Dendritic cells are professional antigen presenting cells, which show an extraordinary capacity to initiate primary immune responses by stimulating T cells. This established function of dendritic cells has attracted much attention in efforts to develop useful vaccines for the treatment of cancer and infectious diseases. Designing effective strategies to generate clinical dendritic cell-based vaccine protocols remains a challenging field of research. The successful realization of immunotherapy utilizing dendritic cells will depend on modifications of these protocols to optimize the natural stimulatory properties of dendritic cells, such as genetic modification of dendritic cells. This review focuses on dendritic cell gene modifications for enhancing the multiple effector functions of dendritic cells, including viral and non-viral gene transfer into dendritic cells, and a variety of transferred genes, such as those encoding antigens, co-stimulatory molecules, cytokines, and chemokines.
A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.
This study aims to investigate the psychological effects of the earthquake. We investigated the psychological conditions of 3,609 students survived from the Marmara Earthquake, which occurred on 17 August 1999. The Beck Depression Inventory (BDI) was employed to assess the levels of depression and other psycho-pathological states. The BDI was classified as mild depression if the score was ≤13, moderate depression (14-24) and serious depression (≥ 25). Depression level was estimated as mild in 71.5% of the students, and serious depression in 9.6% of the students. The prevalence of suicidal tendency/thought was 16.7% in this study. The prospect of suicidal thought was 1.76-time (95% Confidence interval [CI]: 1.40-2.22) higher in the students who were injured or whose relatives were injured seriously enough to require medical treatment. Suicidal thought was higher by 1.57 times (95% CI: 1.28-1.92) in students who lost their relatives and by 1.35 times (95% CI: 1.13-1.63) in those who saw extensive damage or destruction occurred in their home or property. According to logistic regression analyses, the gender influenced the thought of suicide; suicide thought was 0.71 (95% CI: 0.60-0.85) time lower in females than males. The present study indicates that injury to the self or to the loved ones, damage to home or property, or the loss of family members as a result of the earthquake enhances the suicidal tendencies.
We investigated the possible association of solute carrier family 6 member 18 (SLC6A18) with hypertension and blood pressure in Japanese, since the homologous murine XT2 gene was recently reported to be associated with hypertension. The entire coding region of SLC6A18 was sequenced in 30 unrelated Japanese subjects. The deleterious effects of the observed nonsynonymous single nucleotide polymorphisms (SNPs) on the phenotype were predicted using bioinformatics software. We tested the associations of one deleterious SNP (Y319X) with blood pressure and hypertension in a general population of 1,004 subjects in one area of Japan. Both quantitative and qualitative analyses adjusting for age and body mass index (BMI) as covariates were undertaken. Four synonymous (P7P, T32T, G37G and V387V), three missense (S12C, I32T and L478P) and one nonsense (Y319X: g1230757 C > G) polymorphisms were found. One of the synonymous polymorphisms was novel (V387V) by reference to the dbSNP database. The Y319X genotype distribution of CC:CG:GG in this population showed frequencies of 0.382, 0.461 and 0.156, respectively, which followed Hardy-Weinberg equilibrium. The nonsense polymorphism had odds ratios of 0.83 (confidence interval [CI] = 0.59-1.15, p = 0.26) in males and 0.96 (CI = 0.72-1.29, p = 0.80) in females with hypertension or current medication for hypertension. For the quantitative analysis, we excluded the current medication subgroup. The nonsense allele was not a significant predictor for systolic or diastolic blood pressure. This is the first report showing that a single polymorphism in SLC6A18 is not associated with hypertension or blood pressure in Japanese.
Serum lipoperoxidation products such as malondialdehyde (MDA) reflect oxidative stress. There are contradictory results addressing the levels of lipoperoxidation products in chronic phase of ischemic stroke. In the present study, we aimed to determine the serum MDA levels in stroke patients 6 months after the cerebrovascular accident. We also compared serum MDA levels in two major groups of patients with ischemic stroke resulting from small vessel and large vessel diseases, respectively. Serum MDA levels of thirty-eight patients who had ischemic stroke (19 with atherothrombotic ischemic stroke and 19 with lacunar infarction) and 30 healthy volunteers were measured. While there was no significant difference in serum MDA levels between the chronic ischemic stroke subgroups (p = 0.795), the serum MDA levels of patients with atherothrombotic ischemic stroke (p < 0.001) or with lacunar infarction (p < 0.001) were significantly higher compared to the control group. We also demonstrated that serum MDA levels of the patients with and those without hypertension (p = 0.846), diabetes mellitus (p = 0.891), or dyslipidemia (p = 0.38) were not significantly different. In conclusion, serum MDA levels were elevated in chronic stroke patients with small or large vessel diseases. To the best of our knowledge, this is the first report showing that serum MDA levels of these two groups are not sigificantly different. Furthermore, serum MDA levels do not differ solely by the existence or nonexistence of hypertension, diabetes mellitus or hyperlipidemia.
