Search PubMed⌕ Search

Biomedical subjects

A Azuma

Publications and source records attributed to A Azuma.

At least 91 records · Page 5Linked to original sources
PubMed1997

Tumor necrosis factor-alpha production-inhibiting activity of phthalimide analogues on human leukemia THP-1 cells and a structure-activity relationship study.

N-Substituted phthalimides (2-substituted 1H-isoindole-1,3-diones) were prepared and their inhibitory effects on tumor necrosis factor-alpha (TNF-alpha) production by human leukemia cell line THP-1 stimulated with 12-O-tetradecanoylphorbol 13-acetate (TPA) or okadaic acid (OA) were examined. A structure-activity relationship study of these phthalimide analogues revealed that their inhibitory effects on TPA- and OA-induced TNF-alpha production by THP-1 cells are well correlated to each other, i.e. they may involve the same target molecule(s). An analysis by the use of phthalimide analogue-immobilized affinity gels indicated the existence of several phthalimide-binding proteins in THP-1 cell extract.

Drug Screening Assays, Antitumor↗
PubMed1997

Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45.

Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.

Gene Expression Regulation↗
PubMed1997

The flight performance of a damselfly Ceriagrion melanurum Selys

The local circulation method was applied to the free forward flight of the damselfly Ceriagrion melanurum Selys. The kinematic data used in the calculations were obtained by analyzing video-taped images of damselflies in free flight in a transparent container. The inclination of the stroke plane was smaller and the flapping amplitude was larger than those of dragonflies reported in other studies on odonate flight. However, the phase shift between the fore- and hindwings agreed with none of the previously reported patterns for damselflies: the forewings lead the hindwings by approximately a quarter-period. The calculated forces were within the expected range of error. The muscle-mass-specific power was between 40 and 80 W kg-1. The vorticity distribution of trailing and shed vortices in the wake was also analyzed. Strong trailing vortices were observed at the wing tips, whereas shed vortices were concentrated near the wing root as the stroke switched direction.

Journal Article↗
PubMed1997

Photoaffinity labeling of tumor promoter-binding protein (CN-TPBP) and preparation of affinity sorbent gels.

Cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) was photoaffinity-labeled with a specific ligand, 3beta,5alpha-dihydroxycholestan-6-one (YS-64). Analysis by ODS-HPLC of peptide fragments obtained from the labeled CN-TPBP by trypsinization indicated the existence of a single specifically labeled site. Affinity gels for the purification of CN-TPBP were then prepared. As ligands for the affinity gels, 12-O-tetradecanoylphorbol 13-acetate (TPA), a typical phorbol-type tumor promoter, and benzolactam-V8-310 (BL-V8-310), a structural/biological mimic of teleocidin-class tumor promoters, were adopted. The use of these gels afforded a protein that showed a single band of 58 kDa on SDS-PAGE.

Affinity Labels↗
PubMed1997

[Novel biological response modifiers: phthalimides with TNF-alpha production regulating activity].

Tumor necrosis factor alpha (TNF-alpha), an important cytokine produced mainly by activated macrophages, plays a critical role in certain physiological immune systems. But it causes severe damage to the host when produced in excess. Therefore, TNF-alpha can be regarded to possess both favorable and unfavorable effects. These pleiotropic effects indicated that TNF-alpha production-enhancers in some cases and TNF-alpha production-inhibitors in other cases would be useful as biological response modifiers (BRMs) under various circumstances. A possible lead compound is thalidomide, which had been used as a hypnotic/sedative agents but was withdrawn from the market because of it's teratogenicity. Thalidomide is a specific inhibitor of TNF-alpha production, and this effect has been shown to be useful for the treatment of various immunodiseases. Recently, we found that the regulation of TNF-alpha production by thalidomide and related hthalimides was both inducer-specific and cell-type-specific, i.e., (I) the compounds enhance 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced TNF-alpha production by HL-60 cells, while they inhibit TPA-induced TNF-alpha production by another human leukemia cell line THP-1, and (II) the compounds inhibit TNF-alpha production both by HL-60 and THP-1 cells when the cells are stimulated with okadaic acid. We also found that in a optically active phthalimide analogues of thalidomide the inducer specific bi-directional regulation of TNF-alpha production is separated. This implies that the target molecule(s) of the two systems are different each other.

