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Biomedical subjects

M Fujimura

Publications and source records attributed to M Fujimura.

At least 37 records · Page 2Linked to original sources

Cough receptor sensitivity and bronchial responsiveness in normal and asthmatic subjects.

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.

Administration, Inhalation

[Intrapericardial lipoma with stenosis of the left bronchus and pulmonary artery].

In a 1-year-6 month-old girl with asthma, a chest magnetic resonance imaging revealed an intrapericardial lipoma at the site of the transverse sinus behind the great arteries. The tumor compressed the left bronchus and pulmonary artery resulting in the stenosis. Under cardiopulmonary bypass, the tumor was successfully removed. The stenosis of the left bronchus and pulmonary artery were released.

Bronchi

[A multicenter study on panipenem/betamipron in dermatology].

Panipenem/betamipron (PAPM/BP), a new carbapenem, was studied in dermatology. PAPM/BP was used clinically in the treatment of skin and skin structure infections in a multicenter trial. Fifty three patients were enrolled in the trial. Clinical evaluations were made in 50 patients. Most patients received intravenous infusion of PAPM/BP in a dose of 500 mg twice daily. Other dosages were used in some patients. The overall clinical efficacy rate was 78%. When 15 cases of secondary infections were excluded, the rate was 85.7%. Adverse responses were nausea and/or vomiting in 3 patients, redness with itching in 1 patient, headache or head heaviness in 2 patients and diarrhea in 1 patient. The patient with redness and itching had also nausea and vomiting. This occurred 1 hour after the start of the first infusion of this drug. After the discontinuation of the treatment the symptoms went away on the next day. Abnormalities in laboratory test results were observed in 7 out of 53 patients. One patient with liver cirrhosis and hepatocellular carcinoma developed anemia (RBC 372 x 10(4)/mm3----275 x 10(4)/mm3, Hb 11.9 g/dl----8.8 g/dl, 35.1%----26.0%). Other abnormalities were all mild. Penetration of the drug into skin tissues after intravenous infusion of 500 mg of this drug in skin surgery patients was studied. Skin/serum concentration ratios ranged from 0.20 to 0.97. Skin concentrations were higher than the concentration of PAPM inhibiting 80% of clinical isolates over a period of 6 hours. In rats, skin concentrations were much lower than serum concentrations probably due to the difference in in vivo metabolism of PAPM. A few resistant strains of Staphylococcus aureus against PAPM and imipenem (IPM) were isolated. However, PAPM and IPM showed good antibacterial activities compared to other drugs tested. In conclusion, PAPM/BP is considered to be a useful drug in the treatment of skin and skin structure infections.

Adolescent

[Analysis of bronchoalveolar lavage fluid in patients before and after bone marrow transplantation].

We analysed BALF cell findings in 9 patients (group A: 5 patients without lung disease after bone marrow transplantation (BMT), group B: 4 patients with lung disease after BMT) before and after BMT. Before BMT, BALF cell findings in group A were almost normal, whereas a relative increase of lymphocytes was seen in group B. Although total cell counts and cell composition in group A changed little after BMT, CD4/CD8 ratios in BALF lymphocytes decreased. In contrast, a relative increase of lymphocytes and neutrophils was seen in group B and there was variation of CD4/CD8 ratios in BALF lymphocytes after BMT. We there studied the BALF lymphocytes of 3 patients in group A and 4 patients in group B after BMT by means of 2-color analysis. Among CD4+ cell populations, CDw 29+ cells were decreased in both groups after BMT. A relative increase of BALF-CD4+ HLA-DR+ cells and CD8+ HLA-DR+ cells was seen in group A, but was not seen in group B. These findings suggest that there is abnormality of local immunity in the lung after BMT.

Adult

[The relation between bronchial infiltration of eosinophils and bronchial hyperresponsiveness in two cases of eosinophilic pneumonia].

We evaluated the bronchial hyperresponsiveness to methacholine in the two cases of eosinophilic pneumonia with infiltration of eosinophils into bronchial mucosa. Bronchial responsiveness was not increased in either case in spite of marked infiltration of eosinophils into the bronchial mucosa and submucosa. Hypodense eosinophils are reported in the sputum of patients with bronchial asthma. This suggests that infiltration of activated eosinophils into the bronchial mucosa is an essential factor in bronchial hyperresponsiveness.

Adult

Thromboxane A2 synthetase inhibitor (OKY-046) improves abnormal mucociliary transport in asthmatic patients.

