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Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 487 records · Page 27Linked to original sources

[Cisapride, a gastroprokinetic agent, binds to 5-HT4 receptors].

The affinity of cisapride for 5-HT4 receptors was investigated in comparison with those of other 5-HT4 receptor agonists and antagonists, such as 5-HT, 5-MeOT, mosapride, zacopride, metoclopramide, BIMU8, GR113808, SDZ 205-557 and ICS 205-930. Cisapride and the other compounds dose-dependently inhibited specific 3H-GR113808 binding to 5-HT4 receptors in guinea pig striatal membranes, and complete inhibition of specific 3H-GR113808 binding was achieved at the high concentrations of these compounds. Cisapride was 1.9-, 7.3-, 4.3-, 11- and 26-fold more potent than 5-HT, 5-MeOT, mosapride, zacopride and metoclopramide, respectively, in competing for 5-HT4 receptors. To determine the manner of interaction between cisapride and 5-HT4 receptors, Scatchard analysis of 3H-GR113808 specific binding to striatal membranes was performed. Cisapride increased the Kd value of 3H-GR113808 in striatal membranes in a dose-dependent manner without any influence on the binding density (Bmax) of 3H-GR113808. These findings indicate that cisapride binds to 5-HT4 receptors competing with 3H-GR113808 in guinea pig striatal membranes.

Animals↗

[Quantitative autoradiographic analysis of the binding of mosapramine to dopamine D3-receptors].

The affinity of mosapramine, an iminodibenzyl antipsychotic, to dopamine D3-receptors in rat brain was investigated by quantitative autoradiography of [3H]-7-OH-DPAT, a selective D3-ligand. Autoradiograms showed restricted distribution of [3H]7-OH-DPAT binding sites, with very high levels on the islands of Calleja (ICj), olfactory tubercle (Tu) and nucleus accumbens, while low but distinct labeling was observed in the molecular layer of lobule 10 of the cerebellum and caudate putamen (CPu). Binding of [3H]7-OH-DPAT completely disappeared when 1 microM dopamine was added, and it was reduced by the addition of mosapramine in a concentration-dependent manner. The displacing effect of mosapramine was more potent than that of haloperidol or clozapine in the brain regions examined. Mosapramine showed more potent affinity to receptors in Tu and ICj than those in CPu. On the other hand, haloperidol and clozapine did not show such regional differences. These results suggest that the high affinity of mosapramine to D3-receptors participates in, at least in part, the development of the clinical effects of mosapramine.

Animals↗

Determination of a common clonal origin of gastric and pulmonary mucosa-associated lymphoid tissue lymphomas presenting five years apart.

Mucosa-associated lymphoid tissue (MALT) lymphoma is often mis-diagnosed as a benign tumor. Dissemination to other sites occurs in MALT lymphoma. We report a 60-year-old man with gastric and pulmonary tumors of MALT lymphoma which occurred 5 years apart. Initially, the gastric tumor had been diagnosed as reactive lymphoreticular hyperplasia. To determine whether the two tumors arose from the same malignant clone, we amplified and sequenced the complementarity-determining region 3 of the immunoglobulin heavy chain gene using the polymerase chain reaction (PCR). The sequences were identical except for 11-nucleotide difference, suggesting identical clonality.

Base Sequence↗

[A case of hemophagocytic syndrome manifesting adult Still's disease and acute hepatitis].

We report a 20 year-old woman with hemophagocytic syndrome. In February 1993, she developed high fever, arthralgia, salmon-like pink eruption, leukocytosis and splenomegaly. She was diagnosed as adult Still's disease and successfully treated with intravenous immunoglobulin and oral prednisolone. In September 1993, she was re-admitted to our hospital complaining of general fatigue and low grade fever and treated with oral prednisolone at a daily dose of 15 mg. On October 2, 1993, she suddenly developed high fever and salmon-like pink eruption on her leg followed by the marked increase of serum transaminase and LDH levels (GOT 3,270 IU/l, GPT 1,880 IU/l, LDH 5,480 IU/l) on October 7. Since hepatic failure progressed, we started methylprednisolone pulse therapy and plasmapheresis. However, because of the progression of pancytopenia caused by hemophagocytosis, the treatment with VP-16 was initiated. However, she died of DIC on November 2, 1993. Autopsy revealed submassive necrosis of the hepatocytes with moderate infiltration of histiocytes. She was retrospectively diagnosed as hemophagocytic syndrome whose manifestations are very similar to those in adult Still's disease and acute viral hepatitis.

