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Biomedical subjects

S Nakaji

Publications and source records attributed to S Nakaji.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of sodium butyrate on reactive oxygen species generation by human neutrophils.

BACKGROUND: Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms that lead to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen species (ROS) generation by human neutrophils, which are responsible for mucosal injury. METHODS: Human neutrophils incubated with or without sodium butyrate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS generation was largely differentiated with flow cytometry assays of hydroethidine oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen peroxide respectively, and luminol-dependent chemiluminescence for myeloperoxidase-mediated oxidants. RESULTS: Sodium butyrate (up to 50 mM) did not alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium butyrate at a concentration of 25 mM elevated dichlorofluorescein oxidation to 125 + 8% (P = 0.028) of control upon stimulation of OZ and to 191 +/- 30% (P = 0.0016) upon stimulation of PMA. Contrary to these results, sodium butyrate greatly inhibited chemiluminescence responses in a dose-dependent manner. The inhibition by 50 mM sodium butyrate was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA, respectively. CONCLUSIONS: These data indicate that sodium butyrate up-regulates hydrogen peroxide generation but down-regulates generation of myeloperoxidase-mediated oxidants, the latter being more potent in killing microorganisms and in inducing tissue injury. A possible mechanism is suggested whereby sodium butyrate may inhibit myeloperoxidase activity and hence attenuate the destructive activities of neutrophils in UC.

Butyrates↗
PubMed2001

Exercise training and energy restriction decrease neutrophil phagocytic activity in judoists.

PURPOSE: To investigate the effects of weight reduction as the result of exercise training and energy restriction on neutrophil function. METHODS: Eighteen male competitive college judoists participated in the study. In a whole blood assay, oxidative burst activity, phagocytic activity, expressions of Fc gamma receptor 3 (CD16), and complement receptor 3 (CD11b) of neutrophils were measured on a per cell basis by flow cytometry at day 20, 5, and 1 before and at day 7 after the competition. RESULTS: The rate of neutrophil producing reactive oxygen species decreased before the competition, whereas the oxidative burst activity per cell increased significantly in all subjects, which resulted in a significant increase of the total oxidative burst activity. However, there were no significant effect of energy restriction on oxidative burst activity. The rate of neutrophils incorporating opsonized zymosan decreased significantly with energy restriction. The total phagocytic activity of 10,000 neutrophils and the phagocytic activity per cell also decreased significantly by severe energy restriction. The surface antigen expressions of CD11b and CD16 were unaffected by weight reduction. CONCLUSIONS: The results suggest that with respect to the management of health conditions, weight reduction for judoists should be composed of exercise training and energy restriction should be moderate.

Adult↗
PubMed2001

Relationship between mineral and trace element concentrations in drinking water and gastric cancer mortality in Japan.

It is well known that the incidence and mortality from gastric cancer in Japan are the highest in the world. This is thought to be due, in part, to dietary habit, including a high salt intake. There are, however, no epidemiological reports to describe the relationship between ingestion of mineral and trace elements and gastric carcinogenesis. In this study, we determined the concentrations of 14 elements in drinking water from 34 water treatment plants in Aomori Prefecture, Japan, and studied how element concentrations were geographically associated with gastric cancer mortality rate. Gastric cancer mortality was calculated from the data of the Annual Aomori Health Report. Multiple regression analysis (stepwise method of decreasing the number of variables) was performed by using age-adjusted mortality of gastric cancer by gender as objective variables and each element concentration as an explanatory variable. The standardized partial regression coefficient was significant in men for zinc (-0.59, P = 0.004), lead (1.01, P = 0.013), strontium (1.23, P = 0.007), and selenium (-1.62, P = 0.004), whereas it was significant in women for lead (-0.65, P = 0.022), strontium (0.51, P = 0.035), and gold (0.70, P = 0.019). It is suggested that selenium and zinc may aid in the prevention of gastric carcinogenesis. However, the significant relationship of sodium (a component of salt) to gastric carcinogenesis was not observed, although many previous epidemiological studies in Japan have shown this relationship.

Adult↗
PubMed2001

Rapidly functional immobilization of immortalized human hepatocytes using cell adhesive GRGDS peptide-carrying cellulose microspheres.

