Biomedical subjects

M Sekiguchi

Publications and source records attributed to M Sekiguchi.

At least 181 records · Page 10Linked to original sources

PubMed1997

Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis.

The effects of recombinant human (rh) interleukin (IL)-4 or rhIL-13 on survival, and chemotactic activity of human eosinophils were examined. Only rhIL-13 prolonged eosinophil survival in a dose-dependent manner above 3 ng/ml. Eosinophil survival induced by rhIL-13 was inhibited by monoclonal antibodies (mAbs) against IL-3 (p < 0.01) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (p < 0.05), suggesting that rhIL-13 induced IL-3 and GM-CSF production from eosinophils and an autocrine mechanism is responsible for the eosinophil survival. The effects of rhIL-13 on eosinophil chemotactic activity were also examined. rhIL-13 showed chemotactic activity for eosinophils in a dose-dependent manner. Checkerboard analysis revealed that eosinophil migration was dependent on the concentration gradient, confirming that rhIL-13 is a chemotactic factor. rhIL-4 showed no effects. IL-13 may play an important role in the survival and recruitment of eosinophils in allergic diseases.

Cell Degranulation↗

PubMed1997

Inhibitory effects of theophylline and procaterol on eosinophil function.

Eosinophils play a crucial role in bronchial asthma. As theophylline and procaterol (beta 2-agonist) are used for the treatment of bronchial asthma, the specific functions of eosinophils in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet activating factor (PAF) were examined using theophylline and procaterol alone and in combination. Eosinophil degranulation induced by PAF or GM-CSF was inhibited by theophylline (10(-6) M-10(-3) M and 10(-6) M to 10(-3) M, respectively) and procaterol (10(-7) M-10(-5) M and 10(-7) M-10(-5) M, respectively). The combination of 10(-4) M theophylline and various concentrations of procaterol provided higher inhibition than 10(-4) M theophylline or procaterol (10(-7) M-10(-5) M). CD11b, which is a triggering molecule for human eosinophil degranulation, showed a significantly inhibited expression of PAF stimulation with 10(-4) M theophylline. CD11b and another triggering molecule for eosinophil degranulation, CD18, showed a significantly inhibited expression of PAF stimulation using a combination of 10(-4) M theophylline and various concentrations of procaterol (10(-5) M-10(-7) M) compared with the inhibition of 10(-4) M theophylline or procaterol (10(-5) M-10(-7) M), but GM-CSF-stimulated eosinophils were not inhibited. Taken collectively, theophylline and/or procaterol have anti-inflammatory effects.

Asthma↗

PubMed1997

Diffuse pulmonary amyloidosis with monoclonal IgG-kappa gammopathy.

A 62-year-old female with diffuse pulmonary amyloidosis developed abnormal radiographic findings while under observation for hyperimmunoglobulinemia over a ten-year period. Serum immunoglobulin G (IgG) was elevated (4,620 mg/dl), and associated with monoclonal gammopathy (M protein) of the kappa type, but no evident abnormalities were apparent in bone marrow. Chest radiograph and computed tomography showed a diffuse reticulonodular shadow in the bilateral lung. Thoracoscopic lung biopsy specimen revealed depositions of amyloid in the bronchus and pulmonary vessel. We emphasize that diffuse pulmonary amyloidosis should be considered a possible diagnosis in the presence of monoclonal immunoglobulin.

Amyloidosis↗

PubMed1997

[Effects of bilateral lung volume reduction surgery in a patient with severe pulmonary emphysema].

A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume reduction surgery on both upper lobes. By one year after surgery functional residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of 2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had increased and ventilation and pulmonary gas exchange had improved. Performance on a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were abnormally high, but 6 months after the operation the increases in Ppa and Pcwp during exercise were markedly reduced.

Chronic Disease↗

PubMed1997

[Tumor lysis syndrome after treatment for mediastinal non-Hodgkin's lymphoma].

An 18-year man was admitted to the hospital because of acute dyspnea. Roentgenological examination revealed a large anterior mediastinal tumor. Histologic examination of a specimen from a cervical lymph node yielded a diagnosis of non-Hodgkin's lymphoma of, diffuse, large, T-cell type. Acute respiratory failure and a massive pleural effusion developed, and mechanical ventilation was begun. Chemotherapy with adriamycin, vincristine, cyclophosphamide, and prednisolone resulted in rapid shrinking of the mass. Acute renal failure developed because of hypoperfusion of the kidney caused by acute circulatory failure and the tumor lysis syndrome, and rapid increases in the concentrations of lactate dehydrogenase, creatine phosphokinase, and uric acid in serum after the tumor collapsed. Mediastinal malignant lymphoma often forms a bulky mass, and effective chemotherapy, while it can prolong survival, may also cause the tumor lysis syndrome.

