Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 361 records · Page 20Linked to original sources

PubMed1997

Involvement of capsaicin-sensitive sensory nerves in gastric adaptive relaxation in isolated guinea-pig stomachs.

We investigated the role of capsaicin-sensitive sensory nerves (CPSNs), nitric oxide (NO), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in gastric adaptive and receptive relaxation in isolated guineapig stomachs. Changes in intragastric volume and pressure were recorded simultaneously in isolated stomachs in baths containing atropine and guanethidine. Adaptive relaxation was induced by luminal distention, and receptive relaxation was induced by electrical vagal stimulation. We found that desensitization to capsaicin inhibited adaptive relaxation, but not vagally induced relaxation. Extraluminal capsaicin induced gastric relaxation. Adaptive relaxation and capsaicin-induced relaxation were reduced by both tetrodotoxin and NG-nitro-L-arginine (LNNA), but not by hexamethonium. The effect of LNNA was partially reversed by co-incubation with L-arginine. Neither CGRP(8-37) nor VIP(10-28) inhibited all responses of adaptive relaxation, vagally induced and capsaicin-induced relaxation. These findings suggest that activation of CPSNs may be involved in adaptive relaxation, and that NO, but not CGRP or VIP, may be involved in the mechanisms of adaptive relaxation and receptive relaxation.

Adaptation, Physiological↗

PubMed1997

Helicobacter pylori culture supernatant inhibits binding and proliferative response of human gastric cells to epidermal growth factor: implications for H.pylori interference with ulcer healing?

Helicobacter pylori (H. pylori) infection of gastric mucosa is strongly associated with gastritis and peptic ulcer disease. However, the mechanisms of the ulcerogenic action of H. pylori and/or the interference of H. pylori with ulcer healing are unknown. Through binding to its receptor, epidermal growth factor (EGF) accelerates cells migration and triggers epithelial cell proliferation which are both important for the healing of gastroduodenal ulcers. H. pylori seems to interfere with ulcer healing, but the cellular and molecular targets and mechanisms of these actions have not been elucidated. In the present study, we tested the effect of H. pylori culture supernatant (dialyzed to remove molecules smaller than 10 kD) on EGF binding to its receptor and on the proliferative response of human gastric Kato III cells to EGF. H. pylori culture supernatant significantly reduced specific binding of EGF to its receptor and reduced EGF-stimulated gastric cell proliferation. Since ulcer healing requires epithelial cell proliferation and cell migration (re-epithelialization), which are both triggered by EGF binding to its receptor, the alteration in these mechanisms by H. pylori product may be the basis of H. pylori-induced interference with ulcer healing.

Biopsy↗

PubMed1997

A monoclonal antibody against very late activation antigen-4 inhibits eosinophil accumulation and late asthmatic response in a guinea pig model of asthma.

Preferential eosinophil accumulation is a characteristic of airway inflammation in asthma. Although little is known about its mechanism, recent in vitro observations suggest that the very late activation antigen-4 (VLA-4, CD49d/CD29) and vascular cell adhesion molecule-1 (VCAM-1) adhesion pathway may be involved in specific eosinophil migration. To test this hypothesis, we studied the effect of an anti-VLA-4 monoclonal antibody (mAb) on the airway eosinophilia in a guinea pig model of asthma. Guinea pigs were sensitized by repeated inhalation of ovalbumin. After a single inhalation challenge, the animals showed a striking airway eosinophilia and late asthmatic response (LAR). In contrast, when guinea pigs were pretreated intravenously at 2 h before antigen challenge with a rat antimouse VLA-4 mAb, PS2/3, cross-reacting with guinea pig eosinophils and lymphocytes, eosinophil, basophil and lymphocyte infiltration in the tracheal wall was significantly inhibited as well as LAR in a dose-dependent manner. These results suggest that VLA-4 plays a critical role in antigen-induced airway eosinophilia and LAR.

