Morihiro Okazaki

Changes in the Proportions of Bronchoalveolar Lymphocytes, Neutrophils and Basophilic Cells and the Release of Histamine and Leukotrienes from Bronchoalveolar Cells in Patients with Steroid-Dependent Intractable Asthma

The proportion of inflammatory cells in bronchoalveolar lavage (BAL) fluid and the release of chemical mediators from BAL and peripheral blood cells were examined in 40 patients with steroid-dependent intractable asthma (SDIA) to clarify the effects of a long-term glucocorticoid regimen on these cells. The proportion of BAL lymphocytes was significantly reduced (p < 0.01) and the proportion of BAL neutrophils was significantly increased (p < 0.01) in SDIA patients compared with non-SDIA patients. The proportion of basophilic cells (mast cells and basophils) in BAL fluid was significantly lower in SDIA patients compared to non-SDIA patients (p < 0.02). The values of six ventilatory parameters were significantly lower in SDIA patients with a high proportion of BAL neutrophils (more than 10%) compared with the values in non-SDIA patients. The release of histamine and leukotriene C4 (LTC4) from the BAL cells of patients with atopic asthma was significantly reduced in SDIA patients compared with non-SDIA patients (p < 0.05). These results show that the changes in the proportion of BAL cells are observed in patients with SDIA, and these changes are related to suppressed ventilatory function and a reduction in the release of histamine and LTC4 from BAL cells.

Mucus Hypersecretion and Eosinophils in Bronchoalveolar Lavage Fluid in Adult Patients with Bronchial Asthma

Mucus hypersecretion was clinically analyzed in 46 adult patients with bronchial asthma, including 22 with steroid-dependent intractable asthma (SDIA). A large amount of expectoration, over 50 ml/day, was observed in 16 of these patients (34.8%), of whom 12 (75.0%) had SDIA and 13 (81.3%) were women. The mean amount of expectoration increased with increasing patient age, although no significant difference was found among the six age groups. A large amount of expectoration (over 50 ml/day) was clearly correlated with an increased proportion of eosinophils in bronchoalveolar lavage (BAL) fluid. The proportion of BAL eosinophils was significantly higher in patients with expectoration between 50 and 99 ml/day (p < 0.05) and over 100 ml/day (p < 0.01) than in patients whose expectoration volume was between 30 and 49 ml/day. These results show that in bronchial asthma patients, mucus hypersecretion is more often observed clinically in those with SDIA and in women, and that this hypersecretion is closely correlated with BAL eosinophilia, which is a feature of the pathophysiological changes that occur in the airways of these patients.

Production of a monoclonal antibody-bleomycin conjugate utilizing dextran T-40 and the antigen-targeting cytotoxicity of the conjugate

Bleomycin (BLM), a potent anticancer glycopeptide antibiotic, was linked covalently to murine monoclonal anti-HLA IgG1 antibody (H-1) with the use of dextran T-40. As determined spectrophotometrically, the conjugate was composed of 57.5 moles BLM per mole antibody. Of the substituted BLM, 18.4% (10.6 moles BLM per mole antibody) exhibited antimicrobial activity. The BLM-(H-1) conjugate showed stronger cytotoxicity than BLM alone against HLA-bearing cells in cultivation after a 30-min exposure to the drugs. In the same experiment, the conjugate was less toxic than BLM against cells lacking HLA.

Effects of Long-Term Glucocorticoid Therapy on Bronchoalveolar Cells in Adult Patients with Bronchial Asthma

The effects of long-term glucocorticoid therapy on airway inflammation were examined in 84 asthma patients. The proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid was significantly decreased in patients with steroid-dependent intractable asthma (SDIA) compared to results in non-SDIA patients, while BAL neutrophils were significantly increased in SDIA patients compared to results in non-SDIA patients. Regarding age, in patients under the age of 69 (except those between 30 and 39), BAL lymphocyte number was significantly decreased in SDIA compared with non-SDIA subjects, and in patients between 50 and 69, BAL neutrophils were significantly increased in SDIA compared with non-SDIA subjects. The number of BAL lymphocytes was significantly lower in patients with serum cortisol levels of less than 5.0 micrograms/dl than in those with levels of more than 5.1 micrograms/dl. BAL lymphocyte number was also significantly lower in patients who had received glucocorticoid therapy for more than 6 years than in those who had received such therapy for 2 years. These results show that long-term glucocorticoid therapy decreases the number of lymphocytes and increases neutrophil numbers in the airways.

Optimal cut-off point of waist circumference for the diagnosis of metabolic syndrome in Japanese subjects.

