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Biomedical subjects

N Fukuyama

Publications and source records attributed to N Fukuyama.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased nitric oxide in nasal lavage fluid and nitrotyrosine formation in nasal mucosa--indices for severe perennial nasal allergy.

BACKGROUND: The nose contributes the large amount of nitric oxide (NO) to exhaled air. NO is a mediator of vasodilation and yields peroxynitrite (ONOO-) by reacting with superoxide (O2-). ONOO attacks tyrosine residues to form nitrotyrosine. OBJECTIVE: The aim of this study was to examine the pathophysiological role of NO in nasal mucosa in patients with perennial nasal allergy. METHODS: We measured nitrite and nitrate (NO2-/NO3-) and 3',5'-guanosine monophosphate (cyclic GMP) in nasal lavage fluid, and also measured haemoglobin concentration in nasal mucosa as an indicator of blood volume in the patients and healthy volunteers. The deleterious role of NO was also investigated by measuring nitrotyrosine in nasal mucosa. RESULTS: The NO2-/NO3- concentration in the nasal lavage fluid was 39.5+/-2.8 microM in healthy volunteers (n=40), 42.4+/-3.0 microM in patients with mild allergy (mild group, n=32), and 88.7+/-6.6 microM in patients with severe allergy (severe group, n=61). In the patients whose symptoms were improved with treatment, NO2-/NO3- levels decreased to 45.7+/-10.4 microM. The concentration of cyclic GMP in nasal lavage fluid was higher in the severe group than in the healthy volunteers. The mucosal haemoglobin index was 88+/-4 in the healthy volunteers, 67+/-4 in the mild group, and 53+/-2 in the severe group. The formation of nitrotyrosine was expressed 0.58+/-10% to total tyrosine in the severe group (n=11), but was not found in non-allergy patients (n=9). CONCLUSIONS: The production of NO was increased in patients with perennial nasal allergy, but the blood flow in the nasal mucosa of patients was reduced. Nitrotyrosine formation suggests that there is a process of ONOO(-)-induced damage in mucosa of patients with the perennial nasal allergy and this damage may limit the dilatation of blood vessels, despite the presence of excessive NO.

Adult↗
PubMed1998

Peroxynitrite formation in focal cerebral ischemia-reperfusion in rats occurs predominantly in the peri-infarct region.

Peroxynitrite (ONOO-) exhibits potent neurotoxicity and plays an important role in neuronal death, but no evidence shows that it is formed in the brain during ischemia or subsequent reperfusion. To detect the formation of ONOO-, we used a hydrolysis/HPLC procedure to measure the formation of 3-nitro-L-tyrosine (NO2-Tyr), which is considered to reflect attack of ONOO- on L-tyrosine residues of cellular components in the brain. Focal ischemia was produced by occluding the right common carotid and right middle cerebral arteries for 2 hours, and the ischemic area was reperfused by reopening the middle cerebral artery. After 2 hours of ischemia, the values of the ratio of NO2-Tyr to L-tyrosine were 0% +/- 0%, 0.42% +/- 0.13% and 0.29% +/- 0.10% in the noninfarct, periinfarct, and core-of-infarct regions, respectively. After 3 hours of reperfusion following 2 hours of ischemia, the ratio in the periinfarct region reached 0.89 +/- 0.22%, which was significantly higher than that in the core-of-infarct region (0.35 +/- 0.09%). The NO2-Tyr was not detected in 50 mg/kg of N-monomethyl-L-arginine-treated or sham-operated rats. Regional CBF in the periinfarct region decreased to 30.8 +/- 15.9 mL/100 g/min during occlusion, but recovered more rapidly than did that in the core-of-infarct region.

Animals↗
PubMed1998

Inductions of 3-L-nitrotyrosine in motor neurons after transient spinal cord ischemia in rabbits.

