A primary aortoesophageal fistula due to esophageal carcinoma successfully treated with endoluminal aortic stent grafting.
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Aorta, Thoracic↗
Biomedical subjects
Yoshifumi Ikeda
Publications and source records attributed to Yoshifumi Ikeda.
Minimally invasive thyroidectomy.
PURPOSE OF REVIEW: Based on recent advances in ultrasonography, color-Doppler sonography and ultrasound-guided fine needle aspiration biopsy, minimally invasive thyroidectomy has been widely employed for treating thyroid tumors. Minimally invasive procedures have recently been adopted for the surgical treatment of thyroid disease as a means of preventing prominent scars, hypesthesia and paresthesia. RECENT FINDINGS: We have developed axillary and anterior chest approaches for endoscopic thyroidectomy. The mean operating time for the endoscopic procedure was significantly longer than that for conventional open surgery. All patients who were treated using the axillary approach were satisfied with the cosmetic results. The incidence of complaints after endoscopic surgery is significantly lower than that after open surgery. The minimally invasive mini-incision approach has been performed under direct and endoscopic vision to minimize surgical invasiveness and improve cosmetic results. Our procedure differs from conventional thyroidectomy in requiring a 3-cm skin incision, and in not raising of a skin flap and not dissecting the sternohyoid muscle. SUMMARY: Endoscopic thyroidectomy is the procedure of choice in well selected patients with thyroid disease. The present indications for this procedure include benign follicular adenomas less than 4 cm in diameter, low-risk papillary carcinomas less than 10 mm, oxyphilic cell tumors less than 4 cm and Graves' disease as imaged on preoperative ultrasonography. The minimally invasive mini-incision approach is indicated for patients with low-risk, well differentiated carcinomas. Total thyroidectomy and bilateral modified neck dissection is possible, if the tumor is not large.
Biopsy, Needle↗
Beneficial effects of intravenous administration of lipo-prostaglandin E1 on the ischemic gastric tube in pigs.
INTRODUCTION: Lipo-prostaglandin E1 (PGE1) is a new preparation of PGE1 in which it is bound to lipids to slow PGE1 release and delay its rate of metabolism. We investigated the change of the blood flow on impaired microcirculation of the ischemic gastric tube in pigs after saline, unmodified PGE1, and lipo-PGE1 administration. MATERIALS AND METHODS: The gastric tube was constructed using 15 domestic pigs under general anesthesia, and saline, unmodified PGE1, and lipo-PGE1 were infused continuously at a rate of 0.05 microg/kg/min for 10 min. Tissue blood flow (TBF) and the serum PGE1 concentration were analyzed before administration, after administration for 10 min, and 10 min after the end of administration. RESULTS: There were no obvious changes in TBF during the administration of saline. However, TBF during treatment with unmodified PGE1 and lipo-PGE1 was significantly increased to 13.0 +/- 1.3 and 13.9 +/- 1.3 ml/min/100 g, respectively (paired t-test; P < 0.01). Although TBF was significantly decreased to 8.0 +/- 1.0 ml/min/100 g on 10 min after the end of unmodified PGE1 administration (paired t-test; P < 0.01), it was maintained over 10 ml/min/100 g in lipo-PGE1 group. The serum PGE1 concentration during treatment with unmodified PGE1 and lipo-PGE1 was significantly increased to 229 +/- 21 and 225 +/- 9 pg/ml (paired t-test; P < 0.01), however, it was significantly decreased to 59 +/- 5 and 131 +/- 17 pg/ml (paired t-test; P < 0.01), respectively, on 10 min after the end of administration. However, the serum PGE1 concentration in lipo-PGE1 group was significantly higher than that in unmodified PGE1 group (unpaired t-test; P < 0.01). CONCLUSION: Lipo-PGE1 infusion leads to the objectively measurable improvement and the prolonged action in the blood perfusion of the gastric tube in pigs. Therefore, treatment with lipo-PGE1 infusion can increase TBF at the anastomotic site, and it may be beneficial for preventing anastomotic leakage in boluses for a couple of times a day.
Alprostadil↗
Effects of immunosuppressants on induction of regulatory cells after intratracheal delivery of alloantigen.