Acute Disease↗

PubMed1997

[Infected emphysematous bullae in a patient with diabetes mellitus].

A 42-year-old woman with diabetes mellitus was admitted to our hospital because of fever, coughing, and dyspnea. Coarse crackles were audible and respiratory sounds were weak in the right lung field. Laboratory examination revealed a high erythrocyte sedimentation rate, a high level of serum C-reactive protein, a high blood sugar level, and hypoxemia. A chest roentgenogram revealed cystic lesions with fluid levels, and an infiltration shadow in the right lung field. A chest computed tomographic scan revealed many cystic lesions with fluid levels and an infiltration shadow. Our diagnosis was infected emphysematous bullae. A tube was inserted percutaneously for drainage and to allow injection of antibiotics into the cystic lesion. The cystic lesion then vanished. Percutaneous drainage and washing with antibiotics can be used to treat infected emphysematous bulla that have thick closed cystic walls.

Adult↗

PubMed1997

[Two patients with summer-type hypersensitivity pneumonitis in Nagano Prefecture].

We encountered two patients with summer-type hypersensitivity pneumonitis that developed in Nagano Prefecture. Patient 1 was a 61-year-old man who had worked in warm and humid environments as painter. He was referred to our hospital because of fever, coughing and exertional dyspnea. Respiratory symptoms developed during work but were gone within in few weeks. Patient 2 was a 50-year-old housewife who was admitted to our hospital because of persistent coughing and a low-grade fever. In both patients, chest roentgenograms and computed tomograms showed bilateral, small, nodular and reticular shadows. Examination of a specimen obtained from patient 2 by transbronchial lung biopsy revealed alveolitis. In both patients, bronchoalveolar lavage fluid had low CD4/8 ratios, but in patient 1 the lymphocyte fraction was high and in patient 2 the neutrophil fraction was high. A steroid drug was given to patient 1 because of the patients symptoms and prolonged abnormal roentgenographic findings. Patient 2 reacted positively on a provocation test when returned to her house. Serum from both patients contained antibodies to Trichosporon mucoides and T. asahii. We know of no previous reports of summer-type hypersensitivity pneumonitis that developed in Nagano prefecture.

Alveolitis, Extrinsic Allergic↗

PubMed1997

Inhibition of accelerated coronary atherosclerosis with short-term blockade of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in a heterotopic murine model of heart transplantation.

BACKGROUND: Graft arteriopathy limits the long-term survival of allograft recipients. Cardiac allografts in mice develop graft coronary arteriopathy similar to that observed in clinical chronic rejection in human beings. We found that antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) monoclonal antibodies (mAbs) induce immunologic tolerance to mice with cardiac allografts. METHODS: To evaluate the effects of short-term administration of anti-ICAM-1 plus anti-LFA-1 mAbs in preventing graft arteriopathy, we treated C3H/He mice that received cardiac allografts from BALB/c mice with anti-ICAM-1 plus anti-LFA-1 mAbs for the first 5 days after transplantation. For control studies, FK506 was administered daily to other allograft recipients. Allografts were harvested on day 60. Immunohistochemical analysis was used to detect the expression of ICAM-1 and vascular cell adhesion molecule (VCAM)-1, and in situ reverse transcriptase polymerase chain reaction was performed to detect platelet-derived growth factor (PDGF)-B mRNA expression in the graft arteries. RESULTS: Allografts from mice that received FK506 treatment daily showed significant neointimal thickening with increased expression of ICAM-1, VCAM-1, and PDGF-B mRNA, whereas there was almost no intimal thickening and ICAM-1, VCAM-1, and PDGF-B mRNA expression in the mice that received anti-ICAM-1 plus anti-LFA-1 mAbs. CONCLUSION: Short-term blockade of ICAM-1 and LFA-1 adhesion not only induces immunologic tolerance to cardiac allografts but also prevents graft arteriopathy.

Animals↗

PubMed1997

Assessment of tolerance induction to cardiac allograft by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

BACKGROUND: Transplantation tolerance is induced by selective manipulation of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) molecules in the adult mouse. However, the mechanism of this tolerance induction has not been elucidated. METHODS AND RESULTS: C3H/He mice were heterotopically transplanted with BALB/c hearts; recipients were injected with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAbs). Of 3-day administration of both mAbs at 50 micrograms/day, all recipients accepted cardiac allografts indefinitely (n = 20); this also occurred in 5 of 10 mice that were not treated until day +4 or day +5. Long-term cardiac allograft acceptance was also achieved in thymectomized recipients. This tolerance could not be abrogated by the injection of either naive recipient lymphocytes or sensitized lymphocytes taken from the recipient strain mice that rejected the same donor strain hearts. Mixed lymphocyte culture showed that splenocytes from allograft recipient mice treated with the mAbs showed normal allogeneic response without donor alloantigen specificity. CONCLUSIONS: These results demonstrate the unique character of the peripheral tolerance induced by anti-ICAM-1 and anti-LFA-1 mAbs. Further studies are required to elucidate detailed mechanisms of transplantation tolerance development.

