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Biomedical subjects

M Sekiguchi

Publications and source records attributed to M Sekiguchi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Regulatory roles of complexins in neurotransmitter release from mature presynaptic nerve terminals.

Complexins are presynaptic proteins whose functional roles in synaptic transmission are still unclear. In cultured rat hippocampal neurons, complexins are distributed throughout the cell bodies, dendrites and axons, whereas synaptotagmin I and synaptobrevin/VAMP-2, essential proteins for neurotransmitter release, accumulated in the synaptic-releasing sites as early as 1 week in culture. With a maturation of synapses in vitro, complexins also accumulated in the synaptic release sites and co-localized with synaptotagmin I and synaptobrevin/VAMP-2 after 3-4 weeks in culture. Complexins I and II were expressed in more than 90 and 70% of the cultured neurons, respectively; however, they were largely distributed in different populations of synaptic terminals. In the developing rat brain, complexins were distributed in neuronal cell bodies in the early stage of postnatal development, but gradually accumulated in the synapse-enriched regions with development. In mature presynaptic neurons of Aplysia buccal ganglia, injection of anticomplexin II antibody caused a stimulation of neurotransmitter release. Injection of recombinant complexin II and alphaSNAP caused depression and facilitation of neurotransmitter release from nerve terminals, respectively. The effect of complexin was reversed by a subsequent injection of recombinant alphaSNAP, and vice versa. These results suggest that complexins are not essential but have some regulatory roles in neurotransmitter release from presynaptic terminals of mature neurons.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Spontaneous regression of primary mediastinal germ cell tumor.

A case of primary mediastinal germ cell tumor, which demonstrated spontaneous regression, is presented. The serum human chorionic gonadotropin level was elevated on admission and then decreased to the normal range with decrease in the size of the anterior mediastinal mass. Thoracotomy was performed with artificial replacement by grafts between the bilateral brachiocephalic veins and the right atrium. Histological diagnosis of combined teratoma with seminoma was made. After subsequent chemotherapy, the patient has remained alive without recurrence for over 10 years.

Adult↗
PubMed1998

Pharmacokinetic evaluation of amphotericin B in lung tissue: lung lymph distribution after intravenous injection and airspace distribution after aerosolization and inhalation of amphotericin B.

We have studied the pharmacokinetics of amphotericin B (AmB) in lung lymph circulation and bronchial-wash fluid after intravenous infusion and inhalation, respectively. For two experiments with awake sheep, we used lung lymph fistulas and tracheotomy. In experiment 1, AmB concentrations in plasma and lung lymph after intravenous infusion of AmB (1 mg/kg of body weight) over 1.5 h were measured. The mean peak in plasma level was 756.0 +/- 188.8 ng/ml at 3 h after the start of infusion, and the level then decreased gradually to 194.8 +/- 28.9 ng/ml at 24 h. The stable and maximal levels in lung lymph last 5 to 9 h after the start of AmB infusion. The concentrations in lung lymph after 9 h were slightly higher than those in plasma. Thus, the lung lymph-to-plasma ratio of AmB concentrations increased gradually during infusion, and the ratio was more than 1.0 after the end of infusion, suggesting that AmB could be easily moved from plasma to pulmonary interstitium and/or lung lymph circulation. In another experiment, 5 or 30 mg of aerosol AmB was inhaled, and the concentration of AmB in the bronchial-wash fluid was determined by bronchoalveolar lavage. The peak AmB concentration in the fluid was observed at 0.5 h. After that, AmB was slowly eliminated over 24 h. The area under the concentration-time curve for 30 mg of inhaled AmB was higher than that for 5 mg, but maximum concentrations of AmB in serum for 5 and 30 mg were almost similar. These observations identify the pharmacokinetic characteristics of AmB in the lung and may provide a new insight into the strategy for clinical treatment of fungal pneumonia.

Administration, Inhalation↗
PubMed1998

Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona curzoniae (pika) at high altitude.