Acute Disease↗

Serum levels of soluble interleukin-2 receptor in asthma patients.

We measured the serum concentration of soluble interleukin-2 receptor (sIL-2R) in asthma patients and healthy controls to evaluate T-lymphocyte activation in this disease. The SIL-2R concentrations in patients with asthma irrespective of presence of acute attacks were significantly higher than those of the controls (p < 0.001). Although the sIL-2R concentrations were similar in the patients with acute asthma and those in remission, levels in patients with moderate and severe asthma attacks were significantly higher than levels for patients in remission (p < 0.001). These results suggest that T-lymphocyte activation occurs in asthma patients and becomes more prominent during moderate and severe acute attacks.

Adolescent↗

Role of N-methyl-D-aspartate receptor in acute spinal cord injury.

To clarify the role of N-methyl-D-aspartate (NMDA) receptors in acute spinal cord injury, changes in the intraspinal microcirculation after acute spinal cord injury in rabbits were examined. Systemic administration of MK-801, an NMDA receptor antagonist, at a dose of 5 mg/kg, significantly improved motor recovery after injury and significantly reduced edema formation at the injured site without altering spinal cord blood flow or vascular permeability at the injured site. These findings indicate that excitatory amino acids contribute to secondary spinal cord damage, especially edema formation, mediated by NMDA receptors in the early stage after injury.

Acute Disease↗

Inhibition of leukotriene C4 and B4 release by human eosinophils with the new 5-lipoxygenase inhibitor 6-hydroxy-2(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride.

Eosinophils generate and release leukotrienes C4 and B4 (LTC4, LTB4) and platelet activating factor (PAF), all of which have the capacity to cause inflammation and tissue injury in the airways. This study has examined the effects of a new 5-lipoxygenase inhibitor, 6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (CAS 120164-49-0, E6080) on the release of LTC4, LTB4 and PAF by human eosinophils, Eosinophils stimulated by 1 mumol/l calcium ionophore A23187 for 15 min released 37.5 +/- 2.2 ng, 2.3 +/- 0.3 ng and 4.0 +/- 0.3 pmol per 10(6) cells of immunoreactive LTC4, LTB4 and PAF, respectively (mean +/- SEM, n = 4). LTC4 and LTB4 releases were inhibited dose-dependently by the addition of E6080 to the cell suspension. The IC50 values were 0.26 mumol/l for LTC4 and 0.23 mumol/l for LTB4. PAF release was not inhibited. These results suggest that E6080 is a potent inhibitor of LTC4 and LTB4 release from eosinophils and may provide a protective effect against bronchoconstriction during late-phase asthmatic responses.

Asthma↗

Ulcerogenicity and effect on inhibition of prostaglandin generation of indometacin farnesil, a prodrug of indomethacin, in rat gastric mucosa: comparison with indomethacin or loxoprofen.

Indometacin farnesil was compared with indomethacin and loxoprofen in rats to ascertain whether it caused less gastric mucosal damage than the two older drugs. Damage was evaluated in terms of the size of ulcers that formed after oral administration and the changes in concentrations of prostaglandins E2 and I2 in the mucosa. Indometacin farnesil caused less damage than indomethacin and tended to cause less damage than loxoprofen. Indometacin farnesil was less potent than indomethacin in inhibiting prostaglandin generation by gastric mucosa. This property of indometacin farnesil may contribute to the low ulcerogenicity of this compound.

Animals↗

[Effect of BAY u3405-thromboxane A2 receptor antagonist, on biphasic airway responses induced by platelet-activating factor in actively sensitized guinea pigs].

Our previous study in activity sensitized guinea pigs demonstrated an LAR-like increase in respiratory resistance (Rrs) at 3 to 9 hr after PAF inhalation. The result suggested possible involvement of the priming effect of active sensitization and PAF. Mean while, thromboxane A2 (TXA2) is known to be induced by PAF. The present study investigated the involvement of TXA2 in the guinea pig LAR model with a new TXA2 receptor antagonist, BAY u3405. One hr after BAY u3405 administration to guinea pigs sensitized by ovalbumin, the Rrs following inhalation of PAF was subsequently determined. Infiltration of inflammatory cells in the airway tissue 9 hr after PAF inhalation was also observed. While a re-increase in Rrs was found in all the cases in the control group, the re-increase in Rrs was inhibited significantly in the BAY u3405 administration group, 4 to 9 hr after PAF inhalation. The numbers of eosinophils and lymphocytes in the airway tissue were significantly decreased in the BAY u3405 administration group, as compared with the control group. From these results, the possibility is suggested that TXA2 and its direct effect on the airway and the migration-enhancing effect on eosinophils and T lymphocytes, as well as PFA, are involved in the development of LAR by PAF.

