Biomedical subjects

Jun Yamada

Publications and source records attributed to Jun Yamada.

At least 37 records · Page 2Linked to original sources

PubMed2005

Characterization and distribution of bone marrow-derived cells in mouse cornea.

PURPOSE: Bone marrow (BM)-derived stem cells are thought to possess extensive differentiation capacity. The present study was conducted to investigate the characteristics and distribution of these cells in the normal mouse cornea. METHODS: BM cells and BM-derived hematopoietic stem/progenitor cells (HSCs) from enhanced GFP (eGFP) transgenic mice (lin(-), Sca-1(+)) were intravenously transplanted into irradiated wild-type C57BL/6 mice. At 4 to 6 months after transplantation, the mice were killed, and their whole corneas examined by histologic and immunohistochemical methods (CD11c, CD11b, and CD45). RESULTS: At 2 weeks after BM cell transplantation, GFP(+) cells gradually migrated into the cornea from the limbal area. At 2 to 6 months, they were distributed over the entire cornea. In cross sections of whole cornea, GFP(+) cells comprised 27.3% +/- 11.1% (BM) and 24.0% +/- 8.01% (HSC) of total cells in the peripheral corneal stroma. In the center of the corneal stroma, GFP(+) cells were 7.58% +/- 2.63% (BM) and 8.06% +/- 1.76% (HSC) of total cells. Immunohistochemistry showed that GFP(+) CD11c(+), CD11b(+), CD11c(-), and CD11b(-) cells occupied the entire corneal stroma. CONCLUSIONS: The present study provides direct evidence of the distribution of BM-derived cells in the mouse cornea. Immunohistochemical study showed that some of these cells are BM-derived antigen-presenting cells such as dendritic cells and macrophages. Some elements of BM-derived cells may continue to exist in the corneal stroma.

Animals↗

PubMed2005

Inhibitory effects of the 5-HT(1A) receptor agonist buspirone on stress-induced hyperglycemia in mice: involvement of insulin and a buspirone metabolite, 1-(2-pyrimidinyl)piperazine (1-PP).

Effects of serotonergic anxiolytic buspirone on immobilization-induced hyperglycemia were studied in mice. Stress elicited hyperglycemia in mice. Pretreatment with buspirone significantly reduced immobilization-induced hyperglycemia. Buspirone increased serum insulin levels in both non- and stressed mice. The major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP) also increased and this further inhibited immobilization-induced hyperglycemia, since 1-PP increased serum insulin levels in both non-stressed and stressed mice, similar to the increases induced by buspirone. These results suggest that buspirone can reduce stress-induced hyperglycemia by facilitating insulin release. Moreover, 1-PP, a metabolite of buspirone may participate in the effects of buspirone. Since 1-PP is an antagonist of alpha(2) receptors, alpha(2) receptors may be related to effects of 1-PP.

Animals↗

PubMed2005

Comparison of spectrographic records of two syllables pronounced from scripts in hiragana and romaji by students with different familiarity with English.

The same syllables /mu/ and /ra/ written in Japanese hiragana and romaji given on a standard speeded naming task elicited phonetically or acoustically different responses in a syllabic hiragana condition and a romaji condition. The participants were two groups of Japanese college students (ns = 15 and 16) with different familiarity with English as a second language. The results suggested that the phonetic reality of syllables represented in these scripts can differ, depending on the interaction between the kind of script and speakers' orthographic familiarity.

Adolescent↗

PubMed2005

[The effect of cimetidine mainly increases CD4+ cells of peripheral blood T lymphocytes].

Cimetidine, one of the most popular histamine-2 receptor antagonists, has been reported to improve survival in gastrointestinal cancer patients and to activate cell-mediated immune response in surgical patients. NKT cells are a population of T cells that share characteristics with natural killer cells, and their main functions are production of immunoregulatory cytokines and cytolytic activities. In this study, we aimed to investigate the effect of cimetidine on the cell-mediated immunoresponse. Six healthy adult volunteers were given 800 mg of cimetidine per day orally, and their blood samples were taken prior to and at days 1, 3, 5, and 7 days post-administration of cimetidine. Leukocyte counts and differentials were obtained by the conventional hemogram, and the leukocyte subsets were analyzed by flow cytometry. Cimetidine administration caused leukocytosis, dependent on the increase of neutrophils, as well as of the CD3-positive T lymphocytes, and the subset of CD4-positive cells among them. On the other hand, the NK cell subpopulation was decreased, and the NKT cell subpopulation was not affected. The present results suggest that cimetidine is a modulator of the cellular immunity, and may be used as the activator of the tumor specific immunoresponse.

Administration, Oral↗

PubMed2004

Involvement of dopamine receptors in the anti-immobility effects of dopamine re-uptake inhibitors in the forced swimming test.

