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Masanori Niimi

Publications and source records attributed to Masanori Niimi.

17 recordsLinked to original sources

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↗

Reliable cervical anastomosis through the retrosternal route with stepwise gastric tube.

OBJECTIVES: An extra-anatomic reconstruction would be beneficial in preventing recurrent malignant dysphagia. A long gastric tube that allowed a sufficient blood flow was necessary to perform the successful cervical anastomosis through the retrosternal route. METHODS: The gastric tube was created by means of separate division and closure of the seromuscular and submucosal-mucosal layers (stepwise group) in 15 consecutive patients and by means of full-thickness cutting of the stomach and closure of the seromuscular layer (standard group) in 22 patients. We compared these 2 types of gastroplasties in terms of total length of the tube, blood flow, and the incidence of anastomotic leakage. Blood flow was measured with a laser Doppler flowmeter during surgical intervention. RESULTS: The gastric tube in the stepwise group was significantly longer than that in the standard group (P <.01, unpaired t test). Tissue blood flow at the site of anastomosis in the stepwise group was significantly greater than that in the standard group (P <.01, unpaired t test), and the rate of anastomotic leakage in the stepwise group was significantly lower than that in the standard group (P <.05, chi(2) test). CONCLUSION: We consider this technique to be a useful procedure for retrosternal reconstruction after subtotal esophagectomy.

Adult↗

Clinical benefits in endoscopic thyroidectomy by the axillary approach.

BACKGROUND: Surgical treatments for thyroid diseases require skin incisions that can result in prominent scars, complaints resulting from adhesions, hypesthesia, and paresthesia in the neck. We have developed an endoscopic thyroidectomy using an axillary approach. In this article, we compare our original technique with conventional open surgery from the aspects of surgical invasiveness and patients' complaints after surgery. STUDY DESIGN: Each procedure was performed in 20 patients with follicular tumors. The two groups were similar for age, gender, and the mean diameter of the thyroid tumor. No statistically significant difference in the final pathological diagnosis was found between the two groups. Surgical invasiveness and patients' complaints after surgery were compared using results of the operation and a questionnaire. RESULTS: The operating time for open surgery was significantly shorter than that for endoscopic surgery (p < 0.01). In the endoscopic surgery group, the patient questionnaires revealed that 4 patients had severe anterior chest pain on the first postoperative day. The postoperative pain decreased after, and we could not find any difference between the two groups with regard to postoperative pain. Three months after surgery, one patient who had received an endoscopic procedure complained of slight hypesthesia, and none of the patients complained of discomfort while swallowing. Among the patients who underwent open surgery, 13 patients (65%; p < 0.01) complained of hypesthesia or paresthesia and 6 patients (30%; p < 0.05) complained of discomfort while swallowing. All of the patients treated using the endoscopic procedure were satisfied with the cosmetic results, but 15 patients who underwent open surgery complained of unsatisfactory cosmetic results (p < 0.01). CONCLUSIONS: The incidence of postoperative complaints after endoscopic surgery is considerably lower than that after open surgery.

Adult↗

B7/CTLA4 pathway is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice.

BACKGROUND: The mechanism of hyporesponsiveness induced by intratracheal (IT) delivery of alloantigen was examined and its effect on cardiac graft survival was assessed in studies in mice. METHODS: In CBA (H2 ) mice, donor splenocytes were given by IT delivery 7 days before transplantation of a C57BL/10 (H2 ) heart. To determine whether regulatory cells were involved in hyporesponsiveness, splenocytes from mice given IT delivery of alloantigen and antibodies for B7-1, B7-2, or CTLA4 were adoptively transferred to naïve secondary recipients 7 days after delivery; those recipients underwent heart transplantation the same day. Effects on cell proliferation and cytokine production of splenocytes from mice given IT delivery of alloantigen were examined in mixed leukocyte cultures (MLC). RESULTS: Cardiac graft survival was significantly prolonged in mice given IT delivery of alloantigen (median survival time [MST], 81 days); those given syngeneic splenocytes rejected grafts acutely (MST, 7 days; P<0.05). Adoptive transfer of splenocytes also significantly prolonged survival of cardiac grafts in secondary recipients (MST, 62 days). When B7-1, B7-2, or CTLA4 antibody was combined with IT delivery of alloantigen in the first recipient, all grafts were rejected within 14 days in second recipients after adoptive transfer. In mixed leukocyte cultures, splenocytes from these mice did not respond to alloantigen and production of interleukin-4 and interleukin-10 was increased. CONCLUSIONS: Donor splenocytes delivered IT induced hyporesponsiveness and regulatory cells in our animal model, and such induction was dependent on B7-1, B7-2, and CTLA4 signals.

Abatacept↗

Feasibility of dividing the main vessels for enhancement of dynamic graciloplasty.

PURPOSE: The technique of dynamic graciloplasty is not yet-completely satisfactory. Its function could be improved by ensuring total wrapping of the neoanus with the muscular part of the gracilis, but this can only be achieved by dividing the main blood vessels, which are considered essential for blood supply to the flap. We devised a vascular delay technique to preserve the flap without these vessels, which we performed first experimentally, then clinically, with promising results. METHODS: Seventeen Japanese white rabbits were given graciloplasty after electrical stimulation, vascular ligation, or no preparation. The neoanus was assessed manometrically and histologically 5 days later. The good results seen in the animals encouraged us to start performing enhanced dynamic graciloplasty clinically. Five patients were given electrical stimulation and the vascular delay technique was carried out before dynamic graciloplasty. RESULTS: Vascular delay in the rabbits preserved the muscle flap, but electrical stimulation had a limited effect. In all five patients, the neoanus was successfully wrapped with the muscular part of the flap. There were no ischemic symptoms or perioperative complications. Furthermore, the neoanal pressure increased significantly with electrical stimulation from 23.8 cmH(2)O to 89.2 cmH(2)O. Satisfactory continence was achieved in three of the four patients whom we were able to evaluate. CONCLUSION: Dissection of the main vessels of the gracilis muscle with vascular delay and long-term electrical stimulation may optimize the gracilis flap in patients requiring dynamic graciloplasty.

