Search PubMed⌕ Search

Biomedical subjects

Yoshinori Okada

Publications and source records attributed to Yoshinori Okada.

At least 19 recordsLinked to original sources
PubMed2006

Adenovirus mediated IL-10 gene transfer to the airway of the rat lung for prevention of lung allograft rejection.

BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). We examined the feasibility of transferring the viral interleukin-10 (vIL-10) gene into rat lungs by intra-bronchial instillation and the subsequent effects of delivered vIL-10 on acute lung AR. METHODS: First, the adenoviral beta-galactosidase vector (adv-beta-gal) particles were instilled into the airway of the rat lung and protein synthesis of beta-gal was examined by histochemical staining. Next, the ability of the adenoviral vIL-10 vector (adv-vIL-10) transfection to modify AR was examined in a highly histoincompatible rat lung transplant model (BN-->Lew). Donor left lungs were transfected with 3 x 10(8) pfu/0.3 mL of adv-vIL-10 (vIL-10 group) or adv-beta-gal (control group) 3 days before transplantation. On day 6 post-transplant, lung allografts were harvested and AR was graded histologically (stage 0-4). Several pathological categories of inflammation (perivascular, peribronchial, or peribronchiolar mononuclear infiltrates, edema, vasculitis, intraalveolar hemorrhage, and necrosis) were also examined and scored on a scale of 0-4 as previously described. RESULTS: A successful transgene protein synthesis by adv-beta-gal in alveolar epithelial cells and alveolar macrophages was confirmed by histochemical staining with X-gal. The vIL-10 group showed a trend toward an improved stage of AR (3.75 +/- 0.5 vs. 4.0 +/- 0), and also a decreased pathological scores for edema (3.5 +/- 0.6 vs. 4.0 +/- 0), intraalveolar hemorrhage (2.3 +/- 1.0 vs. 2.5 +/- 0.6) and necrosis (1.5 +/- 0.5 vs. 1.75 +/- 1.3) compared with the control group, however, the differences in any pathological scores between the two groups did not reach a statistical significance. CONCLUSIONS: 1. A successful transgene protein synthesis in alveolar epithelial cells was ensured by intra-bronchial instillation of an adenoviral vector encoding beta-galactosidase gene. 2. Transferring the vIL-10 gene into rat lungs by intra-bronchial instillation did not seem to reduce lung AR significantly, as opposed to the results of our previous experiments in a rat cardiac allograft model. This discrepancy may be explained by several potential factors including the immunogenecity of adenoviral vectors in conjunction with the nature of the lung more susceptible to immune response and inflammation.

Adenoviridae↗
PubMed2006

Synaptic connections between eyelet photoreceptors and pigment dispersing factor-immunoreactive neurons of the blowfly Protophormia terraenovae.

Studies using various mutants of Drosophila melanogaster bearing defects in their visual system, including those of the retinal and extraretinal photoreceptor systems, have indicated that the extraretinal photoreceptor known as the Hofbauer-Buchner (H-B) eyelet plays an active, if subsidiary, role in the entrainment of circadian rhythms. In the present study, in the context of unraveling the function of extraretinal photoreception on circadian rhythms and photoperiodic responses, we searched for extraretinal photoreceptors in the blowfly, Protophormia terraenovae, and found that this fly has a homolog of the H-B eyelet. In addition, we show morphologically direct synaptic connections between the eyelet of P. terraenovae (called here Pt-eyelet, after the species' name) and pigment-dispersing factor (PDF)-immunoreactive neurons, which are putative circadian pacemaker neurons, by immunogold electron microscopy combined with intracellular dye injection. The Pt-eyelet was found to reside in the middle of the posterior surface of the optic lobe between the retina and the lamina, as does the H-B eyelet. This extraretinal photoreceptor was composed of at least four photoreceptor cells equipped with well-organized microvillar rhabdomeres. Rhodopsin 6-like immunoreactivity and also the response to light stimuli clearly showed the Pt-eyelet to be functional. The Pt-eyelet terminals in the accessory medulla exhibited synaptic bouton-like appearances and formed divergent multiple-contact output synapses. Synaptic contacts from the Pt-eyelet terminal to the PDF-immunoreactive neurons were identified by the presence of presynaptic ribbons and accumulated synaptic vesicles. Their possible function is discussed in relation to previous studies on circadian rhythm and photoperiodic response of P. terraenovae.

