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The adverse effect of Ti on body-defense macrophage is not well understood. The aims of this study were twofold: (1) to examine the intracellular accumulation of Ti element; and (2) to measure the cell viability, superoxide dismutase (SOD) production, and TNF-alpha secretion of macrophage-like RAW264 cells cultured for two days in medium with 1 ppm Ti prepared from acidic ICP Ti standard solution. PIXE analysis showed that element Ti was accumulated up to 7.3 ppm in RAW264 cells when cultured in the medium with 1 ppm Ti. Further, RAW264 cells cultured in the medium with 1 ppm Ti exhibited cell viability of about 60%, SOD production of about 180%, and TNF-alpha secretion of about 170% relative to those of control cells cultured in the medium without Ti. It was speculated that phagocytosis of minute Ti-containing complex (mostly TiO2) by macrophage caused oxidative stress and inflammatory reaction, leading to cell proliferation arrest and increased production of SOD and TNF-alpha.

Determination of the exposure level of environmental pollutants is essential in studies on environmental toxicology. If concentrations of exposed pollutants in tissues are not affected by formalin-preservation, a preserved specimen will provide not only histopathological information but also the exposure level of environmental pollutants. In the present study, concentrations of nine elements in the liver and kidney were compared between fresh and formalin- or neutral formalin-preserved specimens to validate the ultimate analysis of the preserved specimens. After one year of preservation, various elements had diffused from the specimens into the solutions. The concentrations of iron, copper, zinc (in the case of neutral formalin) and selenium in the central region of the specimens showed no alterations, suggesting that the diffusions of these elements were limited to the surface of the specimens. Therefore, preserved specimens may be available for the determination of these elements if the specimens are large enough for their surface to be removed. Concentrations of other elements in the preserved specimens were different from the original ones, because the diffusion or infiltration also occurred in the deep region of the specimens.

To investigate the relationships between trace elements concentrations in hair and atrial fibrillation (AF) in horses, concentrations of nineteen trace elements were detected in hair using the particle induced X-ray emission (PIXE) method. The horses were assigned to either control (n=22, no abnormalities) or AF groups (n=5) based on electrocardiograph findings. The mean concentrations of Ca and Zn in the hair of the AF group were significantly higher than those in the control group. The Zn/Cu ratio of the hair in the AF group (29.8 +/- 5.5) was significantly higher than that in the control group (23.4 +/- 2.2, P<0.05). The results of the present study suggest that there is a relationship between elevated concentrations of Ca and Zn in hair and AF.

The urinary concentration of 8-hydroxydeoxyguanine (8-OHdG), which is a biomarker of oxidative DNA damage, was measured in 248 healthy Japanese, and its correlations with life style, urinary metal elements, serum antioxidants, and other plasma or serum factors were investigated. The mean urinary concentration of 8-OHdG was 15.2+/-5.71 ng/mg creatinine. Mean urinary 8-OHdG was not significantly different in terms of age (<45, >or=45), gender, smoking (no, <20, >or=20), and alcohol consumption (no, occasionally, sometimes and usually). Moreover, multiple regression analysis showed a significant association between urinary 8-OHdG and urinary arsenic (As) or chromium (Cr), and a tendency for association between the former and aluminum (Al) and nickel (Ni). Age, gender and plasma or serum factors including antioxidants, lipid peroxide, HbA1c, BUN, and iron did not show such an association. The present study suggests that natural exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative DNA damage in healthy people under usual environmental management. Therefore, the measurement of urinary metals such as As, Ni and Cr is prerequisite for the study of the relationship between urinary 8-OHdG and other variable factors.

The influence of atrioventricular block (AV-block) on the trace elemental status in a horse hair was studied. The particle-induced X-ray emission (PIXE) method has provided a reliable, rapid, easy, and relatively inexpensive diagnostic method. Twenty-five elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Hg, K, Mg, Mn, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, Y, and Zn) in mane hair and serum were measured by the PIXE method. A horse hair with first- and second-degree AV-block contained significantly greater amounts of Br, Ca, Sr, and Zn than those of horses without electrocardiographic abnormalities, whereas there was no significant differences in the elemental contents of the serum of the both groups. Those results in contents of a horse hair suggest that the evaluation of the degree of ionic imbalance by this method might be used to predict the susceptibility of a horse to heart disease much before symptoms appear.