To investigate the possible mechanisms of adaptation to chronic hypoxia in the pulmonary circulation, we made direct measurements of pulmonary arterial pressure (Ppa) in 10 awake pika rodents that were transported to Xining, People's Republic of China (altitude 2,260 m) after being captured at 4,300 m and in 10 Wistar rats in a decompression chamber (simulated altitudes of 4,300 and 5,000 m) in Xining. Ppa was obtained at 1 h of exposure to each simulated altitude. The histology and immunohistochemistry of the lung tissues were also studied. Ppa in the pikas after the 4,300- and 5,000-m altitude exposures did not significantly increase, whereas in the rats Ppa rose significantly. Mean changes in Ppa from 2,260 to 4,300 and 5,000 m were 1.48 +/- 0.49 and 4.80 +/- 0.67 mmHg in the pikas and 10.38 +/- 3.36 and 19.10 +/- 2.28 mmHg in the rats. The ratio of right ventricular to left ventricular plus septal weight in the pikas and rats was 0.22 and 0.45, respectively. The pikas maintained levels of Hb, hematocrit, and 2,3-diphosphoglycerate lower than those of the rats. The percent wall thickness of the small pulmonary arteries in the pikas and rats was 9.22 and 27.21%, respectively, and it was well correlated with the degree of Ppa in both groups. Mast cells were observed in the lungs of the rats (7.1 +/- 0.33 cells/mm2) but not in the pikas. There was highly positive staining for mast cell tryptase and transforming growth factor-beta around pulmonary vessels in the rats, whereas no demonstrable reaction was observed in the pikas. We conclude that the pika has adapted to high altitude by losing hypoxic pulmonary vasoconstriction and thin-walled pulmonary arterioles.

Animals↗
PubMed1998

Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity.

Neurological transmitters including ACh, substance P (SP), and calcitonin gene-related peptide (CGRP) play an important role in regulating airway tone, and increased bronchial reactivity to cholinergic stimulation is a well-recognized phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and CGRP might stimulate alveolar macrophages (AMs) to release neutrophil, monocyte, and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were isolated by bronchoalveolar lavage and cultured. AMs released chemotactic activities in response to ACh in a dose- and time-dependent manner (P < 0.05). However, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis revealed that these released activities were predominantly chemotactic. Partial characterization and molecular-sieve column chromatography revealed that low-molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors significantly blocked the release of chemotactic activities (P < 0.05). Leukotriene B4- and platelet-activating factor-receptor antagonists blocked the chemotactic activities. Immunoreactive leukotriene B4 significantly increased in supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor did not. The receptor responsible for the release of the chemotactic activities was the muscarinic M3 receptor. These data demonstrate that ACh stimulates AMs to release lipoxygenase-derived chemotactic activities and plays a role in inflammatory cell recruitment into the airway.

Acetylcholine↗
PubMed1998

Predominant implication of IL-5 in acute eosinophilic pneumonia: comparison with chronic eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare disease with unknown etiology. To examine pathophysiology of AEP we measured the cell number of eosinophils and eosinophil active cytokines in the peripheral blood and bronchoalveolar lavage fluid (BALF) of AEP patients and compared the levels with those measured in chronic eosinophilic pneumonia (CEP) patients. METHODS: Cell number of eosinophils in peripheral blood and BALF from patients with AEP (n = 3) and CEP (n = 3) were measured. Eosinophil active cytokines in serum and BALF from the patients were measured using ELISA. RESULTS: Eosinophil cell number in peripheral blood was 274-1,377/mm3 in AEP and 526-2,500/mm3 in CEP. The percentages of BALF eosinophils were high in AEP and CEP. Eosinophilia disappeared after methylprednisolone pulse therapy (1 g for 3 days) in AEP, however the cell number of eosinophils gradually increased after methylprednisolone pulse therapy and then spontaneously decreased to within normal range without any further medication. The concentrations of IL-5 in AEP were very high in serum and in BALF, however the concentrations in CEP were low in serum and BALF. CONCLUSION: AEP is a disease in which eosinophil active cytokine IL-5 is predominantly involved; CEP is not. The factors involving eosinophil infiltration to inflammatory loci differ between AEP and CEP.

Acute Disease↗
PubMed1998

Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression.