Animals↗
PubMed2006

Rapidly growing endobronchial hamartoma with bone marrow tissue.

A 29-year-old woman presented with a 4 x 3.5 cm circumscribed mass located in the left upper lobe, which had not been detected in a chest roentgenogram that was taken 3 years prior. Bone scintigraphy using technetium-99m methylene diphosphonate revealed an increased uptake of the isotope in the mass, indicating increased osteoplastic activity. She underwent surgical resection of the mass and the pathologic diagnosis was endobronchially located pulmonary hamartoma, which contained bone marrow tissue. An extremely rare case of pulmonary hamartoma showing rapid growth and involving bone marrow tissue is presented.

Adult↗
PubMed2006

Impact of lung preservation solutions, Euro-Collins vs. low-potassium dextran, on early graft function: a review of five clinical studies.

Currently, intracellular fluid type solutions that are prepared by modification of Euro-Collins solution (EC) have been the most commonly used by clinical lung transplant programs, which have been associated with a high rate of reperfusion injury. On the basis of the wealth of experimental data demonstrating the benefit of extracellular fluid type solutions over EC, one of the extracellular solutions, low-potassium dextran solution (LPD), became commercially available and has recently been applied to clinical settings. To date there have been 5 clinical studies comparing the effect of EC with LPD on early lung graft function. This article reviewed these 5 reports to determine whether the beneficial effects of LPD, as observed in experimental settings, can also be identified in clinical lung preservation. Four studies were retrospective reviews and one was a prospective non-randomized study. Of these 5 studies, 3 studies demonstrated significantly improved recipient oxygenation in the LPD group compared with the EC group in the early post-operative period. In addition, a significantly shorter duration on mechanical ventilation in the LPD group was shown in 2 studies, and improved reperfusion scores or pulmonary compliance was shown in one study each. Four of 5 studies concluded that graft preservation with LPD leads to superior early graft function after lung transplantation. The impact of LPD on prolonged lung preservation and also on long term results of graft function will be a subject of future investigation.

APACHE↗
PubMed2005

Identification of tissue-specific vasculogenic cells originating from murine uterus.

Endometrium is a highly regenerative adult tissue that undergoes repeated degeneration and regeneration following menarche. Therefore, it is believed that endometrium contains stem and/or progenitor cells in order to compensate for the regeneration of tissue components. We report here that stem-like cells having vasculogenic potential are present in the uterus. Enzymatically extracted cells from murine uteri were characterized and fractionated into four subpopulations by flowcytometry; CD34(+)/45(-) (Ut-34), CD34(-)/45(-) (Ut-DN) and the remaining CD45(+) cell fractions (CD34(+)/45(+) and CD34(-)/45(+) cells). The Ut-34 and Ut-DN fractions were mostly negative for putative endothelial cell (EC) markers, such as CD31, Flk-1, c-kit and VE-cadherin, although the Ut-DN fraction contained 2.8% CD31(+) cells. Ut-DN cells were further divided into CD31(+) and CD31(-) fractions. Three cell populations were obtained from green fluorescence protein (GFP) transgenic mice and were transplanted into injured wild-type mouse skeletal muscle. At 4 weeks after cell transplantation, donor-derived vascular smooth muscle and ECs were observed in the injured recipient muscle. A similar trend was observed in the Ut-34 group, but differentiation into vascular smooth muscle was predominant. In contrast, the Ut-DN/31(+) cell-transplanted group showed preferential differentiation into vascular ECs, thus suggesting that they were relatively committed preexisting ECs. These characteristics were also seen in vitro, in clonal cell cultures. Interestingly, donor derived Ut-DN/31(+), Ut-DN/31(-) and Ut-34 cells could not be identified after bone marrow (BM) transplantation, thus confirming that they are not derived from BM. It therefore appeared that tissue-specific vasculogenic cells are present in the murine uterus and that they exhibit vascular formation, even in different tissue microenvironments.

