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Biomedical subjects

S Abe

Publications and source records attributed to S Abe.

At least 181 records · Page 10Linked to original sources
PubMed2000

Neurokinin-1 receptor antagonist inhibits short-term sulfuric-acid-induced airway hyperresponsiveness in sensitized guinea pigs.

BACKGROUND: Tachykinins are involved in the development of bronchial inflammation and airway hyperresponsiveness (AHR); however, the role of the neurokinin-1 (NK(1)) receptor in acid-aerosol-induced bronchial impairment in asthmatic patients remains controversial. METHODS: To investigate the effects on the NK(1) receptor antagonist FK888 the neurokinin-2 (NK(2)) receptor antagonist SR48968 on sulfuric-acid (H(2)SO(4))-induced AHR in guinea pigs, specific airways resistance (sRaw) and airways responsiveness to methacholine (MCh) were measured before and after 6 h of exposure to H(2)SO(4) aerosol (pH 1.7, 82 mg/m(3)) in ovalbumin-sensitized guinea pigs. RESULTS: Airway responsiveness to MCh significantly increased (p<0. 05) after the exposure, however sRaw did not. Treatment with FK888 significantly inhibited (p<0.05) H(2)SO(4)-induced AHR in a dose-dependent manner, as did SR48968. CONCLUSIONS: These results suggest that not only NK(2) but also NK(1) receptors might have important roles in the development of acid-aerosol-induced AHR.

Aerosols↗
PubMed2000

Technetium-99m sestamibi/tetrofosmin myocardial perfusion scanning in cardiac and noncardiac sarcoidosis.

Left ventricular (LV) and right ventricular (RV) involvement in sarcoidosis must be firmly confirmed to determine patients' prognosis. We examined whether myocardial perfusion images using technetium-99m single photon emission computed tomography (SPECT) have a diagnostic benefit in the evaluation of biventricular involvement. Sixteen patients with sarcoidosis, aged 21-78 (54 +/- 12) years old, 5 males and 11 females, complicated with cardiac disease (cardiac sarcoidosis, n = 6) including tachyarrhythmias of ventricular origin (n = 5), atrioventricular block (n = 4), and congestive heart failure (NYHA > or = II, n = 1), were enrolled in this study. Myocardial SPECT using technetium-99m sestamibi or tetrofosmin was performed and semiquantitatively scored for comparison with 25 control subjects. Perfusion abnormalities were more frequently recognized in sarcoidosis (LV 5/16, 31% and RV 14/16, 88% vs. LV 0/25, 0% and RV 8/25, 32% in controls). LV involvement had a close correlation with atrioventricular block and with congestive heart failure, and multiple sites of RV involvement correlated with ventricular tachyarrhythmia of RV origin. Total number of defect segments were highest in cardiac sarcoidosis (18/30, 60% vs. 19/60, 32% in noncardiac sarcoidosis, and 11/150, 7% in controls, p = 0.0001), and semiquantitatively evaluated total LV and RV scores (ranging from 0 to 18) were higher than those of controls (15.1 +/- 1.8 vs. 11.4 +/- 3.0 in noncardiac sarcoidosis, and 9.0 +/- 5.0 in cardiac sarcoidosis) and exhibited a significant positive linear correlation with the RV ejection fraction (y = 19.8 + 1.83x, r = 0.786, p = 0.001). Biventricular SPECT using technetium-99m is clinically useful for the noninvasive evaluation of both ventricular involvements in sarcoidosis.

Adult↗
PubMed2000

The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease.