Airway Resistance↗

Anopheles perplexens from artificial containers and intermittently flooded swamps in northern Florida.

Anopheles perplexens was collected from habitats previously unreported for this species in northern Florida. These habitats included intermittently flooded swamps, water-filled tires, and plastic oviposition cups. First-instar An. perplexens larvae were recovered from soil samples collected in an intermittently flooded swamp that were flooded in the laboratory, suggesting that An. perplexens eggs may survive in the soil during dry periods. Anopheles perplexens larvae were collected from water-filled tires and plastic oviposition cups at sites near Gainesville, FL. Of 30 dissected An. perplexens females collected in updraft CDC traps, all had ovarioles in Christophers's stage II and blood was absent in the midgut. The physiological state of these females indicates that updraft CDC traps collect predominately host-seeking females and that females take one blood meal per gonotrophic cycle.

Animals↗

Cyclosporine A reduces T lymphocyte activity and improves airway hyperresponsiveness in corticosteroid-dependent chronic severe asthma.

BACKGROUND: Although cyclosporine A is proving effective for chronic severe asthma, its mechanism of action in this disease is unclear. OBJECTIVE: This open study was conducted to determine whether cyclosporine A therapy would reduce the degree of airway hyperresponsiveness and T lymphocyte activity. METHODS: After a 6-week run-in period, nine patients with corticosteroid-dependent chronic severe asthma were treated with cyclosporine A (initial dose 5 mg/kg per day) for 12 weeks. RESULTS: Weekly mean morning peak expiratory flow significantly increased in six subjects during the last 6 weeks of trial. Geographic mean PC20-acetylcholine (the provocative concentration of acetylcholine required to cause a 20% fall in FEV1) was 0.147 mg/mL before cyclosporine A treatment and increased to 0.216 mg/mL at 6 weeks and to 0.379 mg/mL at 12 weeks after treatment. The increase at 12 weeks was statistically significant (P < .05). The percentage of CD4-positive T lymphocytes bearing IL-2 receptor (a marker of T cell activation) in the peripheral blood decreased significantly at 6 weeks (P < .05), but returned to baseline value at 12 weeks, probably due to cyclosporine A dose reduction in seven subjects. Serum IgE levels and peripheral blood eosinophil counts, however, which are dependent on IL-4 and IL-5, respectively, were still significantly decreased at 12 weeks, suggesting lymphokine production remained suppressed even after cyclosporine A dose was reduced. CONCLUSION: Taken together, these data suggest that cyclosporine A may act in asthma, at least in part, by inhibition of T lymphocyte activation and by reducing the degree of airway hyperresponsiveness.

Adrenal Cortex Hormones↗

[Visual function analysis of diabetic retinopathy using a contrast sensitivity analyser and usefulness of nicardipine hydrochloride].

Contrast sensitivity was measured in patients with mild diabetic retinopathy using a contrast sensitivity analyser on a personal computer to evaluate visual function. The effect of nicardipine hydrochloride for visual function in mild diabetic retinopathy was also evaluated. Suppression of contrast sensitivity in a comprehensive band of spatial frequency was seen in the patients with normal visual acuity. Apparent improvement of contrast sensitivity was seen in the patients after 3 months of nicardipine hydrochloride treatment. It became clear that even if patients with mild diabetic retinopathy have normal visual acuity, measurement of contrast sensitivity is very important to evaluate the visual function. We also found that nicardipine hydrochloride is effective in treating the impairment of visual function in patients with mild diabetic retinopathy.

Adult↗

[Prediction of postoperative visual acuity in retinal detachment with macular involvement].

We used laser interferometry (LI) and a potential acuity meter (PAM) to predict visual acuity after surgery for patients with rhegmatogenous retinal detachment with macular involvement. Thirty one eyes of 31 patients with retinal detachment were treated with scleral buckling procedures. Postoperative visual acuity was correlated with preoperative measurements of the LI and PAM, preoperative visual acuity by Landort's ring, and the estimated duration of macular detachment. The correlation between the duration of macular detachment and the postoperative visual acuity was not good (r = 0.55, p < 0.01). Although the preoperative visual acuity showed a relatively good correlation with postoperative visual acuity (r = 0.62, p < 0.01), the results of the LI and PAM provided a better correlation (LI; r = 0.73, PAM; r = 0.71). Our results suggest that the LI and PAM are useful to predict the visual acuity after retinal reattachment in patients with preoperative macular detachment.