Bronchiectasis is common in developing countries, but its precise underlying mechanism can be detected in only about 40% of the cases. The studies reporting the frequency of atopy and its relation to radiological findings and lung function in bronchiectasis are limited in number, and the results are controversial. The present study was designed to investigate the relationship between atopy and bronchiectasis by means of high resolution computed tomography (HRCT) and pulmonary function tests. Skin prick test, HRCT and pulmonary function tests, including spirometric values of forced expiratory volume in one second (FEV1), FEV1/FVC (forced vital capacity) ratio were performed in 121 bronchiectatic patients of unknown etiology and in 68 healthy controls. Atopy and HRCT scores for the severity of atopy and extent of bronchiectasis respectively were determined for each patient. The rate of atopy (48.8% vs 11.8%) and mean atopy score (14.3 ± 10.1 mm vs 5.5 ± 2.1 mm) were significantly higher in patients with bronchiectasis than those in controls. Atopic patients had significantly worse spirometric values and more extended bronchiectasis than non-atopics. There is a significant correlation between atopy and HRCT scores (r = 0.54, p < 0.001), indicating that the more severe atopy is the more extended bronchiectasis. In conclusion, we suggest that the rate of atopy is higher in bronchiectatic patients than that in healthy controls. Bronchiectatic patients with atopy have lower spirometric values and higher HRCT scores. Atopy might be considered as a deteriorating and/or a causative or contributing factor for development of bronchiectasis.
Aspirin-intolerant asthma (AIA) is a distinct clinical syndrome that refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). It is widely recognized that increased cysteinyl leukotriene (cysLT) biosynthesis is associated with the development and progression of AIA. Leukotriene C4 synthase (LTC4S) is the terminal enzyme in cysLT production and is a strong candidate gene in the pathogenesis of aspirin-intolerant asthma (AIA). In this paper, we report a new single nucleotide polymorphism (SNP) of the LTC4S promoter, -1702G>A, in AIA patients and evaluate its genetic role in the association with the LTC4S-444 A>C polymorphism. We enrolled 110 AIA patients, 125 aspirin-tolerant asthma (ATA) patients, and 125 normal controls. SNP genotyping of the LTC4S-1702G>A and -444A>C polymorphisms was performed using SNP-IT™ assays. Haplotype analyses were performed using Haploview version 2.05, which is based on an estimation-maximization (EM) algorithm. There were no significant differences in the allele or genotype frequencies of the LTC4S-1702G>A and -444A>C polymorphisms among the three groups (p > 0.05), with no significant differences in the observed haplotype frequencies (p > 0.05). Moreover, no significant associations were found between the genotype of each SNP in AIA patients with the clinical characteristics, including a forced expiratory volume in one second (FEV1) %, a provocation concentration of methacholine to induce more than 20% decrease of FEV1 (PC20) to methacholine, and serum total IgE levels (p > 0.05). These results indicate that there is no association between these two promoter polymorphisms of LTC4S and the phenotype of AIA in a Korean population.
Adenosine is a physiologically active molecule produced locally in many sites of the body to regulate various cell functions. Measurement of levels of the factor in organs and biological fluids provides clues to its role and we reported an accurate quantitative high-performance liquid chromatography method for urinary adenosine requiring no preliminary sample preparation, other than filtration. Analyses were performed isocratically with a reversed-phase and a molecular exclusion columns connected by a column switch. Each sample was analyzed automatically in 35 min. Linearity could be verified up to 1,000 μmol/L (r = 0.999) and recovery of adenosine was 94.6 - 98.0%. The coefficients of variation (CV) were established to be 0.56 - 1.32%, intra-assay, and 1.61 - 4.67%, inter-assay. Based on analyses of healthy individuals at different ages, we are here able to provide age-related values, infants (1.51 ± 0.71 μmol/mmol creatinine) and children (1.06 ± 0.36 and 0.83 ± 0.27 μmol/mmol creatinine; aged 1 - 5 and 6 - 10 years), excreting significantly higher amounts of adenosine than adults (0.44 ± 0.08 μmol/mmol creatinine). We also measured urinary adenosine from patients suffering from metabolic disease or severe respiratory failure and found that unfavorable pathophysiologic conditions are associated with appreciable elevation of adenosine.