The effect of a thromboxane A2 synthetase inhibitor (OKY-046, 400 mg po/day) on mucociliary transport was investigated in 19 asthmatic patients. The nasal clearance time, as measured by the saccharin test, was prolonged in asthmatics (60.2 +/- 8.4 SE min) compared with normal controls (15.1 +/- 3.4 SE min). Within 4 weeks after OKY-046 administration, the nasal clearance time had improved (27.4 +/- 4.4 SE min, P less than .01) and the amount of sputum had decreased 30% (P less than .01). These results indicate that thromboxane A2 plays an important role in mucociliary transport in patients with asthma.

Aged

Implication of human papillomavirus in postirradiation dysplasia.

The presence of human papillomavirus (HPV) DNA and association of condylomata acuminata (CA) in the biopsy tissues of postirradiation dysplasia (PRD) of the cervix and/or vagina from 17 patients who previously had radiation therapy for malignancies of the uterine cervix, vagina, and endometrium were evaluated with DNA in situ hybridization. Eight of 17 patients (47.1%) had HPV DNA identified in the lesions of postirradiation dysplasia (PRD). Five of eight cases (62.5%) contained HPV DNA of more than one type. Type 16 HPV DNA (HPV-16) was the most frequently identified type. Several PRD lesions also contained HPV-6, HPV-18, HPV-31, and/or HPV-33 DNA. Eleven patients (64.7%) showed CA in the vicinity of PRD. In two cases, different types of HPV were found in the lesions of PRD and contiguous CA. The frequency of the cases containing HPV DNA, the types of HPV, and the distribution pattern of silver grains in the preparations of in situ hybridization over the nuclei of cells of PRD were very similar to those found in naturally occurring dysplasia. Based on these findings, persistent or repeat HPV infection was the most likely etiologic factor of PRD, which might be facilitated by immunosuppression due to pelvic irradiation.

Adult

Localization of NADPH-diaphorase-containing neurons in sensory ganglia of the rat.

The presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was studied histochemically in the sensory ganglia of the rat. Supraspinally, the trigeminal ganglion possessed only a few cells positively stained for NADPH-diaphorase, while a large number of positive neurons was found in the nodose ganglion. In the dorsal root ganglia, the distribution of positive cells showed a peculiar pattern in relation to spinal levels. Very minor populations (less than 2% of the total ganglionic cells) exhibited positive reaction in ganglia at levels ranging from the first cervical (C1) to fourth thoracic (T4) and from the second lumber (L2) through the entire sacral levels. In the middle to lower thoracic levels (from T5 to L1), however, abundant diaphorase-positive cells were observed. From these positive neurons it was possible to trace intensely stained nerve fibers. In the lower thoracic level, for example, dense positive fibers were seen in the ramus communicans. Retrograde tracing studies revealed that diaphorase-containing neurons in the lower thoracic level project at least partly to the gastric wall and the celiac ganglion. These results indicate that the diaphorase-positive ganglionic neurons in the thoracicolumbar levels may carry autonomic visceral afferent information. Double staining with NADPH-diaphorase histochemistry and peptide immunohistochemistry revealed that NADPH-diaphorase colocalizes with calcitonin gene-related peptide and substance P in many of these visceral afferent neurons.

Animals

Phylogenetic study of serotonin-immunoreactive structures in the pancreas of various vertebrates.

The distribution pattern of serotonin (5HT) in the pancreas was studied immunohistochemically by using a 5HT monoclonal antibody in various vertebrates including the eel, bullfrog, South African clawed toad, turtle, chicken, mouse, rat, guinea-pig, cat, dog and human. In all species examined, except the bullfrog, 5HT-like immunoreactivity was observed in nerve fibers, in endocrine cells, or in both. Positive nerve fibers were found in the eel, turtle, mouse, rat and guinea-pig. These fibers ran mainly along the blood vessels and partly through the gap between the exocrine glands. In the eel and guinea-pig, positive fibers invaded the pancreatic islet. Occasionally, these positive fibers were found adjacent to the surface of both exocrine and endocrine cells, suggesting a regulatory role of 5HT in pancreatic function. 5HT-positive endocrine cells were observed in the pancreas of all species except for the bullfrog and rat. In the eel and in mammals such as the mouse, guinea-pig, cat, dog and human, 5HT-positive cells were mainly observed within the pancreatic islet. In the South African clawed toad, turtle and chicken, the positive cells were mainly in the exocrine region. The present study indicates that the distribution patterns of 5HT in the pancreas varies considerably among different species.

