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.

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.

Primary ovarian failure caused by a solvent containing 2-bromopropane.

Sixteen Korean female laborers who had been exposed to a cleaning solvent composed mainly of 2-bromopropane developed primary ovarian failure. Histologic findings from these patients' ovaries were similar to those observed in ovarian failure caused by radiation or chemotherapy, i.e., reduced number and developmental arrest of primary follicles, interstitial fibrosis and hyalinization of blood vessels. We followed their clinical course for 2 years and found that two patients recovered normal ovarian function spontaneously: one became pregnant and delivered a normal full-term baby, and the other resumed regular menstrual periods with normal hormonal values. Our observations support the idea that the increasing prevalence of ovarian failure in recent years might be due to an increase in presently unidentified environmental toxic agents.

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.

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.

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.

[The development of I. P. Pavlov's conditioned reflex theory].

This paper deals with the theory of Ivan Petrovich Pavlov (1849-1936), a Russian physiologist who presented for the first time the systematic theory of the function of the brain that controls the whole behavior of animals, i.e. higher nervous activity through experimental studies. This paper, principally based on Lectures on Conditioned Reflexes (1928), investigates the development of conditioned reflex theory from its beginning by dividing it into three periods. First, during the period from 1898 to 1906, the fundamental concept of conditioned reflex was established and the study of conditioned reflex became an independent discipline. From 1907 to 1916, the second period, Pavlov theorized on higher nervous activity on the basis of extensive data from his laboratory experiments of conditioned reflex. And Pavlov complemented conditioned reflex theory, during the third period from 1916 to 1928, and extended the boundaries of it through applications of conditioned reflex theory to psychopathology and typology. The study contributes to the understanding that conditioned reflex theory was historically developed, and not presented as a complete form from the beginning, and that Pavlov intended to study the higher nervous activity through the method of neurophysiology.

[Smallpox epidemics and folk's responses in the late Choson period].

Smallpox was one of the most dreadful epidemic diseases in Korea until the early twentieth century. In the Choson period, smallpox came to prevail more frequently and vigorously, and many people died of the disease. To cope with smallpox, the society of Choson had various modes of measures, though they were not always effective, which included the government's rituals, medical men's prescriptions, and folk's recipes. Among various responses to smallpox, the recipes of folklore seem to be very interesting. While attitude toward other contagious diseases (e.g., typhoid fever, or malaria) mainly consisted of exorcism, smallpox was believed to be the passage of the smallpox deity. Sonnim (which means guest), through the body of patient for certain time span, and gods of smallpox were treated hospitably. This attitude toward smallpox was deeply rooted in Korean shamanism, and partly in the natural history of the disease. From 1876 smallpox vaccination was reintroduced and practiced. There were, however, a lot of difficulties in practice of vaccination due to distrust and prejudice. and traditional dealings with smallpox, in spite of vaccination, didn't disappear even after the Japanese compulsory occupation.

[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.

[Division and specialization of the Western European physiology].

The 19th century has been thought to be the turning point that the experimental method began to take strong root as the core to solve many physiological subjects, and the discipline of physiology got firmly fixed as the specialized one in the western Europe. Authors found the following characteristics in the process of the division and specialization of the 19th century western physiology. 1) It was the process of its separation from the discipline of anatomy that was necessary in the development of physiology as the independent, specialized division. Newly grown ideas, that there were working functions specialized study, were the important background and basis of the development of physiology as the specialized discipline. 2) It was not until the force and influence of the metaphysical concept on the living things (vitalism) grew weak that physiology could become the specialized discipline. The new materialistic concept about living things made it possible for the researchers of that time to apply the physico-chemical method in the study of physiological problems. 3) Institutionalization of the physiological research and education accelerated its development and specialization. The followings appeared in the mid-19th century: specialized professorship, division as the separated subject in the undergraduated medical school curriculum, laboratory settings for the purpose of physiological study, establishment of independent academic societies and publication of their own journals. Two main factors, namely, both the settlement of the new physiological thought and method of the very scientific nature and the institutionalization within the academic and medical societies, exerted influences on each other in the ground of the 19th century western Europe. Through that process, the discipline of physiology took root deep as the independent specialized division in the societies of science and medicine.