The effects of dopamine re-uptake inhibitors, bupropion and nomifensine on immobility in the forced swimming test were studied in mice. Bupropion and nomifensine reduced immobility time dose-dependently. Both drugs significantly displayed anti-immobility effects at doses without altering locomotor activity. Anti-immobility effects of bupropion and nomifensine were inhibited by the dopamine D1 receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-HCl (SCH 23390) and the dopamine D2 receptor antagonist sulpiride. These findings suggest that dopamine may be related to depression and dopamine D1 and dopamine D2 receptors play a role in the effects of dopamine re-uptake inhibitors.

Animals↗

PubMed2004

Reactions of a platinum(III) dimeric complex with alkynes in water: novel approach to alpha-aminoketone, alpha-iminoketone, and alpha,beta-diimine via ketonyl-Pt(III) dinuclear complexes.

Reaction of the platinum(III) dimeric complex [Pt(2)(NH(3))(4)((CH(3))(3)CCONH)(2)(NO(3))(2)](NO(3))(2) (1), prepared in situ by the oxidation of the platinum blue complex [Pt(4)(NH(3))(8)((CH(3))(3)CCONH)(4)](NO(3))(5) (2) with Na(2)S(2)O(8), with terminal alkynes CH[triple bond]CR (R = (CH(2))(n)CH(3) (n = 2-5), (CH(2))(n)CH(2)OH (n = 0-2), CH(2)OCH(3), and Ph), in water gave a series of ketonyl-Pt(III) dinuclear complexes [Pt(2)(NH(3))(4)((CH(3))(3)CCONH)(2)(CH(2)COR)](NO(3))(3) (3, R = (CH(2))(2)CH(3); 4, R = (CH(2))(3)CH(3); 5, R = (CH(2))(4)CH(3); 6, R = (CH(2))(5)CH(3); 7, R = CH(2)OH; 8, R = CH(2)CH(2)OH; 9, R = (CH(2))(2)CH(2)OH; 10, R = CH(2)OCH(3); 11, R = Ph). Internal alkyne 2-butyne reacted with 1 to form the complex [Pt(2)(NH(3))(4)((CH(3))(3)CCONH)(2)(CH(CH(3))COCH(3))](NO(3))(3) (12). These reactions show that Pt(III) reacts with alkynes to give various ketonyl complexes. Coordination of the triple bond to the Pt(III) atom at the axial position, followed by nucleophilic attack of water and hydrogen shift from the enol to keto form, would be the mechanism. The structures of complexes 3.H(2)O, 7.0.5C(3)H(4)O, 9, 10, and 12 have been confirmed by X-ray diffraction analysis. A competitive reaction between equimolar 1-pentyne and 1-pentene toward 1 produced complex 3 and [Pt(2)(NH(3))(4)((CH(3))(3)CCONH)(2)(CH(2)CH(OH)CH(2)CH(2)CH(3))](NO(3))(3) (14) at a molar ratio of 9:1, suggesting that alkyne is more reactive than alkene. The ketonyl-Pt(III) dinuclear complexes are susceptible to nucleophiles, such as amines, and the reactions with secondary and tertiary amines give the corresponding alpha-amino-substituted ketones and the reduced Pt(II) complex quantitatively. In the reactions with primary amines, the once formed alpha-amino-substituted ketones were further converted to the iminoketones and diimines. The nucleophilic attack at the ketonyl group of the Pt(III) complexes provides a convenient means for the preparation of alpha-aminoketones, alpha-iminoketones, and diimines from the corresponding alkynes and amines.

Journal Article↗

PubMed2004

Implications of articulatory awareness in learning literacy in English as a second language.

The articulatory awareness task, which was found by Griffiths and Frith (2002) to discriminate ex-dyslexic from non-dyslexic adults, was given to three groups of Japanese college students with different English reading abilities. Two unexpected results emerged: (1) Articulatory awareness performance was generally poor across the groups, thereby suggesting that poor articulatory awareness is not unique to dyslexia but rather to reading difficulty in general, and (2) There was a weak but significant positive correlation between articulatory awareness and English reading ability. Implications are that while articulatory awareness may not function only in dyslexia, it is embedded in a complex information-processing network involving reading acquisition. Specifically, a revised Articulatory Awareness Deficit Hypothesis is formulated, which states that poor articulatory awareness is part of articulation difficulty associated with poor phonological awareness that in turn tends to underlie dyslexia and reading difficulty.

Awareness↗

PubMed2004

An L1-script-transfer-effect fallacy: a rejoinder to Wang et al. (2003).