Animals↗

PubMed1997

Production of IL-8 and release of eosinophil-derived neurotoxin by normal peripheral blood eosinophils.

To study the regulation of IL-8 production and release of eosinophil-derived neurotoxin (EDN) by normal blood eosinophils, we isolated eosinophils from healthy individuals and stimulated them with immobilized secretory IgA with or without exogenous IL-5 for 3, 12, and 24 h, and with different concentrations of ionomycin for 24 h. Eosinophils cultured with secretory IgA for 3 and 12 h showed strong expression of mRNA for IL-8 by reverse transcription polymerase chain reaction. Exogenous IL-5 enhanced mRNA for IL-8 expression by eosinophils after 24 h of incubation. IL-8 secretion increased in a time-dependent manner throughout the 24 h of observation; in contrast, EDN release reached a plateau value after 12 h. Furthermore, at least 2 microM ionomycin was necessary for induction of IL-8 secretion, whereas 0.5 microM induced detectable EDN release by eosinophils. These results suggest that the mechanism of eosinophil degranulation may be different from those of cytokine secretion.

Dose-Response Relationship, Drug↗

PubMed1997

Serum levels of eosinophil cationic protein and IL-5 in patients with asthma without systemic corticosteroids.

We measured the serum levels of eosinophil cationic protein (ECP) and interleukin-5 (IL-5) in 39 patients with asthma (symptomatic 12, asymtomatic 27) without systemic corticosteroids and 49 healthy subjects. There were significant differences in serum levels in both ECP and IL-5 between symptomatic and asymptomatic asthma, and healthy subjects. A significant positive correlation was found between serum levels of ECP and IL-5. No significant correlation was found between %FEV1 and serum level of ECP or IL-5, however, when the analysis was restricted to patients of less than 60 years of age, the correlations were significant. These results suggest that IL-5 is one of the factors that activate eosinophils even in peripheral blood, and that measurement of serum levels of ECP and IL-5 is useful for in vitro monitoring of asthma.

Adult↗

PubMed1997

Comparison of platelet-activating factor receptor mRNA levels in peripheral blood eosinophils from normal subjects and atopic asthmatic patients.

Platelet-activating factor (PAF) modulates the functions of eosinophils, which play an important role in allergic inflammation, through a specific receptor(s) expressed on the cell surface. We compared expression levels of mRNA for the PAF receptor (PAF-R) in peripheral blood eosinophils from atopic asthmatic patients with those from normal healthy subjects using a relative quantification method based on the reverse transcription-polymerase chain reaction (RT-PCR). We found that the levels of PAF-R mRNA in eosinophils from the patients were significantly higher than those in normal subjects. These results suggest that the increased expression of PAF-R in eosinophils may be relevant to the pathogenesis of atopic asthma.

Adult↗

PubMed1997

High affinity binding of azasetron hydrochloride to 5-hydroxytryptamine3 receptors in the small intestine of rats.

The binding affinity of azasetron hydrochloride (azasetron) for the 5-hydroxytryptamine3 (5-HT3) receptor in a tissue preparation of rat small intestine was investigated by using [3H]granisetron as a radioligand. Scatchard analysis of specific [3H]granisetron binding revealed a single population of saturable binding sites in the tissue preparation. At this site, azasetron was concentration-dependently competitive with [3H]granisetron, and it inhibited the specific [3H]granisetron binding with a Ki value of 0.33 nM. Azasetron has a high affinity for 5-HT3 receptor in the gastrointestinal organ, the very site of its antiemetic action against chemotherapy-induced emesis.

Animals↗

PubMed1997

High attenuation lymphadenopathy caused by amyloidosis.

We describe a patient with generalized lymphadenopathy due to amyloidosis which showed on computed tomography as masses with high attenuation. Haemorrhage within lymph nodes caused by vascular amyloid deposition was confirmed at autopsy.