The induction and distribution of 3-L-nitrotyrosine (NO2-Tyr) were examined with HPLC and immunohistochemistry in rabbit spinal cords after 15 minutes of transient ischemia until 7 days of the reperfusion. After the 15-minute ischemia, there was a significant decrease of neurologic scores in the ischemic group compared with the sham-operated control group at 7 days of reperfusion (P = 0.0017), and the majority of motor neurons was selectively lost at 7 days of reperfusion (P = 0.0039). NO2-Tyr was transiently induced at 8 hours of reperfusion in the ventral part of the spinal cord (0.47%+/-0.86%, NO2-Tyr/total tyrosine; P = 0.0021), but was not induced at any time point of reperfusion in the dorsal part of the spinal cord. Strong immunoreactivity for NO2-Tyr was selectively induced in large pyramidal motor neurons at 8 hours of reperfusion and was still weakly present until 7 days of reperfusion. (There may be a difference in sensitivity between the two techniques.) These results suggested that protein tyrosine nitration by nitric oxide plays a role in the selective motor neuron cell damage after transient spinal cord ischemia.

Animals↗
PubMed1998

[Superoxide, nitric oxide and peroxynitrite].

Over the past several years, a large body of evidence has shown the injurious action of superoxide. However, with the discovery that most types of cells can generate nitric oxide (NO), the pathological conditions previously attributed to superoxide must to be re-examined considering the reaction of superoxide and NO. This is particularly important if there are conditions where the production of peroxynitrite is relevant, since peroxynitrite is a very potent oxidant and yielded by the reaction of superoxide and NO with a diffusion controlled rate. In this article, we reviewed various pathological conditions, focusing on the generation of these three reactive substances and demonstrated actual examples of peroxynitrite-related injuries.

Aged↗
PubMed1997

Nitric oxide mediates murine cytomegalovirus-associated pneumonitis in lungs that are free of the virus.

4 wk after intraperitoneal inoculation of 0.2 LD50 (50% lethal dose) of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable in the salivary glands, but not in the lungs or other organs. When the T cells of these mice were activated in vivo by a single injection of anti-CD3 monoclonal antibody, interstitial pneumonitis was induced in the lungs that were free of the virus with an excessive production of the cytokines. In the lungs of such mice persistently infected with MCMV, the mRNA of the cytokines such as IL-2, IL-6, TNF-alpha, and IFN-gamma were abundantly expressed 3 h after the anti-CD3 injection, and the elevated levels continued thereafter. A marked expression of inducible nitric oxide synthetase (iNOS) was then noted in the lungs, suggesting that such cytokines as TNF-alpha and IFN-gamma may have induced iNOS. Although the increase in NO formation was demonstrated by the significant elevation of the serum levels of nitrite and nitrate, the interstitial pneumonitis was not associated with either increased superoxide formation or peroxynitrite-induced tyrosine nitration. Nevertheless, the administration of an NO antagonist also alleviated the interstitial pneumonitis provoked by anti-CD3 mAb. Based on these findings, it was concluded that MCMV-associated pneumonitis is mediated by a molecule of cytokine-induced NO other than peroxynitrite.

Animals↗
PubMed1997

Clinical evidence of peroxynitrite formation in chronic renal failure patients with septic shock.

The production of both nitric oxide (NO) and superoxide increases in septic shock. The cogeneration of these molecules is known to yield peroxynitrite, which preferentially nitrates tyrosine residues of protein and non-protein origins. We present evidence of peroxynitrite production in septic shock by measuring plasma nitrotyrosine. The nitrotyrosine was measured by an HPLC C-18 reverse-phase column and ultraviolet detector in chronic renal failure patients with or without septic shock, and in healthy volunteers. Plasma nitrite + nitrate (NOx) was also measured to evaluate NO production. Nitrotyrosine was selected as an index for production of peroxynitrite because the direct measurement of peroxynitrite in vivo is difficult. Patients with renal failure were selected in order to minimize nitrotyrosine excretion through the kidney. Plasma nitrotyrosine levels were not detectable in volunteers, 28.0 +/- 12.3 microM (1.6 +/- 1.1% of total tyrosine) in renal failure patients without septic shock, and 118.2 +/- 22.0 microM (5.5 +/- 1.2% of total tyrosine) in patients with septic shock. NOx levels were also higher in patients with septic shock than in patients without septic shock (173.9 +/- 104.7 vs. 75.6 +/- 19.1 microM). Although renal failure itself increases plasma concentrations of both molecules, the higher levels in patients with septic shock suggest that peroxynitrite is generated and the nitration of tyrosine residues is increased in this disease.