Although circulating tumor necrosis factor (TNF)-alpha levels have been found to be increased in weight-losing patients with chronic obstructive pulmonary disease (COPD), the main causes for this phenomenon remain to be elucidated. Since hypoxia itself can enhance the production of the TNF-alpha in vitro, we studied the relationship between hypoxemia and activities of the TNF-alpha system, including circulating TNF-alpha and soluble TNF-receptors (sTNF-R; sTNF-R55 and -R75) levels, in 27 COPD patients and 15 age-matched healthy controls. The COPD patients showed a significant weight loss (body mass index = 18.1 +/- 2.8 versus 22.8 +/- 2.2 [mean +/- SD] kg/m(2); p < 0.0001. % fat = 16.3 +/- 5.9 versus 24.3 +/- 4.9 %; p < 0.001), and hypoxemia (Pa(O2 )= 62.2 +/- 9.5 versus 88.6 +/- 5.9 mm Hg; p < 0.0001) as compared with the healthy controls. Serum TNF-alpha (6.15 +/- 1.08 versus 5.41 +/- 1.60 pg/ml; p < 0.05) and plasma sTNF-R55 (1.15 +/- 0.49 versus 0.67 +/- 0.13 ng/ml; p < 0.0001) and sTNF-R75 (3.54 +/- 1.16 versus 2.25 +/- 0.43; p < 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. There were inverse correlations between Pa(O(2)) and circulating TNF-alpha and sTNF-R levels in patients with COPD (TNF-alpha; r = -0.426, p = 0.0297; sTNF-R55: r = -0.587, p = 0.0027; sTNF-R75: r = -0.573, p = 0.0035). In addition, we found inverse correlations between sTNF-R levels and % fat in COPD patients (sTNF-R55: r = -0.442, p = 0.0272; sTNF-R75: r = -0. 484, p = 0.0155). TNF-alpha levels correlated well with sTNF-R levels (sTNF-R55: r = 0.488, p = 0.0127; sTNF-R75: r = 0.609, p = 0. 0019). These relationships were not observed in the healthy controls. These data suggest that systemic hypoxemia noted in patients with COPD is associated with activation of the TNF-alpha system in vivo, which may be a factor contributing to the weight loss in patients with the disease.

Aged↗
PubMed2000

Increased levels of circulating interleukin-18 in patients with advanced tuberculosis.

Interleukin-18 (IL-18) has recently been identified as an interferon- gamma-inducing factor and it plays an important role in the Th1 response. We measured serum levels of IL-18 and interferon-gamma (IFN-gamma) in 43 patients with pulmonary tuberculosis and 25 healthy control subjects. Significantly increased levels of circulating IL-18 and IFN-gamma were found in pulmonary tuberculosis as compared with those in healthy control subjects. Circulating IL-18 and IFN-gamma correlated with the extent of disease in pulmonary tuberculosis. We found significantly increased levels of circulating IL-18 and IFN-gamma in the patients with high-grade fever. Circulating IL-18 significantly correlated with circulating IFN-gamma. IL-18 may play an important role in immune response to human infection with Mycobacterium tuberculosis.

Adolescent↗
PubMed2000

Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis.

To find a less-invasive and lung-specific clinical biomarker, we measured serum levels of surfactant proteins A and D (SP-A and SP-D) by sandwich enzyme-linked immunosorbent assays in 42 patients with progressive systemic sclerosis (PSS) to evaluate their significance in relation to the presence of interstitial lung disease (ILD) and to assess their diagnostic merits. The patients were divided into two groups based on findings by chest computed tomography (CT): 30 patients with ILD (CT-positive ILD group), and 12 patients without any lung abnormalities (CT-negative ILD group). The CT-positive ILD group was further divided into two groups: 24 patients with ILD detectable by chest plain radiography (X-ray-positive ILD group) and six patients with ILD showing no abnormality (X-ray-negative ILD group). The levels of SP-A and SP-D in sera were significantly higher in the CT-positive ILD group than in the CT-negative ILD group. They were also significantly higher in the X-ray-positive ILD group than in the CT-negative ILD group. In the X-ray-negative ILD group, their levels were higher than those of the CT-negative ILD group. We next estimated sensitivity and specificity of SP-A, SP-D, and X-ray for detecting ILD on CT. Sensitivity of SP-D was high (77%) as well as that of X-ray (80%), whereas SP-A showed a low sensitivity (33%). Remarkably, five of six patients in the X-ray-negative ILD group showed SP-D concentrations over its cut-off level, thereby demonstrating that an SP-D assay contributes to the detection of ILD overlooked by X-ray. Moreover, a combination of X-ray and SP-D dramatically increases sensitivity to 97%. Specificity of SP-A, SP-D, and X-ray to the CT-negative ILD group was 100%, 83%, and 100%, respectively. In conclusion, this study indicates that elevated levels of serum SP-A and SP-D reflect well the presence of ILD and that the combination of SP-D and X-ray contributes to reduce the risk of clinicians overlooking ILD complicated by PSS, although a repetition in another set of subjects is needed to confirm these indications.