Depression, Chemical↗
PubMed1997

[A calculation of an index of the coronary flow reserve using exercise and rest myocardial SPECT with 99mTc-tetrofosmin].

We designed a new method to evaluate the rate of change of myocardial 99mTc-tetrofosmin (TF) uptake between exercise and rest images with a 1-day protocol. Fifteen normal cases were studied. A 370 MBq of TF was injected at peak exercise. Initial (TF1) and delayed (TF2) exercise SPECT images were acquired 30 min and 3 hr after the injection. A 740 MBq of TF was reinjected soon after TF2 acquisition, and rest SPECT images (TF3) were obtained 30 min after the reinjection. Myocardial counts of TF1, TF2 and TF3 were defined C1, C2 and C3 respectively. Then, the rate of change of myocardial TF uptake between exercise and rest (delta MTU: delta myocardial TF uptake) was determined by the following formula. delta MTU = [(C1/(C3-C2)] x R-1] x 100 (%) (R: dose ratio). delta MTU was 57.8 +/- 9.9% in normal cases and roughly correlated with maximal heart rates and double product. If the extraction fraction of TF is not changed under the exercise and resting condition, delta MTU may have some relation with the coronary flow/cardiac output ratio at exercise. In conclusion, delta MTU is a useful index to evaluate coronary flow reserve non-invasively.

Adult↗
PubMed1997

[Analysis of pulmonary manifestations in patients with rheumatoid arthritis].

We studied chest X rays of 911 patients with rheumatoid arthritis (RA). The findings showed interstitial shadow in 28 patients (3.1%), pleuritis in 13 patients (1.4%) and nodular shadow in 3 patients (0.3%). RA patients with interstitial pneumonia were commonly male and older. And they had significantly high levels of rheumatoid factor (RF), RAPA and IgG-RF in serum, but they were not associated with high score of Lansbary index. All patients with more than 1500 IU/ml in RF value had a complication of interstitial pneumonia. These results suggest the importance of chest X-ray in the management of RA patients with high titer in RF.

Aged↗
PubMed1997

[Usefulness of 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT in a congestive heart failure patient with isolated coronary ostial stenosis].

We reported a 47-year-old female with congestive heart failure (CHF) of unknown origin. In this case, it was suggested that 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT images were useful in the diagnosis of CHF of unknown origin. She had complained of easy fatigability and dyspnea on effort since Sep. 1995. She was admitted to our hospital because of worsening of symptoms in Dec. 1995. Slightly decreased uptake in anterior, lateral and apical walls was recognized in 99mTc-tetrofosmin SPECT images, meanwhile 123I-BMIPP SPECT images showed markedly reduced uptake in the same areas. This discordance in the distribution between 123I-BMIPP and 99mTc-tetrofosmin myocardial SPECT suggested that CHF was not due to dilated cardiomyopathy, but ischemic myocardial disease. Coronary angiography revealed 90% stenosis at the just proximal of left coronary artery. This case was diagnosed an isolated coronary ostial stenosis with CHF, because she was menstruated middle aged woman and did not have a history of aortitis syndrome, syphilis and coronary risk factor before.

Coronary Disease↗
PubMed1996

Cell type-/inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production and its enantio-dependence.

Regulation by thalidomide and phenylphthalimide analogs (FPP-33 and PPS-33) of TNF-alpha production is specific to cell type and to inducer, i.e., (i) the compounds enhance TPA-induced TNF-alpha production by human leukemia HL-60 cells, while they inhibit TPA-induced TNF-alpha production by another human leukemia cell line, THP-1, and (ii) the compounds inhibit TNF-alpha production by both HL-60 and THP-1 cells when the cells are stimulated with okadaic acid (OA). The structure-activity relationships of these compounds are similar in the four assay systems (TPA/HL-60, TPA/THP-1, OA/HL-60, and OA/THP-1). However, optically active analogs, (S)- and (R)-alpha-methylthalidomides, show distinct bidirectional regulatory effects on TNF-alpha production, i.e., only the (S)-form shows TNF-alpha production-enhancing activity in the TPA/HL-60 assay system, while the (R)-form shows much more potent TNF-alpha production-inhibiting activity than the (S)-form in the other assay systems.

HL-60 Cells↗
PubMed1996

Inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production.

