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Biomedical subjects

Y Ikeda

Publications and source records attributed to Y Ikeda.

At least 109 records · Page 6Linked to original sources
PubMed2002

The phytochemical lindleyin, isolated from Rhei rhizoma, mediates hormonal effects through estrogen receptors.

Some plant compounds or herb mixtures are popular alternatives to conventional therapies and contain organic compounds that bind to some nuclear receptors, such as the estrogen receptor (ER), to exert various biological effects. We studied the effect of various herbal extracts on ERalpha and ERbeta isoforms. One herbal extract, Rhei rhizoma (rhubarb), acts as an agonist to both ERalpha and ERbeta. The phytochemical lindleyin, a major component of rhubarb, might contribute to this estrogenic activity through ERalpha and ERbeta. 4-Hydroxytamoxifen, an ER antagonist, completely reversed the estrogenic activity of lindleyin. Lindleyin binds to ERalpha in vitro, as demonstrated using a fluorescent polarization assay. The in vivo effect of rhubarb extract was studied using a vitellogenin assay system in the freshwater fish, Japanese medaka (Oryzias latipes). There were marked increases in serum vitellogenin levels in male medaka exposed to rhubarb extract. We conclude that lindleyin, a component of some herbal medicines, is a novel phytoestrogen and might trigger many of the biological responses evoked by the physiological estrogens.

Cells, Cultured↗
PubMed2002

[Comparison of mediansternotomy approach vs left thoracotomy approach for distal aortic arch aneurysm, and their postoperative complications].

We performed surgery for distal arch aneurysm in 22 patients; through a mediansternotomy in 11 patients (group M), and through a left thoracotomy approach in 11 patients (group L). If the distal position of an aneurysm was located at the pulmonary hilus without severe calcification of the ascending aorta, the mediansternotomy approach was chosen, whereas if we suspected that distal anastomosis would be difficult due to severe calcification of the descending aorta or aortic dissection type B, the left thoracotomy approach was selected. The mean cardiopulmonary bypass time (min.) was 229 +/- 56 in group M and 225 +/- 47 in group L, the mean circulation arrest time (min.) was 39 +/- 19 in group M and 31 +/- 5 in group L, and the mean lowest temperature (degree C) was 22 +/- 1 in group M and 20 +/- 2 in group L. No severe cerebral or cardiac complications developed in any patients. The hospital mortality was 9% (1/11) in group M and 9% (1/11) in group L. Following discharge, 8 (73%) patients from group M and 9 (92%) from group L resumed a normal lifestyle. There were no significant differences between the 2 groups and the operative results of both approaches proved satisfactory. Therefore our indications for each surgical approach to treat distal arch aneurysm seemed appropriate.

Aged↗
PubMed2001

A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia.

KChIP2, a gene encoding three auxiliary subunits of Kv4.2 and Kv4.3, is preferentially expressed in the adult heart, and its expression is downregulated in cardiac hypertrophy. Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2(-/-) mice are highly susceptible to the induction of cardiac arrhythmias. Single-cell analysis revealed a substrate for arrhythmogenesis, including a complete absence of transient outward potassium current, I(to), and a marked increase in action potential duration. These studies demonstrate that a defect in KChIP2 is sufficient to confer a marked genetic susceptibility to arrhythmias, establishing a novel genetic pathway for ventricular tachycardia via a loss of the transmural gradient of I(to).

Action Potentials↗
PubMed2001

Operational tolerance induced by pretreatment with donor dendritic cells under blockade of CD40 pathway.

