Publications by authors named "Aoyama A"

The implementation of decentralization policies in the health sector of many developing countries has been a major issue in international health. The objectives were to focus on health sector reform, health financing system, and human resource development. However, less attention has been paid to the institutional capacity development of health systems.

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OBJECTIVE. This study explored factors related to cognition of social capital among Japanese older people. METHOD.

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A series of 3-(4-alkoxypheny)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound (TIPP-204) exhibited extremely potent PPARdelta transactivation activity, comparable to that of the known PPARdelta-selective agonist GW-501516.

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Background: The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung during ischemia. In this study we investigated the effect on lung ischemia-reperfusion injury of administering synthetic ANP (carperitide) at the onset of reperfusion after warm ischemia.

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Background: Thioredoxin is a ubiquitous protein with anti-oxidative, anti-apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T, Yokomise H et al. Attenuation of ischaemia reperfusion injury by human thioredoxin.

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Background: We have previously reported the successful induction of renal allograft tolerance in non-human primates using a nonmyeloablative conditioning regimen to produce a mixed-chimeric state in the recipient. In the present study, we applied this same technique to lung allotransplantation in cynomolgus monkeys.

Methods: Nine pairs of fully major histocompatibility complex (MHC)-mismatched cynomolgus monkeys were used.

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Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are responsible for the hepatic uptake of organic anions. They share similar sequences and structures with 12 putative transmembrane domains (TMs). Their substrate specificities are very broad and overlap each other, whereas each transporter specifically recognizes certain substrates.

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Background: The control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle.

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Objective: A method to compensate for the donor shortage may be the utilization of donation after cardiac death. The control of lung injury against warm ischemia is crucial in manipulating donors after cardiac death. Nebulization is a simple and feasible drug delivery route after cardiac death.

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Purpose: The *2 and *3 alleles of CYP2C9, with decreased enzymatic activity, are highly polymorphic and contribute to inter-individual differences in pharmacotherapy of CYP2C9 substrates. Here, we sought for a simplified theoretical method to predict the pharmacokinetic changes with minimal in vivo data.

Methods: The changes in clearances of CYP2C9 substrates in subjects with these alleles were quantitatively estimated by parameters from literature data: intrinsic metabolic clearance and the enzyme expression level of mutated CYP2C9, contribution of CYP2C9 to the CYP-mediated clearance (f (m2C9)), and the contribution of the dominant metabolic pathways to the total clearance (f (h)).

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Background: Outcome for highly immunogenic lung transplantation remains unsatisfactory despite the development of potent immunosuppressants. The poor outcome may be the result of a lack of minimally invasive methods to detect early rejection. There is emerging clinical evidence that, paradoxically, expression of forkhead box P3 (FOXP3, a specific marker for the regulatory T cells) is upregulated within rejecting grafts.

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Background: A lower temperature, namely below 0 degrees C, has been thought to be desirable for organ preservation because of the lower rate of metabolism; however, its benefits are still poorly understood. Supercooling is a non-freezing state of liquid below the freezing point, and the new development of a refrigerator for supercooling has now made it possible to preserve organs at sub-zero temperatures in a non-frozen state without cryoprotectants.

Methods: Rat lungs were ventilated and perfused for 60 minutes in the 3 groups (n = 7 each): (1) the fresh group, in which the lungs were reperfused immediately after harvesting; (2) the 4 degrees C group, in which the lungs were stored after harvesting in ET-Kyoto solution at 4 degrees C for 17 hours before reperfusion; and (3) the supercooling group, in which lungs were preserved in ET-Kyoto solution at -2 degrees C for 17 hours.

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Transverse thoracosternotomy is the standard approach for bilateral lung transplantation (BLT), but all measures must be taken to prevent breakdown of the sternal wound. We report a case of sternal dehiscence with subcutaneous and peristernal air collections, which occurred 1 month after BLT, performed through a transverse thoracosternotomy, in a 38-year-old man. Surgical exploration revealed that the sternal wires had cut through the bone, causing air leakage of both lungs.