BACKGROUND: We previously reported that intratracheal delivery (ITD) of alloantigen generated regulatory cells in mice. Here, we examined the effect of various doses of conventional immunosuppressants (FK506, cyclosporine A, azathioprine, mycophenolate mofetil, and rapamycin) on inducing regulatory cells in our model. METHODS: CBA mice (primary recipients) were given C57BL/6 splenocytes by ITD and either no additional treatment or various doses of an immunosuppressant. Seven days later, splenocytes from these mice were adoptively transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac grafting the same day. RESULTS: Adoptive transfer from primary recipients given ITD of splenocytes alone induced prolonged allograft survival in secondary recipients (median survival time [MST], 50 days), suggesting that regulatory cells were generated. When ITD of alloantigen was combined with daily administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was similarly prolonged (MST 55 and 50 days, respectively). When combined with 20 or 40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients demonstrated indefinite survival (MST, >100 days in all groups). When ITD of alloantigen was combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine A; or 1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST 7-13 days). CONCLUSION: Generation of regulatory cells by ITD of alloantigen was facilitated by mycophenolate mofetil and high doses of rapamycin but abrogated by cyclosporine A, azathioprine, and high doses of FK506. Low doses of rapamycin and of FK506 did not interfere with generation of regulatory cells.
Adoptive Transfer↗
Cervical excision using superior sternum lifting method for large mediastinal parathyroid gland.
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Adult↗
Interleukin-10 but not transforming growth factor-beta is essential for generation and suppressor function of regulatory cells induced by intratracheal delivery of alloantigen.
BACKGROUND: We previously reported that intratracheal delivery of alloantigen-induced regulatory cells in mouse heart-transplantation model. Here, we investigated roles of interleukin (IL)-10 and transforming growth factor (TGF)-beta in induction and effector phases of the regulatory cells. METHODS: CBA mice were pretreated with intratracheal delivery of C57BL/10 splenocytes and administration of neutralizing anti-IL-10 or anti-TGF-beta monoclonal antibody (mAb). Seven days after the pretreatment, naive CBA mice (secondary recipients) were given adoptive transfer of splenocytes from the pretreated mice and underwent heart grafting from C57BL/10 mice. To determine roles of these cytokines in the effector phase of the regulatory cells, anti-IL-10 or anti-TGF-beta mAb was administered weekly into the secondary recipients after the adoptive transfer. RESULTS: Adoptive transfer of splenocytes from CBA mice that had been pretreated with intratracheal delivery of C57BL/10 splenocytes significantly prolonged the survival of C57BL/10 allograft (median survival time [MST] 68 days) as compared with adoptive transfer from untreated CBA mice (MST 12 days). In the induction phase, anti-IL-10 mAb abrogated development of the regulatory cells that afforded prolonged allograft survival in the secondary recipients (MST 20 days), whereas anti-TGF-beta mAb did not abrogate it (MST 88 days). In the effector phase, anti-IL-10 mAb abrogated prolonged allograft survival afforded by adoptive transfer of the regulatory cells in the secondary recipients (MST 27 days), whereas anti-TGF-beta mAb did not abrogate suppressor function of the regulatory cells (MST 53 days). CONCLUSION: IL-10 but not TGF-beta was required for generation and suppressor function of the regulatory cells induced by intratracheal delivery of alloantigen.
Animals↗
Selective cyclooxygenase 2 inhibitor induces indefinite survival of fully allogeneic cardiac grafts and generates CD4+ regulatory cells.
BACKGROUND: Selective inhibition of cyclooxygenase 2 has been reported to have not only anti-inflammatory effects but also effects on the immune response. We investigated ability of a cyclooxygenase 2 inhibitor to inhibit alloimmune response in a murine cardiac transplantation model. METHODS: CBA (H2(k)) mice underwent transplantation of C57BL/10 (H2(b)) hearts. On the day of transplantation, the recipients received either no treatment or single administration of aspirin (a cyclooxygenase 1 and 2 inhibitor) or the selective cyclooxygenase 2 inhibitor NS-398. Naive CBA mice (secondary recipients) underwent adoptive transfer of splenocytes from treated mice with long-surviving grafts (primary recipients) to determine whether regulatory cells developed after NS-398 treatment. Histologic, cell-proliferation, and cytokine studies were also performed. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time, 8 days). The majority of recipients given aspirin rejected their grafts within 20 days (median survival time, 11 days). In mice given NS-398, the majority of the grafts survived indefinitely (median survival time, >100 days). Secondary CBA recipients given CD4+ splenocytes from primary CBA recipients treated with NS-398 also had indefinite survival of C57BL/10 hearts (median survival time, >60 days). Graft acceptance and proliferative hyporesponsiveness were also confirmed by the histologic and cell-proliferation studies, respectively. Production of interleukin 4 and 10 from splenocytes of the recipients treated with NS-398 were significantly higher than that from untreated recipients. CONCLUSIONS: In our model administration of cyclooxygenase 2 inhibitor induced indefinite survival of fully mismatched cardiac grafts and generated CD4+ regulatory cells. Cyclooxygenase 2 inhibitor could warrant consideration for use as an immunomodulating agent in clinical transplantation.
