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We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n=79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (>15 micromol/L) was detected in 11% of the controls (n=19) and 37% of CAD patients (n=60) (p=0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p=0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +- 4.4 micromol/L), and the difference from the ACS patients with 1- and 2-vessel involvement was significant (p=0.03). In patients with 1-vessel involvement, tHcy was correlated with NOx (r=0.62, p=0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n=51) had a higher mean number of vessel involvement and tHcy (p<0.001, p<0.05, respectively) but lower NOx (p<0.05) when compared to the low-risk patients (n=28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.

Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.

The purposes of this study were to examine whether body sway is altered immediately after strabismus surgery in children and to find preoperative clinical factors associated with body sway. In a prospective study, body sway was measured on 1-3 days before surgery and on the third day after surgery; for the measurements, computerized static stabilometry was carried out on 28 consecutive patients with strabismus (age range: 3 to 12 years old; mean: 7.4) who underwent strabismus surgery under general anesthesia. The linear length of the sway path (cm), the linear length of the sway path in a particular unit of time (cm/second), and the area of the sway path (cm2), indicative of the extent of body sway, all increased significantly among a total of 28 patients in both conditions of the patient's eyes open and closed, as well as among those in a subgroup of 16 patients with exotropia, after they had undergone strabismus surgery (p < 0.05, Wilcoxon signed ranks test). The center of pressure along the Y axis of orientation from the toe to the heel was found to deviate significantly toward the heel postoperatively, as compared with the preoperative center in the subgroup of 16 patients with exotropia (p < 0.05). Before surgery, 15 patients with no stereoacuity exhibited a greater amount of body sway when their eyes were open than did 13 patients with measurable stereoacuity (p < 0.05, Mann-Whitney U-test). In the subgroup of 16 patients with exotropia when their eyes open, 3 patients with abnormal head posture exhibited more extensive body sway than did 13 patients without abnormal head posture (p < 0.05). Body sway was found to significantly increase immediately after strabismus surgery in children with strabismus. Stereoacuity and abnormal head posture are 2 clinical factors associated with preoperative postural instability.

We attempted to prepare colloidal iron within tissues by means of microwave irradiation. Mouse tissue blocks were fixed with a mixture of paraformaldehyde and ferric chloride in a cacodylate buffer, immersed in a cacodylate buffered ferric chloride solution, and irradiated in a microwave processor. Colloidal iron was prepared within tissues or cells, and was observed in the form of electron dense fine granules (1-2 nm in diameter) by transmission electron microscopy. Collagen fibrils in the connective tissue showed colloidal iron deposition at regular periodical intervals. Cells in the splenic tissue showed that fine colloidal granules were deposited on the ribosomes but not on the nuclear chromatin. This finding suggests that ferric ions could not diffuse into the nucleus, which was surrounded by the nuclear envelope. The podocyte processes of the renal glomerulus were stained diffusedly. Though this microwave in situ colloidal iron preparation method has some limitations, it is convenient for use in biomedical specimen preparation in transmission electron microscopy.

Previous EEG studies have shown that transcendental meditation (TM) increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC) algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC), it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

To evaluate recent improvements in lung cancer screening, we compared the results of recently conducted lung cancer screening with those of a previous screening. This study compared the survival of lung cancer patients detected by lung cancer screening conducted between 1976 and 1984 (early period) with that conducted between 1989 and 1997 (late period). Two hundred seventy-six patients with lung cancer were detected in the early period and 541 patients with lung cancer were detected in the late period. The median survival time (late : 49.8 vs. early : 27.8 months) and the 5-year survival rate (late : 47.8 vs. early : 34.8%) of the patients with lung cancer detected in the late period were significantly better than those in the early period (p = 0.0054). Among patients undergoing resection, the proportion of pathological stage I patients in the late period was significantly higher than that in the early period (late : 60.8 vs. early : 54.9%, p = 0.005). Multivariate analysis showed that the screening time period was a significant prognostic factor (hazard ratio = 0.685, 95% confidence interval : 0.563-0.832, p = 0.0002). These results were consistent with the findings of case-control studies of lung cancer screening programs in the late period recently conducted in Japan, which also showed a greater efficacy for screening than for previous case-control studies in the early period.

We describe here a patient with a recurrent hemangiopericytoma of the superior mediastinum 23 years after an initial complete resection. In the current biopsy specimen, the tumor cells were much more anaplastic than those seen 23 years ago. Although the patient was treated with chemotherapy, which consisted of ifosfamide and epirubicin, the tumor was unresponsive and he died 6 months later from disease progression. Careful long-term follow-up is mandatory for patients with hemangiopericytomas because recurrence with greater malignancy can develop following an extended disease-free interval.