With the development of biotechnology, hepatic support by a hybrid artificial liver (HAL) using hepatocytes has been given much attention. Because the availability of human livers is limited, we have established a tightly regulated immortal human hepatocyte cell line, NKNT-3, for developing HAL. Because high-density cell culture allows the compactness of the HAL device and its easy use under emergency circumstances, we have developed cell adhesive GRGDS peptide-containing cellulose microspheres (GRGDS/CMS). The GRGDS/CMS efficiently immobilized NKNT-3 cells within 24 h in a stirred suspension culture. Electron microscopic examinations demonstrated glycogen granules and well-developed endoplasmic reticulum and mitochondria in NKNT-3 cells attached to the GRGDS/CMS. The cells showed ammonia clearance activity, whereas HepG2-transformed human liver cells did not remove the loaded ammonia. An efficient adenoviral delivery of the lacZ reporter gene was performed in GRGDS/CMS-immobilized NKNT-3 cells. In this study we present rapid immobilization of NKNT-3 immortal human hepatocytes using cellulose microspheres carrying GRGDS peptides. These microspheres satisfied immediate preparation of NKNT-3 cells in sufficient quantity and of adequate quality.

Ammonia↗
PubMed2000

Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans.

To investigate the mechanisms of exercise-induced immune perturbations, we measured promising immunomodulatory hormones and cytokines in plasma of 16 male marathon runners before and after a competitive 42.195-km race. Interleukin 1-beta (IL-1beta) and interferon gamma (IFN-gamma) concentrations remained unchanged after the marathon. The cytokines IL-12, IFN-alpha and tumour necrosis factor alpha (TNF-alpha) could not be detected even using highly sensitive specific immunoassays, indicating at least that overshooting responses of these cytokines had not occurred after exercise. As mechanisms for the small changes in these cytokines, we demonstrated for the first time a significant rise in concentrations of inhibitory cytokine IL-10 in addition to the immunosuppressive hormone cortisol, although concentrations of IL-4 and transforming growth factor-beta (TGF-beta) were unaffected by the race. Furthermore, concentrations of IL-1 receptor antagonist (IL-1ra) and IL-6, which are negative-feedback inhibitors of cytokine production, increased by more than 100 times. As for humoral mediators of neutrophil mobilization, concentrations of growth hormone (GH), cortisol and granulocyte colony-stimulating factor (G-CSF) increased significantly. In addition, concentrations of neutrophil-priming substances (IL-6, IL-8, G-CSF, GH and prolactin) also increased significantly and the induction of IL-8 and G-CSF with exercise was demonstrated for the first time in the present study. In contrast, IL-2 concentration decreased, by 32%, and this was correlated with the induction of nitric oxide (NO) production. Muscle damage, monitored using changes in concentrations of creatine kinase and myoglobin, was also observed. These results suggested that exercise-induced pathogenesis including previously reported immunosuppression and neutrophil hyper-reactivity might be attributed, at least partly, to the systemic dynamics of the above bioactive substances.

Adult↗
PubMed2000

Evaluation of the applicability of the gastric carcinoma risk index for intestinal type cancer in Japanese patients infected with Helicobacter pylori.

The gastric carcinoma risk index is a histological criteria to Helicobacter pylori-infected patients with a high risk of gastric cancer. The aim of this study was to examine the applicability of this index for the intestinal-type gastric cancer in Japanese patients with H. pylori infection. In 55 patients with early intestinal-type gastric cancer and 69 control subjects, we calculated the gastric cancer risk index score by evaluating the grade of mononuclear cell (MNC) and polymorphonuclear cell (PMN) infiltration and the presence of intestinal metaplasia. The gastric cancer index score was significantly higher in patients with gastric cancer (P<0.01). The presence of intestinal metaplasia was significantly more frequent in cancer patients than in controls, while infiltration of MNCs or PMNs in the corpus was not different in the two groups. Within the gastric cancer risk index, the presence of intestinal metaplasia was the only criteria associated with the development of intestinal-type gastric cancer in Japan. The gastric cancer risk index may not be applicable to identify H. pylori-positive patients at high risk of developing intestinal-type gastric cancer in Japan.

Duodenal Neoplasms↗
PubMed2000

Effect of decaglycerol monooleate on phagocytosis and respiratory burst activity of human neutrophils: an in vitro study.

