenosis. METHODS: We attempted stent assisted angioplasty in 14 patients with symptomatic high grade stenosis (>60%) on the proximal portion of the MCA, who had experienced either recurrent transient ischaemic attacks (TIAs) resistant to medical therapy or one or more stroke attacks. Patient records were analysed for angiographic characteristics, degree of stenosis, pre-procedural regimen of anti-platelet and/or anti-coagulation agents, use of devices, procedure related complications, pre-operative and post-operative single photon emission computed tomography (SPECT) findings, and clinical and radiographic outcomes. RESULTS: Stent assisted angioplasty was successfully performed in 8 of 14 patients without any serious complications and unsuccessful in 2 of 14 patients due to the tortuous curve of the internal carotid artery siphon. Four patients had complications. Two patients had an arterial rupture; one patient was rescued by an additional stent and balloon tamponade, the other patient died. Complications in the other two patients included thrombotic occlusion and distal thrombosis. Residual stenosis was less than 50% in diameter in all the patients. All eight patients who underwent follow up cerebral angiography had no restenosis. Follow up SPECT showed improved perfusion in the affected MCA territory in all the tested patients with TIA and in one of three stroke patients. Using the modified Rankin Scale at follow up, four of five TIA patients and five of six stroke patients were assessed as functionally improved or having a stable clinical status. CONCLUSION: Although the re-stenosis rate in stent assisted angioplasty seems to be better than in primary balloon angioplasty as reported previously, the complication rate is still high. Elective stenting is an alternative therapeutic method for the prevention of secondary ischaemic stroke in stroke patients with MCA stenosis, and seems to be a potentially effective but also hazardous therapeutic technique in patients with recurrent TIAs. This study indicates the need for randomised control trial data of this intervention. Additionally, long term follow up data and additional clinical experience are required to assess the durability of this procedure.

Homozygous C677T mutation in the MTHFR gene as an independent risk factor for multiple small-artery occlusions.

INTRODUCTION: Hyperhomocysteinemia is an independent risk factor for cerebrovascular disease and the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene can induce hyperhomocysteinemia. However, the association between this 677TT genotype and ischemic stroke still remains controversial. Therefore, we carried out this study to determine whether the MTHFR TT genotype is associated with certain subtypes of ischemic stroke. MATERIALS AND METHODS: We enrolled 195 ischemic stroke patients and 198 healthy individuals and checked their fasting plasma homocysteine levels and analyzed the C677T polymorphism in the MTHFR gene. RESULTS: Our findings concur with previous reports that stroke occurrence is associated with hyperhomocysteinemia, but not with the 677TT genotype. However, when we re-analyzed the data based on a subtype classification, the adjusted odds ratio (AOR) and 95% confidence intervals (CI) of the 677TT genotype were found to be significantly higher in patients with small-artery occlusion than that in controls (AOR, 2.92; 95% CI, 1.01-8.48). Moreover, the AOR of the 677TT genotype was found to be much bigger in patients with multiple small-artery occlusions (AOR, 6.90; 95% CI, 1.70-27.99), but not in those with single small-artery occlusion (AOR, 1.19; 95% CI, 0.27-5.35). CONCLUSIONS: The homozygous C677T mutation in the MTHFR gene is associated with multiple small-artery occlusions, but not with single small-artery occlusion. Our findings suggest a genetic basis for certain subtypes of ischemic stroke.

Endovascular rescue from arterial rupture and thrombosis during middle cerebral artery stenting.

Intravascular stents are being used with increasing frequency in interventional neuroradiology. Iatrogenic arterial rupture is an uncommon but serious complication. We present a case of arterial rupture and subarachnoid haemorrhage during middle cerebral artery stenting, treated by emergency additional, overlapping stenting and balloon tamponade of the dissected vessel. Thrombotic occlusion of the artery was managed by intra-arterial abciximab. Normal vessel patency was re-established within 20 min and the patient recovered with no neurological deficit.

Evaluation of ictal brain SPET using statistical parametric mapping in temporal lobe epilepsy.