Animals↗
PubMed2005

Functional recovery of damaged skeletal muscle through synchronized vasculogenesis, myogenesis, and neurogenesis by muscle-derived stem cells.

BACKGROUND: Recent studies have shown that skeletal muscle-derived stem cells (MDSCs) can give rise to several cell lineages after transplantation. However, the potential therapeutic uses of MDSCs, the functional significance of the transplanted tissue, and vasculogenesis, myogenesis, and reconstitution of other tissues have yet to be investigated in detail. In addition, the relationship between MDSCs and mesenchymal bone marrow cells is of interest. METHODS AND RESULTS: We developed a severe-damage model of mouse tibialis anterior muscle with a large deficit of nerve fibers, muscle fibers, and blood vessels. We investigated the potential therapeutic use of freshly isolated CD34+/45- (Sk-34) cells. Results showed that, after transplantation, implanted cells give rise to myogenic, vascular (pericytes, vascular smooth muscle cells, and endothelial cells), and neural (Schwann) cells, as well as contributing to the synchronized reconstitution of blood vessels, muscle fibers, and peripheral nerves, with significant recovery of both mass and contractile function after transplantation. Investigation of Sk-34 cell transplantation to the renal capsule (nonmuscle tissue) and fluorescence in situ hybridization analysis for the transplanted muscle detecting the Y chromosome revealed the intrinsic plasticity of the Sk-34 cell population. In addition, there were no donor-derived Sk-34 cells in the muscle of lethally irradiated bone marrow-transplanted animals, indicating that the Sk-34 cells were not derived from bone marrow. CONCLUSIONS: These findings indicate that freshly isolated skeletal muscle-derived Sk-34 cells are potentially useful for reconstitution therapy of the vascular, muscular, and peripheral nervous systems. These results provide new insights into somatic stem and/or progenitor cells with regard to vasculogenesis, myogenesis, and neurogenesis.

Animals↗
PubMed2005

Polarization switching in a columnar liquid crystalline urea as studied by optical second-harmonic generation interferometry.

The polar order and its switching characteristics have been investigated by means of optical second-harmonic generation interferometry in a compound N, N'-bis(3,4,5-trialkoxylphenyl)urea (R=n- C16 H33) being connected by intermolecular hydrogen bondings to form a columnar liquid crystalline phase. The polar structure is formed along the column by applying an electric field and is cooperatively switched by reversing the field. The polar order is relaxed to a nonpolar state within a few milliseconds by terminating the field. No macroscopic polar order exists at least in a range of a visible wavelength scale in the absence of a field.

Journal Article↗
PubMed2005

A dopamine D4 receptor antagonist attenuates ischemia-induced neuronal cell damage via upregulation of neuronal apoptosis inhibitory protein.

Neuronal apoptosis inhibitory protein (NAIP/BIRC1), the inhibitor of apoptosis protein (IAP) family member, suppresses neuronal cell death induced by a variety of insults, including cell death from ischemia and stroke. The goal of the present study was to develop an efficient method for identification of compounds with the ability to upregulate endogenous NAIP and to determine the effects on these compounds on the cellular response to ischemia. A novel NAIP-enzyme-linked immunosorbent assay (ELISA)-based in vitro drug-screening system is established. Use of this system identified an antagonist of dopamine D4 receptor, termed L-745,870, with a potent NAIP upregulatory effect. L-745,870-mediated NAIP upregulation in neuronal and nonneuronal cultured cells resulted in decreased vulnerability to oxidative stress-induced apoptosis. Reducing NAIP expression via RNA interference techniques resulted in prevention of L-745,870-mediated protection from oxidative stress. Further, systemic administration of L-745,870 attenuated ischemia-induced damage of the hippocampal CA1 neurons and upregulated NAIP expression in the rescued hippocampal CA1 neurons in a gerbil model. These data suggest that the NAIP upregulating compound, L-745,870, has therapeutic potential in acute ischemic disorders and that our NAIP-ELISA-based drug screening may facilitate the discovery of novel neuroprotective compounds.