Animals↗

PubMed1997

[Estimation of 123I-metaiodobenzylguanidine lung uptake in heart and lung diseases--with reference to lung uptake ratio and decrease of lung uptake].

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 64 patients with heart and lung diseases. Distribution of MIBG in the chest was evaluated by planar images, using counts ratios of the heart to the mediastinum (H/M) and the unilateral lung to the mediastinum (Lu/M). Most of patients with heart diseases showed obvious lung uptake of MIBG. The ratios of H/M were 1.75 +/- 0.20 in the group without heart failure and 1.55 +/- 0.19 in the group with heart failure. The ratios of Lu/M in the right and left lung were 1.56 +/- 0.16 and 1.28 +/- 0.16 in the group without heart failure. And those were 1.45 +/- 0.16 and 1.19 +/- 0.15 in the group with heart failure. But 3 patients complicated with chronic pulmonary emphysema and one patient with interstitial pneumonia due to dermatomyositis showed markedly decreased lung uptake. The ratios of Lu/M in the right and left lung of these patients were 1.20, 1.17; 1.17, 1.13; 1.01, 0.97 and 1.27, 0.94, respectively. These results suggest that the lung uptake of MIBG may reflect the state of pulmonary endothelial cell function in clinical situations, considering that it has been demonstrated that MIBG may be useful as a marker of pulmonary endothelial cell function in the isolated rat lung.

3-Iodobenzylguanidine↗

PubMed1997

[Myocardial scintigraphic studies with 123I-MIBG, 201Tl and 99mTc-PYP in patients with cardiac amyloidosis].

Myocardial scintigraphic studies, using 123I-metaiodobenzylguanidine (MIBG), 99mTc-pyrophosphate (PYP) and 201Tl were performed in 4 patients with cardiac amyloidosis. In MIBG myocardial images, 2 patients with familial amyloid polyneuropathy (FAP) showed complete or partial defect and the other 2 with primary amyloidosis had normal myocardial uptake of MIBG. In PYP myocardial images, diffuse myocardial uptake of PYP was mild in 2 patients with FAP and moderate in the other 2. 201Tl myocardial images revealed normal myocardial uptake of 201Tl in 2 patients with FAP and 1 with primary amyloidosis, and intense myocardial uptake in the other one with primary amyloidosis. These results suggest that myocardial scintigraphies with PYP and 201Tl may be useful for the detection of cardiac amyloidosis and estimation of its pathophysiology. And MIBG myocardial scintigraphy may provide useful information about sympathetic nerve abnormalities which vary with type of the fibril protein, clinical syndromes and disease process of cardiac amyloidosis.

3-Iodobenzylguanidine↗

PubMed1996

Subaortic stenosis due to accessory tissue of the mitral valve associated with Ebstein's anomaly in an adult.

A 26-year-old man with a history of effort-induced syncopal attacks was found to have Ebstein's anomaly. A cardiac catheterization revealed a pressure gradient of 77 mmHg between the left ventricle outflow tract which was caused by mitral accessory tissue. The accessory tissue was resected, the aortic valve was replaced, and the Ebstein's anomaly was corrected. The degree of mitral regurgitation was seen to increase following surgery. This is the first reported case of an accessory mitral valve complicated with Ebstein's anomaly.

Adult↗

PubMed1996

Imaging of Ca2+/calmodulin-dependent protein kinase II activity in hippocampal neurones.

Our aim was to visualize the dynamic features of Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. In order to do so, we synthesized a new reagent by conjugating a fluoroprobe, 6-acryloyl-2-dimethylaminonaphthalene (acrylodan), to syntide 2, a specific peptide substrate for CaMKII. In cell-free conditions, the conjugate was found to be an effective indicator of calmodulin activation by Ca2+ and the subsequent activation of CaMKII. The reagent is cell-permeable and can stain living cells when bath-applied. Using this technique we were able to obtain fluorescence images of stained cells and analyse the dynamic features of CaMKII inside the cells by means of image processing. Regional heterogeneity of CaMKII activation in cultured hippocampal neurones was seen following L-glutamate administration.

Animals↗

PubMed1996

Dissociation of SNAP-25 and VAMP-2 by MgATP in permeabilized adrenal chromaffin cells.