Regulation by thalidomide [N(alpha)-phthalimidoglutarimide] of tumor necrosis factor (TNF)-alpha production was found to be inducer-specific. Thalidomide enhances TNF-alpha production by human leukemia HL-60 cells induced with 12-O-tetradecanoylphorbol 13-acetate (TPA), while it inhibits TNF-alpha production induced with okadaic acid (OA) in the same cell line. Some phthalimide analogs, included PP-33 [2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione] and its 4,5,6,7-tetrafluora derivative FPP-33), also showed such an inducer-specific bidirectional TNF-alpha production-regulating activity. The structure-activity relationships of the compounds tested are similar, but not identical, in the TPA-stimulated HL-60 and OA-stimulated HL-60 assay systems.

Carcinogens↗
PubMed1996

Estimation of coronary flow reserve with the instantaneous coronary flow velocity versus pressure relation: a new index of coronary flow reserve independent of perfusion pressure.

Our goal was to develop a new method to evaluate coronary flow reserve independent of perfusion pressure by equipping dogs with a Doppler flow probe in the left anterior descending artery. The slope of the linear portion of the velocity-pressure loop in the late diastolic phase was defined as VP slope; the hyperemic:basal ratio of the VP slope was defined as VP slope ratio, and the hyperemic:basal ratio of the mean coronary blood flow velocity was defined as coronary flow reserve (CFR). We measured VP slope ratio and CFR, altering aortic pressure by aortic banding and inferior vena cava occlusion. VP slope ratio was independent of aortic pressure, but CFR increased with increments in aortic pressure. The VP slope ratio and CFR decreased in the presence of coronary stenoses. In conclusion, VP slope ratio is considered to be a physiologic index of the severity of coronary stenosis, which is independent of perfusion pressure. This measure is easily applicable in clinical practice.

Angioplasty, Balloon, Coronary↗
PubMed1996

Aerodynamic characteristics of the wings and body of a dragonfly

The aerodynamic characteristics of the wings and body of a dragonfly and of artificial wing models were studied by conducting two types of wind-tunnel tests and a number of free-flight tests of gliders made using dragonfly wings. The results were consistent between these different tests. The effects of camber, thickness, sharpness of the leading edge and surface roughness on the aerodynamic characteristics of the wings were characterized in the flow field with Reynolds numbers (Re) as low as 103 to 104.

Journal Article↗
PubMed1996

Augmentation by phthalimides of phorbol ester-induced expression of tumor necrosis factor alpha message.

N(alpha)-Phthalimidoglutarimide (thalidomide), 2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (PP-33) and its 4,5,6,7-tetrafluoro derivative (FPP-33) augmented 12-O-tetradecanoylphorbol 13-acetate-induced production by human leukemia HL-60 cells of both tumor necrosis factor alpha (TNF-alpha) mRNA and secreted TNF-alpha protein. Intracellular TNF-alpha protein production was increased to a lesser extent.

Blotting, Northern↗
PubMed1996

Inducer-specific regulators of tumor necrosis factor alpha production.

Novel potent regulators of tumor necrosis factor alpha (TNF-alpha) production by a human promyelocytic leukemia cell line, HL-60, were prepared. All the compounds showed inducer-specific and bidirectional regulation of TNF-alpha production, i.e., they enhanced 12-O-tetradecanoylphorbol-13-acetate-induced TNF-alpha production, while they inhibited okadaic acid-induced one.

Carcinogens↗
PubMed1996

Restriction fragment length polymorphism analysis in the HLA class III genes of patients with diffuse panbronchiolitis.

Although diffuse panbronchiolitis (DPB) is known to be positively associated with certain major histocompatibility complex (MHC) class I antigens, e.g., HLA-B54 in Japanese patients, it is not clear whether the MHC genes predispose to the disease or are markers for other disease susceptibility gene(s). Because the HLA class III genes such as tumor necrosis factor (TNF) or the fourth component of complement (C4) are localized in the proximity of the HLA-B locus, one or more of these genes might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B54 association in 32 patients with DPB, and subsequently, studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in DPB patients and normal individuals. The HLA-B54 antigen was significantly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p < 0.001), however, we did not detect a significant association between DPB and gene polymorphisms of either TNF-alpha/beta or C4A/B. Furthermore, there was no evidence of C4A gene deletion in patients with DPB. These results suggest that the HLA-B54 antigen itself might be directly involved in the pathogenesis of DPB.

Bronchiolitis↗