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S Fujishima

Publications and source records attributed to S Fujishima.

At least 19 recordsLinked to original sources

Flow cytometric detection of cell-associated interleukin-8 in alveolar macrophages in vivo from patients with hypersensitivity pneumonitis and sarcoidosis.

In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs.

Adult↗

CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis.

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases. In the present study, the roles of chemokines in a rat model of radiation pneumonitis/ pulmonary fibrosis were examined. Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients. Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.

Aged↗

Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema.

BACKGROUND: Nicotine is responsible for smoking dependence and is mainly metabolised by CYP2A6. Several types of genetic polymorphism of CYP2A6 have been reported, but their relation to smoking habit and chronic obstructive pulmonary disease (COPD) phenotypes has not been fully clarified. METHODS: 203 current or ex-smokers (lifelong cigarette consumption (CC) >/=10 pack years) with subclinical and established COPD phenotypes were clinically evaluated and pulmonary function tests and a chest CT scan were performed (smoker group). The non-smoker group consisted of 123 healthy volunteers. CYP2A6 genotypes were determined in both groups. RESULTS: The percentage of subjects with a CYP2A6del allele (genotype D) was lower in heavy smokers (20.5%, n=88, CC >/=60 pack years) than in light smokers (37.4%, n=115, CC 10-59 pack years, chi(2)=6.8, p=0.01) or non-smokers (36.1%, n=122, chi(2)=6.0, p=0.01); lower in ex-smokers (20.7%, n=111) than in current smokers (41.3%, n=92, chi(2)=10.1, p<0.01); and lower in smokers with a high LAA (low attenuation area) score on the chest CT scan (18.4%, n=76, LAA >/=8.0) than in those with a low LAA score (37.0%, n=127, LAA <8.0, chi(2)=7.8, p<0.01). CONCLUSIONS: Subjects with the CYP2A6del allele tend not to be heavy habitual smokers but can be light habitual smokers. The CYP2A6del polymorphism may inhibit smokers from giving up smoking, but appears to function as a protective factor against the development of pulmonary emphysema independent of smoking habit.

Aged↗

Experience-dependent plasticity of mouse visual cortex in the absence of the neuronal activity-dependent marker egr1/zif268.

Neuronal activity elicits a rapid increase in the expression of several immediate early genes (IEGs). To clarify a role for IEG response in activity-dependent development, we examined the contribution of the egr1/zif268 gene during visual cortical processing and plasticity in mice. We first analyzed the expression of egr1 mRNA in wild-type (WT) mice using Northern blot hybridization. In the visual cortex, expression of egr1 mRNA increased dramatically after eye opening, systemic injection of kainate, or 30 min of photostimulation after a brief (5 d) period of dark adaptation. Thus, the expression of egr1 is regulated by synaptic activity in the mouse visual cortex, as it is in other species (e.g., monkeys, cats, and rats). To evaluate whether this transcription factor is directly involved in activity-dependent plasticity, mice lacking Egr1 were deprived of the use of one eye during the developmental critical period [postnatal day 24 (P24)-P34]. Extracellular in vivo single-unit recordings from the binocular zone of the visual cortex revealed that visual responses developed normally in egr1 knock-out (KO) mice. Moreover, a similarly significant shift of responsiveness in favor of the open eye was produced in both KO and WT mice by either brief (4 d) or long-term (>2 weeks) occlusion of one eye. There was no apparent compensation among egr2, egr3, or c-fos mRNA and protein expression in the visual cortex of egr1 KO mice. Taken together, these results indicate that egr1 is a useful marker of sensory input in mice but is not intrinsically necessary for the experience-dependent plasticity of the visual cortex. Our findings underscore a mechanistic distinction between sensory plasticity and long-lasting forms of synaptic potentiation in the hippocampus, for which egr1/zif268 was recently found to be essential.

Aging↗

Engineering neoglycoproteins with multiple O-glycans using repetitive pentapeptide glycosylation units.