An automated voxel-based analysis of brain images using statistical parametric mapping (SPM) is accepted as a standard approach in the analysis of activation studies in positron emission tomography and functional magnetic resonance imaging. This study aimed to investigate whether or not SPM would increase the diagnostic yield of ictal brain single-photon emission tomography (SPET) in temporal lobe epilepsy (TLE). Twenty-one patients (age 27.14 +/- 5.79 years) with temporal lobe epilepsy (right in 8, left in 13) who had a successful seizure outcome after surgery and nine normal subjects were included in the study. The data of ictal and interictal brain SPET of the patients and baseline SPET of the normal control group were analysed using SPM96 software. The t statistic SPM¿t¿ was transformed to SPM¿Z¿ with various thresholds of P<0.05, 0.005 and 0.001, and corrected extent threshold P value of 0.05. The SPM data were compared with the conventional ictal and interictal subtraction method. On group comparison, ictal SPET showed increased uptake within the epileptogenic mesial temporal lobe. On single case analysis, ictal SPET images correctly lateralized the epileptogenic temporal lobe in 18 cases, falsely lateralized it in one and failed to lateralize it in two as compared with the mean image of the normal group at a significance level of P<0.05. Comparing the individual ictal images with the corresponding interictal group, 15 patients were correctly lateralized, one was falsely lateralized and four were not lateralized. At significance levels of P<0.005 and P<0.001, correct lateralization of the epileptogenic temporal lobe was achieved in 15 and 13 patients, respectively, as compared with the normal group. On the other hand, when comparison was made with the corresponding interictal group, only 7 out of 21 patients were correctly lateralized at the threshold of P<0.005 and five at P<0.001. The result of the subtraction method was close to the single case analysis on SPM at P<0.05. However, at higher thresholds (P<0.005 and 0.001) the subtraction method was comparable to the SPM results only when individual ictal images were compared with the normal control group, and not when comparison was with the interictal group. It is concluded that SPM is an alternative diagnostic method for the localization or lateralization of the seizure focus in temporal lobe epilepsy and that interictal SPET could be omitted if a normal brain SPET database were to be established. The medical cost of seizure localization would thereby be reduced.

[Development of National Institute of Health, Korea].

The National Institute of Health (NIH) under the Ministry of Health and Welfare of the Korean Government was established in 1963, integrating four institutes: National Institute of Health, National Chemical Laboratories, National Laboratory of Herb Medicine and National Institute of Public Health Training. The root, however, goes down to the Bacteriology Laboratory, opened in 1912 with the function for microbiological testing and pox vaccine development, which was absorbed into the former National Institute of Health in 1948 when the government of the Republic of Korea was inaugurated. The Institute opened a satellite office, the Masan Branch in 1977, and was further expanded, adding the Divisions of AIDS and Biotechnology in 1988. In 1996, as part of restructuring the Government organizations, Korea Food and Drug Administration (KFDA) ws founded by expanding the Toxicology Research Institute, to which all the functions of testing and certifying foods and drugs were transferred. Simultaneously, a new department, the Department of Biomedical science was organized, which currently consists of five divisions; the Divisions of Cancer Research, Degenerative Diseases, Cardiovascular Diseases, Metabolic Diseases and Genetic Diseases. In 1999, in order to provide a rapid and effective disease control, the Department of Communicable Diseases was newly founded, merging the Division of Disease Control and Prevention from the Ministry of Health and Welfare. With these steady and significant changes, the NIH, together with the training of health manpower, has become the national organization for research, prevention and control of various diseases of public health importance in Korea.

Inflammatory pseudotumor of carotid artery: a case report.

Inflammatory pseudotumor is an uncommon round and spindle cell proliferative lesion of unknown etiology that occurs most commonly in the lung. But it also occurs in diverse extrapulmonary locations such as the abdomen, retroperitoneum, pelvis, heart, head and neck, upper respiratory tract, trunk, bladder and extremities. The extrapulmonary inflammatory pseudotumor is often larger, less well circumscribed and multinodular. Proximity of the tumor to vital structures or involvement of vital organs compromises the opportunity for complete resection, thus higher recurrence rates are often reported even after surgical treatment. The authors report a case of inflammatory pseudotumor originating from the common carotid artery in a 42-year-old female patient with a rapidly growing neck mass, treated by en-bloc resection of inflammatory pseudotumor and a long segment of common carotid artery followed by PTFE graft interposition.

Distribution of carcinoembryonic antigen and biologic behavior in colorectal carcinoma.