Do different L1 (first language) writing systems differentially affect word identification in English as a second language (ESL)? Wang, Koda, and Perfetti [Cognition 87 (2003) 129] answered yes by examining Chinese students with a logographic L1 background and Korean students with an alphabetic L1 background for their phonological and orthographic processing skills on English word identification. Such a conclusion is premature, however. We propose that the L1 phonological system (rather than the L1 writing system) of the learner largely accounts for cognitive processes in learning to read a second language (L2).

Humans↗

PubMed2004

APC0576 decreases production of pro-inflammatory chemokine and extracellular matrix by human Tenon's capsule fibroblasts.

PURPOSE: To control intraocular pressure in patients treated by trabeculectomy, progressive inflammation, fibroblast proliferation, and the enhanced expression of extracellular matrix (ECM), causes of scar formation at the bleb, must be prevented. Using human Tenon's capsule fibroblasts (TCFs), we examined the effect of APC0576, a suppressor of NF-kappaB-dependent gene activation of human vascular endothelial cells that does not adversely affect cell viability, on the production of pro-inflammatory chemokine and ECM. Its effect on TCF proliferation was also assessed. METHODS: Enzyme-linked immunosorbent assay was used to detect the pro-inflammatory cytokines IL-8 and MCP-1 in the supernatant of TCFs stimulated with IL-1alpha in the presence or absence of APCO576 and ECM proteins, COOH-terminal peptide of type I procollagen (PIP), fibronectin (FN), and laminin (LN) in supernatants and lysates of TCFs stimulated with IL-1alpha or TGF-beta. The proliferative response of IL-1alpha-stimulated TCFs was examined using the SF formazan solution reaction. RESULTS: APC0576 significantly suppressed the production by TCFs of IL-8 (p<0.0001), MCP-1(p<0.0001), PIP (supernatants: p<0.0001, cell lysates: p<0.0001), LN (supernatants: p<0.0001, lysates: p<0.0001), and FN (supernatants: p<0.0001, lysates: p<0.0001) as well as their proliferation (p<0.0001). CONCLUSIONS: APC0576 suppressed pro-inflammatory chemokine and ECM production in TCFs as well as their proliferation. It may represent a novel candidate for the postoperative management of patients treated by trabeculectomy.

Aged↗

PubMed2004

Capsular tension ring use in a patient with congenital coloboma of the lens.

Cataract surgery was performed in a 63-year-old man with bilateral coloboma of the lens. There was no traumatic history, but the patient had lower zonule deficiency and zonular weakness in both eyes, leading us to suspect congenital coloboma of the lens. In the first eye having cataract surgery, it was impossible to rotate the cataractous lens and place the intraocular lens (IOL) centrally in the capsular bag because the lens capsule was not round. The second eye had similar problems, and capsular tension ring implantation improved cataract lens rotation and phacodonesis, enabling central IOL implantation in the capsular bag. The visual acuity recovered to 20/20 in both eyes. Capsular tension ring implantation can facilitate cataract surgery in coloboma of the lens, even in long-term and continuous lens capsule deformity.

Capsulorhexis↗

PubMed2004

Concept and clinical application of cultivated epithelial transplantation for ocular surface disorders.

Corneal epithelial replacement using a tissue engineering technique holds much promise for ocular surface reconstruction in cases of corneal epithelial stem cell deficiency. However, even though an autologous cultivated corneal epithelial stem cell sheet is the safest and most reliable form of sheet, bilaterally affected ocular surface disorders cannot be treated by this method. To treat bilateral cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. In the case of the former, immunological reaction is a threat. Thus, understanding of the immunological background of ocular surface reconstruction using allogeneic tissues is essential. In the case of the latter, the transplanted sheet is not exactly the same as corneal epithelium, and understanding ocular surface epithelial biology is important. In this review, we summarize and explain the concept and clinical application of cultivated mucosal epithelial transplantation for ocular surface disorders.

Journal Article↗

PubMed2004

Promotion of corneal allograft survival by the induction of oxidative macrophages.

PURPOSE: A Th1-type immune response was detected in allotransplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. METHODS: N,N'-diacetyl-L-cystine dimethylester (NACOMe)(2) was injected intraperitoneally into BALB/c (H-2(d)) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2(b)), B10.D2 (H-2(d)), and DBA/2 (H-2(d)) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-gamma, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. RESULTS: In (NACOMe)(2)-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)(2) treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe)(2)-treated mice did not (P < 0.01). Lymphocytes from (NACOMe)(2)-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NACOMe)(2)-treated mice prolonged corneal allograft survival (P < 0.003). CONCLUSIONS: The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.

Adoptive Transfer↗

PubMed2004

Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice.

The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [(3)H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant K(i) value for [(3)H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg(-1)), paroxetine (1 mg kg(-1)) and sertraline (10 mg kg(-1)) brought about significant increases in the K(m) value for [(3)H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [(3)H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [(3)H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort.