BACKGROUND: Brochial asthma is characterized by infiltration of inflammatory cells such as lymphocytes and eosinophils. Theophylline is one of the most widely used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE) inhibition is thought to be an important mechanism of its anti-inflammatory actions. However, the detailed effects of PDE inhibition on eosinophils still remain unclear. METHODS: Eosinophils in peripheral blood obtained from normal subjects and patients with mild off-season allergic rhinitis were purified using CD16 negative selection. The following effects of theophylline (nonselective PDE inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III inhibitor), procaterol (beta2-adrenoceptor agonist) and N6, 2'-O-dibutyryladenosine 3'5'-cyclic monophosphate (dB-cAMP; AMP analogue) on eosinophils were examined: (1) survival in the presence of interleukin-5, (2) degranulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet-activating factor (PAF), (3) CD11b expression under GM-CSF or PAF stimulation and (4) intracellular cAMP level. RESULTS: Eosinophil survival was inhibited by theophilline, KF19514 or procaterol. GM-CSF- or PAF-induced degranulation was inhibited by theophylline, KF19514, procaterol or dB-cAMP. CD11b up-regulation by PAF was inhibited by theophylline, KF19514 or dB-cAMP, while GM-CSF-stimulated CD11b up-regulation was not significantly inhibited by any of the drugs tested. The levels of intracellular cAMP were increased by theophylline, KF19514 and procaterol. CONCLUSIONS: Intracellular cAMP is an important factor in the regulation of eosinophil biological functions. PDE IV inhibitors and beta2-agonists are suggested to be useful for the treatment of bronchial asthma through inhibition of eosinophil effector function.

Bucladesine↗
PubMed1998

Successful stenting of bilateral renal artery stenosis due to fibromuscular dysplasia assessed by use of pressure guidewire technique: a case report.

An 18-year-old woman with renovascular hypertension had stenosis due to fibromuscular dysplasia (FMD) of the bilateral renal arteries, and this did not respond to conventional balloon angioplasty owing to marked elastic recoil. Implantation of Palmaz-Schatz stents resulted in successful dilation of the stenosis and remission of hypertension. Transstenotic pressure gradients were measured by use of a pressure-monitoring guidewire. It is suggested that stenting is a very useful adjunct to balloon angioplasty in the treatment of renal artery stenosis due to FMD.

Adolescent↗
PubMed1998

Analysis of BAL fluid in M. avium-intracellulare infection in individuals without predisposing lung disease.

The purpose of this study was to investigate the characteristics of pulmonary inflammation caused by Mycobacterium avium-intracellulare (MAI) in individuals with neither predisposing lung disease nor immunodeficiency. We reviewed the records of 20 patients with pulmonary MAI infection (including 19 female patients) whose past history and previous chest radiographs revealed no predisposing lung disease. We analysed the bronchoalveolar lavage fluid (BALF) from these 20 patients and from six normal female controls. The BALF was recovered directly from the relevant segment that was identified with chest-computed tomography. The BALF cell profiles showed significantly elevated counts for total cells, lymphocytes and neutrophils, but the macrophage cell count was not elevated. The CD4+ lymphocyte count and CD4+/CD8+ ratio were significantly increased compared with those in the controls. The lymphocytes demonstrated phenotypical evidence of activation, with increased expression of human leukocyte antigen-D-related antigen (HLA-DR). The tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and IL-8 concentrations were significantly increased. The neutrophil elastase concentration was also increased, and it was significantly correlated with the neutrophil cell count in the BALF. These findings suggest that the increased counts of activated CD4+ lymphocytes and neutrophils and the elevated concentrations of proinflammatory cytokines and neutrophil elastase appear to be common characteristics in Mycobacterium avium-intracellulare infection.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Hepatitis C virus infection and heart diseases: a multicenter study in Japan.

As a collaborative research project of the Committees for the Study of Idiopathic Cardiomyopathy, a questionnaire was sent out to 19 medical institutions in Japan in order to examine the possible association between hepatitis C virus (HCV) infection and cardiomyopathies. Hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with hypertrophic cardiomyopathy (mean age, 57.7 years) and in 42 of 663 patients (6.3%) with dilated cardiomyopathy (mean age, 56.5 years); these prevalences were significantly higher than that found in volunteer blood donors in Japan (2.4%, 50-59 years of age, each p<0.0001). The prevalence was significantly higher in patients suffering from hypertrophic cardiomyopathy as opposed to those with dilated cardiomyopathy (p<0.01). The presence of HCV antibody was detected in 650 of 11,967 patients (5.4%) patients seeking care in 5 academic hospitals. Various cardiac abnormalities were found among these patients, arrhythmias being the most frequent. These observations suggest that HCV infection is an important cause of a variety of otherwise unexplained heart diseases.

Cardiomyopathies↗
PubMed1998

Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of radionuclide imaging for differential diagnosis.

