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Biomedical subjects

M Toyoshima

Publications and source records attributed to M Toyoshima.

At least 55 records · Page 3Linked to original sources

Heparin-coated circuits reduce the formation of TNF alpha during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) causes a systemic inflammatory response. TNF alpha, which is a major inflammatory mediator, has been found in the circulation during and after CPB. Although previous studies have shown that heparin coating of the extracorporeal circuits reduces complement and granulocyte activation, and the inflammatory response, the possible effect of heparin coating on TNF alpha formation and the inflammatory response has not been fully investigated. METHODS: Eighteen patients scheduled for coronary artery bypass grafting were divided randomly into two groups. One group of patients had extracorporeal perfusion using heparin coated circuits (HC group, n = 9). The other group had extra-corporeal perfusion using an identical circuit that was not coated (UC group, n = 9). Blood samples were drawn before, during, and after CPB for measurement of plasma TNF alpha, plasma IL-8, neutrophil count, and neutrophil elastase. RESULTS: Plasma levels of TNF alpha increased during CPB in the UC group but not in the HC group. Plasma concentrations of IL-8 increased similarly during and after CPB in both groups. Coating the circuits with heparin did not affect the levels of IL-8. In both groups, the neutrophil count increased after the release of the aortic cross clamp and remained elevated for three days. In the HC group, however, the increase of neutrophil count was significantly lower compared with the UC group. Plasma concentrations of neutrophil elastase were significantly increased during and after CPB in both groups. However, the levels of elastase were significantly lower at certain time points in the HC group. CONCLUSION: From these observations, we conclude that heparin coating of the extracorporeal circuits reduces the TNF alpha formation during CPB, which may reduce neutrophil activation.

Anticoagulants↗

Bronchiolar disease in rheumatoid arthritis.

The pulmonary manifestations of rheumatoid arthritis (RA) include bronchiolar diseases such as follicular bronchiolitis (FB) and bronchiolitis obliterans (BO). In this study, we investigated the clinical and pathologic features of FB and BO, as well as the effect of erythromycin (EM) on these diseases. The subjects included 15 RA patients with biopsy-proven bronchiolar disease (eight with FB, seven with BO). None of the patients had Sjögren's syndrome. Eleven patients (73%) had chronic sinusitis, and 14 (93%) had a chronic cough with sputum. Bacterial culture of sputum was positive in 50% and 71% of the FB and BO patients, respectively. High-resolution computed tomography (HRCT) revealed small nodular shadows in the centrilobular regions (FB and BO), patchy areas of low attenuation (BO), and peribronchial thickening (FB and BO). Eleven patients who received EM therapy showed a significant improvement of symptoms. In addition, none of the 15 patients died of the bronchiolar disease during follow-up. In conclusion, RA patients with FB or BO basically have a chronic clinical course with main complaint of productive cough, and EM may be useful for the management of these diseases.

Anti-Bacterial Agents↗

A clinical study of minocycline-induced pneumonitis.

We studied the clinical features of minocycline-induced pneumonitis in seven patients. Acute symptoms included fever, dry cough and dyspnea, indicating acute respiratory failure. Diffuse ground glass shadows with Kerley's B lines, bronchial wall thickening, swelling of vascular bundles and pleural effusion were visible on radiography. Bronchoalveolar lavage or transbronchial lung biopsy confirmed pulmonary eosinophilia. Cessation of minocycline led to rapid remission with no treatment or only short-term steroid therapy. The lymphocyte stimulation test for minocycline with peripheral blood lymphocytes was not found to be useful for diagnosis.

Acute Disease↗

[Follicular bronchiolitis associated with rheumatoid arthritis].

A 52-year-old man with an 8-year history of rheumatoid arthritis was admitted to the hospital because of coughing and purulent sputum. A chest X-ray film obtained on admission showed small nodular shadows without overinflation in both lower lung fields, and a high-resolution CT scan showed many micronodular shadows in the centrilobular regions. Follicular bronchiolitis was diagnosed from the results of an open-lung biopsy, and prednisolone therapy was started at a dosage of 40 mg/day. Sinusitis developed 4 years later. Five years after the start of steroid therapy, dilation of bronchi and thickening of bronchial walls appeared on a CT scan, which also showed areas of low attenuation that were presumed to be bronchiolitis obliterans. These findings suggest that the pattern of airway disease can vary during the course of rheumatoid arthritis.