Decaglycerol monooleate (DGMO), a type of polyglycerol esters of fatty acids (PGEF), was evaluated for its in vitro effect on phagocytosis and respiratory burst activity of isolated human neutrophils using flow cytometric assay. Opsonized zymosan particles labelled with FITC (FITC-OZ) were employed as an indicator of phagocytosis. Fluorescence of FITC-OZ attached on to the surface of neutrophils was quenched by addition of trypan blue solution. After 10 minutes of incubation with DGMO up to a concentration of 10 mg/ml, neutrophil phagocytosis was not affected markedly. At the same time, the DGMO emulsion left little influence on complement receptor type three (CR3) that is associated with phagocytosis. On the other hand, oxidation of hydroethidine, which was used as an indicator of intracellular generation of reactive oxygen species (mainly for superoxide anion), was significantly inhibited by DGMO over 1 mg/ml. However, this phenomenon was not seen in DGMO-treated neutrophils when DGMO was removed after incubation. The present data suggest that DGMO does not affect phagocytosis of human neutrophils but down-regulates respiratory burst activity.

Adult↗
PubMed2000

Association of gastric epithelial apoptosis with the ability of Helicobacter pylori to induce a neutrophil oxidative burst.

Both polymorphonuclear cell infiltration and increased epithelial apoptosis are seen in gastric mucosa in the presence of Helicobacter pylori infection. This study examined the association between bacterial ability to stimulate an oxidative burst in neutrophils and epithelial apoptosis. Biopsy specimens were obtained from 15 patients to detect apoptotic cells by the TUNEL method. H. pylori strains isolated from corresponding stomach biopsy samples were tested for the ability to stimulate an oxidative burst in human neutrophils. Neutrophils were isolated from healthy subjects without H. pylori infection and the oxidative burst was measured by flow cytometry with dichlorofluorescein diacetate. Stimulation with H. pylori increased both the percentage of activated cells and fluorescence intensity. There was a significant positive correlation between the number of epithelial apoptotic cells and fluorescence intensity. Increased neutrophil oxidative burst stimulated by H. pylori may play a role in enhanced gastric mucosal DNA damage and consequent atrophic gastritis and gastric cancer.

Apoptosis↗
PubMed2000

Long-term prognosis of patients with ulcerative colitis in Japan.

Even though it is important in improving the quality of life to evaluate the long-term prognosis of patients with ulcerative colitis in comparison with the general population, it is unknown in detail. One hundred and seventeen cases followed-up for 10 years or more were evaluated to define the long-term prognosis of ulcerative colitis by the person-years method. The estimated number of death (E) was 14.5, and the observed number of death (O) was 20. The O/E ratio was 1.38 and confidence interval was 0.84-2.13, showing no significant difference between E and O. Evaluation of change in the O/E ratio at 5-year intervals revealed a decrease in both the males and females, with a significant difference observed between the ratios in 1960 and 1965 (each p < 0.05). Generally, the death rate was significantly higher in the patients with ulcerative clitis than in the general population between 1953 and 1965 but did not significantly differ thereafter. On the other hand, the E from malignant tumors was 3.94, and the O was 4; the O/E ratio was 1.02 and 95% confidence interval was 0.27-2.60, showing no significant difference between E and O.

Adolescent↗
PubMed2000

A new approach to develop a biohybrid artificial liver using a tightly regulated human hepatocyte cell line.

Currently patients with liver failure have been treated with a various liver support systems including a whole liver perfusion, a non-biological artificial liver, and a biohybrid artificial liver. In a hepatocyte-based bioreactor, porcine hepatocytes or transformed human liver tumor cells have been utilized because of the ease of preparation. According to the clinical data reported as of now, satisfactory results have not been obtained from the use of currently available liver support devices. One of the problems is limited availability of primary human liver cells for developing live support systems because of the shortage of human liver. To resolve this issue, human hepatocytes were immortalized with a retroviral vector SSR#69 which contained the genes of simian virus 40 large T antigen (SV40Tag) and herpes simplex virus-thymidine kinase (HSV-TK). One of the immortal cell lines, NKNT-3, showed the gene expression of differentiated liver functions, grew steadily in chemically defined serum-free CS-C medium, and doubled in number in about 48 hours. Essentially unlimited availability of NKNT-3 cells supports their clinical use for liver support devices. To realize the high density culture of NKNT-3 cells in a bioartificial liver device, we have developed cellulose microspheres (CMS) which contain cell adhesive GRGDS (Gly-Arg-Gly-Asp-Ser) peptides. Within 24 hours after starting a stirring suspension culture, GRGDS-CMS efficiently immobilized NKNT-3 cells. An electron microscopic examination demonstrated that NKNT-3 cells attached on GRGDS-CMS had well-developed mitochondria, rough reticulums, and villous extensions. In this article, we review the history of extracorporeal liver support systems and describe an attractive strategy for developing a novel extracorporeal liver assist device using NKNT-3 cells and GRGDS-coated cellulose microspheres.