PURPOSE: Carcinoembryonic antigen is assumed from the results of several experiments to be associated with invasion of colorectal carcinoma by adhesion or contact inhibition. The patterns and the intensity of carcinoembryonic antigen distribution in colorectal carcinoma were assessed to verify whether they were correlated with malignant potential from those biologic characteristics. METHODS: Carcinoembryonic antigen distribution was tested in the archival samples of 149 colorectal carcinomas by immunohistochemistry, using three characterized anti-carcinoembryonic antigen monoclonal antibodies: T84.66, PR1A3, and PR3B10. The distribution patterns in neoplastic tissue were categorized into unstained, apicoluminal, and diffuse cytoplasmic patterns. Tumor, invasive tumor margin, and tissue surrounding the tumor were examined. RESULTS: Although all three antibodies revealed a positive correlation, T84.66 showed better discrimination than the others. Although none of the negative staining of the tumor or invasive tumor margin showed recurrence, the apicoluminal pattern showed recurrence, and the diffuse pattern showed the most frequent recurrence (P < 0.01). Recurrence was also associated with staining intensity in the apicoluminal pattern in both the tumor and invasive tumor margin (P < 0.05). Infiltrative tumor growth and lymph node metastasis were more frequent in cases of positive staining in tissue surrounding the tumor. Patients with the apicoluminal pattern achieved longer survival than patients with the diffuse-cytoplasmic pattern in the invasive tumor margin (P = 0.024) by a multivariate analysis including tumor stage and histologic differentiation. CONCLUSION: The distribution of carcinoembryonic antigen in tumors and surrounding tissue seems to be closely correlated with invasiveness and metastatic behavior in colorectal carcinoma. Carcinoembryonic antigen immune staining can be considered as an efficient tool to determine groups with risk of recurrence.

Human c-Jun N-terminal kinase expression and activation in the nervous system.

Differential expression and localization of c-Jun N-terminal kinases (JNKs) in the human brain may reflect transduction of a variety of extracellular stimuli to selective cellular responses. Of the three JNKs, JNK1 and 2 are widely distributed in tissues and JNK3 is predominantly restricted to brain where it is expressed in neurons. Although there is considerable molecular conservation among all three JNKs, we distinguished expression of each by in situ hybridization, immunoblot analysis with a panel of antibodies, and stress-activation using c-Jun as substrate. In the human central nervous system (CNS), there are at least 10 isoforms: JNK3alpha1 and JNK1alpha1 were the major JNK isoforms expressed; JNK2 was not detected. On immunoblots of brain homogenates, antibody selectivity identified JNK3alpha1 as a 45-kDa protein, JNK1alpha1, a slightly lower band at 44 kDa, and a 50-kDa band of unknown specificity. Recombinant human JNK3alpha1, transfected either into CHO, COS-1, or Neuro2A (N2A) cells, was strongly expressed as a 45-kDa protein in each. Transfected JNK3alpha1, and endogenous JNK1, each immunoprecipitated from N2A cells, phosphorylated recombinant forms of human c-Jun. Kinase activity of each JNK was modestly stimulated in N2A cells by anisomycin but not by ceramide, UV irradiation, or heat shock. Endogenous JNK activation, especially at a low level, may reflect a chronic and cumulative stress process that contributes to hyperphosphorylation of cytoskeletal proteins such as those found in Alzheimer's disease (AD), and ultimately, induction of apoptosis.

Primary myxoid leiomyoma of the liver.

We describe a case of hepatic leiomyoma in a 41-year-old woman who complained of abdominal discomfort due to a right upper quadrant abdominal mass. A computed tomographic scan revealed a large hepatic mass with unusual cystic change. Light and electron microscopic findings and an immunohistochemical study demonstrated diffuse and scattered proliferation of smooth muscle cells in a myxoid matrix. In contrast to previously reported cases of primary leiomyoma of the liver, the present tumor developed in a patient without an immunosuppressive condition. To the best of our knowledge, this is the first reported case of primary "myxoid" leiomyoma of the liver.

Primary hepatic carcinoid tumor with a paranuclear clear zone: a case report.

Carcinoid tumors having distinct paranuclear clear zones seen on hematoxylin and eosin stain are rare and few cases have been reported in the literature. Furthermore, primary hepatic carcinoid tumor with a paranuclear clear zone is extremely rare. We recently experienced a case from a 48-year-old man who presented a large single mass, 12 cm in largest diameter, in the right lobe of the liver. Histologically, the tumor revealed characteristic organoid pattern with central hyaline degeneration. The tumor cells had a prominent paranuclear vacuolated dear zone. On immunohistochemistry, tumor cells were diffusely positive for synaptophysin and focally stained for chromogranin A. Ultrastructural examination revealed paranuclear aggregation of intermediate filaments and membrane-bound clear vesicles, which corresponded to the paranuclear vacuolated clear zone.