Anti-infection immunity against cytophilic bacteria such as Mycobacteria, Salmonella and Listeria depends on cellular immunity and can be induced by the inoculation of an attenuated live vaccine but not by the inoculation of a killed or component vaccine. In this study, we analyzed mechanisms of inducing anti-infection immunity against cytophilic bacteria using an experimental model of mouse Salmonellosis and examined the use of this system for the treatment of tumor-bearing mice.
Our results suggest that bacterial antigen binds to stress protein (heat shock protein : HSP), which is newly produced in macrophages after stimulation with live bacteria, and the resulting antigen-HSP complex stimulates antigen-presenting cells (APC) to produce IL12p70, leading to the development of type 1 helper T (Th 1) cells and the induction of cellular immunity.
An anti-tumor effect was observed in metastatic tumor-bearing mice after inoculation wily : live attenuated Salmonella, especially when a combined treatment of a small dose of anti-cancer agent and live Salmonella was used.

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Nonmyeloablative stem cell transplantation (NST) have been developed over the past several years. NST is designed to reduce intensity of preparative myeloablation, and to induce graft-versus-tumor (GVT) effect by engraftment of donor T cells. Compared with conventional allogeneic stem cell transplantation, NST provides lower treatment-related mortality. The degree of GVT effect is generally correlated with the degree of the graft-versus-host disease. Through this novel procedure, allogeneic stem cell transplantation can be applied to elderly or clinically ill patients having variable hematologic disorders or solid tumors. Disease-specific studies with longer follow-up are needed to evaluate this potentially promising therapy. Here we review the preliminary clinical results of NST as immunotherapy for hematologic disorders and solid tumors.

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Backgrounds and Aims : Many patients suffering from severe ischemic limb disease inevitably experience amputation, despite the use of intensive therapies such as the administration of prostaglandins, a sympathectomy and hyperbaric oxygen therapy. Preclinical studies have established that the implantation of bone marrow-mononuclear cells in ischemic limbs increases collateral vessel formation. We used this new therapy in patients with thromboangiitis obliterance. Patients and Methods : The implantation of autologous bone marrow-mononuclear cells was performed in five patients with ischemic limbs caused by peripheral arterial disease. Bone marrow-mononuclear cells were collected from approximately 500ml of bone marrow blood, and then injected into the muscles in the ischemic region. Results : Although the extent of the improvement was not consistent among the five cases, all of the patients experienced some improvement in their symptoms. No side effects were observed in the five patients. Conclusion : The autologous implantation of bone marrow-mononuclear cells appears to be a safe and effective treatment for therapeutic angiogenesis, based on the natural ability of marrow cells to supply endothelial progenitor cells and to secrete various angiogenic factors and cytokines.

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Background and Aim : The survival rate of extremely low birth weight infants has been improving in Japan. We investigated the changes in the outcomes of extremely low birth weight infants at our hospital.
Patients and Methods : We analyzed the mortality rate of 298 infants with a birth weight of<1000 g who were admitted to our hospital within 24 hours of birth during the period of 1982-2001.
Results : The mortality rate has decreased with time. The mortality rates wlrl 38% and 22% for the periods between 1982-1991 and 1992-2001, respectively ; this difference was statistically significant with regard to the cause of death, the freguey of air leaks was decreased while the fregueuaies of severe infection and necrotizing enterocolitis or gastrointestinal perforations increased. Conclusions : The mortality rate of extremely low birth weight infants has decreased, and the use of new medical treatments, such as surfactant replacement therapy and high-frequency oscillatory ventilation, has likely contributed to this trend. The prevention of severe infections and necrotizing enterocolitis will be important for achieving further reductions in the mortality rate.

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Pyogenic granuloma occurs in soft tissue, mainly on the skin and mucous membrane. The oral mucosa is thought to be one of the most common sites of pyogenic granulomas. Histopathologically, the pyogenic granulomas are characterized by endothelial proliferation, the formation of abundant vascular spaces, and the infiltration of numerous inflammatory cells.
We experienced two cases of pyogenic granuloma arising in the lower lip and the tongue, respectively. The lesions and the surrounding tissue were excised under local anesthesia. The postoperative prognosis of both cases was excellent, and no evidence of recurrence has been seen to date.