Animals↗
PubMed2005

[Effects of peroxisome proliferator-activated receptor gamma ligands on monocrotaline-induced pulmonary hypertension in rats].

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily, which regulates transcription of target genes in a ligand-dependent manner. Ligands for PPARgamma have been shown to attenuate proliferation of vascular smooth muscle cells, and to induce apoptosis in several cell lines in vitro. Since monocrotaline (MCT)-induced pulmonary hypertension in rats is characterized by proliferation of pulmonary vascular smooth muscle cells, we hypothesized that PPARgamma ligands may reduce MCT-induced pulmonary hypertension. To test this hypothesis, we treated MCT-injected rats with pioglitazone and troglitazone, synthetic ligands for PPARgamma, for three weeks and measured pulmonary artery pressure and pulmonary vessel wall thickness. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunostaining for proliferating cell nuclear antigen (PCNA) were utilized to assess apoptosis and cell proliferation in the pulmonary arterial walls of pioglitazone-treated rats. MCT with pioglitazone or troglitazone treatment significantly reduced pulmonary hypertension and wall thickening of the pulmonary arteries. TUNEL-positive apoptotic cells were not seen in the pulmonary arterial walls of either MCT-injected or control rats with or without pioglitazone. PCNA-positive cells were only seen in the thickened pulmonary arterial walls of MCT rats, but not in the pulmonary arterial walls of controls and of pioglitazone-treated MCT rats. We conclude that PPARgamma ligands reduce MCT-induced pulmonary hypertension and pulmonary vascular wall thickening in rats. Inhibition of MCT-induced cell proliferation in the pulmonary arterial walls may account for this effect

Animals↗
PubMed2004

Anti-allergic agent tranilast decreases development of obliterative airway disease in rat model of heterotopic tracheal transplantation.

BACKGROUND: Tranilast is an anti-allergic agent known to inhibit the release of histamine, interleukin-1beta, transforming growth factor beta1, and platelet-derived growth factor from various cells and currently is used to treat allergic diseases, keloids, and hypertrophic scars. We evaluated the ability of tranilast to inhibit the development of obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation. METHODS: We transplanted tracheal segments from donor rats (Brown Norway) into subcutaneous pouches in major histocompatibility complex-incompatible recipient rats (Lewis). At Days 21 and 28 after transplantation, we histologically assessed the harvested allografts scored the degree of OAD, on a scale from zero to 4 as previously described, caused by fibroproliferative tissue. RESULTS: Recipient animals treated orally with 400 mg/kg/day tranilast throughout the experiment showed significantly decreased OAD compared with control animals, with a histologic score of 1.1 +/- 0.4 vs 3.0 +/- 1.3, respectively (mean +/- SD, p=0.007), at Day 21 after transplantation and 2.0 +/- 1.4 vs 3.9 +/- 0.4, respectively (mean +/- SD, p=0.017), at Day 28 after transplantation. CONCLUSION: These results showed that treatment with tranilast significantly decreased fibroproliferative airway changes associated with allograft rejection in a rat model of tracheal transplantation, suggesting that tranilast may be useful in preventing bronchiolitis obliterans after lung transplantation.

Administration, Oral↗
PubMed2004

[Criteria for postoperative discharge of the patients managed by anesthesiologists in an ambulatory surgery unit].