Adult↗
PubMed2000

Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening, interstitial lung disease of unknown etiology. For optimal therapeutic management of IPF an accurate tool is required for discrimination between reversible and irreversible types of the disease. However, such noninvasive tools are few, and even with high-resolution computed tomography (HRCT), which is the most trusted method for doing so, the nature of the disease activity in IPF cannot always be accurately predicted. The aims of the present study were to assess the values of surfactant protein (SP)-A and SP-D in semiquantifying the extent of disease in IPF and in predicting deterioration in restrictive pulmonary function and survival over a follow-up period of 3-yr. SP-A and SP-D in sera were measured with enzyme-linked immunosorbent assays as previously described. Fifty-two IPF patients were studied to evaluate the association between serum SP-A and SP-D and disease extent on HRCT, deterioration in pulmonary function, and survival during 3 yr of follow-up. Both SP-A and SP-D concentrations were significantly correlated with the extent of alveolitis (a reversible change), whereas they did not correlate with the progression of fibrosis (an irreversible change). The SP-D concentration, unlike that of SP-A, was also related to the extent of parenchymal collapse and the rate of deterioration per year in pulmonary function. The concentrations of SP-A and SP-D in patients who died within 3 yr were significantly higher than in patients who were still alive after 3 yr. We propose that assays of SP-A and SP-D in sera from IPF patients are useful tools for understanding some pathologic characteristics of the disease, that SP-D may be a good predictive indicator of the rate of decline in pulmonary function, and that a combination of the assays for SP-A and SP-D may be helpful in predicting the outcome of patients with IPF.

Aged↗
PubMed2000

Increased levels of interleukin-18 in patients with pulmonary sarcoidosis.

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.

Adult↗
PubMed2000

Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells.

Macrolide antibiotics are known to be effective for the treatment of chronic inflammatory airway diseases including diffuse panbronchiolitis, chronic bronchitis, and bronchial asthma. Other than having antimicrobial activities, macrolides have antiinflammatory effects, such as the inhibition of cytokine production. In the present study we investigated the effects of clarithromycin (CAM) on interleukin (IL)-8 gene expression and protein levels, using the human bronchial epithelial cell line BET-1A. Northern blot analyses showed that CAM inhibited tumor necrosis factor (TNF)-alpha-induced IL-8 gene expression in a dose- and incubation time-dependent manner. The half-life of IL-8 messenger RNA transcripts in TNF-alpha-treated BET-1A cells did not change with CAM. Transfection studies with BET-1A cells, using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene, demonstrated potent promoter activity in a 174-bp segment (-130 to +44 bp relative to the transcription start site). This segment includes activator protein (AP)-1 and nuclear factor (NF)-kappaB-like sites, and exhibited its strongest response to TNF-alpha. TNF-alpha-induced promoter activity in this segment showed a significant repression by CAM. However, a 156-bp segment (-112 to +44 bp) that does not include an AP-1 site but includes an NF-kappaB-like site did not show a significant repression of TNF-alpha-induced promoter activity by CAM. Mutation of the AP-1 binding site abrogated the suppression by CAM of TNF-alpha-induced enhancement of luciferase activity. In accord with promoter analyses, an electrophoretic mobility shift assay showed that CAM repressed AP-1 binding in TNF-alpha-treated BET-1A cells; however, TNF-alpha induced both AP-1 and NF-kappaB binding activities in BET-1A cells. These data suggest that macrolides such as CAM repress IL-8 gene transcription mainly via the AP-1 binding site in human bronchial epithelial cells. Our findings provide a novel mechanism for the antiinflammatory function of macrolides, implicating a target for the development of new drugs for treating chronic airway inflammation.

5' Untranslated Regions↗
PubMed2000

Diesel exhaust (DE)-induced cytokine expression in human bronchial epithelial cells: a study with a new cell exposure system to freshly generated DE in vitro.

