Objectives: Vascular endothelial cells are exposed to an acidic pH, but its influence on chemokine receptors
expressed in the vascular endothelial cells is unclear. We investigated the role of coupling factor 6 (CF6), a novel
stimulator of proton importer, in the regulation of chemokine receptors in the vascular endothelial cells. Methods and Results: In microarray analysis, there were the increased expression of CC chemokine receptor 9 (CCR9) and CX3C chemokine receptor 1 (CX3CR1) and the decreased expression of CXC chemokine receptor 4 (CXCR4) in the human umbilical vascular endothelial cells (HUVEC) that were exposed to CF6. The ratio of CXCR4 to GAPDH mRNA was decreased in HUVEC that were exposed to either CF6 at 10⁻⁷M or hypoxia to a similar degree. Apoptotic cells, measured by annexin-V propidium iodide kit, were increased in HUVEC that were exposed to CF6 for 24 hours in normoxia. Conclusions: CF6 influences the expression of chemokine receptors and induces apoptosis in the vascular endothelial cells.
Background: Bronchial asthma in children often resolves as they grow. In persons with resolved asthma,
spirometry measurements such as FEV1 and FEV1/FVC show almost normal values. The forced oscillation technique
(FOT) is a new index of pulmonary function, and seems to be useful in detecting small changes that are not seen on
spirometry. This study aimed to compare spirometry, exhaled nitric oxide fraction (FeNO), and FOT between the
subjects with resolved asthma and normal subjects. Methods: We recruited 484 subjects from our university (mean age, 18.5; male, 257). A questionnaire about past history including bronchial asthma and other allergic diseases, spirometry, FeNO measurement, and FOT were
completed by 119 resolved asthma patients and 365 normal subjects. Results: FEV1/FVC was significantly lower and FeNO was higher in resolved asthma patients than in controls.
There were significant differences between resolved asthma patients and controls in X5, Fres, and ALX as reactance
parameters. There were, however, no differences in the resistance parameters such as R5, R20. Conclusions: There is a group of patients whose childhood asthma has resolved with respiratory impairment. Further study will be required to determine whether spirometry, FeNO, and FOT are useful in making an early diagnosis of asthma relapse.
We examined the relationship between the amount of exhaled hydrogen and neutrophil ROS production to investigate the effect of hydrogen on oxidative stress at normal state among the general population comprising subjects who had participated in “The Iwaki Health Promotion Project in 2007”, which was held in the Iwaki area, Hirosaki-city in Aomori prefecture in northern Japan. Subjects with diabetes mellitus (diagnosed by a medical doctor), malignant tumors, immune disorders or those who were pregnant at the time of the study, taking antimicrobial drugs, anticancer medication or hormones were excluded from the study, and a total of 656 subjects (252 males and 404 females) were finally enrolled. Smoking habits, alcohol use, exercise habits and HbA1c were surveyed. A positive correlation was seen between exhaled hydrogen concentration and total reactive oxygen species production in stimulated neutrophils in subjects less than 60 y.o. (p<0.05), but such a trend was not seen in other age groups or in female subjects. In conclusion, levels of body hydrogen as an antioxidative substance were suggested to have increased as a response to increased production of ROS by neutrophils as mechanisms against oxidative stress.
The CXC chemokine growth-related oncogene protein-α （GRO-α） has a wide variety of biological activities including as neutrophil trafficking or migration of vascular endothelial cells. In addition, studies have shown a crosstalk between tumor cells and vascular endothelial cells; GRO-α released by endothelial cells induces invasion of tumor cells toward endothelial cells, indicating an importance of GRO-α in a tumor environment. Oral squamous cells are reported to produce GRO-α in response to cytokines such as tumor necrosis factor-α (TNF-α). However, little is known about how GRO-α is involved in oral cancer. Here, we investigated the biological role of GRO-α for both tumor growth and angiogenesis in oral squamous cell carcinoma cells. We first evaluated the effect of TNF-α on GRO-α expression in three oral cancer cells from different origins. Among the cell lines we used, KOSC-2 cells expressed the highest amount of GRO-α mRNA in response to TNF-α. TNF-α-treated condition medium from KOSC-2 cells enhanced endothelial cell chemotaxis and the chemotactic activity was partially inhibited by the addition of neutralizing anti-GRO-α antibody. In addition, GRO-α exerted tumor cell migration of KOSC-2. From these results, we conclude that GRO-α may contribute to both angiogenesis and proliferation in oral cancer.