Animals↗
[Calcitonin gene-related peptide (CGRP)].
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Adrenal Gland Neoplasms↗
[5'-nucleotide phosphodiesterase isoenzyme-V].
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Biomarkers, Tumor↗
Role of CC chemokines and their receptors in multiple aspects of mast cell biology: comparative protein profiling of FcepsilonRI- and/or CCR1-engaged mast cells using protein chip technology.
Apart from the FcepsilonRI-mediated mechanism, mast cells are activated by chemokines. Evidence has accumulated indicating that there is cross-talk between the FcepsilonRI-mediated signalling pathway and CC chemokine receptor (CCR)-mediated signalling pathways in mast cells. We have found that costimulation with IgE/antigen and CC chemokine ligand 3 (CCL3) enhances degranulation but inhibits chemotaxis of rat basophilic leukaemia (RBL)-2H3 cells expressing human CCR1 (RBL-CCR1 cells). We hypothesize that this signalling cross-talk in mast cells may play important roles in the orchestration and focusing of the allergic response. In this study, we have sought information about global protein networks either enhanced or inhibited following cross-talk between the FcepsilonRI-mediated and CCR-mediated signalling pathways in mast cells. We believe this information may be useful for providing an understanding of mast cell function and in the establishment of new anti-inflammatory drugs for allergic diseases. Proteomics is a promising tool for studying protein profiles within biological samples and facilitates an understanding of the complex responses of an organism to a stimulus. Here, we show comparative data of protein profiles derived from FcepsilonRI-engaged and/or CCR1-engaged RBL-CCR1 cells using protein chip array technology, a proteomic technology. We also discuss our view of the role of CC chemokines and CCRs in regulating multiple aspects of mast cell biology.
Animals↗
Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracheal delivery of alloantigen.
BACKGROUND: Programmed death (PD)-1 has been implicated in peripheral tolerance. The authors investigated the roles of PD-1 and its ligands, PD-L1 and PD-L2, in the induction of regulatory cells by intratracheal delivery of alloantigen. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of C57BL/10 (H-2b) splenocytes and administration of monoclonal antibody (mAb) specific for PD-1, PD-L1, or PD-L2. Seven days later, C57BL/10 hearts were transplanted into the pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes from the pretreated CBA mice and transplantation of C57BL/10 heart. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST], 7 days). Pretreatment with intratracheal delivery of C57BL/10 splenocytes prolonged graft survival significantly (MST, 65 days). Administration of control immunoglobulin (Ig) G or anti-PD-L2 mAb did not significantly affect the prolongation (MST, 72 and 68 days, respectively). In contrast, anti-PD-1 or anti-PD-L1 mAb abrogated the prolongation (MST, 18 and 17 days, respectively). Adoptive transfer from mice pretreated with intratracheal delivery of alloantigen plus control IgG or anti-PD-L2 mAb prolonged survival of C57BL/10 grafts in secondary CBA recipients (MST, 72 and 56 days, respectively). However, concurrent administration of anti-PD-1 or anti-PD-L1 mAb abrogated prolonged survival after the adoptive transfer (MST, 14 and 20 days, respectively). CONCLUSIONS: PD-1-PD-L1 interaction was essential for induction of regulatory cells by intratracheal delivery of alloantigen.
Adoptive Transfer↗
Are there significant benefits of minimally invasive endoscopic thyroidectomy?
Minimally invasive surgery using endoscopic vision is widely employed for the treatment of thyroid diseases. We have performed endoscopic thyroidectomy by the axillary approach (axillary approach) and video-assisted thyroidectomy via a 3 cm cervical incision (video-assisted approach). In this study, we evaluated the efficacy of these two procedures. Each procedure was performed in 20 consecutive consenting patients. The degree of invasiveness after surgery was compared using postoperative results. The amount of pain and satisfaction with surgery was evaluated by grade (1-5) using a patient questionnaire. All thyroidectomies were completed successfully. No recurrent laryngeal nerve palsies occurred. Operating time for the video-assisted approach was significantly shorter than that for the axillary approach (p < 0.01). The amount of pain for the axillary approach on 1, 3, and 5 days after operation, respectively, was graded 3.2+/-0.7, 2.1+/-0.6, and 1.6+/-0.7 compared to 2.7+/-1.1, 1.7+/-0.7, and 1.1+/-0.2 for the video-assisted approach. The postoperative course was significantly less painful in patients undergoing the video-assisted approach on postoperative days 3 and 5 (p < 0.01). The degrees of satisfaction for the axillary approach and the video-assisted procedure were 1.2+/-0.4 and 2.4+/-1.0, respectively (p < 0.01). The video-assisted approach is less "invasive" than the axillary approach, but the axillary approach may be indicated for patients who are anxious about the visible cosmetic results.