The concentrations of 28 elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) were measured in mane hair by the particle-induced X-ray emission method. Except for Br, Cl, K, S, and P, the trace element concentrations in mane hair of horses are similar to literature values for human hair. The values obtained are not dependent on the horse's age, breed, and sex and could be used as reference values in the assessment of diseases and nutritional status in equines.

The influence of hair color on the trace elemental status in horse's hair has been studied. A current analytical technique such as particle-induced X-ray emission (PIXE) used in this study has provided reliable, rapid, easy, and relatively inexpensive diagnostic methods. Twenty-eight elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) in mane hair were detected by the PIXE method. The gray hair contains significantly greater amounts of Cu, Ti, and Zn, and lower amounts of Br, Ca, Se, and Sr than those in other colored horse hairs (p<0.05). Those results measured in the horse's hair were similar to those found in human and dog hair. When interpreting a result, it should be kept in mind that hair color, especially gray hair, influences the concentrations of some elements in horse hair.

Arsenic trioxide, As(2)O(3) (ATO), has been established to be an effective agent for treating acute promyelocytic leukemia, but its effect on solid tumors has not been fully explored. In the present study in a murine xenograft system, we found that ATO significantly inhibited tumor growth of the inoculated human hepatocellular carcinoma cell line HuH7 when administered either intravenously or intratumorally. Pathological examination revealed that ATO induced extensive cell death in the tumor. Some of the dead cells in intratumorally ATO-treated mice showed characteristic features of apoptosis, such as nuclear condensation and fragmentation, and were TUNEL-positive. The measurement of arsenic by using particle induced X-ray emission revealed that arsenic was accumulated more in the tumor than in brain, kidney or liver after the intravenous injection of ATO, which is consistent with the hemorrhagic cell death observed in ATO-treated tumor tissues. Thus, ATO appears to have potential for the treatment of solid tumors, as well as hematopoietic malignancies.

A 57-year-old man who had worked as a welder for about 40 years was admitted to our hospital. Every year he had had medical examinations in his workplace. On March 17, 1999, there was no finding of pneumoconiosis, but he had worked in a tunnel on a special arc welding project from December 20, 1999 to January 10, 2000. On admission, chest radiography revealed reticular shadows in the middle and lower lung fields. CT scans showed ground-glass opacities in both lungs. Serum iron was high (231 micrograms/dl) and serum ferritin was extremely high (2,309 ng/ml). Many iron particles were detected in the alveoli of the transbronchial biopsy specimen, and also in the sputum. A pathological diagnosis of siderosis was therefore made, and, considering the patient's occupation, the condition was termed arc welder's lung. This rapidly developing case was characterized by reticular shadows on chest radiography.

The purpose of this study is to clarify the chemical characterization of PM2.5 and PM10 in diesel exhaust particles (DEP). Sampling of PM2.5 and PM10 in DEP was carried out in November 1999 using an automobile exhaust testing system at the National Traffic Safety and Environment Laboratory, with a diesel truck (engine type: direct injection, displacement: 7,961 cc, carrying weight: 2,020 kg, equivalent inertia weight: 5,600 kg) placed on a chassis dynamometer. Sampling conditions included idling, constant speed of 40 km/h, M-15 test pattern and 60%-revolution/40%-load of maximum power. Samples were collected on a polycarbonate membrane filter (Nuclepore, pore size: 0.8 microm) using a MiniVol Portable Air Sampler (Airmetrics Co., Inc.). The concentrations of several elemental and ionic species in the PM2.5 and PM10 samples were determined by particle induced X-ray emission (PIXE) and ion chromatography analysis. PIXE analysis of the PM2.5 and PM10 samples revealed 15 elements, of which Na, Mg, Si, S, Cl, Ca, Fe and Zn were found to be the major components. Ionic species were Cl-, NO2-, NO3-, SO4(2-), Na+, NH4+, K+ and Ca2+. Concentrations of elements and ionic species under the sampling condition of 60%-revolution/40%-load were highest in comparison with those of the other sampling conditions. The elemental and ionic species data were compared for PM2.5 and PM10; PM2.5 concentrations were 70% or more of PM10 concentrations for the majority of elements, and concentrations of ionic species in PM2.5 and PM10 were almost identical.