Anti-Inflammatory Agents↗

Purification and characterization of the platelet-aggregating sialoglycoprotein gp44 expressed by highly metastatic variant cells of mouse colon adenocarcinoma 26.

A platelet-aggregating sialoglycoprotein with a molecular weight of 44,000 (gp44) was immunochemically purified from highly metastatic mouse adenocarcinoma cells. The rat monoclonal antibody (mAb) 8F11 used in the purification procedure has been generated previously against NL-17 cells derived from the mouse colon 26 cell line, mAb 8F11 inhibits NL-17 cells from inducing platelet aggregation and suppresses their experimental metastasis to the lung. The purified gp44 induced mouse platelet aggregation in a dose-dependent manner without any plasma component. This aggregation was completely inhibited by mAb 8F11. The gp44 was partially characterized by sequential enzymatic hydrolysis of carbohydrates and was found to be O-glycans enriched. When gp44 was sequentially treated with N-glycanase and neuraminidase, it lost platelet aggregation activity. Further treatment with O-glycanase resulted in a loss of the reactivity to mAb 8F11. These results suggest that sialylated carbohydrate chains of gp44 are involved in the induction of platelet aggregation and may play an important role in the colonization of NL-17 cells in the lung.

Adenocarcinoma↗

[Serum phospholipase A2 activity in patients with aspirin-induced asthma].

Urinary excretion of leukotrienes is greater in patients with aspirin-induced asthma (AIA) than in other patients with asthma in remission, and is greater still during an aspirin-induced attack. We therefore hypothesized that increased phospholipase A2 (PLA2) activity leads to increased leukotriene synthesis when non-steroidal antiinflammatory drugs inhibit cyclooxygenase in patients with AIA, and that PLA2 activity increases further during an aspirin induced attack. To test this hypothesis, we measured the serum PLA2 activity in adult asthmatic patients, and compared the activity in those with AIA to the activity in those without AIA. The subjects were 43 patients with asthma in remission, 17 with AIA and 26 without AIA. Serum PLA2 activity was also measured before and after intravenous administration of lysine-aspirin in three patients with AIA and in one without AIA. Serum PLA2 activity was measured by radioimmunoassay. Serum PLA2 activity in patients with AIA, in those without AIA, and in healthy controls was 300.9 +/- 52.9, 294.4 +/- 65.3 and 171.7 +/- 41.8 pmol/ml/min, respectively. Serum PLA2 activity in asthmatic patients was significantly higher than in healthy controls (p < 0.01), but there was no difference between patients with and without AIA. Intravenous lysine-aspirin provoked asthmatic attacks in three patients with AIA. However, intravenous lysine-aspirin did not significantly change serum PLA2 activity in the three patients with AIA or in the patient without AIA. These results indicate that although PLA2 may be involved in the pathogenesis of bronchial asthma, it is not specific to AIA. Thus, the pathophysiology of AIA remains unclear and further investigation is needed.

Adult↗

Lipoxygenase inhibitor-provoked acute asthma in a patient with asthma relieved by aspirin.

BACKGROUND: A very small number of patients with asthma show symptomatic improvement after administration of aspirin and other cyclooxygenase inhibitors. The clinical features of such patients with so-called aspirin-relieved asthma are similar to those with aspirin-induced asthma, but the pathogenesis is unclear. METHODS: We encountered one confirmed aspirin-relieved asthma patient and investigated the effects of cyclooxygenase and lipoxygenase inhibitors on his condition. RESULTS: Our patient showed a marked improvement of the forced expiratory volume in one second (FEV1) after administration of aspirin and three other cyclooxygenase inhibitors (indomethacin, mefenamic acid, and ketoprofen). A 5-lipoxygenase inhibitor (AA861, Takeda, Japan), however, evoked acute asthma, and repeated administration of this drug resulted in some desensitization, but not complete tolerance. CONCLUSIONS: These results suggest an altered balance of arachidonic acid metabolism may play a critical role in the pathophysiology of aspirin-relieved asthma.