Adult↗

Thoracoscopic esophagectomy combined with mediastinoscopy via the neck.

Although thoracoscopic techniques have been introduced to esophageal surgery, the identification of the left recurrent laryngeal nerve and lymph node dissection along the nerve remain quite difficult. A mediastinoscopic technique via the neck enables an excellent visual field to be created in the upper mediastinum, especially near the left recurrent laryngeal nerve. Therefore, a thoracoscopic esophagectomy combined with this technique allows mediastinal lymph nodes along the left recurrent laryngeal nerve to be easily and safely dissected.

Esophageal Neoplasms↗

Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells.

We have previously reported that intratracheal delivery of donor splenocytes in mice induces hyporesponsiveness to fully allogeneic cardiac grafts and generates regulatory cells. Here, we examined whether an allopeptide would produce the same results. A 15-mer (54-68) peptide corresponding to a hypervariable region of the K(b) molecule was given intratracheally or intravenously to CBA (H2(k)) mice 7 days before transplantation of a C57BL/10 (H2(b)) or BALB/c (H2(d)) heart and was also used in adoptive transfer experiments. Cardiac grafts in recipients given K(b) peptide intratracheally experienced a median survival time (MST) of 56 days, whereas those in recipients given the peptide intravenously were rejected acutely (MST=7.5 days). Adoptive transfer of splenocytes from mice pretreated intratracheally with K(b) peptide to naïve secondary recipients prolonged survival of cardiac grafts (MST = 35 days). Intratracheal delivery of a single major histocompatibility complex class I peptide induced hyporesponsiveness to allogeneic cardiac grafts and generated regulatory cells.

Adoptive Transfer↗

Direct mini-incision thyroidectomy.

We recently developed a new surgical technique for carrying out thyroidectomy, to minimize surgical invasiveness and improve the cosmetic result. Our procedure differs from conventional thyroidectomy in requiring a 3-cm skin incision and no raising of the skin flap. Since this technique decreased tissue trauma by obviating unnecessary neck exploration, hypesthesia or paresthesia in the neck and discomfort while swallowing, related to a large skin incision and raising of the skin flap, are minimized. Since thyroidectomy is performed after delivering the thyroid gland through the small skin incision, sufficient exposure for dissection of the pretracheal and paratracheal space can be obtained. Therefore, injuring the recurrent laryngeal nerve and the parathyroid gland can be avoided. Although the number of patients that we have treated in this manner is still small, we believe that our new procedure constitutes a useful surgical treatment for patients with thyroid disease.

Adult↗

Direct mini-incision parathyroidectomy.

We describe our technique for performing a mini-incision parathyroidectomy in patients with hyperparathyroidism. Since our procedure differs from conventional parathyroidectomy in requiring a 2- or 3-cm skin incision and no raising of skin flap, this technique resulted in a good cosmetic status and less invasiveness. Hypesthesia or paresthesia in the neck and discomfort while swallowing related to a large skin incision and raising of skin flap are minimized. Although the cosmetic results of endoscopic techniques are better than those of our procedures, endoscopic instruments remain traumatic, can easily inflict iatrogenic lesions to parathyroid adenomas and enhance the risk of tumor cell exfoliation, especially if the parathyroid adenoma is manipulated by the instruments. Our surgical procedure can be less technically demanding and time-consuming. Although the number of patients whom we have treated in this manner is still small, we believe that our new procedure constitutes a useful surgical treatment for hyperparathyroidism.

Humans↗

Gas gangrene in patient with atherosclerosis obliterans.

Clostridia are the main cause of nontraumatic spontaneous gas gangrene. Poor blood flow due to arterial occlusion exacerbates the anaerobic condition. Fulminant gas gangrene in a 54-year-old man with atherosclerosis obliterans was treated by revascularization of the iliac artery using endarterectomy, and his gangrenous lower leg was amputated. However, he died from renal failure.

Amputation, Surgical↗

Conformal radiation therapy for liver metastasis of esophageal carcinoma.

Recently, aggressive hepatectomies or hepatic arterial infusion chemotherapy for liver metastasis from gastric or colorectal carcinoma have been performed, and the number of successful studies of liver metastasis have increased. However, there have been few successful cases of liver metastasis from esophageal carcinoma by surgery or chemotherapy. Herein, we show the benefits of radiation therapy for the treatment of liver metastasis from esophageal carcinoma. A 60-year-old woman with a 5-cm solitary liver metastasis from esophageal squamous cell carcinoma was treated with radiation therapy. The treated volume was encompassed by the anteroposterior and right lateral opposing fields, shaped by a multileaf collimator. The daily fraction size was 1.8 Gy, 5 days per week, for a total dose of 54 Gy. During the course of treatment, the patient did not experience any complications. After radiotherapy, abdominal computed tomography showed that the enhanced solid tumor had changed to a very low-density mass lesion with a clear margin, and the size was decreasing gradually between the 6 months. Radiotherapy could be a treatment of choice in patients with liver metastasis from esophageal squamous cell carcinoma.

Carcinoma, Squamous Cell↗