Adult↗
PubMed1997

Early reperfusion induces alveolar injury in pulmonary embolism.

STUDY OBJECTIVE: To observe (1) whether the reperfusion is one of the causes underlying the development of diffuse alveolar injury following pulmonary embolism, and (2) whether polymorphonuclear leukocyte (PMN) accumulation occurs in the reperfused lobe, and (3) whether the production of superoxide is increased from cells obtained by BAL. DESIGN: The condition of pulmonary embolism was simulated by occluding the pulmonary artery branch using a balloon catheter in anesthetized closed-chest dogs. The occlusion was maintained for 24 h in the occlusion group, and a 2-h period of occlusion was followed by reperfusion in the reperfusion group. Histologic examination was performed at 24 h after occlusion in both groups (n = 8). Using a different group of dogs (n = 12), local cellular changes in the occluded and reperfused lobes were evaluated through BAL performed at 1, 2, and 3 h after reperfusion in the reperfusion group and at 3 h after occlusion in the occlusion group. Superoxide generation from BAL cells was measured by the chemiluminescence method. RESULTS: There was no histologic evidence of alveolar injury in the occluded lobe, but there were numerous leukocytes and erythrocytes along with exudate and damaged alveoli in the reperfused lobe. In the BAL study, the total cell counts recovered by BAL remained unchanged in all groups. However, the number of PMNs increased significantly in the late stages of reperfusion. Enhanced superoxide generation was observed in BAL cells obtained from reperfused lobe. CONCLUSION: Reperfusion is one of the causes underlying the development of alveolar injury in pulmonary embolism by triggering immigration of PMNs to alveoli, which results in the increased superoxide generation in BAL cells.

Animals↗
PubMed1996

Peroxynitrite formation from activated human leukocytes.

We showed direct evidence of peroxynitrite formation from polymorphonuclear cells (PMN) with the nitration of 4-hydroxyphenylacetic acid (HPA) to 4-hydroxy-3-nitrophenylacetic acid (NO2HPA). Human PMN from healthy volunteers was stimulated with phorbol-12-myristate-13-acetate (PMA, 10 ng/ml) at 37 degrees C in 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid-buffered Hank's balanced salt solution (pH 7.4) with HPA (1 mM). NO2HPA was detected under PMA stimulation only in the presence of myeloperoxidase inhibitor. NO2HPA was eliminated by N-monomethyl-L-arginine (100 microM). The inhibition of myeloperoxidase appears to be essential to demonstrate the production of NO2HPA since myeloperoxidase itself or its product, hypochlorite, reacted with peroxynitrite and hampered the formation of NO2HPA.

Animals↗
PubMed1992

[Multicenter cooperative study of pre- and post-operative adjuvant chemotherapy in the treatment of colorectal cancer. North Kyushu Co-operative Study Group for Cancer Chemotherapy].

The usefulness of pre- and post-operative adjuvant chemotherapy in colorectal cancer patients was studied by the North Kyushu Co-operative Study Group for Cancer Chemotherapy (21 participating institutions). Comparisons were made among group I given a tegafur suppository preoperatively+tegafur oral preparation postoperatively, group II given a tegafur suppository preoperatively+UFT oral preparation postoperatively and group III given a tegafur oral preparation postoperatively. No differences were seen in the incidence of postoperative complications depending on whether or not tegafur suppositories were administered preoperatively. There were also no differences in the symptom or incidence of side effects due to postoperative administration of tegafur or UFT. In a study of 5-FU concentration in the lymph nodes due to preoperative tegafur administration and recurrences, the concentration of 5-FU was significantly higher in the lymph nodes of cases without recurrences than in those with recurrences, and it was suggested that a relation exists between the concentration of agent and recurrences. The concentration of 5-FU in the lymph nodes of Dukes B patients was significantly higher in cases without recurrences than in those with recurrences. The non-recurrence rate (healthy rate) was better in the group given UFT postoperatively than in that administered tegafur postoperatively although the difference was not significant.