BACKGROUND: Dendritic cells can mount immune response as competent antigen presenting cells. Recently, it has been reported that immature dendritic cells induce prolongation of allograft survival. However, the ability of mature dendritic cells to induce operational tolerance is unclear. Therefore, in this study, we examined the ability of splenic mature dendritic cells to induce operational tolerance to fully allogeneic antigens using mouse heterotopic heart transplantation model. METHODS: CBA (H2k) mice received i.v. injections with donor splenic dendritic cells or B cells in the absence or presence of monoclonal antibody (mAb) specific for CD40 ligand or CD80/CD86 2 weeks before transplantation of a C57BL/10 (H2b) heart. RESULTS: When donor dendritic cells were injected i.v. 2 weeks before transplantation, rejection response was accelerated compared with that of naive mice [median survival time (MST) = 7 and 8 days, respectively]. However, when CD40 pathway was blocked by anti-CD40 ligand mAb, i.v. injection of donor dendritic cells but not B cells induced indefinite graft survival (MST >100 and 20 days, respectively). Mice treated with anti-CD40 ligand mAb alone rejected their grafts with a MST of 18 days. Intravenous injection of donor dendritic cells and B cells in combination with anti-CD80/CD86 mAbs was less effective to induce graft prolongation (MST = 9.5 and 13 days, respectively). CONCLUSIONS: Therefore, under blockade of CD40 pathway, mature dendritic cells were tolerogens in vivo independent of CD80/86 pathways.

Adoptive Transfer↗
PubMed2001

Endoscopic total parathyroidectomy by the anterior chest approach for renal hyperparathyroidism.

BACKGROUND: During the past 3 years, minimally invasive procedures have been adopted for the surgical treatment of primary hyperparathyroidism, and we have tried to perform endoscopic total parathyroidectomy for renal hyperparathyroidism. METHODS: Five 5-mm trocars were inserted through the skin of the anterior chest under a general anesthesia. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed. RESULTS: Endoscopic procedure was successfully performed in five patients. The mean duration of total parathyroidectomies was 236 min. No evidence of injury to the recurrent laryngeal nerve was observed in any cases. At follow-up, the serum calcium and parathyroid hormone levels had returned to within the normal range in all patients. Postoperative cosmetic status was excellent. CONCLUSION: We believe that endoscopic total parathyroidectomy by the anterior chest approach will find a role in the treatment of renal hyperparathyroidism.

Female↗
PubMed2001

Endoscopic thyroidectomy and parathyroidectomy by the axillary approach. A preliminary report.

BACKGROUND: The use of endoscopic procedures leads to a reduction in the size of the surgical scar, making it more inconspicuous. In this paper, we evaluated the merits and limits of endoscopic neck surgery. METHODS: Between August 1999 and July 2000, 102 patients underwent neck surgery in our department for thyroid or parathyroid disease. Twenty-eight of them were treated by the axillary. A 12-mm and two 5-mm trocars were inserted through the skin of the axilla. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed. RESULTS: Endoscopic procedures were performed successfully in 26 cases (19 thyroidectomies and seven parathyroidectomies). There were two conversions to open procedures. The mean operating times for the thyroidectomies and parathyroidectomies were 212 and 171 min, respectively. No evidence of injury to the recurrent laryngeal nerve was observed in any of the cases. The postoperative cosmetic status of the patients was excellent. CONCLUSION: We believe that endoscopic thyroidectomy and parathyroidectomy by the axillary approach will find a role in the treatment of endocrine diseases in the neck.

Adenocarcinoma, Follicular↗
PubMed2001

Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice.

We found that intraperitoneal injection of organic acids, such as propionic and lactic acid, are able to develop writhing responses in mice similarly as that of acetic acid. These acid-induced writhing reactions were significantly attenuated by capsazepine, a VR1 receptor-specific antagonist, but the phenylbenzoquinone-induced one was not, suggesting that the acids but not phenylbenzoquinone activate the VR1 receptor, which is involved in polymodal pain perception. Hoe 140, a bradykinin B2 receptor antagonist, also suppressed the acid-induced writhing response. Furthermore, these writhing responses were significantly suppressed after neonatal treatment with capsaicin, which treatment is known to destroy peripheral sensory afferent C-fibers. Capsazepine and Hoe 140 did not further attenuate the already reduced writhing responses of capsaicin-treated mice, suggesting that the acids stimulate the VR1 and the bradykinin B2 receptor in the pathway comprising sensory afferent C-fibers. On the other hand, indomethacin further significantly suppressed the writhing number of the capsaicin-treated animals, suggesting that the acid-induced pain perception requires prostanoid receptors not only in the pathway via capsaicin-sensitive C-fibers but also in other sensory pathways. These results provide the first evidence for the involvement of the vanilloid receptor in the acid-induced inflammatory pain perception via sensory C-fibers in addition to the known mediators bradykinin, neurokinins, and prostanoids.