Controlled protein remodeling with O-linked glycans has been limited by our incomplete understanding of the process of glycosylation. Here we describe a secretable fibroblast growth factor (FGF) with multiple mucin-type O-glycans produced by introducing a minimum pentapeptide glycosylation unit in a decarepeat format at its N- or C-terminus. Expressed in Chinese hamster ovary cells, chemical and biochemical analyses of the resultant proteins (Nm10-FGF and Cm10-FGF, respectively) demonstrated that all O-glycosylation units were glycosylated and the dominant structure was sialylated Gal[beta1-3]GalNAc. This indicates that minimum O-glycosylation unit in multirepeat format serves as a remarkably efficient acceptor in CHO cells. The Nm10-FGF and Cm10-FGF proteins maintained the mitogenic activity to vascular endothelial cells. In addition, intact Cm10-FGF and its desialylated form interacted with several lectins in the same way as mucin-type glycoproteins. The intact Cm10-FGF with multiple sialylated O-glycans exhibited a longer lifetime in circulating blood, whereas the Cm10-FGF with desialylated O-glycans exhibited a shorter lifetime than the deglycosylated form of Cm10-FGF. Our approach would thus appear to be highly effective for engineering neoglycoproteins, the characteristics of which are determined by their multiple mucin-type O-glycans.

Animals↗

Myocardial imaging with 123I-metaiodobenzylguanidine in essential hypertension and renovascular hypertension.

Iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging is considered to reflect cardiac sympathetic function. We performed myocardial MIBG scintigraphy and echocardiography in 27 patients with essential hypertension (EHT), 7 patients with renovascular hypertension (RVHT), and 8 normotensive subjects (NT) to investigate alterations in MIBG myocardial imaging in the presence of hypertension and left ventricular hypertrophy (LVH). EHT were divided into two groups based on LV wall thickness; EHT with LVH group (> or = 13 mm, n = 15) and EHT without LVH group (< 13 mm, n = 12). The delayed uptake of MIBG was decreased, and the washout rate of MIBG was greater in the EHT with LVH group than EHT without LVH group or NT group. The washout rate was correlated with LV mass and LV diastolic function (as assessed by mitral flow). In RVHT group, the MIBG washout rate increased even without LVH, compared with NT and EHT without LVH groups. In summary, the washout rate of MIBG increased in parallel with the development of LVH in EHT and increased independently of the LV mass in RVHT. Cardiac sympathetic function could be altered in hypertensive LVH and in renovascular hypertension.

3-Iodobenzylguanidine↗

Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia.

Chronic eosinophilic pneumonia (CEP) is characterized by chronic or recurrent pulmonary infiltrates with eosinophils, but the precise mechanism of eosinophil accumulation has not been fully elucidated. Eotaxin is one of the CC chemokines that selectively recruits eosinophils and contributes to the pathogenesis of allergic airway diseases including asthma, but its roles in pathogenesis of CEP have not been fully elucidated. The authors measured concentrations of eotaxin and other CC chemokines, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted, macrophage inflammatory protein-1alpha, and the eosinophil activating Th2 cytokine interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid from CEP patients (n=11), and compared these concentrations with those from control subjects (n = 6). The eotaxin (904 +/- 203 versus 29 +/- 7 pg x mL(-1), p = 0.0001), MCP-1 (194 +/- 57 versus 15 +/- 2 pg x mL(-1), p < 0.05), and IL-5 (7.8 +/- 2.0 versus 2.7 +/- 0.6 pg x mL(-1), p < 0.05) levels were significantly higher for cases with CEP in comparison to those serving as controls. Proportions of eosinophil and lymphocyte counts were greater in BAL fluid from CEP patients. Eotaxin and IL-5 levels correlated with the proportion of eosinophils in BAL fluid from CEP patients. MCP-1 correlated with the relative lymphocyte numbers. In short, eotaxin, interleukin-5, and monocyte chemoattractant protein-1 levels were higher in the BAL fluid of CEP patients and these levels may contribute to eosinophil and lymphocyte recruitment and activation in the airways as found with this disorder.

Adult↗

Transcranial doppler sonography and ambulatory blood pressure monitoring in patients with hypertension.