Amphibians

Light and electron microscopy of neuropeptide Y-containing nerves in human liver, gallbladder, and pancreas.

Neuropeptide Y-containing nerve fibers were identified by light and electron microscopic immunocytochemistry in the human liver, gallbladder, and pancreas. In the liver, neuropeptide Y-containing nerve fibers were distributed richly in Glisson's sheath and were prominent around the walls of the interlobular vein, interlobular hepatic artery, and hepatic bile duct. The fibers also formed a dense network surrounding the hepatocytes. The nerve terminals were found close to the endothelial cells of blood vessels, as well as being distributed in Disse's space, where they appeared to terminate. Occasionally these terminals contacted directly the membrane of a hepatocyte. In the gallbladder, neuropeptide Y fibers were found in each layer, with an especially dense network in the lamina propria. The fibers also ran close to the epithelium and parallel to the muscle bundles. Blood vessels throughout the gallbladder were well supplied with such nerve fibers. In the pancreas, neuropeptide Y fibers were found mainly near blood vessels and partly in gaps between exocrine glands, seeming to terminate on certain endocrine cells. Nerve terminals were located in the vascular walls and adjacent to the surface of exocrine acinar cells. These studies provide a basis for correlating the neuropeptide Y distribution with pharmacological and physiological studies in humans.

Gallbladder

Interaction of thromboxane A2 and leukotrienes in guinea pig airways in vivo.

Effects of a thromboxane A2 receptor antagonist (S-1452) on bronchoconstriction induced by inhaled leukotriene C4 and a leukotriene receptor antagonist (AS-35) on bronchoconstriction caused by inhalation of a thromboxane A2 mimetic (STA2) were studied in anesthetized, artificially ventilated guinea pigs in order to examine the interaction of thromboxane A2 and leukotrienes in airways. 0.01-1.0 mu g/ml of leukotriene C4 and 0.1-1.0 mu g/ml of STA 2 inhaled from ultrasonic nebulizer developed for small animals caused dose-dependent increase of pressure at the airway opening (Pao) which is considered to be an index representing bronchial response. Pretreatment of the animals with inhaled S-1452 (0.01, 0.033 mg/ml) significantly reduced the airway responses produced by 0.01,0.033,0.1,0.33 and 1.0 mu g/ml of leukotriene C4 in a dose dependent manner. While pretreatment with inhaled AS-35 (1mg) did not affect the STA2 dose-response curve. These findings suggest that leukotriene C4 activates thromboxane A2 generation while thromboxane A2 does not influence 5-lipoxygenase pathway in the airways.

Administration, Inhalation

Effect of a thromboxane A2 receptor antagonist (AA-2414) on bronchial hyperresponsiveness to methacholine in subjects with asthma.

Bronchial hyperresponsiveness (BHR) to various stimuli is one of the major clinical features of bronchial asthma. In this study, the effect of a thromboxane A2 (TXA2) receptor antagonist, AA-2414, on BHR to methacholine was evaluated in 15 patients with asthma. The methacholine inhalation test was performed before and after oral administration of AA-2414 for 4 days (20 or 40 mg/day). The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20) was measured as an index of BHR. There was a significant increase in PC20 (p less than 0.01) from 0.43 (geometric SEM, 1.42) mg/ml to 0.93 (geometric SEM, 1.43) mg/ml after 40 mg/day of AA-2414, whereas baseline values of FVC and FEV1 were not changed by the treatment. Twenty milligrams per day of AA-2414 did not alter the PC20 value nor the parameter of baseline pulmonary functions. These findings might support our hypothesis that the subthreshold concentration of TXA2 in the bronchial tissues, which has no effect on bronchomotor tone per se, may be involved in BHR in asthma. Further studies with more potent and specific TXA2 receptor antagonists are needed to confirm the conclusion.

Adult

Immunohistochemical features of Paget's disease of the vulva with and without adenocarcinoma.