BACKGROUND: Postoperative care following ambulatory surgery is done at home. Therefore, it is important to establish qualitative clinical discharge criteria that can be used to determine when patients can go home safely for the care by friend or relative. METHODS: This study included 213 patients who had been managed by anesthesiologist in an ambulatory surgery unit. We compared the discharge times achieved by post-anesthesia discharge scoring system with the times that the patients were actually discharged from the ambulatory surgery unit. RESULTS: On an average, patients who could be discharged safely on the same day required 161 minutes postoperatively to achieve a post-anesthesia discharge score of at least 9. The actual postoperative discharge time was 255 minutes. 53.6% of the patients who had been admitted could have obtained a post-anesthesia discharge score of at least 9, but they wanted to stay in hospital. CONCLUSIONS: A discharge scoring system is effective to determine the optimal length of stay in the ambulatory surgery unit and to achieve the prompt and safe discharge of patients. In order to popularize ambulatory surgery and reduce admission rate, it is necessary for us to make an effort to change patients' mind for ambulatory surgery.

Adolescent↗
PubMed2003

Growth and differentiation potential of main- and side-population cells derived from murine skeletal muscle.

Skeletal muscle-derived CD34+/45- (Sk-34) cells were identified as a new candidate for stem cells. However, the relationship between Sk-34 cells and side-population (SP) cells is unknown. Here, we demonstrate that Sk-34 cells prepared from murine skeletal muscles consist wholly of main-population (MP) cells. The Sk-34 cells included only a few SP cells (1:1000, SP:MP). Colony-forming units of Sk-34 cells of both SP and MP possessed the same potential to differentiate into adipocytes, endothelial, and myogenic cells and showed the same colony-forming activity (1.6%). In addition, the colony-forming units of the CD34-/45- (double negative: DN) population were found to begin CD34 expression and to possess the potential to differentiate into myogenic and endothelial cells. We also found that expression of CD34 antigen precedes MyoD expression during the myogenic process of DN cells. Furthermore, both Sk-34 and DN cell populations were mostly negative for CD73 (93-95%), whereas the CD45+ cell population was >25% positive for CD73, and this trend was also seen in bone marrow-derived CD45+ cells. These results indicate that the MP cell population is about 99.9% responsible for the reported in vitro myogenic-endothelial responses of skeletal muscle-derived cells.

5'-Nucleotidase↗
PubMed2003

Reduction of recipient macrophages by gadolinium chloride prevents development of obliterative airway disease in a rat model of heterotopic tracheal transplantation.

BACKGROUND: Recent studies have shown the possible role of growth factors and the involvement of macrophages as a source of them in the pathogenesis of bronchiolitis obliterans (BO) after lung transplantation. OBJECTIVE: The authors intended to determine whether depletion of recipient macrophages by gadolinium chloride (GdCl3) resulted in decreased obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation. METHODS: A tracheal segment of donor rats (Brown Norway) was transplanted into a subcutaneous pouch of fully major histocompatibility complex-incompatible recipient rats (Lewis). Recipients were injected intravenously with 80 mg/kg of GdCl3.6H2O or saline on days 0, 7, and 14 posttransplant. Allografts were harvested on days 7, 14, 17, and 21 and the degree of OAD resulting from fibroproliferative tissue was pathologically scored on a scale of 0 to 4. A portion of allografts was submitted to reverse-transcriptase polymerase chain reaction analysis to examine mRNA expression for platelet-derived growth factor (PDGF), basic fibroblast growth factor, and transforming growth factor-beta1. RESULTS: Immunohistochemical studies confirmed reduction in the number of ED2+ macrophages in tracheal allografts by GdCl3 injection. GdCl3 treatment significantly decreased OAD of allografts, with the histologic score of 1.4+/-0.3 in the treated animals compared with 3.0+/-0.5 in the controls (mean+/-SE, P=0.02) at day 21 posttransplant, and this was accompanied by decreased PDGF-A and PDGF-B gene expression in the GdCl3 group at day 17 posttransplant. CONCLUSIONS: Macrophage reduction by GdCl3 resulted in significantly decreased OAD development and reduced PDGF mRNA expression in allografts. This suggests a potential effectiveness of therapies targeting recipient macrophages in preventing BO after lung transplantation.