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The solution structures of complexes between calcium-saturated calmodulin (Ca (2+)/CaM) and a CaM-binding domain of the HIV-1 matrix protein p17 have been determined by small-angle X-ray scattering with use of synchrotron radiation as an intense and stable X-ray source. We used three synthetic peptides of residues 11-28, 26-47, and 11-47 of p17 to demonstrate the diversity of CaM-binding conformation. Ca (2+)/CaM complexed with residues 11-28 of p17 adopts a dumbbell-like structure at a molar ratio of 1:2, suggesting that the two peptides bind each lobe of CaM, respectively.

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A cross-sectional seroprevalence study on leptospirosis, using microscopic agglutination test (MAT), was conducted in rural villages in Khammouane Province, Lao People's Democratic Republic, in December 2006. The overall prevalence of leptospiral infection among 406 subjects was 23.9% (95% confidence interval [CI] 19.

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Liver X receptors (LXR), which were originally reported as oxysterol-activated nuclear receptors, were recently found to recognize glucose as a physiological ligand. On this basis, we have already developed novel LXR antagonists based upon alpha-glucosidase inhibitors derived from thalidomide. Here, to clarify the relationship between alpha-glucosidase inhibition and LXR modulation, we investigate the alpha-glucosidase-inhibitory activity of typical LXR ligands and the LXR-modulating activity of typical alpha-glucosidase inhibitors.

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Following our previous discovery of LXR antagonistic activity of 2'-substituted phenylphthalimides derived from thalidomide-related glucosidase inhibitors, structure-activity studies and further structural development led to 5-chloro-N-2'-n-pentylphenyl-1,3-dithiophthalimide (5CPPSS-50), with IC50 values of about 10 and 13 microM for LXRalpha and LXRbeta, respectively.

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Brain activity was measured by magnetoencephalography to investigate the spatiotemporal stage of visual processing at which predictive and sensory integration begins. We examined the consequences of a visual mismatch between preliminary prediction and incoming stimulus. Following auditory cues (1000- and 1250-Hz tones) for prediction, congruent and incongruent images, pictures of two musical keys, were presented to volunteers.

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It is important for diagnosis of glaucoma to grasp 3-D structure of an optic nerve head (ONH). The quantitative 3-D reconstruction of the ONH is required for the diagnosis. We propose a technique to obtain the depth value from stereo image pair of a retinal fundus for the 3-D reconstruction of the ONH.

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We experienced 3 cases of viral infections after lung transplantation. Case 1: Fifty-two-year-old male with pulmonary emphysema underwent left single lung transplantation from a cadaveric donor. Three months after transplantation he presented Epstein-Barr virus (EBV) viremia, resulting in multiple lymphadenopathy.

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Purpose: To investigate the long-term clinical course of acute primary angle closure (APAC) and acute primary angle-closure glaucoma (APACG) in Japanese patients.

Methods: We retrospectively reviewed our records of 66 consecutive APAC or APACG eyes observed between February 1992 and December 2003 (mean follow-up, 42.1 months).

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Among postoperative pleural space problems after pulmonary resections, it is more difficult and troublesome to manage this space after left upper lobectomy in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective study focusing on the elevation of ipsilateral hemidiaphragm of the 36 patients with or without COPD after left upper lobectomies, by measuring diaphragmatic dome length (DDL) with a plain posteroanterior roentgenogram. They were divided into two groups: group I (forced expiratory volume in 1 s (FEV1) % predicted < 70%, n = 5); and group II (FEV1) % predicted > or = 70%, n = 31).

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A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPARdelta transactivation activity, comparable with or somewhat superior to that of the known PPARdelta-selective agonist, GW-501516.

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Alpha-glucosidase inhibitors with a chlorinated phthalimide or a thiophthalimide skeleton, derived from thalidomide, were found to possess liver X receptor (LXR) antagonistic activity. Novel LXR antagonists with a 2'-substituted phenylphthalimide skeleton were obtained by structural development of glucosidase inhibitors derived from thalidomide.

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