Metabolic syndrome (MetS) has been redefined by a new criterion in Japan, in which waist circumference cut‐off points, that is 85 cm for men and 90 cm for women, are used; however, objections are rising against this criterion. The present study examined the criterion for waist circumference to predict the accumulation of the components of MetS. In the present study, we used data for 5972 Japanese people who received annual health examinations, and 621 men (16.3%) and 51 women (2.4%) were diagnosed as having MetS. A cut‐off point as a predictor for two or more components of MetS was evaluated by the sensitivity/specificity and a receiver operating characteristic analysis. The optimal point of waist circumference was estimated as being approximately 84 cm for men and 80 cm for women. We therefore recommend revising the cut‐off value for the criterion of MetS in women according to our results and studies from other investigators. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00020.x, 2010)

An Increased Level of Specific IgG4 Antibodies Against Candida albicans in Patients with Bronchial Asthma

Specific IgG4 antibodies against Candida albicans in sera were measured in 76 asthmatics. The increased level of specific IgG4 was found in cases 10-40 years old sensitive to house dust mite and/or Candida albicans, in cases with steroid-dependent intractable asthma (SDIA) and in elderly cases. The frequency of SDIA was the highest in cases 41 to 60 years old with higher frequency of increased IgG4 antibodies. The results show that specific IgG4 increases in relation to IgE-mediated immune response, long-term steroid therapy, and aging. All of these conditions may induce depressed cell-mediated immunity.

Production of a macromomycin (MCR)-monoclonal antibody conjugate and its biological activity

Macromomycin (MCR), an unique membrane-reactive anticancer antibiotic, was incubated with murine monoclonal anti-HLA IgG1 antibody (H-1) in the presence of carbodiimide. The resulting mixture was fractionated with a Sephadex G-200 column. The first and second fractions were shown to contain MCR-(H-1) conjugate by the elution profile, as well as by the Sarcina lutea growth inhibition assay and Ouchterlony double-diffusion method. A membrane immunofluorescence test with anti-MCR and anti-mouse IgG antibodies demonstrated specific localization of MCR-(H-1) on the surface of HLA-bearing NALL -1 cells. MCR-(H-1) inhibited the growth of HLA-lacking NS-1 cells statistically less effectively than MCR alone (p less than 0.01). On the other hand, the conjugate and free MCR equally inhibited the growth and 3H-TdR incorporation of HLA-bearing NALL -1 cells. These results indicate that the antibody-bound MCR retained both MCR and antibody activities, and thus exerted antibody-targeting MCR cytotoxicity in vitro.

Myocardial Sarcoidosis With A Tumor-Like Left Atrial Thrombus

We report here an elderly woman who started vague complaints around the age of 50, was proved to be a sarcoidosis by negative skin reaction with purified protein derivative, bilateral hilar lymphadenopathy, and sarcoid lesions in biopsied liver and lymph nodes, and died of cardiac insufficiency after 15 years of the illness. Necropsy revealed a huge tumor‐ like left atrial thrombus with nonspecific fibrous lesions throughout the myocardium, a pulmonary hamartoma, pneumonia, liver cell necrosis, and cholecystopathy. To our knowledge, this may be the first case of myocardial sarcoidosis associated with this kind of atrial thrombus, although the sarcoidosis and thrombus may have occurred independently.

FDG-PET/CTが診断に有用であった大動脈炎症候群の1例

A 60-year-old female patient was admitted to our hospital in April, 2010 because of low-grade fever and malaise for several months. Physical examination on admission revealed no abnormalities except for a body temperature of 37.2℃. Blood examinations showed moderate anemia and a high erythrocyte sedimentation rate. There were no other specific abnormal findings. A systemic CT scan study disclosed diffuse thickening of the artery wall through the ascending, descending and abdominal aorta to the bilateral iliac arteries. In order to evaluate the quality of the vessel lesions, a FDG-PET/CT study was performed and revealed abnormal accumulation of 18F-FDG in the thickened wall, suggesting an inflammatory process in the lesion. Taking all these findings into consideration, we made the diagnosis of Takayasus arteritis, and treated the patient with prednisolone. The treatment was effective and her symptoms improved. A later CT scan revealed that the artery wall became somewhat thinner. Takayasus arteritis is a disease whose diagnosis is difficult to make because there are neither specific signs nor diagnostic laboratory findings in its early stage. We found that FDG-PET/CT was helpful in the diagnosis and evaluation of lesions in a patient with Takayasus arteritis.

FDG-PET/CT is useful in the diagnosis of early phase Takayasu's arteritis : A case report

A 60-year-old female patient was admitted to our hospital in April, 2010 because of low-grade fever and malaise for several months. Physical examination on admission revealed no abnormalities except for a body temperature of 37.2℃. Blood examinations showed moderate anemia and a high erythrocyte sedimentation rate. There were no other specific abnormal findings. A systemic CT scan study disclosed diffuse thickening of the artery wall through the ascending, descending and abdominal aorta to the bilateral iliac arteries. In order to evaluate the quality of the vessel lesions, a FDG-PET/CT study was performed and revealed abnormal accumulation of 18F-FDG in the thickened wall, suggesting an inflammatory process in the lesion. Taking all these findings into consideration, we made the diagnosis of Takayasus arteritis, and treated the patient with prednisolone. The treatment was effective and her symptoms improved. A later CT scan revealed that the artery wall became somewhat thinner. Takayasus arteritis is a disease whose diagnosis is difficult to make because there are neither specific signs nor diagnostic laboratory findings in its early stage. We found that FDG-PET/CT was helpful in the diagnosis and evaluation of lesions in a patient with Takayasus arteritis.