Humans↗

[Pharmacokinetic and clinical studies on SY5555 dry syrup in children].

SY5555 is a new oral penem antibiotic. Pharmacokinetic and clinical studies using SY5555 dry syrup (powder which is dissolved before use) were performed in pediatric patients. 1. Pharmacokinetic investigation Peak plasma concentrations of SY5555 after dose of 5 mg/kg, 10 mg/kg and 15 mg/kg were, respectively, 1.58 +/- 0.37 micrograms/ml, 2.78 +/- 0.54 micrograms/ml and 5.28 micrograms/ml at 1 hour. The average half-life with 5 mg/kg administration was 0.94 +/- 0.05 hours, that with 10 mg/kg was 1.46 +/- 0.31 hours and that with 15 mg/kg was 0.88 hours. 2. Clinical investigation Enrolled in the study were 15 patients including 5 with acute otitis media, 5 with urinary tract infections and 1 each with pharyngitis, tonsillitis, bronchitis, pneumonia and subcutaneous abscess. Responses were excellent in 4 patients, good in 8 patients, fair in 2 patients and poor in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 10 strains of organism identified previous to treatment were eradicated and 2 strains were unchanged, hence the eradication rate was 80.0%. 3. No adverse reactions attributable to the drug were observed and good drug compliance were obtained. From the above results, it has been concluded that SY5555 is a highly effective and safe agent for mild to moderate respiratory and urinary tract infections in children.

Administration, Oral↗

Presurgical diagnosis of a primary carcinoid tumor of the thymus with MIBG.

A primary carcinoid tumor of the thymus showing ectopic ACTH syndrome was evaluated scintigraphically with four radiopharmaceuticals and a fluorescence method. Iodine-123-MIBG and 201Tl-Cl scintigraphy clearly demonstrated the tumor. Gallium-67-citrate and 99mTc(V)-DMSA showed no tumor uptake. The fluorescence method confirmed numerous storage granules of norepinephrine. Iodine-123-MIBG scintigraphy could be useful in the presurgical diagnosis of carcinoid tumors of the thymus.

3-Iodobenzylguanidine↗

[Evaluation of gastric adaptive relaxation in isolated stomach from the guinea-pig].

To evaluate the mechanism of gastric adaptive relaxation (GAR), we designed and established the experimental system for the measurement of GAR in isolated stomach from the guinea-pig by modifying the method of Desai. We also investigated the roles of non-adrenergic, non-cholinergic (NANC) nerves and endogenous nitric oxide (NO) in GAR by using this system. The rapid increase in the capacity of isolated stomach was observed over a certain pressure as GAR. GAR was abolished by tetrodotoxin (10(-6) M) in the presence of atropine (3 x 10(-6) M) and guanethidine (5 x 10(-6) M). NG-nitro L-arginine (LNNA) (10(-4) M), a NO synthesis inhibitor, also abolished GAR. L-arginine (10(-3) M), a precursor for NO synthesis, reversed LNNA-induced impairment of GAR. Sodium nitroprusside (10(-6)-10(-4) M), a NO-donor, induced the gastric relaxation. These results suggest that GAR is mediated by NANC nerves, possibly via endogenous NO.

Adaptation, Physiological↗

Effects of endothelin on serum gastrin level and acid secretion in rats.

Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered microcirculation due to vasoconstriction may cause gastric mucosal injury. In a previous study we found ET in gastric mucosal cells, especially chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was done to find whether ET affects G-cell function, particularly gastrin release and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. into male Wistar rats. Blood samples were collected just before and 15, 30, or 60 min after injection and serum gastrin levels were assayed by RIA. The effects of BQ123-Na (Banyu), an ET receptor antagonist, pirenzepin, or an intragastric pH of 2 on changes in the gastrin levels brought about by ET-1 were examined. The gastric contents of rats with the pylorus ligated were collected for 1 h and then for the next 4 h after the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immunostained with antigastrin. The serum gastrin levels at 15, 30, and 60 min after ET-1 injection (220 +/- 94, 204 +/- 77, and 366 +/- 191 pg/ml, respectively) were significantly higher than those before the injection (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained for gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited the increase in gastrin caused by ET-1, but pirenzepin had no effect. At pH 2, ET-1 had no effect on gastrin. ET-1 decreased acid output (2.6 +/- 2.3 microEq/h and 239 +/- 80 microEq/4 h, respectively) vs. controls (63 +/- 55 microEq/h and 346 +/- 81 microEq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduction of acidity.

Animals↗