11C-methionine positron emission tomography (PET) and proliferating cell nuclear antigen (PCNA) staining were performed in 13 cases of glioma to investigate the relationship between the uptake of L-[methyl]-11C-methionine and the degree of malignancy and proliferative potential. The 11C-methionine uptake was significantly greater in high-grade gliomas compared to low-grade gliomas (P<0.05). The PCNA indexes were also significantly higher in the high-grade cases (P<0.05). Moreover, a strong positive correlation was found between the 11C-methionine values and the PCNA indexes (P<0.005), demonstrating that higher 11C-methionine uptake was associated with greater proliferative potential and greater malignancy. 11C-methionine PET is a potentially useful preoperative method to discriminate the malignancy of glioma.

Numerous cytokines and chemokines are involved in inflammatory and immune response. Whereas some of them inhibit virus replication in vitro directly or increase the patients' T4-lymphocyte level, others effects are not so clear. Using human immunodeficiency virus (HIV) and cell cultures we have studied the antiviral effect of complexes of salmon DNA with metals and of a new factor(s) (antiviral factor, AVF) induced in cells by the complexes. The Fe3+/DNA complex possessed the highest antiviral activity. It was found that MT-2, MT-4, CEM and Jurkat cells treated with the complexes secreted AVF which inhibited the replication of nine HIV-1 isolates, was noncytotoxic and stimulated cell proliferation. AVF did not inactivate HIV. The molecular mass analysis of AVF showed that its antiviral activity is associated with its fraction of M(r) of 3 K. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA from MT-4 cells treated with the complexes showed an increase in the the expression of genes for interleukin-1 alpha (IL-1 alpha), tumour necrosis factor alpha (TNF-alpha) and TNF-beta while expression of genes for IL-1-beta, IL-2, IL-4, IL-6, IL-8. IL-10, IL-12; 35p, 40p, IL-13, GMCSF, GSF and RANTES was not detected at all. However, the anti-HIV activity of the cell culture supernatant in vitro cannot be explained by mere presence of the inflammatory substances mentioned above, because they do not possess such activity and their M(r) is higher than that of AVF. Our findings raise the possibility that AVF(s) may be involved in the mechanism of cell resistance against HIV.

Although a number of hemostatic drugs are currently used during surgery to reduce hemorrhage, their effects on bleeding are still controversial. Furthermore, few studies have been made on their prophylactic effects. The purpose of this study was to clarify the effects of hemostatic drugs on bleeding. Thirty adult patients undergoing upper abdominal surgery were randomly assigned to receive carbazochrome sodium sulfonate and tranexamic acid immediately after induction of anesthesia (group H,n=15) or no hemostatic drugs (group C,n=15). Common coagulation-tests [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB)], thromboelastography [reaction time (R), coagulation time (K), maximum amplitude (MA), clot formation rate (α)], and determination of bleeding time were conducted before induction of anesthesia and just before the completion of surgery. PT, R, and K decreased significantly in both groups, while MA and α increased and FIB decreased significantly in group C. No significant difference in blood loss was observed between the groups. Our findings, therefore, suggest that these two hemostatic drugs do not have prophylactic effects on intraoperative bleeding. Further studies are, however, necessary before applying these results to all surgical patients.

The concentrations of Br, Cu, Fe, Se, Zn, Mg were determined by particle-induced X-ray emission (PIXE) in serum and cerebrospinal fluid (CSF) of 13 untreated, 7 L-dopa treated parkinsonian patients and 25 controls. There were significant positive correlations between serum concentrations and CSF concentrations of Br, Cu, Fe. The Cu/Zn ratio in the serum and the CSF/serum ratio of Br were significantly increased with age in normal controls. The mean CSF concentration of Mg in both treated and untreated parkinsonian patients was lower than in controls. PIXE is a valuable method for multielemental analysis of the serum and CSF.