Acute Disease↗

[Responses of TNF alpha, IL-8, and leukocyte adhesion molecule CD18 to cardiopulmonary bypass].

To evaluate the inflammatory response to the cardiopulmonary bypass, we investigated the serum levels of tumor necrosis factor alpha (TNF alpha), interleukin 8 (IL-8), and the expression of leukocyte adhesion molecule CD18. Six patients who underwent elective coronary artery bypass grafting were studied. TNF alpha was elevated significantly 30 minutes after the start of CPB and returned to the baseline 60 minutes after CPB. IL-8 increased significantly after the start of CPB and reached a peak at 10 minutes after release of the aortic cross-clamp, remaining significantly elevated until 10 minutes after the end of CPB (P < 0.05). Circulating neutrophil count and granulocyte elastase increased significantly 10 minutes after release of the aortic-cross clamp and remained high until the first postoperative day. The increase of the neutrophil CD18 expression was not observed. This study demonstrates elevated TNF alpha and IL-8 levels during CPB followed by increases of the neutrophil and the granulocyte elastase, which may be of importance in the systemic inflammatory response to CPB, especially in the development of postperfusion lung injury.

CD18 Antigens↗

[Two cases of intrapulmonary lymph node associated with either progressive systemic sclerosis or idiopathic pulmonary fibrosis].

We encountered 2 cases of intrapulmonary lymph node. Case 1 was in a 48-year-old woman who had been given a diagnosis of progressive systemic sclerosis. Case 2 was in a 49-year-old woman with idiopathic pulmonary fibrosis. In each patient, a follow-up chest CT scan showed a pulmonary nodule, which could not be seen on chest X-ray film. Each nodule has an irregular margin and a linear shadow resembling pleural indentation. Histological examination of the open biopsy specimens revealed that these nodules were intrapulmonary lymph nodes surrounded by interstitial pneumonia. Previous case reports and these 2 cases indicate that unless a thoracotomy is done intrapulmonary lymph nodes are difficult to distinguish from lung cancers.

Diagnosis, Differential↗

[Arterial infusion chemotherapy with human tumor necrosis factor (TNF): an experimental study using rabbits bearing VX2 tumor].

To evaluate the direct effects of TNF on tumor vessels, three groups of Japanese white rabbits bearing VX2 tumor received 5000 U, 25000, U, and 5000 U of TNF respectively. Angiograms were obtained before, and at 1, 15 and 30 minutes after arterial TNF injection. At 1 minute after TNF injection, dilated tumor vessels and dense tumor stains, depending on the dose of TNF, were demonstrated. At 30 minutes after injection these findings had disappeared However, there were no changes in normal vessels. It is suggested that arterial TNF injection influenced tumor vessels without damaging on normal vessels, indicating that it is effective as cancer therapy.

Animals↗

A clinical study of idiopathic eosinophilic pneumonia.

To better characterize idiopathic eosinophilic pneumonia (IEP), we studied the clinical and laboratory features of 27 patients. Patients with IEP could be divided into those with chronic eosinophilic pneumonia (CEP) (n = 14) and acute eosinophilic pneumonia (AEP) (n = 13). CEP was characterized by (1) multiple and dense areas of consolidation on chest radiographs and computed tomographic (CT) scans, (2) persistent symptoms, (3) a requirement for steroid therapy, and (4) possible relapses. On the other hand, AEP was characterized by (1) diffuse ground-glass and micronodular infiltrates on radiographs and CT scans (in mild cases, the lesions were sparse or localized), (2) acute onset with high fever, (3) spontaneous improvement, and (4) no relapse. In addition, peripheral blood eosinophil count was significantly higher in patients with CEP than in patients with AEP at the first examination. However, the eosinophil fraction also became markedly elevated during the subsequent courses of AEP. Analysis of bronchoalveolar lavage fluid revealed that the percentage of eosinophils was higher in patients with CEP than that in patients with AEP, whereas the percentage of lymphocytes was significantly greater in patients with AEP than patients with CEP. It was also noted that 75 percent of patients with CEP and 82 percent of patients with AEP had allergic diathesis, suggesting that both conditions are likely to occur in atopic individuals.