Administration, Oral↗
PubMed1991

[Simple process of management of central venous catheter].

In our institution, central venous catheterization is a routine procedure in terms of keeping the veins in terminal cancer patients and postoperative patients, as well as on purpose to perform high calorie transfusion. Here we describe our efforts to simplify the process. The process is characterized by the intermittent transfusion with filling up of 100-fold diluted heparin; no use of filter at the usage; but free side infusion from a trigonal active plug, which is also used for blood transfusion. These patients are permitted to bathe and stay out. During a recent 2 years, a total of 111 patients was managed with this process. Duration of catheterization ranged from the shortest of 5 days to longest of 96, with a mean of 27.5 and total days of 3058. Catheter-induced fever as a complication was observed in only 3 cases (2.7%). This procedure has a considerably simplified process, which can be said to depart from the conventional ones in terms of keeping clean, however, in actual clinical routine, it is extremely safe and valuable.

Catheterization, Central Venous↗
PubMed1991

[Multihospital co-operative study of post-operative adjuvant chemotherapy in the treatment of gastric cancer-(Part 3). Comparisons between tegafur and UFT. North Kyushu Co-operative Study Group for Cancer Chemotherapy].

The North Kyushu Co-operative Study Group for Cancer Chemotherapy (21 participating facilities) carried out a comparative study of post-operative adjuvant chemotherapy in the treatment of 243 patients after surgery of gastric cancer in stages II, III and IV over 27 months period starting from October 1983. The patients were divided randomly into group A (treated with 20 mg of MMC on the day of the surgery and 10 mg of MMC on the following day, and with a daily dose 600 mg of orally administered tegafur starting from two weeks after the surgery. In addition to the above treatments, patients with Stage IV were treated with 10 mg of MMC every three months starting from four weeks after the surgery) and group B (treated with MMC in a similar manner to group A, and with 600m g of UFT instead of the tegafur). Thirty-three patients (13.6%) were excluded or dropped out, and the remaining 210 cases were analyzed. No severe side effects appeared in either of the groups, and a long-term administration was safe. The five-year survival rate among the radical surgery patient was significantly higher in the UFT group compared with the tegafur group (p less than 0.05). Significantly higher survival rate in the UFT group was observed (p less than 0.05) for the cases of poorly-differentiated adenocarcinoma. From the above results it appears that an addition of UFT to the treatment with MMC is useful in post-operative adjuvant chemotherapy for gastric cancer.

Adenocarcinoma↗
PubMed1990

Carcinosarcoma of the gallbladder. A case report with immunohistochemical and ultrastructural studies.

The authors present the histologic features, immunohistochemical findings, and ultrastructure of a carcinosarcoma of the gallbladder containing rhabdomyosarcoma as a mesenchymal element. A pedunculated polypoid tumor protruded into the lumen from the fundus of the gallbladder. The neoplasm contained two divergent components. One was malignant mesenchymal tissue with rhabdomyoblastic differentiation; the other was ordinary adenocarcinoma which was observed predominantly at the base of the polyp. Immunohistochemically, the cytoplasm of the rhabdomyoblasts stained with anti-myoglobin, myosin, and muscle actin antibodies. Ultrastructurally, there were a large number of malignant mesenchymal tissues in which various stages of differentiated rhabdomyoblasts were noted. Ultrastructural study was particularly valuable for the identification of sarcomatous elements.

Carcinosarcoma↗
PubMed1989

Evaluation of a one-way airflow system in an animal room based on counts of airborne dust particles and bacteria and measurements of ammonia levels.