To appraise the value of transcranial Doppler sonography (TCD) for assessment of hypertensive cerebrovascular damage, the relationship between ambulatory blood pressure (BP) and indices of cerebral circulation determined by TCD was investigated. Subjects were 55 inpatients with or without hypertension, including 13 patients with histories of cerebrovascular attacks. Mean flow velocity (MFV) in the middle cerebral artery was measured by TCD, then the cerebrovascular resistance index (CVRI; mean BP/MFV) and the Fourier PI1 (pulsatility index of the first Fourier harmonic of the flow-velocity waveform) were determined as indices of cerebrovascular resistance. CO2 reactivity of MFV was estimated as an index of cerebrovascular flow reserve. CVRI positively correlated with both daytime and nighttime BP as well as with age (p<0.01). Fourier PI1 positively correlated with nighttime BP and age (p<0.01). CO2 reactivity did not correlate with any of the ambulatory BP parameters, but negatively correlated with age (p<0.01). LV mass index significantly correlated with ambulatory BP parameters, CVRI, and Fourier PI1 but did not correlate with CO2 reactivity. Multiple regression analyses showed that nighttime systolic BP was a significant correlate for CVRI and Fourier PI1, but not for CO2 reactivity, and that history of cerebrovascular attack was significant for CVRI and CO2 reactivity. We conclude that cerebrovascular resistance determined by TCD accords with the results of ambulatory BP and LVMI, and thus could be successfully used to detect the early stage of hypertensive cerebrovascular change. Cerebrovascular flow reserve would be relatively preserved in hypertensive patients without cerebrovascular diseases.

Adult↗

Purification and Characterization of N-Acetylglucosamine-6-phosphate Deacetylase from a Psychrotrophic Marine Bacterium, Alteromonas Species.

A psychrotrophic bacterium, strain Mct-9, which produced an N-acetylglucosamine-6-phosphate deacetylase, was isolated from a deep-seawater sample in the Mariana Trough. The Mct-9 strain was identified as Alteromonas sp. The native enzyme had a molecular mass of 164,000 Da, and was predicted to be composed of four identical subunits with molecular masses of 41,000 Da. The purified enzyme hydrolyzed N-acetylglucosamine (GlcNAc), GlcNAc-6-phosphate, and GlcNAc-6-sulfate. Considering the low K(m) and high k(cat)/K(m) for GlcNAc-6-phosphate, it probably acts as a GlcNAc-6-phosphate deacetylase in vivo. The enzyme was functional in the temperature range of 5 degrees to 70 degrees C and displayed optimal activity at 55 degrees C. The optimal temperature was higher than that of the deacetylase from the mesophilic bacterium Vibrio cholerae non-O1. The characteristics of the GlcNAc-6-phosphate deacetylase from Alteromonas sp. are unique among psychrotrophs and psychrophiles, whose intracellular enzymes are mostly thermolabile.

Journal Article↗

Importance of interleukin-8 in the development of reexpansion lung injury in rabbits.

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.

Animals↗

Diagnostic value of a bedside test for cardiac troponin T in the patient with chest pain presenting to the emergency room.

Identification of patients with acute chest pain due to acute coronary syndrome is a common and difficult challenge for emergency physicians. A prospective study was conducted to assess the diagnostic value of a bedside test of cardiac troponin T in the emergency room setting. Forty-nine consecutive patients, who visited the emergency room within 6 hours of the onset of acute chest pain, were enrolled. Of the 26 patients who were ultimately diagnosed as having acute coronary syndrome, seven patients (27%) had positive cardiac troponin T assay results, whereas none of the patients without acute coronary syndrome had positive results (0%). For patients with acute coronary syndrome who presented later than 3 hours after the onset (n = 4), the test was positive in all cases (positive predictive value: 100%, negative predictive value: 100%, p < 0.01). However, the positive rate was only 14% for those who presented earlier than 3 hours after the onset (n = 22) (positive predictive value: 100%, negative predictive value: 47%, p = 0.84). In conclusion, bedside troponin T test results should be evaluated considering the time interval from the onset of chest symptoms.