The purpose of this study is to examine the morphological and kinematical changes of the uterus induced by electrical stimulation applied to the skin just above the second and fourth posterior sacral foramens (sacral surface electrical stimulation [ssES]) in 26 healthy subjects. Out of them, eight subjects who had severe pain subjectively during every menstruation received ssES just in menstruation. Morphological and functional changes of the uterus were examined by using T2-weighted magnetic resonance (MR) imaging and T1-weighted MR cinematography, respectively. Cyclic electrical stimulation for 15 min with 5 sec ON and 5 sec OFF was applied just before MR scanning. A decrease in thickness of the muscular layer of the uterus was observed in every subject after ssES for 15 min and was significant as compared with the thickness before ssES. Periodic uterine movement during menstruation was observed in the subjects with severe menstrual pain in MR cine and the power spectrum analysis of the movement showed a marked decrease in peak power and frequency after ssES treatment. We conclude that ssES causes a reduction of static muscle tension of the uterus in all menstrual cycle periods and suppression of uterine peristalsis during menstruation in the subjects with severe menstrual pain. Possible neural mechanisms for these static and dynamic effects of ssES on the uterus at spinal level are discussed.
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are closely related molecules. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a main molecule that binds IGF-I. GH, IGF-I and IGFBP-3 have important roles in growth and development. In this study, we investigated the effects of exercise during pregnancy on maternal plasma levels of GH, IGF-I and IGFBP-3 and on fetal development. We also recorded the weights of placenta, lengths of umbilical cord, fetal body weights, fetal heights, and weights of fetal tissues. Pregnant Wistar Albino rats were divided into two groups: exercise and control groups (n = 7 for each). A treadmill exercise was performed as 20 m/min for 20 min/day, once per day for 19 days in exercise group. Blood samples were collected from pregnant rats on 0, 7th, 14th and 20th days of gestation (D) under anesthesia with intracardiac puncture, and maternal plasma levels of GH, IGF-I and IGFBP-3 were determined. Fetuses were taken with cesarean section on D20, and various parameters for fetal growth were measured. Plasma GH and IGF-I levels were elevated in exercising pregnant rats on D14 and D20, respectively, when compared to controls, and IGFBP-3 levels were increased on D14 and D20. Among the growth parameters examined, only fetal body weights and weights of fetal liver were significantly decreased in the exercise group (p < 0.01 and p < 0.05, respectively). These results indicate that maternal exercise significantly increases plasma levels of GH, IGF-I and IGFBP-3 in the late period of pregnancy but causes adverse effects on fetal growth.
In recent years, intra-abdominal visceral fat leads to obesity-related complications. A simple indicator that reflects the mass of visceral fat is also needed to enable practical screening of patients. The present study was designed to establish new body mass index (BMI) criteria of central obesity for male Japanese. The subjects were 516 men aged from 19 to 80 years old who were examined at the physical examination center in the regular health check conducted by their company. Correlations between visceral fat area (VFA) or subcutaneous fat area (SFA) and BMI in the subjects were investigated. Receiver Operating Characteristics (ROC) curve was used to find out the optimal cut-off values of BMI to predict central obesity. We compared the percentile ranks corresponding to VFA of 100 cm2, BMI of 25 kg/m2 and new BMI criteria to check to see whether the present BMI criteria classify correctly Japanese men as central obesity. Further evidence for the effectiveness of BMI for VFA is needed. The correlation coefficient between VFA or SFA and BMI was 0.59 or 0.67, respectively. At the cut-off for BMI that maximized sensitivity and specificity for predicting central obesity was 24 kg/m2. Moreover, the percentile value corresponding to VFA of 100 cm2, BMI of 24 kg/m2, and BMI of 25 kg/m2 was the 53, 50 and 61 percentile, respectively. It is necessary to lower a cut-off point for central obesity from BMI of 25 kg/m2 to 24 kg/m2.
Migraine is a significant health problem due to its frequency and accompanying morbidity, which includes disability and loss of performance. We aimed to estimate the prevalence of migraine and assess the disability and preferences of treatment among university students in Afyon, a Turkish city. This is the first cross-sectional prevalence study of migraine conducted on university students in Turkey. The study has been carried out in two stages. The first stage aimed to identify the students with migraine by using a standardized International Headache Society (IHS) questionnaire. In this questionnaire, the students were asked about medical consultations and medicines used during attacks. The standard questionnaire was applied to 1,029 students, and migraine was found in 128 students (12.4%). Of these headache sufferers, 104 students were using non-prescribed drugs during headache attacks, while the remaining 24 students were using the drugs on advice of physicians. At the second stage, we evaluated the impact of disease on daily life in these students by the Migraine Disability Assessment Scale (MIDAS) questionnaire, showing that the degrees of disability are minimal in 11 students (8.6%), mild in 30 students (23.4%), moderate in 34 students (26.6%), and severe in 53 students (41.4%). In conclusion, migraine attacks are associated with a considerable degree of handicap in activities of daily living. However, many university students with migraine do not consult a physician and continue to treat their headaches with simple analgesics. Global educational programs are required for patients to recognize the importance of effective migraine treatment.