The morphological changes of the vestibular ganglion induced by gentamicin (GM) were investigated using light, scanning and transmission electron microscopy. The guinea pigs were injected 4 mg of GM into the middle ear for 5 days. The vestibular ganglion was observed up to 4 weeks after the treatment. Three days after the treatment the degenerative change was first noted in the vestibular ganglion. The degenerative process started from the destruction of mitochondrial cristae and vacuolization of the cytoplasm of the Schwann cell. The cytoplasmic organelles in the ganglion cell gradually deteriorated with swelling of the endoplasmic cisterns as well as Golgi apparatus. At the later stage, the myelin sheath around the ganglion cell disappeared and the number of the cells reduced. These changes of the ganglion cell may be due to the direct action of GM.

1. Long-term results of posterolateral lumbar and lumbosacral spinal fusion were evaluated in 40 patients who had been treated by this technique 10 years or more (mean: 14 years and 6 months). 2. In the clinical evaluation employing the criteria for assessment by the Japanese Orthopaedic Association (JOA score), the total score averaged 24.2 points. The roentgenographically assessed bone union rate was 93.2%. At the site of operation, the angular displacement was within 5 degrees and the horizontal displacement ranged from 0.7% to 1.4%. Thus, a long-term stability was confirmed. 3. Although age-related problems such as osteoporosis remain unsolved, the long-term results were so good that this technique can be recommended as a salvage operation in patients with an unstable spine or those requiring decompression from the posterior approach.

Two tenths ml of 5% fosfomycin sodium solution (10 mg) was injected into the tympanic cavity of guinea pigs once a day for 7 days. Auditory brain stem response (ABR) was performed to examine the effect of the drug on the experimental animals. Additionally, a scanning electron microscopic study was also performed to observe the effect of the drug on outer hair cells of the organ of Corti and on vestibular sensory epithelia. No degenerative changes were observed in outer hair cell cilia of the organ of Corti and the vestibular sensory cilia at 1 day, 7 days, 14 days and 1 month after injection. No changes of the threshold of ABR were also noticed.

A randomized controlled trial was carried out on 38 pharyngeal and 59 laryngeal previously untreated cancers to evaluate the effects of adjuvant immunochemotherapy using 5-FU with and without OK-432. After each fundamental therapy, 5-FU was given orally at a dose of 200-300 mg/day for more than a year. OK-432 was intracutaneously administered at a dose of 5KE once a week for more than a year. Three-year survival rates and disease-free intervals were estimated for the two groups. In cases of pharyngeal cancer, the 3-year survival rate was 58% in both groups and the disease-free interval rates for up to 3 years after the fundamental therapy was 49% in the OK-432 + 5-FU group and 52% in the 5-FU group. These results showed no statistically significant difference. In laryngeal cancers, the 3-year survival rate was 96% in the OK-432 + 5-FU group and 82% in the 5-FU group. These results also showed no statistically significant difference. The disease-free interval rates were 87% in the OK-432 + 5-FU group and 64% in the 5-FU group, revealing a statistically significant difference (p less than 0.1). This suggests that OK-432 is more effective in producing a higher survival rate in cases of laryngeal cancer.

To evaluate left ventricular systolic and diastolic function in patients with pulmonary hypertension secondary to chronic pulmonary diseases, 86 patients were studied using equilibrium radionuclide angiography with forward and reverse gating from the R wave. At rest left ventricular function, both in systolic and diastolic properties, in patients with pulmonary hypertension was significantly lower than in normal subjects (LVEF; P less than 0.05, PER; p less than 0.05, PFR; P less than 0.025, FF; P less than 0.025). During exercise left ventricular systolic function did not increase as much as in normals (LVEF; N.S., PER; N.S.). Left ventricular diastolic function during exercise was significantly lower than at rest (PFR; P less than 0.05, FF; P less than 0.001). The indices of left ventricular function obtained from radionuclide angiography had no close correlation with pulmonary hemodynamics or with blood gases. These results demonstrated that left ventricular dysfunction in patients with pulmonary hypertension was observed both at rest and during exercise, and might play an important role in reduced exercise tolerance.