Acetic Acid↗
PubMed2001

Branchiogenic motoneurons innervating facial, masticatory, and esophageal muscles show aberrant distribution in the reeler-phenotype mutant rat, Shaking Rat Kawasaki.

Shaking Rat Kawasaki (SRK) is an autosomal recessive mutant rat that is characterized by cerebellar ataxia. Although previous studies indicated many points of similarity between this mutant rat and the reeler mouse, nonlaminated structures such as the facial nucleus have not been studied in this mutant rat. Nissl-stained sections through the brainstem showed that the cytoarchitecture of the facial, motor trigeminal, and ambiguus nuclei was abnormal in SRK, especially in the lateral cell group of the facial nucleus and the compact formation of the ambiguus nucleus. To examine whether orofacial motoneurons are also malpositioned in the SRK rat, horseradish peroxidase (HRP) was injected into the facial, masticatory, and abdominal esophageal muscles of the SRK rats and normal controls to label facial, trigeminal, and ambiguus motoneurons, respectively. HRP-labeled facial, trigeminal, and ambiguus motoneurons of the SRK rat were distributed more widely than those of their normal counterparts, as in the case of the reeler mouse, with the one exception that labeled facial motoneurons innervating the nasolabial muscle were distributed more widely in the ventrolateral-to-dorsomedial direction in comparison with those of the reeler mutant. These data demonstrate that nonlaminated structures in the brainstem of the SRK rat are affected severely, as is the case in the reeler mutant mouse.

Animals↗
PubMed2001

Superficialization of hemodialysis access using a video-assisted procedure.

Brachiocephalic fistula is one of the main options to gain blood access for hemodialysis. Although the fistula is easy to establish, puncture becomes increasingly difficult because the cephalic vein runs deep and fibrous tissue is being continually deposited over the cephalic vein. Although superficialization-i.e., the removal of fibrous tissue along the basilic vein-has been performed with conventional surgery, the long incision along the cephalic vein induces the buildup of hard fibrous tissue so that puncture may remain difficult even after the operation. To avoid this problem, we tried superficialization of hemodialysis access using a video-assisted procedure and obtained a good result.

Arm↗
PubMed2001

Specific inhibiting characteristics of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine 'Chuanxiong,' on platelet thrombus formation under high shear rates.

We have investigated the effects of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus formation under flow conditions. We demonstrate herein that tetramethylpyrazine inhibits shear-induced platelet aggregation under relatively high shear rate of 10,800 s(-1) with modest inhibition of those occurring under relatively low shear rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also demonstrate that platelet activation induced by shearing in the absence of exogenous platelet-activating agents such as ADP as evidenced by P-selectin surface expression and microparticle release detected by quantitative flow cytometry was also inhibited by tetramethylpyrazine. Moreover, we also demonstrate platelet thrombus formation on the collagen and von Willebrand factor (vWF) surface at high shear rates without significant influences on those occurring under relatively low shear rates. Because platelet thrombus formation occurring under high shear rates is known to be mediated by the vWF interaction with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated process of platelet thrombus formation. Our findings, indicating the unique antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the platelet thrombus formation under high shear rates, provide good reasons for developing chemical analogs having biological functions similar to or more potent than those of tetramethylpyrazine as antiplatelet agents having unique biological functions.

Blood Platelets↗
PubMed2001

STAT5 induces macrophage differentiation of M1 leukemia cells through activation of IL-6 production mediated by NF-kappaB p65.

We recently demonstrated that STAT5 can induce a variety of biological functions in mouse IL-3-dependent Ba/F3 cells; STAT5-induced expression of pim-1, p21(WAF/Cip1), and suppressor of cytokine signaling-1/STAT-induced STAT inhibitor-1/Janus kinase binding protein is responsible for induction of proliferation, differentiation, and apoptosis, respectively. In the present study, using a constitutively active STAT5A (STAT5A1*6), we show that STAT5 induces macrophage differentiation of mouse leukemic M1 cells through a distinct mechanism, autocrine production of IL-6. The supernatant of STAT5A1*6-transduced cells contained sufficient concentrations of IL-6 to induce macrophage differentiation of parental M1 cells, and STAT3 was phosphorylated on their tyrosine residues in these cells. Treatment of the cells with anti-IL-6 blocking Abs profoundly inhibited the differentiation. We also found that the STAT5A1*6 transactivated the IL-6 promoter, which was mediated by the enhanced binding of NF-kappaB p65 (RelA) to the promoter region of IL-6. These findings indicate that STAT5A cooperates with Rel/NF-kappaB to induce production of IL-6, thereby inducing macrophage differentiation of M1 cells in an autocrine manner. In summary, we have shown a novel mechanism by which STAT5 induces its pleiotropic functions. Cytokines

Animals↗
PubMed2001

Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure.