Acute Disease↗

Dyskeratosis congenita showing usual interstitial pneumonia.

A 46-year-old man was admitted to our hospital with cough and dyspnea on exertion. A chest X-ray film showed diffuse interstitial shadows. He had hyperpigmentation forming a network pattern around his neck and dystrophy of the fingernails and toenails, and was diagnosed as having dyskeratosis congenita. Histological examination of the lung specimen obtained from the left S4b by open lung biopsy revealed usual interstitial pneumonia pattern with neither asbestos bodies nor silicotic nodules. Taken together with previously published findings, pulmonary involvement is considered to be an important complication of dyskeratosis congenita.

Age Factors↗

Weekly low-dose methotrexate therapy for sarcoidosis.

Low-dose methotrexate therapy has been used to treat a variety of chronic inflammatory diseases; a few studies have discussed the efficacy of this therapy for sarcoidosis. We present a patient with symptomatic sarcoidosis who was successfully treated with low-dose methotrexate after being refractory to steroids. This patient showed significant clinical improvement without development of any severe side effects. These findings suggest that low-dose methotrexate therapy may be a useful alternative treatment for sarcoidosis.

Adult↗

[A case of aspirin-induced cough without bronchoconstriction. A new type of aspirin hypersensitivity].

A 54-year-old woman was admitted to our hospital because of an asthmatic attack. Her first asthma attack occurred when she was 53 years old. It was followed by a flu-like infection, and was preceded for one year perennial rhinitis and loss of the sense of smell. Symptoms were perennial, and unrelated to the seasons. Because these clinical findings resembled those of aspirin-induced asthma (AIA), an aspirin-DL-lysine i.v. challenge test was done. Cough, perspiration, and flushing was provoked within 15 min after aspirin-DL-lysine injection, but FEV1 did not change. Respiratory sounds were normal and no wheezing was audible. Other cyclooxygenase inhibitors (ketoprofen, sulpyrine and acetaminophen) provoked the same symptoms. Successively increasing doses of injected aspirin-DL-lysine resulted in complete tolerance to this stimulus. We propose that aspirin-induced cough without bronchoconstriction is a new type of aspirin hypersensitivity.

Aspirin↗

[A case of acute interstitial pneumonia caused by blasticidin S].

A 41-year-old male developed acute interstitial pneumonia after inhalation of Blasticidin S, an antibiotic effective against rice blast disease. He presented with diarrhea, followed by dry cough, dyspnea and fever. A chest roentgenogram showed bilateral diffuse ground glass appearance, superimposed by patchy shadows. Arterial blood gas analysis revealed severe hypoxemia. Bronchoalveolar lavage fluid specimen showed moderate increase in total cell count, lymphocytes, neutrophils and eosinophils with marked elevation of CD4/8 ratio. Antibiotic therapy with minocycline failed to improve his condition, and methylprednisolone pulse therapy followed by methylprednisolone (48 mg) resulted in clinical remission with resolution of the chest roentgenogram findings. Blasticidin S should be kept in mind as a causative agent of acute interstitial pneumonia.

Acute Disease↗

[Transjugular intrahepatic portosystemic shunt--early experience in eleven liver cirrhosis patients].

Eleven liver cirrhosis patients with variceal bleeding and/or ascites were treated by transjugular intrahepatic portosystemic shunt. Four of the patients were combined with hepatoma, and 2 had portal thrombosis. Ten of the patients were successfully achieved TIPS, but one patient who had portal thrombosis was failed because of portal vein occlusion; success rate of 90%. An average decrease of 14mmHg in portal vein pressure was measured in the 10 patients. All of the successful patients including 4 with hepatoma were observed the disappeared or diminished varices and ascites without technical complication. Mild encephalopathy was encountered in 2 patients but who responded well to medical therapy. Three dimension MRA before TIPS was helpful for understanding the anatomical relationship between portal vein and hepatic vein. It is concluded that TIPS is an effective and safe treatment, indicating for the patients who have uncontrollable variceal bleeding and/or ascites even with hepatoma.

Adult↗