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Biomedical subjects

M Suga

Publications and source records attributed to M Suga.

At least 127 records · Page 7Linked to original sources
PubMed1996

Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals.

The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated. Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2). Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma. Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy. In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung. Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration. Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung. These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase. In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses. On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice.

Animals↗
PubMed1996

Subcapsular hematoma of the liver and pylethrombosis in the setting of cholestatic liver injury.

We describe a subcapsular hematoma of the liver and pylethrombosis in a patient who developed cholestasis 4 days after severe burn injury. On the 44th hospital day, severe anemia suddenly appeared with no determinable cause. This was the initial manifestation of hepatic hematoma. Cholestatic liver injury of unknown cause lasted throughout the clinical course. The patient subsequently died of hepatic failure 27 months after the burn injury. An autopsy confirmed pylephlebitis and pylethrombosis, which were considered to have contributed to the hepatic failure. This was a rare case of hepatic hematoma and pylephlebitis and pylethrombosis that developed after burn injury.

Aged↗
PubMed1996

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa.

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.

Animals↗
PubMed1996

Effect of antibacterial antibody on bactericidal activities of superoxide and lysosomal enzyme from alveolar macrophages in rabbits.

Alveolar macrophages (AM) have many Fc receptors for IgG, but are less reactive to lymphokines. They have a well-developed oxidative metabolism and contain large amounts of lysosomal enzyme. This suggests that the antibacterial antibody plays an important role in early resistance by AM to intracellular bacterial infection and that a bactericidal agent, dependent on oxygen and lysosomal enzyme, participates in the effects of the antibacterial antibody on bactericidal activities of superoxide (O2-) and lysosomal enzyme from rabbit AM. The number of Listeria monocytogenes in AM increased after pretreatment with saline or normal IgG but decreased by 60% after pretreatment with anti-Listeria and 120 min incubation. Alveolar macrophage-phagocytized Listeria monocytogenes and Bacille Calmette Guérin (BCG) bound with antibacterial antibody enhanced release of O2-, and nitroblue tetrazolium (NBT) formazan reduced by O2- was observed around the bacteria in the phagosomes of AM. We also confirmed that Listeria and BCG were killed extracellularly by O2-released by a superoxide-generating system in vitro and/or by lysosomal concluded that the antibacterial antibody of the IgG class enhances the antibacterial activity of AM thereby increasing the production of 02- and lysosomal enzyme in the phagosome. This finding may be important in the early resistance to intracellular bacteria infection by AM in the alveolar spaces.

Animals↗
PubMed1996

Heterogeneity of eosinophils in chronic eosinophilic pneumonia.

It has previously been shown that patients with chronic eosinophilic pneumonia can be divided into 2 groups according to the chemotactic response of their eosinophils to 5 different eosinophil chemotactic factors (ECFs) and laboratory findings. In contrast, eosinophils obtained by bronchoalveolar lavage from both groups responded to all 5 ECFs. The correlation between the two groups and the expression of several antigens (VLA-4, CD69, ICAM-1 and CD11b) on eosinophils. The VLA-4 expression of group 1 eosinophils was higher than that of group 2 eosinophils. More interestingly, eosinophils that migrated towards ECF-PI9 expressed less CD69 than those that migrated towards other STO-2-derived ECF. The heterogeneous response of eosinophils to STO-2-derived ECFs suggests that the population of eosinophils is heterogeneous.

Antigens, CD↗
PubMed1996

[Endobronchial treatments made possible by extracorporeal lung assist in a patient in status asthmaticus refractory to mechanical ventilation].

A 19-year-old endotracheally intubated women was admitted to our hospital in severe status asthmaticus that was not relieved by inhalation of beta 2-agonists or by epinephrine, aminophylline, or corticosteroids. A chest radiography revealed pneumomediastinum and subcutaneous emphysema. Pressure-limited mechanical ventilation at a peak airway pressure of 20--30 cmH2O failed to ventilate the lungs, and caused a left pneumothorax and atelectasis. Extracorporeal lung assist (ECLA) was begun and enabled repeated suctioning through a fiberoptic bronchoscope for more than a minute with no serious complications. During ECLA aerosol therapy with a large dose of a beta 2-agonist (procatherol 0.15 mg) increased the tidal volume with no adverse effects. Atelectatic areas of the lungs re-expanded, pulmonary function improved, and ECLA was stopped 86 hours after it had been started. We suggest that, although it is highly invasive, ECLA can be useful in patients with status asthmaticus refractory to mechanical ventilation, and can allow endobronchial suctioning to be done safely.