Adult↗
Roles of chemokines in ocular allergy and possible therapeutic strategies.
The mechanism of ocular surface allergy in the forms of atopic conjunctivitis and vernal keratoconjunctivitis has been highlighted by specific functions of chemokines. In the context of late-phase allergic responses, these molecules have key roles in recruitment and activation of leukocytes. Their interaction with ligands is redundantly regulated; however, results from strategies to block subsets of chemokines have revealed unexpected or highly organized roles of these mediators. Exemplified by analyses of CCL11 function, current concepts of ocular allergy support CCL11 as central mediator. We emphasize the functions as modulator of mast cell activation/differentiation. With the prospect of understanding these functions, new modalities of drugs specifically developed to target CCL11/CCR3 interaction have been discussed.
Anti-Allergic Agents↗
Induction of operational tolerance and generation of regulatory cells after intratracheal delivery of alloantigen combined with nondepleting anti-CD4 monoclonal antibody.
BACKGROUND: We previously showed that intratracheal delivery of alloantigen induced prolonged survival of fully allogeneic cardiac grafts in mice. Here, this treatment protocol was combined with nondepleting anti-CD4 monoclonal antibody (mAb) to induce operational tolerance. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of whole splenocytes from C57BL/10 (H-2b) mice or a 15-mer Kb peptide, with or without intraperitoneal administration of nondepleting anti-CD4 mAb (YTS177). Seven days later, C57BL/10 hearts were transplanted into the pretreated CBA mice. In addition, some naive CBA mice underwent adoptive transfer of splenocytes from pretreated CBA mice and transplantation of a C57BL/10 heart on the same day. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time, 12 days). Mice given intratracheal delivery of whole splenocytes or Kb peptide demonstrated prolonged graft survival (median survival time, 84 and 76 days, respectively). Concurrent administration of YTS177 and intratracheal delivery of splenocytes or Kb peptide resulted in indefinite graft survival. Mice with long-surviving C57BL/10 cardiac grafts showed acceptance of skin grafts from C57BL/10 mice but not BALB/c mice, demonstrating that operational tolerance had been induced. Adoptive transfer of splenocytes from mice pretreated with intratracheal delivery of splenocytes or Kb peptide plus YTS177 induced indefinite survival of cardiac grafts in secondary recipients, indicating that regulatory cells had been generated. CONCLUSION: In a murine model, intratracheal delivery of donor splenocytes or Kb peptide combined with YTS177 induced operational tolerance and generated regulatory cells.
Adoptive Transfer↗
CD27/CD70, CD134/CD134 ligand, and CD30/CD153 pathways are independently essential for generation of regulatory cells after intratracheal delivery of alloantigen.
BACKGROUND: We investigated whether blockade of tumor necrosis factor receptor-ligand pathways could generate regulatory cells induced by intratracheal delivery of alloantigen. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of splenocytes (1x10(7)) from C57BL/10 (H-2b) mice and intraperitoneal administration of monoclonal antibody (mAb) specific for CD70, CD134 ligand (CD134L), CD153, or CD137L. Seven days later, C57BL/10 hearts were transplanted into pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes (5x10(7)) from pretreated CBA mice and transplantation of a C57BL/10 heart on the same day. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST] 12 days). Pretreatment with intratracheal delivery of C57BL/10 donor splenocytes prolonged graft survival significantly (MST 84 days). Mice given intratracheal delivery of alloantigen plus anti-CD70, anti-CD134L, or anti-CD153 mAb, but not those given intratracheal delivery of alloantigen plus anti-CD137L mAb, rejected their graft acutely (MST 16, 14, 10, and 65 days, respectively). Adoptive transfer of splenocytes from mice pretreated with intratracheal delivery of alloantigen plus anti-CD70, CD134L, or CD153 mAb did not prolong survival of C57BL/10 cardiac grafts in naive secondary CBA recipients (MST 14, 11, and 11 days, respectively), whereas adoptive transfer of splenocytes from mice given intratracheal delivery of alloantigen plus anti-CD137L mAb did (MST 75 days). CONCLUSION: The CD27/CD70, CD134/CD134L, and CD30/CD153 pathways are independently required for generation of regulatory cells in our model.
Adoptive Transfer↗
Role of the CTLA4 pathway in hyporesponsiveness induced by intratracheal delivery of alloantigen.