Administration, Oral↗

PubMed2003

Hyperleptinemia elicited by the 5-HT precursor, 5-hydroxytryptophan in mice: involvement of insulin.

Mechanisms for hyperleptinemia elicited by a serotonin (5-hydroxytryptamine, 5-HT) precursor, 5-hydroxytryptophan (5-HTP), were investigated. 5-HTP elicited apparent increases in serum leptin levels of mice. Administration of 5-HTP did not alter expression of leptin mRNA in white adipose tissues. Furthermore, neither 5-HTP nor 5-HT increased leptin secretion from isolated fat pads of mice. Since insulin is known to enhance leptin release, involvement of insulin in 5-HTP-induced hyperleptinemia was examined. 5-HTP significantly elevated serum insulin levels. In mice treated with streptozotocin, which depletes insulin, 5-HTP did not increase serum leptin levels. These results suggest that hyperinsulinemia participates the elevation of serum leptin levels elicited by 5-HTP.

5-Hydroxytryptophan↗

PubMed2003

Role of serotonergic mechanisms in leptin-induced suppression of milk intake in mice.

Effects of leptin on milk consumption in food-deprived mice were investigated. In this feeding model, systemic administration of leptin reduced milk intake of mice dose-dependently. Decreases in milk intake elicited by leptin were significantly reduced by the serotonin (5-HT) synthesis inhibitor p-chlorophenylalanine (PCPA). The suppressive effects of leptin on milk intake were antagonized by the 5-HT(2B/2C) receptor antagonist SB206553, while the 5-HT(1B) receptor antagonist GR55562 and the 5-HT(2A) receptor antagonist ketanserin did not affect it. Our results indicated that the 5-HT depleter PCPA and the 5-HT(2B/2C) receptor antagonist SB206553 attenuated leptin-induced suppression of milk intake. Therefore, leptin-induced hypophagic effects may be mediated by enhancement of serotonergic neurons, resulting in activation of the 5-HT(2B/2C) receptor.

Animals↗

PubMed2003

Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor.

A 47-year-old woman was admitted because of hypermenorrhea. Transvaginal ultrasonography revealed an ovarian tumor and myoma uteri, and total hysterectomy with bilateral salpingo-oophorectomy was performed. Histology revealed signet-ring cell carcinoma in the right ovary. In order to find out the primary site of this tumor, gastroendoscopy was performed after the operation, and showed a IIc lesion in the lower body of the stomach; biopsy specimens showed signet-ring cell carcinoma similar to that in the right ovary. Total gastrectomy revealed that the lesion was an early gastric cancer confined to the mucosa, but there was lymphatic invasion slightly beneath the muscularis mucosa, with regional lymph node metastasis. In the light of a review of the seven cases of early gastric cancer with Krukenberg tumor previously reported, lymphatic metastasis seemed to be the most likely pathway of ovarian metastasis in early gastric cancers.

Female↗

PubMed2003

Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury.

Proinflammatory cytokines, including interleukin-1 (IL-1) have been implicated in the inflammation that follows corneal alkali injury. The purpose of this series of experiments was to test whether topically applied interleukin-1 receptor antagonist (IL-1ra) could suppress corneal inflammation and promote transparency after alkali injury. Alkali injury was induced on day 0 by application of 1N NaOH to both eyes of Wistar rats (n = 28). Immediately thereafter, eyes received either topical IL-1ra (20 mg ml(-1)) in 0.2% sodium hyaluronate or vehicle alone three times daily during days 0-14. Biomicroscopic features including corneal opacity and neovascularization were assessed using a standard grading scheme. Inflammation was quantified histologically. Corneas excised at day 3 and 7 (randomly selected six eyes in each group per time point studied) were homogenized, and levels of IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, and RANTES were quantified by enzyme-linked immunosorbent assay. Epithelial wound healing was examined by computed analysis of fluorescein stained corneal photographs taken daily until day 14. According to these evaluations, eyes treated with IL-1ra maintained corneal transparency with minimal neovascular invasion. Additionally, corneal damage and cell infiltration were reduced on day 7 (infiltration cells were almost 40% decreased). All cytokine/chemokine levels in IL-1ra treated eyes were significantly lower at day 3, and IL-6 and IL-10 remained significantly lower at day 7 compared to vehicle-treated eyes. IL-1ra treatment retarded epithelial wound healing in the early stage (day 1-4); however, subsequently IL-1ra treated eyes had enhanced healing with full epithelial closure at nearly the same time point as vehicle-treated eyes (day 10). We conclude that local antagonism of IL-1 after alkali injury can significantly decrease corneal inflammation and lead to enhanced corneal transparency.

Animals↗

PubMed2003

Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by pyrogallol or hypoxia/reoxygenation.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