Bispectral index (BIS) monitoring is widely used for assessing the depth of anesthesia using a unilateral forehead electroencephalogram. We previously experienced a case of low BIS during general anesthesia in a patient with subacute unilateral cerebral infarction (CI). We hypothesized that patients with unilateral CI sequelae show asymmetric BIS values during propofol-based general anesthesia. Fifty patients with or without CI sequelae (25 patients each) were enrolled in this study. BIS was monitored by symmetrically attaching BIS sensors to the forehead, while anesthesia was induced and maintained with mainly propofol. The primary endpoint was the laterality of BIS and 95% spectral edge frequency (SEF) during surgery in the CI group. The median CI duration was 48
months (interquartile range, 23–96). There was no significant BIS and SEF laterality in the control group (P=0.174
and P=0.417, respectively). In the CI group, BIS and SEF laterality failed to achieve statistical significance (P=0.069
and P=0.381, respectively). In addition, there was no significant difference in BIS and SEF asymmetry between
groups (P=0.271 and P=0.238, respectively). Therefore, the findings for patients with chronic CI in this study were
not consistent with those of our previous case.
Altered expression of cyclophilin B (CyPB) in chemically induced hepatocarcinogenesis of rat, which was subjected to the Solt-Farber protocol, was analyzed by anti-N-terminal peptide antibody for CyPB. In a group of the partially hepatectomized rats after administration of diethylnitorsamine (DEN) interperitoneally followed by the oral administration of 2-acethylaminofluorene (FAA), marked induction of a tumor-specific marker GST-P and the formation of the precancerous lesion in rat liver were observed. A band of approximately 20 kDa molecular weight was detected by anti-N-terminal peptide antibody in the normal liver and testis. This band was estimated as a CyPB protein．The levels of CyPB in the precancerous lesion were increased from 1 week after hepatectomy, and the increase was approximately 2–fold up to 6 weeks. In addition, the levels of CyPB in serum were gradually increased from 4 to 7 week with delayed kinetics in the liver. The levels of CyPB were increased approximately 1.6-fold at the point of 7 week after the hepatectomy. These results suggested the possible role of CyPB as a tumor marker of the hepatocellular carcinoma.
We measured the sensitivity of anticancer drug for about 10 tumor tissues by using HDRA method. As a result, 5-FU showed sensitivity-positive for all tumor tissues. In addition to 5-FU, CDDP also showed similar sensitivity to many types of tumor tissues; however, the average inhibition rate by CDDP was lower than that by 5-FU.
The inhibition rate of the sensitivity in no neoadjuvant chemotherapy with 5-FU in esophageal cancer was 71.9 ± 11.6 % (n = 6). No significant difference between control and neoadjuvant 5-FU therapy was observed in the inhibition rate. These indicated that no patient was chemotherapy-resistant by the neoadjuvant 5-FU therapy in this study. Among patients who received adjuvant chemotherapy with S-1 patients, those who were sensitive to 5-FU prolonged survival time, compared with those who were resistant to 5-FU chemotherapy.
Sensitivity to 5-FU and GEM in pancreatic cancer indicated the availability of either 5-FU or GEM in pancreatic cancer.
It was possibly suggested that in mass spectrometric analysis, increased signals were useful as markers of 5-FU-resistance in chemotherapy.
We investigated the effects of dehydration after a soccer match on immune function in 15 female university soccer players. Investigations were performed before and after a 90-minute soccer match. Body composition, serum myogenic enzymes, leukocyte counts and neutrophil functions (reactive oxygen species
[ROS] production capability and phagocytic activity [PA]) were measured. All subjects showed significant body weight loss after the match due to loss of body water. Therefore, subjects were divided into two groups (the mild dehydration [MD] and severe dehydration [SD] groups) according to the changes in total protein concentration and the results were compared. Serum myogenic enzymes were found to increase significantly after the match in both groups, but the change ratios were not significantly different between groups. Leukocyte counts were found to increase significantly after the match in both groups, and the changes ratio in the SD group was significantly greater compared to the MD group. ROS production tended to increase in the MD group but decrease in the SD group, and PA significantly decreased in the SD group. These results suggested that immunosuppression is more likely to occur for those whose degree of dehydration is higher after physical exercise.
Objective: To compare physical function and 24-h activity in home-care patients with Parkinson's disease
with those in healthy elderly people. Methods: Physical function (range of motion, muscle strength, activities of daily living, gait, and balance) was
measured in 10 home-care patients with Parkinson's disease (PD group) and 10 healthy elderly subjects (healthy
group). As an indicator of the amount of physical activity per day, a triaxial accelerometer was used to measure the
24-h total impulse value; simultaneously, behavior recorders were used to measure 24-h posture. Results: The healthy group scored significantly higher in activities of daily living, walking speed, and balance. No
significant difference was observed between groups in terms of range of motion, muscle strength, cadence, amount of
physical activity per day, and number of postural changes. However, the PD group spent significantly more time per
day standing and in a supine position. Conclusion: In the PD group, the amount of physical activity per day was comparable to that in the healthy elderly group, despite the decreased levels of activity caused by their impaired performance in activities of daily living.