Amyloidosis↗

PubMed1997

New aspects of gastric adaptive relaxation, reflex after food intake for more food: involvement of capsaicin-sensitive sensory nerves and nitric oxide.

To accommodate the intake of food or liquid, gastric reservoir functions are important as the physiological reflex. There exist two major responses as a reservoir function of the stomach; adaptive and receptive relaxations. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. The mechanisms of these two types of functional responses are to some extent different, although a nitric oxide (NO) dependent non adrenergic, non cholinergic neural pathway is involved in the both relaxation reflexes. Adaptive relaxation is an intragastric pressure induced reflex. Stretch of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which generate impulses carried by the capsaicin-sensitive afferent sensory neuron. The sensory neuron can synapse on the inhibitory efferent neuron directly or activate it via interneurons of the myenteric plexus. This leads to the release of NO from the nitroxergic efferent neuron, which causes relaxation of circular muscle and hence of the fundus. Alternatively, an axon reflex causes the NO release from the sensory neuron, resulting in hexamethonium resistant gastric relaxation. Receptive relaxation is mediated by vagal motor fibers. In contrast with the pressure-induced adaptive relaxation, ganglionic nicotinic transmission is essential in the vagally induced relaxation. VIP and CGRP are important neurotransmitters of the inhibitory sensory neuron, which, however, may not mediate both adaptive and receptive relaxations. Disorders of these reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia.

Adaptation, Physiological↗

PubMed1997

Transient hypertension due to adrenal hemorrhage in a patient with von Recklinghausen's disease.

A 29-year-old man with von Recklinghausen's disease suddenly developed severe epigastric pain and was admitted to hospital. Physical examination revealed elevated blood pressure (200/130 mmHg) and tachycardia (162 bpm). Initially, he was suspected to have appendicitis, and appendectomy was performed immediately; however, appendicitis was not demonstrable pathologically. Retroperitoneal hematoma was found incidentally during the operation. Further clinical and laboratory examination demonstrated a marked increase in the urinary excretion of catecholamines. There was no evidence of pheochromocytoma on computed tomography or magnetic resonance imaging; however, these imaging studies simply showed a hematoma at the right adrenal gland. Transient hypertension and tachycardia, resembling pheochromocytoma, was caused by adrenal hemorrhage.

Adrenal Gland Diseases↗

PubMed1997

Combination chemotherapy for malignant paraganglioma.

Treatment with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and dacarbazine for malignant paraganglioma with hepatic metastasis is reported. A 51-year-old male presented with tumors in the retroperitoneal space and liver. The patient was diagnosed as having paraganglioma based on elevated levels of serum neuron-specific enolase, urinary catecholamine and vanillylmandelic acid, and on histological findings of the liver specimen. The patient was treated with this combination chemotherapy in repeated 21-day cycles. Temporary improvement in laboratory findings and a 20% reduction in the size of the hepatic masses were observed without severe adverse effects.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Response to psychological test in elderly patients with hand-arm vibration syndrome and healthy controls.

We investigated the parasympathetic nervous response to psychological test using heart rate variation (HRV) during deep breathing in elderly patients with hand-arm vibration syndrome and healthy controls. Average age (SD) of 16 patients with vibration-induced white finger (VWF), 13 patients without VWF and 12 healthy controls was 60.1 (2.8), 60.6 (4.2) and 58.8 (3.8), respectively. After an initial supine rest for 40 min, psychological test (Stroop color word test and mirror drawing test) was performed for 20 min. The indexes of HRV (Mean R-R, SD, RMSSD and CV) were calculated. Blood pressure and heart rate were also measured. The indexes of HRV did not differ between the groups before exposure. The SD, RMSSD and CV of the patients without VWF during supine deep breathing after 3 min post-exposure supine rest were significantly lower than those of the control group (p < 0.05). The Mean R-R of the patients without VWF significantly increased (p < 0.05). Blood pressure did not differ in either before or after exposure measurements. The results suggest that the post-exposure response of the parasympathetic nervous system to psychological test reduced in the patients without VWF.