In Japan, pulmonary thromboembolism (PTE) is rare and the therapy of this disease, especially the thrombolytic therapy, has not been established yet. We studied the effect of thrombolytic therapy by urokinase (UK) in eighteen patients with PTE. We also compared the results with those in Europe and the United States. Eighteen patients (male 7, female 11) were 27 yo to 77 yo (mean 55 yo). Seven cases were mild and 11 cases were moderate to severe. The initial dosage of UK administration was 2.4 x 10(5) to 7.2 x 10(5) IU with the mean of 4.1 x 10(5) IU, which was approximately the double of those in Europe and the US. The duration of UK therapy was 1 to 9 days with the mean of 4.8 days. It was longer than in Europe and the US (12-24 hours). Total amount of UK in each case ranged 4.8 x 10(5) to 42 x 10(5) IU (mean 19.3 x 10(5) IU) with the daily dosage of 4.0 x 10(5) IU in average. They were almost half of those in Europe and the US. Clinical signs and laboratory findings subsided in 1-7 day by UK administration in 14 cases (87%) with the reduction of defects on perfusion lung scans and all of these cases survived. No severe complications were found in any cases. We conclude that the thrombolytic therapy with UK in Japan might be acceptable from the results of this present study. However, the prospective study of thrombolytic therapy on a larger scale remains to be done in the future.

The morphological changes of the vestibular sensory epithelia and the vestibular ganglions induced by Gentamicin(GM) were investigated using scanning electron microscope, transmission electron microscope and light microscope. The guinea pigs were injected with a single application of 4 mg (0.1ml) of GM into the middle ear through the tympanic membrane. The vestibular organs and the ganglions were observed up to 6 months after the treatment. Four days after the injection, fused, ballooned and missing cilia were observed in the vestibular sensory epithelia. These changes progressed and extended toward the periphery of the crista and the macula. The changes of the vestibular ganglions were first observed one month after the treatment. The degenerative process started from destruction of the mitochondrial cristae and vacuolization of the cytoplasm in the Schwann cell. The next step of the change was dissociation of the myelin sheath around the ganglion cell. The cytoplasmic organelles in the ganglion cell gradually deteriorated. At the later stage, the myelin sheath around the ganglion cell disappeared and the number of the cell reduced. Furthermore, the myelin sheath of the nerve fiber was dissociated. In this study the signs of the vestibular ganglion damage were later than that of the vestibular organ. However, we thought the changes in the ganglion are probably due to direct influence of GM, since the degeneration was found to develop in a relatively short period.

To improve the spatial and density resolution of Compton radiography, the authors utilized direct magnification with a pin-hole collimator and contrast magnification with the Shinozaki color TV system, a digital color display. Great improvement was attained in spatial resolution. Contrast magnification resulted in sharp delineation of soft-tissue lesions including cancer and its infiltrations into normal surrounding breast tissue. It is expected that in the future, Compton radiography will have wide raiological application with reduced radiation dosage.

A case of simultaneous pleomorphic adenomas of the right parotid and ipsilateral submandibular glands was reported. The patient was a 68-year-old woman who had a ten-year history of an otherwise asymptomatic non-enlarging mass in the parotid gland and a slowly enlarging mass in the submandibular gland. Microscopically, the parotid tumor consisted of predominant spindle-shaped cell proliferations with myxoid stroma in places. The submandibular gland tumor showed tubular and trabecular formations with stroma consisting of hyalinized fibrous connective tissues. Simultaneous pleomorphic adenomas in the salivary glands are so rare that only 23 cases can be found in the literature. Additionally, only five tumors occurring simultaneously in the parotid and submandibular glands are reported in the literature. Our case seems to be the sixth of simultaneous pleomorphic adenomas of the parotid and submandibular glands.

The instantaneous uptake of CO in the lungs was measured with a water-filled body plethysmograph in normal man. First, control measurements of plethysmograph pressure were made while the subject held his breath for 7 sec after breathing gas mixtures prepared to bring his alveolar P(O2) and P(CO2) close to mixed venous levels. Then, CO uptake measurements were made while he held his breath after inhaling the same gas mixtures with added CO (2.0%). The change in lung volume on CO minus the change in lung volume during the control measurement was a measure of the CO uptake in the lungs. Cardiopneumatic changes in lung gas volume were subtracted electrically. All of five subjects showed pulsatile CO uptake. The mean CO uptake was 103 ml/min. A peak uptake of 2.0 (range 1.6-2.3) times the mean uptake occurred 0.3-0.4 sec after the R wave of the EKG and a minimum uptake of 0.4 (range 0.2-0.5) times the mean uptake occurred during the tenth of a second before the R wave of the EKG. These results suggest that pulmonary capillary blood volume is pulsatile during the cardiac cycle.