In digitonin-permeabilized adrenal chromaffin cells, Ca(2+)-induced catecholamine release can be resolved into at least two sequential steps: a MgATP-dependent priming step and a MgATP-independent Ca(2+)-triggered step. Botulinum neurotoxins types A and E cleaved SNAP-25, and blocked MgATP-independent Ca(2+)-induced catecholamine release from the permeabilized chromaffin cells. When the permeabilized cells were primed by pretreatment with MgATP, the amount of SNAP-25 associated with VAMP-2 decreased, and the fraction of SNAP-25 proteolyzed by the neurotoxins increased. These results suggest that dissociation of SNAP-25 and VAMP-2 occurs during the MgATP-dependent priming step, and SNAP-25 plays some important roles in the subsequent MgATP-independent step.

Adenosine Triphosphate↗

PubMed1996

Bradykinin stimulates alveolar macrophages to release neutrophil, monocyte, and eosinophil chemotactic activity.

Bronchial asthma is accompanied with inflammatory cell infiltration in the airway. Because kinin activity was detected in bronchoalveolar lavage fluid (BALF) from asthmatic patients, and because the concentrations of kallikrein and kinins in BALF increased after allergen challenge, we evaluated the potential that bradykinin (BK) might stimulate alveolar macrophages (AM) to release neutrophil, monocyte, and eosinophil chemotactic activity (NCA, MCA, and ECA). To test this hypothesis, bovine AM were isolated by bronchoalveolar lavage and cultured. The supernatant fluids of AM were tested for chemotactic activity by a blind well chamber technique. AM released NCA, MCA, and ECA in response to BK in a dose-and time-dependent manner (p < 0.01). The released activities were chemotactic by checkerboard analysis. Partial characterization and molecular sieve column chromatography revealed that these released activities were heterogeneous, suggesting predominant low-m.w. lipid soluble activity and weak high-m.w. peptide activity. Lipoxygenase inhibitors blocked the release of chemotactic activities (p < 0.01). The chemotactic activities were partly inhibited by leukotriene B4 (LTB4) and platelet-activating factor (PAF) receptor antagonists (p < 0.05, respectively). Immunoreactive LTB4 significantly increased in supernatant fluids in response to BK (p < 0.05), but PAF was detected only two out of six samples stimulated by BK. The receptor responsible for the release of LTB4 involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate AM and play a role in bronchial inflammation by recruiting inflammatory cells into the airway.

Animals↗

PubMed1996

Nonmuscle and smooth muscle myosin heavy chain expression in rejected cardiac allografts. A study in rat and monkey models.

BACKGROUND: Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta. METHODS AND RESULTS: To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs. CONCLUSIONS: Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.

Animals↗

PubMed1996

Acceptance of primary skin graft after treatment with anti-intercellular adhesion molecule-1 and anti-leukocyte function-associated antigen-1 monoclonal antibodies in mice.

Although a short-term blockade of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) adhesion allows induction of specific tolerance to solid organs, their effect on primary skin allografts is not yet known. Effects of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAb) on primary skin allograft survival were investigated. Recipient mice were treated with either a combination of anti-ICAM-1 and anti-LFA-1 mAbs or a control mAb for the first 22 days. The survival of BALB/c skin in the C3H/He recipient was not prolonged. Subsequently, MHC class I (bm1)- or class II (bm12)-disparate skin grafts were transplanted into C57BL/6 mice. Remarkable prolongation was observed in these combinations. Four of 10 bm12 grafts and 4 of 9 bm1 grafts were accepted for more than 120 days. These results suggest that mouse strain combination is an important factor for skin graft acceptance. We suggest that unique immunogenicity and a lack of vascularization of skin allografts account for the weak immunosuppression produced by anti-adhesion molecule mAbs.

Animals↗

PubMed1996

Three-dimensional structure of a DNA repair enzyme, 3-methyladenine DNA glycosylase II, from Escherichia coli.

The three-dimensional structure of Escherichia coli 3-methyladenine DNA glycosylase II, which removes numerous alkylated bases from DNA, was solved at 2.3 A resolution. The enzyme consists of three domains: one alpha + beta fold domain with a similarity to one-half of the eukaryotic TATA box-binding protein, and two all alpha-helical domains similar to those of Escherichia coli endonuclease III with combined N-glycosylase/abasic lyase activity. Mutagenesis and model-building studies suggest that the active site is located in a cleft between the two helical domains and that the enzyme flips the target base out of the DNA duplex into the active-site cleft. The structure of the active site implies broad substrate specificity and simple N-glycosylase activity.

Amino Acid Sequence↗