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A 34-year-old female with acute lymphoid leukemia was admitted to hospital in May 2002. She received induction chemotherapy and achieved a complete remission (CR). She subsequently received one course of consolidation chemotherapy, after which she suffered a relapse. Re-induction chemotherapy was performed, and a second CR was achieved. As a cautionary measure, we searched for an HLA-matched donor but were unable to find one among her family or in the Bone Marrow Bank. In October 2002, while in complete remission, she underwent an unrelated umbilical blood transplant after undergoing total body irradiation (TBI) and was subsequently treated with cyclophosphamide (CY). For graft versus host disease (GVHD) prophylaxis, she was given tacrolimus and methotrexate. The infused umbilical blood provided 3.02×10 (7) nucleated cells per kg ; the HLA profile contained 3 mismatched loci (2 mismatches at the A locus and 1 mismatch at the B locus). Engraftment was obtained on post-transplant day 22, and no evidence of clinical acute GVHD was seen. The use of tacrolimus, administered by drip infusion on post-transplant days 1-42 and orally after day 42, was discontinued altogether on post-transplant day 100. She is currently in good condition eight months after undergoing the umbilical blood transplantation.

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A 61-year old man was admitted to hospital complaining of back pain. Four years earlier, the patient had undergone an extended thymectomy combined with a left upper lobectomy and a partial aortectomy for the treatment of advanced thymic cancer. The reconstructed subclavian artery had become occluded, and a femoro-axillar bypass had been performed one year prior to the present hospital admission. A computed tomogram revealed a pseudoaneurysm of the distal aortic arch and a Stanford type B aortic dissection with a narrowed true lumen. An endovascular approach was considered to be a high-risk treatment option in this case. Furthermore, a thoracotomy or standard median sternotomy to peel off the periaortic tissue was thought to be very difficult because of the severe postoperative adhesion that was present. We decided to treat the patient by implanting an endovascular stentgraft through the proximal aortic arch under deep hypothermic circulatory arrest and selective cerebral perfusion. The stentgraft was composed of a thin-wall woven Dacron graft reinforced with a selfexpandable Z-stent and inserted into a flexible sheath with a 22 French-size diameter. The postoperative course was almost uneventful, and the patient is doing well 32 months after the operation.

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Aims : To evaluate the extent of the problem caused by the absence of generic drugs (following drugs) listings in Japanese drug handbooks.
Methods : During the period between April 2002 and March 2003, we encountered many generic drugs in our daily practice. A Japanese drug handbook, Konnichi-no-chiryoyaku, was consulted to determine whether each generic drug we encountered was listed or not.
Results : Among the 85 generic drugs examined in this study, 29 generic drugs (34.1%) were not found in the handbook.
Conclusions : The descriptions of several generic drugs are not included in Japanese drug handbooks, making it difficult for physicians to determine the exact composition of some generic drugs. We propose that the name of generic drugs should be composed by combining innovator drug's name (or generalized name) and manufacturer's name.

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Backgrounds and Aims : We examined the relationship between the existence of Helicobacter pylori (HP) and Kampo medicines used in patients. Methods : In Toyama Medical and Pharmaceutical University Hospital, we investigated HP infection in patients who were continuously administered Kampo medicines. During upper GI endoscopy, two specimens were obtained from the greater cavature of the antrum and upper body of the stomach, and then were processed for rapid urease test, the CLO-test. Results : Among 34 consecutively enrolled patients, CLO was positive in 18 patients (52.9%). Patients in HP-positive and -negative groups had taken various Kampo medicines for more than one month, and every Kampo medicine except one in both groups contained herbs that had been reported to have an in vitro anti-HP effect. Conclusion : Kampo medicine may not be indicated for eradication therapy for HP in clinical situations.

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[in Japanese]

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