A 62-year-old woman with skin sarcoidosis was admitted to our hospital to ascertain whether she had cardiac involvement. Although she displayed no cardiac signs or symptoms, the electrocardiogram showed first-degree atrioventricular block, right bundle branch block with left anterior fascicular block, and giant negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy localized in the basal portion of the interventricular septum (IVS) without systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise thallium-201 myocardial imaging revealed redistribution in the anteroseptal region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy revealed abnormal uptake in the myocardium. These findings disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP scintigraphy were useful and necessary to differentiate this type of cardiac sarcoidosis from HCM.

Cardiomyopathies↗
PubMed1998

Familial sick sinus syndrome with atrioventricular conduction disturbance.

A family with sick sinus syndrome is presented: a mother and her 2 daughters affected with sinus node dysfunction. Electrophysiological studies revealed abnormal atrioventricular conduction in the 2 daughters. All 3 individuals were implanted with a permanent pacemaker to relieve their symptoms. Endomyocardial biopsy from the right ventricle of one daughter showed disarrangement, degeneration, myocyte necrosis and interstitial fibrosis suggestive of myocardial disease.

Adult↗
PubMed1998

Elevated serum CA19-9 level and regional lymphadenopathy in a young man with allergic bronchopulmonary aspergillosis.

A 21-year-old man with bronchial asthma who suffered from productive cough; his chest X-rays and computed tomographic (CT) scans revealed central atelectasis and pulmonary infiltrates with paratracheal and hilar lymphadenopathy. The serum CA19-9 level was elevated. He was suspected to have malignant neoplasms on admission, but he was diagnosed with allergic bronchopulmonary aspergillosis (ABPA) by Rosenberg's criteria. After steroid therapy, his symptoms and radiographic findings improved and the serum CA19-9 level decreased. ABPA should be considered in the differential diagnosis of asthmatic patients with or without lymphadenopathy and an elevated serum CA19-9 level.

Adult↗
PubMed1998

Massive pericardial effusion in an adult case of congenital hypothyroidism due to a sublingual thyroid.

Acquired hypothyroidism is known to cause cardiac tamponade. However, pericardial effusion in cretinism in adulthood has rarely been reported. A 27-year-old dwarfish woman suffering from congestive heart failure was diagnosed with congenital hypothyroidism due to the presence of a sublingual thyroid. The patient had never received thyroid therapy until the time of diagnosis at age 27. Despite the existence of massive pericardial effusion, the patient had hypertension. Her metabolic abnormality responded dramatically to L-thyroxin. Pericardial effusion disappeared one year after the initiation of medical treatment.

Adult↗
PubMed1998

[Mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery for severe emphysema].

To investigate the mechanism of short-term improvement in exercise tolerance after lung volume reduction surgery (LVRS) for severe emphysema, we performed six-minute walk tests and pulmonary-function tests, and studied their correlation before and 3-to-5 months after LVRS in 7 patients with severe emphysema who underwent bilateral lung reduction via median sternotomy. Results of the tests showed a 59% increase in the 1-second forced expiratory volume (FEV1), a 25% reduction in the functional residual capacity (FRC), a 49% increase in the maximum voluntary ventilation (MVV), and a 20% increase in the distance walked in 6 minutes (6 MD). The degree of improvement in 6 MD correlated significantly with the degree of improvement in FEV1 (r = 0.97, p < 0.01), in FRC (r = 0.86, p < 0.05), and in MVV (r = 0.87, p < 0.05), and did not correlate with the degree of improvement in pulmonary gas exchange. These results support the hypothesis that an increase in lung elastic recoil after targeted emphysematous resection reduces airflow limitation, and thus leads to a short-term improvement in exercise tolerance after LVRS.

Aged↗
PubMed1998

[A case of paragonimiasis westermani].

A 45-year-old man, who had eaten fried fresh water crabs (Geothelphusa dehaani), was admitted to our hospital because of productive cough and bloodysputum. Blood chemistry showed increased levels of white blood cells and C-reactive protein, but peripheral blood eosinophil counts and serum IgE values were not elevated. Chest roentgenogram and chest computed tomographic scan revealed infiltration of the right middle and left upper lung fields. He was diagnosed as having pneumonia, but his symptoms and radiological examination findings did not improve with antibiotics. The diagnosis of paragonimiasis was confirmed by immunoserological examination and detection of ova in sputum, stool and bronchoalveolar lavage fluid samples. Transbronchial lung biopsy showed infiltration and degranulation of eosinophils. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After uneventful completion of treatment all clinical symptoms and radiological abnormalities disappeared. This is the first case in which ova of paragonimiasis westermani were identified in Nagano prefecture.

Adult↗