Range of motion and muscle strength may have been maintained by these patients' self-training and by training at
day-care centers. Our results suggest the importance of practicing postural transfers from the standing and supine
positions and of intervention and guidance that aim to improve impaired performance in daily living.
Aim: Hepatic steatosis is a major cause of steatohepatitis and is observed in several diffuse liver diseases.
We studied the efficacy of a novel ultrasound application, acoustic structure quantification (ASQ), for analyzing the
amount of fat deposition in the liver parenchyma. Methods: Forty-three patients who received a hepatectomy at our institution participated in this study. An ultrasound machine equipped with a software application for ASQ was used to detect steatosis prior to surgery. Non-tumoral liver parenchyma obtained by hepatectomy was pathologically evaluated according to the three-grade system. Results: Histopathologically, twenty-three patients did not present steatosis, seventeen presented grade 1, and the remaining three presented grade 2 steatosis. The median “focal disturbance ratio” (FD-ratio), a representative index obtained by ASQ, decreased with the steatosis grade, from 0.157 (range: 0.039-0.410) at steatosis grade 0, 0.085 (range: 0.021-0.159) at steatosis grade 1, and 0.039 (range: 0.021-0.048) at steatosis grade 2. There were significant differences in the FD-ratio between steatosis grades 0 and 1 and between steatosis grades 0 and 2 (p = 0.001 and p = 0.007, respectively). Conclusions: ASQ can be useful during a quantitative examination of the fat accumulation in the liver parenchyma and offers a reliable marker for the early detection of liver injury.
Objectives: We examined the effects of age on the speed and variability of continuous tapping movement
of the hands and feet over 3 min. Methods: Tapping speed and variability of tapping interval during 3-min self-paced tapping tasks for the index finger and ankle-toe were compared between groups of 20 young people and 20 active elderly people. Results: No effect of age on tapping speed was found, but the variability of tapping interval decreased with age. Both groups showed no correlation between speed and variability, and the speed of the ankle-toe task was slower than that of the index finger task. There was a correlation between variability of the index finger task and that of the ankle-toe task in the elderly group. Movement speed was slower in the second half of the 3-min task time in both groups, but there was no difference in the degree of variability. Conclusions: Variability in self-paced single-joint tapping movement of the hands and feet may reflect regressive changes in the mechanisms of internal rhythm formation. In addition, for clinical screening, it is sufficient to conduct the task for 1.5 min to evaluate any changes in movement speed and variability.
Aims: The purpose of the current study was to evaluate the significance of the endothelin system in
catecholamine release and synthesis in the adrenal gland. Main Methods: Primary cultures of isolated bovine adrenal medullary cells were prepared. Gene expression,
intracellular calcium changes, epinephrine release, and other factors were investigated. Key findings: Expression of endothelin receptors in the rat adrenal gland was confirmed. Intravenous infusion of endothelin-1 (1.0 nmol) increased blood pressure (systolic and diastolic). Endothelin-1 stimulated intracellular calcium changes, resulting in increased nuclear factor of T cell (NFAT) activity and epinephrine release from cultured adrenal medullary cells. Furthermore, endothelin-1 increased catecholamine synthesis and caused hypertrophic changes in the cell size. Significance: Our findings indicate involvement of the endothelin system in the sympathetic regulation of the adrenal medulla.
Children with Down syndrome (DS) have an increased incidence of acute megakaryoblastic leukemia (DS-AMKL). Almost all DS-AMKL patients harbor somatic mutations in GATA1. These mutations lead to exclusive expression of the protein lacking the N-terminal domain (GATA1s). Few AMKL patients without DS (non-DS-AMKL) harbor the mutations. Recently, we found a novel GATA1 mutation (c.721_732del) that causes an in-frame deletion of amino acid residues 241-244 in one of 19 non-DS-AMKL cases. The patient who showed leukocytosis from birth was diagnosed with AMKL at one month of age and had a blast cell karyotype of 46,XY. During the validation of the mutation, we identified another large deletion (c.221-33_553del) that results in the splicing of exon 3. Both mutations were located on the same allele. The mutant protein (referred to as #135) revealed decreased transactivation activity (about 60%) compared to full-length GATA1. From cell proliferation assays using DS-AMKL cell line KPAM1, cell proliferation was markedly reduced by transduction with a retrovirus expressing full-length GATA1. In contrast, expression of GATA1s or #135 moderately restricted proliferation. These results indicate that the #135 mutant is involved in the pathogenesis of non-DS-AMKL.