BACKGROUND: The authors previously reported that intratracheal delivery (ITD) of donor alloantigen induced donor-specific hyporesponsiveness to C57BL/10 cardiac allografts in CBA recipients and that blockade of the B7 pathways abrogated that hyporesponsiveness. In this study, the authors used a CD28-deficient model to evaluate which signal, either through CD28 or cytotoxic T-lymphocyte-associated antigen (CTLA4), is involved in the induction of hyporesponsiveness. METHODS: Seven days before transplantation of hearts from C3H/HeJ (H2k) mice into C57BL/6 (H2b) or CD28-deficient (C57BL/6 background) mice, the transplant recipients were given ITD of donor splenocytes (1 x 10(7)), alone or in combination with human CTLA4-immunoglobulin (Ig) (200 microg). RESULTS: ITD of C3H splenocytes induced donor-specific hyporesponsiveness to C3H cardiac grafts in C57BL/6 recipients (graft median survival time [MST], 40 days). Administration of CTLA4-Ig concurrently with ITD abrogated the prolonged allograft survival (MST, 12 days). Interestingly, ITD of C3H splenocytes induced prolonged survival of C3H allografts in CD28-deficient recipients (MST, 55 days). Furthermore, administration of CTLA4-Ig combined with ITD of C3H splenocytes abrogated the prolonged survival of C3H allografts in CD28-deficient recipients (MST, 7 days), whereas recipients given isotype-control antibody in combination with ITD of splenocytes had prolonged survival of C3H allografts (MST, 58 days). CONCLUSIONS: Taken together, the authors' findings indicate that a signal through CTLA4, rather than through CD28, plays an important role in the induction of hyporesponsiveness by ITD of alloantigen in this model.
Abatacept↗
Induction of indefinite survival of fully allogeneic cardiac grafts and generation of regulatory cells by intratracheal delivery of alloantigens under blockade of the CD40 pathway.
BACKGROUND: The authors previously showed that intratracheal delivery (ITD) of donor splenocytes induced prolonged survival of fully allogeneic cardiac grafts in mice. In this study, this treatment protocol was combined with blockade of the CD40 pathway in an attempt to induce operational tolerance. METHODS: CBA mice were given donor splenocytes (1x107) or Kb peptide (100 microg) by ITD with or without antibody specific for mouse CD40 ligand (MR1, 200 microg) 7 days before transplantation of a C57BL/10 heart. Also, splenocyte (5 x 107) from primary recipient CBA mice given ITD of donor splenocytes or Kb peptide plus MR1 were adoptively transferred into naive CBA secondary recipients 7 days after the pretreatment and C57BL/10 hearts were transplanted into those recipients the same day. RESULTS: ITD of donor splenocytes and Kb peptide induced prolonged survival of cardiac grafts (median survival time [MST], 74 and 56 days, respectively), whereas naive control mice and mice pretreated with syngeneic splenocytes had acute graft rejection (MST in both groups, 7 days). When MR1 was included, all grafts survived indefinitely (>200 days), but mice pretreated with MR1 alone had graft rejection (MST, 54 days). Mice bearing cardiac grafts had acceptance of skin grafts from C57BL/10 but not BALB/c mice, demonstrating that operational tolerance was induced. Secondary recipients given adoptive transfer of splenocytes from primary recipients of the combined treatment had acceptance of C57BL/10 grafts, suggesting that regulatory cells were generated within 7 days of pretreatment. CONCLUSIONS: ITD of donor splenocytes or Kb peptide under blockade of the CD40 pathway induced operational tolerance and generated regulatory cells.
Adoptive Transfer↗
High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells.
BACKGROUND: The authors investigated whether antithrombin III (AT-III) could induce unresponsiveness to alloantigens. METHODS: CBA mice were given intravenous injection of 50 or 500 U/kg AT-III or control plasma the same day as transplantation of a heart from a C57BL/6 mouse. An adoptive transfer study and mixed leukocyte culture analysis were also performed. RESULTS: Naive CBA mice rejected C57BL/6 cardiac grafts acutely (median survival time [MST], 9 days). The 50-U/kg dose of AT-III induced a moderate increase in graft survival (MST, 25 days), whereas control mice rejected their graft acutely (MST, 7 days). With the 500-U/kg dose of AT-III, all grafts survived indefinitely (>100 days) and regulatory cells were generated. In vitro, AT-III suppressed proliferation of mixed leukocyte responses and generation of interleukin-2. CONCLUSION: AT-III can be not only an antithrombotic agent but also a strong immunomodulating agent when used at high dose.
Animals↗