Animals↗
PubMed1999

Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage.

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in "delayed onset" and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

Adult↗
PubMed1999

Trace element levels in drinking water and the incidence of colorectal cancer.

We determined the levels of 15 elements in drinking water from 34 water treatment plants in Aomori Prefecture and studied how element levels relate to colorectal cancer incidence by district. Colorectal cancer incidence was calculated from the data of Aomori Colorectal Cancer Registry. Multiple regression analysis was performed by using age-adjusted incidences of rectal cancer and colon cancer by gender as object variables and each element level as an explanatory variable. The standardized partial regression coefficient was significant in gold (p < 0.01), magnesium (p < 0.01), selenium (p < 0.01) and tin (p < 0.05) for age-adjusted rectal cancer incidence in men as objective variable; in gold (p < 0.05), calcium (p < 0.01) and phosphorus (p < 0.01) with age-adjusted colon cancer incidence in men as the objective variable; and in sodium (p < 0.05), phosphorus (p < 0.05), tin (p < 0.05) and strontium (p < 0.01) with age-adjusted colon cancer incidence in women as the objective variable. These results confirm the need to further study trace elements in drinking water and food, and relationship to colorectal carcinogenesis.

Colorectal Neoplasms↗
PubMed1998

Specific immunoadsorbent for myasthenia gravis treatment: development of synthetic peptide designed to remove antiacetylcholine receptor antibody.

We have developed Medisorba MG, a new immunoadsorbent column for myasthenia gravis (MG). The alpha 183-200 segment of the Torpedo Californica acetylcholine receptor (AChR) is recognized as the acetylcholine binding site by the blocking antibody, which is one of the anti-AChR antibodies involved in the pathogenesis of MG. As a specific affinity ligand to remove the blocking antibody, Torpedo alpha 183-200 was synthesized and immobilized covalently to porous cellulose beads. This immunoadsorbent showed specific removal of the blocking antibody without reducing IgG and albumin levels significantly in clinical evaluation and in vitro study. Clinical improvement was found in 78% of the cases, and no adverse effects were observed in any case. The Medisorba MG column has been confirmed as a useful device for the treatment of MG.

Acetylcholine↗
PubMed1998

[A study on the effects of physical load placed on high school baseball managers during midsummer games].

We examined the influence of physical load placed on high school baseball managers during midsummer games under extremely hot and humid conditions. The factors used to determine physical load were the following: body weight, oral temperature, amount of walking, pedometer count, heart rate, and serum biochemical elements. These factors were measured before and after the games. Twenty-two managers participated in this study. All games were played under high temperatures of 32.4 +/- 3.5 (mean +/- S.D) degrees Celsius dry-bulb, 27.1 +/- 3.0 degrees Celsius wet-bulb, 33.8 +/- 3.6 degrees Celsius black-glove, 29.1 +/- 3.3 degrees WBGT, which are likely to cause heart-related illness. The results were as follows. 1. After the games, significant body weight loss and oral temperature rise were found. Those findings were thought to be caused by the rise in oral temperature in a hot environment which was accompanied by hyperhidrosis. 2. The average hemoconcentration ratio based on the changes in total protein during the games was 105 percent, suggesting that hemoconcentration and dehydration were caused by sweating in a hot environment. 3. A significant increase in total protein, albumin, LDH, high density lipoprotein cholesterol, calcium, hemoglobin, and a decrease in triglyceride were observed after the games, which were thought to be influenced by sweating and by increased metabolism in a hot environment. 4. The values of triglyceride, Fe, uric nitrogen, calcium and hemoglobin after the games which were adjusted by the hemoconcentration ratio were significantly lower than those before the games. 5. A prolonged game time caused a significant increase in total protein value during the games and a decrease in hemoglobin between the level before the games and the adjusted level after the games compared with those values in the short game time group. From the above, even though high school baseball managers join in practices in a hot environment and become accustomed to it, we found that they had a great physical load on their bodies during the games in midsummer.

Adolescent↗
PubMed1998

[A study of the effects of physical load on umpires during the national high school baseball games--the effects of physical load on umpires at the Koshien stadium in a summer-heat environment].