Aged↗

PubMed1997

Resistance to apoptosis induced by serum depletion and all-trans retinoic acid in drug-resistant leukemic cell lines.

The relation between resistance to anticancer drugs and resistance to apoptosis has been investigated in the human leukemic cell line(KY-821) and its drug-resistant sublines. Under serum depletion conditions, drug-resistant cell lines showed apoptotic resistance when compared with the parental cell line. Drug resistant cell lines also showed resistance to apoptosis when treated with all-trans retinoic acid. DNA fragmentation was low in drug resistant cell lines under both stimulations. Flowcytometry analysis did not show any alterations of the Fas antigen, p53, bcl-2 and c-myc protein expression toward inhibition of apoptotic response in drug-resistant sublines. These results indicate that drug-resistant leukemic cells still show resistance to apoptosis-inducing stimulation such as poor nutrition and differentiation-inducing agents.

Antineoplastic Agents↗

PubMed1997

A comparison of young and aged populations for the diphtheria and tetanus antitoxin titers in Japan.

The antitoxin levels for diphtheria and tetanus were measured with samples of a young group immunized with diphtheria-tetanus-acellular pertussis combined vaccine and those of an aged group, members of which had not received vaccination in their youth. In the young group members of which had already received basic immunization with diphtheria-tetanus-acellular pertussis combined vaccine, the levels of both antitoxins rose well after injection at 11 to 12 years old with diphtheria-tetanus combined toxoids and remained high until 20 years of age. In the aged group, more than 80% showed antitoxin levels above 0.01 u/ml for diphtheria, while all had levels below that for tetanus, except three persons with confirmed tetanus immunization history. Maintenance of the protective antitoxin levels in the population by vaccination is necessary to prevent outbreaks of infection among unvaccinated or only partially immunized persons.

Adolescent↗

PubMed1997

[Neuropathology of the basal ganglia in Parkinson's disease with a special reference to its responsible lesion].

It took approximately one century to discover the neuropathologic lesion responsible for Parkinson's disease, of which clinical manifestations were originally described in 1817. Namely, the lesion is located in the substantia nigra pars compacta and is histologically characterized by loss of pigmented nerve cells, formation of Lewy bodies and proliferation of astrocytes. The neuronal loss is observed predominantly in the lateral portion of the pars compacta, more conspicuously in its ventral region where immunoreactivity to tyrosine hydroxylase is also decreased. The formation of Lewy bodies, which are found to be peculiar in Parkinson's disease, may hold a clue to the elucidation of the mechanism of neuronal degeneration. An animal model induced by MPTP stimulates a search for environmental factors capable of initiating the disease.

Animals↗

PubMed1997

[Effectiveness of continuous pulmonary perfusion during total cardiopulmonary bypass to prevent lung reperfusion injury].