We devised a new in vitro cell exposure system to freshly generated diesel exhaust (DE), different from conventional in vitro culture systems, to examine the effects of DE on human epithelial cells. Using this system, we investigated the effects of DE on cytokine gene expressions in BET-1A human bronchial epithelial cells. DE significantly decreased [(3)H]thymidine incorporation into BET-1A cells. DE had a significant stimulatory effect on interleukin (IL)-8 release to a marked degree. IL-8 and transforming growth factor (TGF)-beta1 messenger RNA (mRNA) expression were induced by DE in a time-dependent manner. The gas obtained by filtration of DE alone did not show a sustained increase in IL-8 protein levels and showed no induction of IL-8 mRNA, suggesting that DE particles (DEPs) play an important role in the induction of IL-8 at both mRNA and protein levels. Antioxidants, pyrrolidine dithiocarbamate, and N-acetyl-L-cysteine significantly inhibited IL-8 mRNA and protein levels by BET-1A cells. These results indicate that freshly generated DEPs may be important in the induction of cytokines such as IL-8 and TGF-beta1 relevant to allergic airway inflammation.

Acetylcysteine↗
PubMed2000

Three novel PHEX gene mutations in Japanese patients with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder characterized by renal phosphate wasting, abnormal vitamin D metabolism, and defects of bone mineralization. The phosphate-regulating gene on the X-chromosome (PHEX) that is defective in XLH has been cloned, and its location identified at Xp22.1. It has been recognized to be homologous to certain endopeptidases. So far, a variety of PHEX mutations have been identified mainly in European and North American patients with XLH. To analyze the molecular basis of four unrelated Japanese families with XLH, we determined the nucleotide sequence of the PHEX gene of affected members. We detected a new nonsense mutation (R198X) in exon 5, a new 3 nucleotides insertion mutation in exon 12 and a new missense mutation (L160R) in exon 5 as well as a previously reported nonsense mutation in exon 8 (R291X). These results suggest that: 1) PHEX gene mutations are responsible for XLH in Japanese patients, and 2) PHEX gene mutations are heterogeneous in the Japanese population similarly to other ethnic populations.

Adult↗
PubMed2000

Involvement of transglutaminase in the receptor-mediated endocytosis of mouse peritoneal macrophages.

We investigated the effect of extracellular Ca2+ on the uptake of immunoglobulin G (IgG)-coated normal sheep red blood cells (SRBC) by the mouse peritoneal macrophages. The uptake of SRBC was dose dependently enhanced by Ca2+ concentration. We also investigated the effect of ryanodine on the uptake of SRBC. Ryanodine showed approximately 15% inhibition of the uptake. The activity of transglutaminase (TGase) in the cytosolic fraction of macrophages was enhanced as the Ca2+ concentration increased. The uptake of SRBC decreased by the addition of histamine, a TGase inhibitor. These results suggest that TGase is involved in the receptor-mediated endocytosis system of mouse peritoneal macrophages.

Animals↗
PubMed2000

[Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice].

The prophylactic effects of a Basidiomycetes preparation, AHCC, against experimental opportunistic infections were investigated in leukopenic mice. In cyclophosphamide-induced leukopenic mice, oral or intraperitoneal administration of the AHCC at doses of 1000 or 50 mg/kg/day, respectively, for 4 consecutive days prior to Candida albicans infection significantly prolonged the survival periods of the infected mice, and decreased the viable counts of C. albicans cells recovered from their kidneys. Similarly, the oral treatment with AHCC protected mice from lethal infection with Pseudomonas aeruginosa and intraperitoneal one also protected mice from infection with methicillin-resistant Staphylococcus aureus (MRSA). These results suggest a potential usefulness of the AHCC as a prophylactic agent for the management of patients with opportunistic infections.

Animals↗
PubMed2000

G1 cyclins are involved in the mechanism of cardiac myocyte hypertrophy induced by angiotensin II.

The importance of the cell cycle in proliferating cells is well known, but little is known about the role of cell cycle regulatory proteins in cardiac myocytes, which are fully differentiated cells. The present study determined, in vitro, the effect of angiotensin II (Ang II) treatment of neonatal rat cardiac myocytes on protein levels of cyclins and retinoblastoma gene product (pRb) phosphorylation. The role of G1 cyclin/cdk in Ang II-induced cardiac myocyte hypertrophy by overexpressing cdk inhibitor p21Cip1/Waf1 or p16INK4a was also examined using recombinant adenoviral vectors encoding these genes. Western blot analysis revealed that Ang II stimulated cyclin D1, D2, D3 and A protein levels in cardiac myocytes. Moreover, Ang II phosphorylated pRb on serine 780, which is known to occur in mitotic cells during cell cycle progression. Cultured cardiac myocytes treated with Ang II and infected with either control or recombinant adenovirus indicated that expression of p21 and p16 inhibited Ang II-induced cardiac myocyte hypertrophy, [3H]leucine incorporation into total cellular proteins, and skeletal alpha-actin (SK-A) and atrial natriuretic peptide (ANP) mRNA accumulation. Control virus had no effects on these parameters. These results suggest that G1 cyclins play an important role in cardiac myocyte hypertrophy stimulated by Ang II.