This study was carried out to determine whether an extracorporeal membrane oxygenation (ECMO) support could be sufficiently conducted by the right ventricle alone from the viewpoint of the hemodynamics and blood gas state. Six infant dogs underwent a bypass between the left pulmonary artery and left atrium with an in-line oxygenator after a left pneumonectomy. Partial ECMO support was conducted simply by opening the circuit, and total ECMO support was conducted by ligating the right pulmonary artery. After the establishment of partial ECMO, approximately one-third of the right ventricular output was passively shunted through the bypass circuit, and the cardiac index and central venous pressure did not change. The mean pulmonary arterial pressures increased significantly. After a complete ligation of the right pulmonary artery, all 6 dogs survived for 12 h, but the cardiac output and blood pressure decreased significantly. The blood gas state was sufficiently maintained throughout the experiment. The results suggest the possibility of using the pumpless ECMO support. However, the flow resistance of the membrane oxygenator proved to still be too high for use in a total pumpless ECMO. Further studies on long-term ECMO and the development of a membrane oxygenator with a considerably low flow-resistance are needed.

We report herein the disappearance of macular hard exudates after the introduction of hemodialysis in diabetic patients. A 62-year-old woman and a 52-year-old man with diabetes mellitus showed hard exudates in the macula of the left eyes. Both patients had previously undergone panretinal photocoagulation in both eyes. During the follow-up, hemodialysis was introduced for deteriorating chronic renal failure caused by diabetic nephropathy. Half a year later, macular hard exudates in the left eyes disappeared dramatically in both patients, but the visual acuity remained the same. No additional laser treatment was done during the observation period. Hemodialysis is considered to have accelerated the resolution of macular hard exudates in both patients. The deposition of macular hard exudates in diabetic patients is due in part to concurrent poor renal function.

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.

A 52-year-old obese woman was admitted to our institution for evaluation of dyspnea and pulmonary hypertension (PH). Polysomnography revealed severe obstructive sleep apnea (OSA) with an apnea hypopnea index of 99.8. Treatment with nocturnal continuous positive airway pressure (CPAP) resulted in correction of daytime hypoxemia, hypercapnia, and near-normalization of pulmonary artery pressure. To our knowledge, this is the most severe case of OSA-associated PH (approximately70 mmHg) reported to date, and it was successfully treated with nocturnal CPAP. This case demonstrates that OSA should be considered and polysomnography performed in all patients with PH, irrespective of severity, and that nocturnal CPAP has therapeutic effects on both OSA and daytime PH.

Type III collagen is found in fetal skin and blood vessels. Previously, we characterized the proximal promoter of the human alpha1(III) collagen gene (COL3A1) using the human rhabdomyosarcoma cell line, A204, and NIH3T3 cells (Yoshino et al., Biochim Biophys Acta, 2005). In the present study, we further analyzed this promoter using additional cell lines, namely a human embryonal rhabdomyosarcoma cell line (RD) and bovine vascular smooth muscle cells (vSMCs), both of which show high expression of type III collagen. Using a luciferase assay, electrophoretic mobility shift assays (EMSA), and DNase footprinting assay, 2 types of multifactor complexes were shown to bind to the DNA region in the vicinity of the B element (- 80 to - 58), depending on the cell type. Next, we used cells stably transfected with a GFP-linked type III collagen promoter fragment for analysis of promoter expression. Usually, transfected cells retained the characteristics of the original cells. However, in several clones derived from RD cells, promoter expression as well as cell shape changed to patterns characteristic of the A204 cell line. Nuclear factors expressed by these clones were also characteristic of the A204 line.

This study assessed total and segmental distribution of fat mass (FM) in athletes with spinal cord injury (SCI) and examined the relationships between segmental distribution of fat mass and age, injury level, athletic history, and training load in order to provide useful information for improvements in their physical strength and training. Twenty-five male athletes with SCI participated in the study. The whole bone composition was measured by a dual-energy X-ray absorptiometry (DXA) method for the calculation of bone minerals, FM, and fat-free mass. The percent fat of the trunk, arms, and legs was also calculated. The percent fat in the legs was highest in comparison with that in the trunk and arms (p < 0.001), and the percent fat in the trunk was higher than that in the arms (p < 0.001). The body fat (p < 0.01), waist circumference (p < 0.01), and waist-to-hip ratio (p < 0.0001) were higher in the group aged 40 or older in comparison with that aged 39 or younger. Path analysis revealed that training load was a factor decreasing the percent fat on the arms and trunk (p < 0.01), and athletic history was a factor reducing the percent fat on the arms (p < 0.05). Our study suggests that exercise is effective in reducing the waist circumference, waist-to-hip ratio, and percent body fat of SCI individuals, and that such effects can help to enhance athletic performance and likely to protect against development of metabolic syndromes resulting from a sedentary lifestyle.