The oxygen free radicals and the interaction between neutrophils and endothelium have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass (CPB), and in the setting of total CPB, the ischemia-reperfusion injury has been suspected as the mechanism of lung injury. To prevent this reperfusion induced lung injury, we performed continuous pulmonary perfusion during total CPB. We studied 26 infants less than 1 year of age who underwent patch closure of ventricular septal defect. Intermittent mechanical ventilation (5/min) and continuous perfusion of pulmonary artery (30 ml/kg/min) were performed during total CPB in 7 infants (Group P). Whereas 19 infants underwent ordinary CPB (Group N). PaO2/FiO2 ratio was employed for the predictor of lung injury and was calculated before and after CPB. PaO2/FiO2 ratio decreased from 3 to 12 hours after CPB and then increased by 24 hours after CPB in both groups. The lowest PaO2/FiO2 ratio measured at 12 hours after CPB correlated with age and body weight at operation (Spearman's correlation coefficient, 0.59; p = 0.01 and 0.61; p = 0.009, respectively) and strongly correlated with preoperative Rp/Rs ratio (-0.73; p = 0.003). PaO2/FiO2 ratio, however, did not correlate with duration of CPB and aortic cross clamping, preoperative Pp/Ps and Qp/Qs ratio in group N. PaO2/FiO2 ratio of group P at 3, 6, and 12 hours after CPB were higher than those of group N, although there were no significant difference When analysis was made on the infants with high pulmonary vascular resistance (preoperative Rp/Rs ratio > or = 0.1), PaO2/FiO2 ratio of group P (n = 6) at 3, 6 and 12 hours after CPB were higher than those of group N (n = 11), and the difference was statistically significant at 12 hours after CPB (291.1 +/- 15.5 versus 199.6 +/- 27.0, p = 0.027. These results implicate that young age, low body weight and especially high pulmonary vascular resistance were incremental risk factor of lung injury after CPB and, furthermore, ischemia reperfusion injury can be the initiating factor of lung injury. The results also suggest that continuous pulmonary perfusion during total CPB is an effective mean to prevent lung injury particularly for the infants with high pulmonary vascular resistance.

Cardiopulmonary Bypass↗

PubMed1997

Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1 beta.

The production of several cytokines such as interleukin (IL)-1 in gastric mucosa is increased in subjects infected with Helicobacter pylori, a bacterium associated with ulcer recurrence. This study was performed to determine whether the administration of IL-1 beta can cause recurrence of gastric ulcers in rats. Rats with healed ulcers received an injection of IL-1 beta (0.01 to 1 microgram/kg) or vehicle alone. Some rats received an injection of antiserum to rat neutrophils at the same time as 1 microgram/kg IL-1 beta or an injection of monoclonal antibodies against adhesion molecules (anti-intercellular adhesion molecule-1, anti-CD11a, and anti-CD11b) at 0, 12, and 24 hours after the initial injection. At this dose of IL-1 beta, the numbers of neutrophils and monocytes/macrophages infiltrating the scarred mucosa were higher at 12 and 24 hours than without injection of IL-1 beta. By 48 hours, seven of the eight bealed ulcers in the group treated with 1 microgram/kg IL-1 beta had recurred, as had one of the seven healed ulcers in the group given 0.1 microgram/kg IL-1 beta. No recurrence was found in the rats treated with 0.01 microgram/kg IL-1 beta or vehicle alone. Treatment with antiserum to neutrophils or antibodies to adhesion molecules inhibited both neutrophil infiltration into the scarred mucosa and the ulcer recurrence caused by IL-1 beta. These findings suggest possible mechanisms of recurrence of human peptic ulcers.

Acetic Acid↗

PubMed1997

[Activation status of eosinophils in the bronchial mucosa in symptomatic and asymptomatic asthmatics].

Although eosinophils are generally thought to play a central role in the pathogenesis of asthma, there is a few evidence not to support this view. In order further to test this hypothesis, we studied whether the magnitude of eosinophil infiltration in the bronchial mucosa and their activation status are related to clinical manifestations. Bronchial biopsies were obtained from 15 symptomatic asthmatics, 17 asymptomatic asthmatics, 11 patients with asthma who had been taking oral prednisolone for at least 1 month, and 16 controls, then stained immunohistochemically with a EG2 monoclonal antibody. The serial sections were stained with Hansel. In 15 subjects, criostal sections were immunostained with anti CD3, CD4, CD8 and CD25 antibodies. There was a significant increase in the numbers of Hansel staining-positive cells, EG2 positive cells and % of EG2 positive cells in symptomatic asthmatics. There was a significant positive correlation between the numbers of Hansel-staining positive cells and CD3, CD4 and CD25 positive cells, and between the numbers of EG2 positive cells and CD4, CD25 positive cells. These results confirm the hypothesis that eosinophils play a key role in the pathogenesis of asthma, and T cells are controller cells in the recruitment and activation of eosinophils.

Adult↗