Adult↗

[An adult case of cervico-mediastinal tuberculous lymphadenitis].

We reported a case of cervico-mediastinal tuberculous lymphadenitis followed by the development of pulmonary lesions and recurrent laryngeal nerve palsy. A 48-year-old man was admitted to our hospital due to fever, dry cough, and loss of body weight. He had no medical history of tuberculosis or other significant diseases. On admission, a right cervical tumor was palpable and chest X-ray films revealed widened superior mediastinum. Chest computed tomography showed multiple swollen mediastinal lymph nodes, including multiple low-density areas and contrast medium-enhanced septa and margins. Gallium-67 scintigraphy demonstrated abnormal uptake in the right cervix and mediastinum. A PPD skin test was strongly positive and ribosomal RNA of tubercle bacilli was detected in aspirated gastric juice. Although anti-tuberculous chemotherapy was initiated, fever and cough persisted, and hoarseness due to left recurrent laryngeal nerve palsy developed. One month later, chest X-ray films showed abnormal infiltration in the left upper lung field. The patient was sero-negative for HIV. To confirm the diagnosis, right supraclavicular lymph node biopsy was performed. Microscopic examination of the biopsy specimen revealed acid-fast bacilli and granuloma with central caseous necrosis surrounded by Langhans' giant cells and epithelioid cells. After 9 months of extended anti-tuberculous chemotherapy, the cervical and mediastinal masses receded and the abnormal chest X-ray shadows disappeared. Because the incidence of tuberculosis in Japan is gradually increasing among young people as well as the elderly, the differential diagnosis of this disease will become more necessary.

Aged↗

Effect of moisture content on anaerobic digestion of dewatered sludge: ammonia inhibition to carbohydrate removal and methane production.

The purpose of this study is to investigate the effect of moisture content on anaerobic digestion of dewatered sewage sludge under mesophilic condition. The moisture contents of sludge fed to reactors were 97.0%, 94.6%, 92.9%, 91.1% and 89.0%. The VS removal efficiency changed from 45.6% to 33.8%, as the moisture content of sludge fed to digester decreased from 97.0% to 89.0%. The carbohydrate removal efficiency also decreased from 71.1% to 27.8%. Methane production decreased when the moisture content of sludge was lower than 91.1%. The number of glucose consuming acidogenic bacteria was decreased from 3.1 x 10(6) to 3.1 x 10(8) (MPN/mL) as the moisture content decreased from 91.1% to 89.0%. The numbers of hydrogenotrophic and acetoclastic methanogenic bacteria decreased by one order of magnitude when the moisture content was lower than 91.1%. The decrease in numbers of glucose consuming acidogenic bacteria and methanogenic bacteria was found to correspond to the decrease in the carbohydrate removal efficiency and the accumulation of propionic acid. Batch experiments showed that acetoclastic methanogenic bacteria were acclimated to high ammonia concentration, on the other hand, glucose consuming acidogenic bacteria were inhibited.

Ammonia↗

Chaos and spectral analyses of heart rate variability during head-up tilting in essential hypertension.

To investigate nonlinear and linear components of heart rate variability (HRV) in essential hypertension (EHT), we analyzed HRV by chaos and spectral analyses in patients with EHT (n = 18) and normotensives (n = 10) during head-up tilting. We used the correlation dimension (CD) and Lyapunov exponents as the parameters of chaos. The CD, an index of complexity, was lower at rest in EHT group than in normotensives, and did not change in EHT group in response to head-up tilting, but decreased in normotensives. Head-up tilting did not change the Lyapunov exponents, an index of sensitive dependence on initial condition, a hallmark of chaos, in both groups. In the spectral analysis, the normalized high-frequency component (%HF) was decreased in EHT group at rest, and head-up tilting increased the low- to high-frequency ratio (L/H) and reduced the %HF in both groups. The CD and Lyapunov exponents at rest were correlated with the %HF and L/H. These results suggest that chaos analysis can assess the different aspect of HRV from spectral analysis and that nonlinear components of HRV may be associated with hypertension through an impaired dynamic regulation of HRV.

Adult↗