Animals↗
PubMed2003

Endobronchial carcinoid tumor combined with pulmonary non-tuberculous mycobacterial infection: report of two cases.

We report here two cases of endobronchial carcinoid tumor complicated with pulmonary infection with non-tuberculous mycobacteria (NTM). Case 1 was an 81-year-old woman with the left lower lobe atelectasis. Bronchoscopy showed complete obstruction of the left basal bronchus by a tumor and a sleeve lower lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left basal bronchus and many caseous granulomas containing mycobacteria in the lung parenchyma distal to the bronchus. Bacterial examinations of sputum and gastric juice after the operation showed a growth of Mycobacterium kansasii. Case 2 was a 50-year-old woman with the atelectasis of the left upper division. Bronchoscopy showed complete obstruction of the left upper division bronchus by a tumor and a left upper lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left upper division bronchus and many caseous granulomas in the lung parenchyma distal to the bronchus. The Ziehl-Neelsen stain showed many mycobacteria in these granulomas and they were identified as Mycobacterium avium by PCR analysis. Although NTM are not well recognized as possible pathogens of pulmonary infection related to bronchial obstruction by endobronchial carcinoma, our experiences rouse a caution to consider NTM as potential pathogens. We also discuss the possible mechanisms responsible for the specific relationship between carcinoid tumor and TNM.

Aged↗
PubMed2003

hnRNP B1 protein may be a possible prognostic factor in squamous cell carcinoma of the lung.

Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is an RNA-binding protein that is required for the maturation of mRNA precursor. It was previously reported that hnRNP A2/B1 was overexpressed at the early clinical stage of lung cancer, and that hnRNP B1 protein, a splicing variant of hnRNP A2 mRNA, was elevated in lung cancer tissues. In this study, we applied the immunohistochemical method, using anti-hnRNP B1 antibody to analyze the usefulness of the hnRNP B1 antibody as a prognostic marker and also as a marker useful for early detection. A total of 206 specimens were examined. Histological examination revealed this protein to be positive in 79 (71.2%) of 111 squamous cell carcinomas and in 45 (64.3%) of 70 adenocarcinomas, respectively. This protein was also expressed in 24 (63.2%) of 38 roentgenographically occult carcinomas and in seven (63.6%) of 11 dysplastic lesions. These findings suggest the possible participation of this protein in early carcinogenesis. Furthermore, the survival curve of the squamous cell carcinoma patients with hnRNP B1 overexpresseion showed a better prognosis compared with that of the patients without hnRNP B1 expression (P=0.014), whereas in adenocarcinoma patients, there was no such a difference between them (P=0.889). These findings indicate that hnRNP B1 could be a useful marker for the early detection of bronchogenic squamous cell carcinoma and that it may be a prognostic factor in this cell type.

Biomarkers, Tumor↗
PubMed2003

Peripheral targets of centrally located putative accessory neurons of MRO in the isopod Ligia exotica.

The three centrally located putative accessory neurons of the muscle receptor organ (MRO) of the isopod Ligia exotica were identified to the third segmental nerve (N3) of the thoracic ganglion by backfilling with Lucifer Yellow. These neurons were then studied intracellularly and extracellularly to determine whether they suppressed the stretch-activated responses of thoracic stretch receptors. Intracellular injection of depolarizing currents into these three putative accessory neurons revealed that only neuron #3 had an inhibitory effect, suggesting that it is an inhibitory accessory neuron related to thoracic stretch receptors. We searched for the peripheral targets of neurons #1 and #2 by intracellular filling with Lucifer Yellow or by recording of junctional potentials in extensor muscles, and show that they are motor neurons that innervate the deep extensor and superficial extensor muscles, respectively.

Animals↗