Adolescent↗
PubMed1996

[Bronchobiliary fistula].

A 57-year-old woman with congenital syphilis had a productive cough, fever, cholecystolithiasis, and paralytic ileus. She had a 30-year history of recurrent bronchitis accompanied by yellowish serous sputum. A chest radiograph showed bilateral infiltrates resulting from aspiration pneumonia, and a reduction in volume of the right middle and right lower lobes. After recovering from paralytic ileus, she still had fever and biliptysis. Bronchoscopy revealed bile filling the right basal bronchi. Emergency laparotomy and throacotomy revealed a gall stone, splenomegaly, marked atrophy of the right lobe of the liver, and adhesion between the right pleura and the diaphragm. A T-tube cholangiogram showed that the right hepatic duct communicated with the right basal bronchus. Despite ligation of the right hepatic duct, biliptysis continued. The patient died due to rapidly progressing hepatorenal failure. Syphilis gummosa due to congenital syphilis was suspected as a cause of the bronchobiliary fistula, but was not confirmed pathologically. The surgical specimen showed only nonspecific fibrosis with calcification. Bronchobiliary fistula is rare in Japan; we know of only 6 other reported cases.

Biliary Fistula↗
PubMed1996

[Retroperitoneal fibrosis with involvement up to the mediastinal space].

A 60-year-old man presented with sudden palpitations in September 1993, and was admitted to hospital with a diagnosis of atrial fibrillation and heart failure. The patient was suspected of having collagen disease, because of a positive test for antinuclear antibodies and a high sedimentation rate. He was referred to lou hospital. Chest radiographic findings were suggestive of cardiomegaly and cardiac murmurs were audible, which indicated the presence of heart disease. A chest Ct scan revealed a lesion surrounding the intramediastinal large vessels and the heart from the level of the confluence of the left brachiocephalic vein and the superior vena cava. Suspicion of a mediastinal tumor led the patient to be admitted to the respiratory department. Percutaneous needle biopsy with a Trucut needle revealed non-specific chronic inflammation. An abdominal CT scan showed that the lesion surrounding the descending aorta traversed the diaphragm, reached the renal pelvis along both renal arteries, and caused narrowing of the ureter and left hydronephrosis. Based on these findings, retroperitoneal fibrosis was diagnosed. Treatment with steroids caused the lesion to shrink.

Anti-Inflammatory Agents↗
PubMed1996

[Saprophytic pleuritis with Candida parapsilosis].

A 73-year-old man was admitted to our hospital with pneumonia in the right S6 induced by Streptococcus milleri and with left pleural thickening. He had histories of diabetes mellitus for 30 years and pulmonary tuberculosis 35 years ago. The pneumonia resolved completely after administration of ceftazidime and clindamycin for 10 days, but the pleural thickening remained and computed tomography revealed that it was an encapsulated effusion without calcification. An aspirate was turbid yellow with a high concentration of lipids, and consisted of dominant crystals and scattered cells, 80% of which were yeasts and 20% of which were macrophages phagocytizing them. Only Candida parapsilosis developed in culture. The same silent pleural shadow was identified on chest X-ray films obtained over the previous 7 years. The persistent pleuritis was diagnosed as saprophytic infection with C. parapsilosis.

Aged↗
PubMed1996

[Scavenger receptor gene--regulation of scavenger receptor gene expression in alveolar macrophages and the pathogenesis of pulmonary alveolar proteinosis].

It was previously reported, that scavenger receptors expressed on the surface membrane of human alveolar macrophages, mediated endocytosis of a diverse group of negatively charged macromolecules. Moreover, it was reported that scavenger receptors might contribute to host-defense function and it was also reported that the expression of scavenger receptors was suppressed by some cytokines, interferon-gamma, tumor necrosis factor-alpha, and transforming growth factor-beta 1. In our previous study, we suggested that one of the pathogenesises of pulmonary alveolar proteinosis may be involved in the suppressed expression of scavenger receptors by TGF-beta 1. In this paper, the regulation of scavenger receptor gene expressions is summarized and further we refer to the pathogenesis of pulmonary alveolar proteinosis.

Animals↗
PubMed1996

[Evaluation of hepatic arterial infusion chemotherapy for gastric cancer].