Six cases of vulvar Paget's disease (VP) with associated adenocarcinoma and 10 cases of VP without adenocarcinoma were compared immunohistochemically with B72.3, a pan-carcinoma marker developed against human mammary tumor cells, anti-carcinoembryonic antigen (anti-CEA), anti-epithelial membrane antigen (anti-EMA), anti-gross cystic disease fluid protein (anti-GCDFP-15), antihuman estrogen receptors (anti-ER), and anti-S-100 protein (anti-S-100). B72.3 reacted with 15/16 (94%) of the cases, anti-CEA reacted with 15/16 (94%), anti-EMA reacted with 16/16 (100%), anti-GCDFP-15 reacted with 14/16 (81%), and none of the 16 cases reacted with anti-ER or anti-S-100. There was no statistically significant difference in the percentage of cases binding antibodies between VP without adenocarcinoma and VP with adenocarcinoma. However, B72.3 and anti-CEA stained VP without adenocarcinoma significantly more strongly than VP with adenocarcinoma (p less than 0.05 and p less than 0.025). VP without adenocarcinoma tended to bind anti-GCDFP-15 more strongly than VP with adenocarcinoma, but without statistical significance. Paget cells stained differently than the cells in their associated adenocarcinoma in two of six cases. In both of these cases, the Paget cells and adenocarcinoma were noncontiguous. In contrast, three of the remaining four cases contained adenocarcinoma contiguous with Paget cells. Immunocytochemistry with B72.3 seems to be as useful as anti-GCDFP-15 in identifying VP.

Adenocarcinoma

Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A2 production in guinea-pigs.

This study was designed to examine whether an inhaled beta 2-agonist, procaterol, inhibits thromboxane A2 (TXA2) production induced by antigen challenge in passively sensitized guinea-pigs in vivo. Antigen-induced bronchoconstriction was markedly inhibited by pre-treatment with procaterol. Inhaled procaterol significantly reduced in a dose-dependent manner the increment in TXB2 concentration in bronchoalveolar lavage fluid obtained 5 min after antigen challenge. Aerosol administration of procaterol significantly inhibited bronchoconstriction induced by inhaled histamine. These results suggest that inhalation of procaterol has an inhibitory effect on antigen-induced TXA2 production as well as a protective effect against bronchoconstriction induced by bronchoactive agents.

Administration, Inhalation

Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs.

Effect of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4, histamine and a thromboxane A2 analogue (STA2) was studied in anesthetized, artificially ventilated guinea pigs in order to evaluate the effectiveness of inhalation of OKY-046 on an unfavorable mechanism of secondary release of thromboxane A2. 0.01-1.0 micrograms/ml leukotriene C4, 25-400 micrograms/ml histamine and 0.033-1.0 micrograms/ml STA2 inhaled from an ultrasonic nebulizer developed for small animals caused a dose-dependent increase of pressure at the airway opening (Pao), which is considered to be an index representing bronchial response. Pretreatment of the animals with aerosol OKY-046 (0.035 and 0.35 mg/animal) significantly reduced the airway responses produced by inhalation of leukotriene C4 and STA2, in a dose-dependent manner, while the pretreatment did not affect the histamine dose-response curve. These findings suggest that aerosol leukotriene C4 and STA2 activate thromboxane synthesis in the airway, and inhalation of OKY-046 may be useful for preventing the secondary release of thromboxane A2, which is an unfavorable mechanism in asthma.

Administration, Inhalation

Complement function and the synthesis of lung surfactant may be a regulation which preterm infants have in common.

The levels of CH50, the complement components, C1q, C4, and C3, C3 degradation fragments, and factor B were determined in the cord blood of 128 newborn infants. The levels of C3, C4, and C3d3 (an index of chronic in vivo complement activation) were clearly lower in the 28 infants with respiratory distress syndrome (RDS) than in the infants with other lung diseases or with normal lungs. CH50 and factor B levels were also low in RDS. Levels of C1q and other serum components in RDS infants were similar to the average levels in other infants without RDS at a corresponding gestational age. Lung surfactant is synthesized in alveolar type 2 cells, in which the complement components C4, C3, and factor B, but not C1q, have been reported to be synthesized. It seems possible that common factors regulate the synthesis of some complement components and surfactant.

Complement C1q

Effect of oral administration of a prostacyclin analog (OP-41483) on pulmonary function and bronchial responsiveness in stable asthmatic subjects.

To examine whether prostacyclin has an attenuating effect on nonspecific bronchial responsiveness in asthma, we measured provocative concentration of methacholine producing a 20% fall in forced expiratory volume in 1 second (PC20-FEV1) before and after oral administration of a chemically stable prostacyclin analog (OP-41483) (200 micrograms 4 times a day for 4 days) in 8 patients with stable asthma. Neither baseline pulmonary function nor PC20-FEV1 significantly improved after the treatment. These results suggest that prostacyclin may have no direct effect on bronchial responsiveness in asthmatics. Further studies using more potent and long-lasting prostacyclin mimetic will be needed to confirm the conclusion.

Acetylcholine