This study attempted to measure the physical load on national high school baseball umpires during games played at Koshien stadium under extremely hot and humid conditions in the summer. Thirty-one umpires participated in this study. Thirteen of them were evaluated twice while eighteen were evaluated only once. The factors used to determine physical load were the following: body weight, oral temperature, blood pressure, heart rate, and serum biochemical elements. These were measured before and after the games. Heart rate was measured at one-minute intervals. The results were as follows. 1) All the games were played under conditions of extremely high temperatures--32.1 degrees celsius dry-bulb, 27.0 degrees celsius wet-bulb, 36.8 degrees celsius black-globe, 29.5 degrees--WBGT which are likely to cause heat-related illnesses. 2) The physical load of baseball umpires during the game showed a 1.69 percent decrease in average body weight due to perspiration, a 0.43 degrees C increase in oral temperature and an increase in heart rate. An examination of the serum biochemical elements showed that muscle deviation enzymes changed due to muscular activity and blood condensed due to perspiration. The physical load levels of baseball umpires were influenced by extreme heat and physical activity during the game. 3) There were no observable differences in either the amount of physical activity or the extreme heat environment among the umpires of different field positions. But the chief umpire's physical load showed a greater decrease in body weight, more blood condensation due to perspiration as a result of the heavier equipment he wore, more muscular activity and higher energy consumption than his counterparts on the bases. 4) The umpire's heart rates were higher during games than before games. The moment they were on the playing field. Their heart rates rose to an average of 134. It remained above 115 for about two hours, apparently caused by physical activity and heart load.

Adult↗
PubMed1998

[Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men].

We investigated the effects of acute endurance exercise and habitual physical activity for health maintenance on human neutrophil function in 12 untrained men. The acute exercise condition was a continuous exercise for 90 minutes at the intensity of 50% and 55% of maximal oxygen uptake (VO2max) on an ergometer. The training program was 3 km jogging three times per week for 8 weeks. The capacity of neutrophils to produce reactive oxygen species (ROS) was detected with lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL) on stimulation with opsonized zymosan (OZ) and phorbol myristate acetate (PMA). As for the acute exercise effects, both LgCL and LmCL responses of neutrophils, stimulated using PMA consistently increased after exercise at 50%VO2max, whereas those stimulated with OZ remained unchanged. At 55%VO2max, LgCL responses to both stimulants increase maximally 1 h after exercise, and then decreased 3 h after exercise, whereas LmCL responses to both stimulants increased continuously after exercise at 55%VO2max. These phenomena observed at 55%VO2max compared to 50%VO2max suggests the improved capacity of producing ROS neutrophils after exercise. The number of neutrophils also increased maximally 1 h after exercise, due to the mobilization of band neutrophils (shift to the left), suggesting that functional changes was associated with cell mobilization. The increase in the capacity of neutrophils to produce ROS and marked neutrophilia following the acute endurance exercise suggests that a large quantity of ROS may be produced in vivo. As for the training effects, the LgCL and LmCL responses were maintained in the exercise group as compared to the decreased ones in the control group. The difference between the exercise group and the control group was observed only in LgCL response to OZ. Humoral immune factors (IgG, IgA, IgM, C3, C4) and serum opsonic activity were also unaltered. These phenomena suggest that homeostasis might be kept constant in terms of immunity through regular physical activity.

Adult↗
PubMed1998

[The effects of interferon-alpha on oxygen radical production by human neutrophils].

This study was done to determine if the production and metabolism of reactive oxygen species from human neutrophils were modulated by the treatment of interferon-alpha (IFN-alpha). Luminol-dependent Chemiluminescence (LmCL) responses were inhibited by a high concentration of IFN-alpha (more than 1 x 10(4) IU/ml) when opsonized zymosan (OZ) and phorbol 12-myristate 13-acetate (PMA) were used as stimulants. However, these responses were increased by 1 x 10(3) IU/ml of IFN-alpha with Ca(2+)-ionophore A23187 stimulation. Lucigenin-dependent Chemiluminescence (LgCL) responses were inhibited by all concentrations. These findings suggest the possibility that IFN-alpha inhibits activation of protein kinase C (PKC), whereas the resulting effect might be due to the inhibition of myeloperoxidese (MPO) degranulation. Preincubation of human neutrophils with IFN-alpha for 30, 60 or 120 minutes and subsequent stimulation with OZ, PMA and Ca(2+)-ionophore A23187 caused an increase LgCL responses, while inhibiting LmCL responses. These findings suggest that preincubation of human neutrophils with a high concentration of IFN-alpha might enhance the NADPH-oxidase activity, although a relative increase of LgCL was due to the inhibition MPO degranulation.

Acridines↗