Hepatic arterial infusion chemotherapy (HAIC) using implantable reservoir was performed for liver metastases of gastric cancer and the therapeutic effects were evaluated. A catheter was placed in the hepatic artery via left subclavian artery or by direct insertion at laparotomy. Cisplatin, adriamycin and 5-FU were administered. The liver metastases of gastric cancer without unresectable primary tumors and hepatectomy were divided into two groups, 16 HAIC cases (11 synchronous, 5 metachronous metastases) and 23 systemic chemotherapeutic cases (10 synchronous, 13 metachronous metastases). As a result, HAIC revealed a 62.5% response rate. The 50% survival period was 395 days for HAIC, and it was significantly prolonged compared with 198 days for systemic chemotherapy (p < 0.01). But 4 among 10 cases responding to HAIC showed subsequent extrahepatic spread of the disease. Treatment of these extra-hepatic lesions is difficult.

Adult↗
PubMed1996

Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats.

Two types of pulmonary granulomatosis were produced in rats by intratracheal instillation of zymosan or silica. In both models, immunostaining with anti-rat monoclonal antibody for inducible nitric oxide synthase (iNOS), ANOS11, showed that the intensity of iNOS immunoreactivity in the inflammatory lesions peaked at 3 days and declined thereafter. Immunohistochemical double staining and in situ hybridization demonstrated the expression of iNOS in neutrophils, monocyte-derived macrophages, and bronchiolar epithelial cells in the pulmonary lesions. Electron spin resonance spectroscopy revealed the production of an excessive amount of nitric oxide (NO) in the pulmonary lesions. Immunostaining with a polyclonal antibody against nitrotyrosine indicated the formation of nitrotyrosine residues in the granulomatous lesions, particularly in the periphery of the lesions, providing indirect evidence for the generation of peroxynitrite anion in the zymosan- or silica-instilled lungs. Administration of N omega-nitro-L-arginine methyl ester or S-methylisothiourea sulfate, which significantly suppressed NO production, resulted in marked reduction of monocyte/macrophage infiltration as well as in inhibition of induction of monocyte chemoattractant protein-1 in the lesions. These data indicate that NO and its more reactive product peroxynitrite anion may be important mediators of granuloma formation in the lung.

Animals↗
PubMed1996

[Acute effects of human recombinant erythropoietin on cardiovascular dynamics and vasoactive substances].

Treatment with human recombinant erythropoietin (r-EPO) can dramatically improve renal anemia, whereas it has been reported that such improved anemia may involve or worsen hypertension. When we administered a single dose of r-EPO at 9,000 units to 16 patients with end-stage renal failure requiring examination with a right cardiac catheter immediately before the introduction of dialysis, we measured cardiovascular dynamics and various vasoactive substances. The mean blood concentration of EPO was 3,035 units/ml 15 minutes after administration. As compared with the value of 107.6 +/- 3.2 mmHg obtained before administration, the mean arterial blood pressure significantly increased following the administration of r-EPO to 111.5 +/- 3.8 mmHg after 5 minutes, 112.4 +/- 4.2 mmHg after 10 minutes, 113.7 +/- 4.3 mmHg after 20 minutes, and 113.6 +/- 4.3 mmHg after 30 minutes (p < 0.05). The mean pulmonary arterial blood pressure tended to increase to 17.9 +/- 1.8 mmHg after 10 minutes from the level of 16.3 +/- 1.8 mmHg before administration (p = 0.096). The pulmonary vascular resistance index (PVRI) was 165.0 +/- 18.0 mmHg before administration and significantly increased to 193.2 +/- 19.0 and 199.0 +/- 16.6 dyn.S.cm-5.m2 after 10 and 30 minutes, respectively (p < 0.01, p < 0.05). The systemic vascular resistance index (SVRI) also significantly increased to 2,587 +/- 195 dyn.S.cm-5.m2 after 30 minutes from the level of 2,454 +/- 207 dyn.S.cm-5.m2 before administration (p < 0.05). Changes in SVRI showed a bimodal pattern, as with changes in PVRI. Angiotensin-II concentration significantly decreased to 13.7 +/- 4.4 pg/ml after 15 minutes from the level of 15.7 +/- 3.2 pg/ml before administration (p < 0.05). There were no significant changes in endothelin, prostaglandin, or adrenaline concentration after the administration of r-EPO. From these results, it was revealed that pulmonary intra-arterial administration of r-EPO has the acute effect of increasing pulmonary vascular resistance, thereby pointing to a direct effect of r-EPO in pulmonary vasoconstriction. Although no changes in vasoactive substances were observed in the present investigation, further studies with more sensitive measuring methods may be necessary.

Angiotensin II↗