BACKGROUND: Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). METHODS AND RESULTS: Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 microg/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (P<0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (P<0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (+10% versus +3%, P<0.05). They showed significantly higher cardiac output (315+/-49 versus 266+/-31 mL. min(-1). kg(-1), P<0.05) and LV dP/dt(max) (5738+/-908 versus 4363+/-973 mm Hg/s, P<0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15+/-3% to 19+/-3%, P<0.05). CONCLUSIONS: Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.

Animals↗
PubMed2001

Autoreactive CD4(+) T-cell clones to beta2-glycoprotein I in patients with antiphospholipid syndrome: preferential recognition of the major phospholipid-binding site.

Autoreactive CD4(+) T cells to beta2-glycoprotein I (beta2GPI) that promote antiphospholipid antibody production were recently identified in patients with antiphospholipid syndrome (APS). To further examine antigen recognition profiles and T-cell helper activity in beta2GPI-reactive T cells, 14 CD4(+) T-cell clones specific to beta2GPI were generated from 3 patients with APS by repeated stimulation of peripheral blood T cells with recombinant beta2GPI. At least 4 distinct T-cell epitopes were identified, but the majority of the beta2GPI-specific T-cell clones responded to a peptide encompassing amino acid residues 276 to 290 of beta2GPI (KVSFFCKNKEKKCSY; single-letter amino acid codes) that contains the major phospholipid-binding site in the context of the DRB4*0103 allele. Ten of 12 beta2GPI-specific T-cell clones were able to stimulate autologous peripheral blood B cells to promote anti-beta2GPI antibody production in the presence of recombinant beta2GPI. T-cell helper activity was exclusively found in T-cell clones capable of producing interleukin 6 (IL-6). In vitro anti-beta2GPI antibody production induced by T-cell clones was inhibited by anti-IL-6 or anti-CD40 ligand monoclonal antibody. In addition, exogenous IL-6 augmented anti-beta2GPI antibody production in cultures of the T-cell clone lacking IL-6 expression. These results indicate that beta2GPI-specific CD4(+) T cells in patients with APS preferentially recognize the antigenic peptide containing the major phospholipid-binding site and have the capacity to stimulate B cells to produce anti-beta2GPI antibodies through IL-6 expression and CD40-CD40 ligand engagement. These findings are potentially useful for clarifying the pathogenesis of APS and for developing therapeutic strategies that suppress pathogenic antiphospholipid antibody production in these patients.

Adult↗
PubMed2001

Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP-sensitive potassium channels during myocardial ischemia.

BACKGROUND: During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K(ATP)) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC. METHODS AND RESULTS: Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K(ATP) channel opener, nicorandil (25 microg. kg(-1). min(-1) IV), decreased dNE at 40 minutes of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine. CONCLUSIONS: Cardiac sympathetic nerve injury during myocardial ischemia was attenuated by PC via the activation of K(ATP) channels, but the trigger of the PC effect is unlikely to be NE release in dog hearts.

Adenosine Triphosphate↗
PubMed2001

Endoscopic thyroidectomy by the axillary approach.

Neck surgery has recently become one of the newest fields for the application of endoscopic surgery because the resultant scar is small and inconspicuous. Still, some patients feel even a small scar on the neck is not cosmetically acceptable. We therefore have developed a new technique of endoscopic thyroidectomy by the axillary approach that leaves no scar on the neck at all. When this method is used, the small scar in the axilla is completely covered by the patient's arm in a natural manner. The cosmetic result is excellent, and sensory loss in the neck is negligible because the area of surgical dissection is small. We believe that endoscopic thyroid surgery by the axillary approach will find a role in the treatment of thyroid disease.

Axilla↗
PubMed2001

Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.

Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.

Acyltransferases↗