Air cleanliness in the working area of an animal room equipped with a conventional turbulent flow air distribution systems was compared with that in a similar room fitted with a one-way-flow air distribution system; in this, the supply air flowed from the working area through the racks of cages and was removed from the exhaust side. Before the introduction of animals, the air in the working and exhaust areas of both rooms was ascertained to be Class 100. With animals in situ, however, whereas in the turbulent airflow room both the workspace and exhaust air reached about Class 10,000 (with particle counts, bacterial counts and ammonia levels being almost the same) in the one-way-flow room, the air in the work space only went up to about Class 1000. With the addition of sliding doors or curtains in front of the rack in the one-way-flow room the work space air was maintained at Class 100 with almost no dust particles over 1 microns in size, airborne bacteria or ammonia being detectable. A comparison of all factors measured showed that whereas in the turbulent flow room the contamination of the work space air was 91% of that of the exhaust air, in the one-way-flow room it was only 47%, with curtains added this was reduced to 7% and with sliding doors to only 2%. In the latter case, contamination levels increased markedly on both sides during and immediately after cage changing, but recovered to the pre-cage changing levels within 30 min in the personnel working area and within 60 min on the exhaust side.

Air Conditioning↗
PubMed1989

[Multihospital randomized study on adjuvant chemotherapy with mitomycin C and futraful or UFT in gastric cancer--(Part 2). Comparisons between futraful and UFT. North Kyushu Co-operative Study Group for Cancer Chemotherapy].

A comparative multicenter study was carried out on postoperative adjuvant chemotherapy on 243 gastrectomy patients from October 1983 to December 1985. The medications were assigned at random to 2 groups of patients by the envelope method: group A (administered 20 mg of MMC on the day of surgery and 10 mg of MMC on the day after surgery, and started on tegafur at a dose of 600 mg/day 2 weeks after surgery); group B (similarly treated with MMC and started on UFT at a dose of 600 mg/day 2 weeks after surgery). Further, patients presenting in stage IV were administered MMC intravenously every 3 months, starting 4 weeks after surgery. The final drug effect evaluations were made in 210 patients excluding 33 dropouts (13.6%). The incidence of side effects was somewhat higher in group B than in group A, but their frequency was low and no serious symptoms were observed. For patients with poorly differentiated adenocarcinoma and were carried out curative operation, the 3-year survival rate was significantly higher in group B than in group A.

Adenocarcinoma↗
PubMed1987

[Multihospital randomized study on adjuvant chemotherapy with mitomycin C and futraful or UFT in gastric cancer (Part 1). Comparison between futraful and UFT. North Kyushu Co-operative Study Group for Cancer Chemotherapy)].

The present study was undertaken to evaluate the effect of postoperative adjuvant chemotherapy for 232 cases of gastric cancer by a co-operative study group consisting of 21 hospitals. The present paper describes the side effects and the 2-year survival rates in patients. Side effects observed during long-term treatment with Futraful or UFT were considered to be minor, although incidence of toxicity in the UFT group was slightly higher than in the Futraful group. As for 2-year survival, elevated survival was found in stage III cases of poorly differentiated adenocarcinoma. This suggested that UFT is more useful than Futraful.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

[Circadian rhythm of air-borne bacteria and dust particles in a mouse breeding room].

The circadian rhythm of air-borne bacteria and dust particles in a mice breeding room was studied at 1-hour intervals on the first, third and fifth day after accommodation of the animals. The numbers of air-borne bacteria in the room increased day by day after accommodation, and showed a circadian rhythm which went down at about noon and rose with three peaks at about 20:00, 1:00 and 8:00. The numbers of dust particles tended to decrease from day to day, and they showed almost the same circadian rhythm as the air-borne bacteria. Correlations between air-borne bacteria and dust particles were not significant for each particle level on the first day, but were significant for all the particle levels of 0.3, 1, 2, and 5 microns at the third day, and were also significant at particles levels of 0.5 micron or more on the fifth day.

Air Microbiology↗