Angiotensin II↗
PubMed2000

Role and relation of p70 S6 and extracellular signal-regulated kinases in the phenotypic changes of hypertrophy of cardiac myocytes.

Cardiac hypertrophy is characterized by increased cardiomyocyte protein synthesis, increased cell volume, and a shift in cardiac-specific gene expression to fetal isoforms. Using neonatal rat cardiomyocytes stimulated with fetal calf serum (FCS) as a model for cardiac hypertrophy, the present study investigated the role of 2 signal transduction pathways, extracellular signal-regulated kinase (ERK) and p70S6 kinase (p70S6K), in the attendant phenotype changes. FCS evoked both ERK and p70S6K activity, peaking at 20-40min, and simultaneously increased cardiac myocyte protein synthesis (evaluated by [3H]leucine incorporation and total cellular protein content), cell size (evaluated by morphometry and fluorescence-activated cell sorter analysis) and expression of a fetal isoform of the muscle specific gene skeletal alpha-actin (SKA). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. PD98059, which inhibited ERK activity, attenuated cardiac-specific gene expression in a dose-dependent manner, but had no influence on protein synthesis or cell size. These results indicate divergent roles for the ERK and p70S6K pathways in the phenotypic changes associated with cardiac hypertrophy.

Actins↗
PubMed2000

Usefulness of transesophageal echocardiographic monitoring in transluminal endovascular stent-graft repair for thoracic aortic aneurysm.

The endovascular stent-graft has been devised for the treatment of thoracic aortic aneurysm (TAA) to reduce complications associated with conventional surgical repair. The present study assessed the usefulness of transesophageal echocardiography (TEE) for intra- and post-operative examinations in patients treated with transluminal endovascular stent-graft repair for TAA. Nine patients with TAA and 2 with chronic type B aortic dissection were studied. Immediately after stent-graft deployment, perigraft leakage was evaluated with both intraoperative TEE and aortography. In 9 of 11 patients, TEE and aortography immediately after stent-graft deployment revealed the same perigraft leakage results. TEE might therefore be useful for evaluating perigraft leakage and thrombus formation after stent-graft repair for TAA and could be an alternative to aortography, especially for patients with renal dysfunction who have the possibility of contrast agent-induced complications.

Aged↗
PubMed2000

Morphological study of the femur in osteopetrotic (op/op) mice using microcomputed tomography.

Osteopetrosis is an inherited metabolic disorder in which normal bone remodelling is inhibited. Its primary cause is considered to be disruption of the functional balance between osteoblasts and osteoclasts as well as a reduction in the quantity of osteoclasts. The purpose of this study was to observe morphological characteristics of the femur in osteopetrotic (op/op) mice, in which the pathogenic mechanism of osteopetrosis has been shown to operate, using microcomputed tomography (micro-CT), in addition to macro-anatomical observations. Previously, micro-CT has been used mainly for morphometry of a small portion of cancellous bone. However, with recent improvements it has become possible for three-dimensional (3D) observations of bone using slightly larger samples to be made. In this study, the accuracy of reconstructed 3D images of the femur produced by micro-CT was confirmed by comparison with the original femur. In addition, an arbitrary cross-section could be displayed on the screen for detailed examination of its internal structure, and the volume percentage of trabecular bone in a particular region of interest could be measured in three dimensions. The results of this study revealed that the femur was smaller and malformed in the op/op mouse compared with the controls, and the differences were greater at the age of 18 weeks than at 5 weeks. In the control mice, bone marrow occupied a large space in the centre of the body of the femur, whereas this area was occupied by calcified bone tissue in the mutant mice. Moreover, when 3D bone density was measured in the region of interest, the value was greater in the mutants than in the controls at both 5 weeks and 18 weeks of age. This study also showed that micro-CT can be applied to 3D morphometric analyses.

Animals↗