Background-Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Natural killer T (NKT) cells, which integrate proinflammatory cytokines, have been demonstrated in the atherosclerotic lesions and in visceral adipose tissue. Objective-To determine whether NKT cells are involved in glucose intolerance and adipose tissue inflammation in diet-induced obese mice. Methods and Results-To determine whether NKT cells are involved in the development of glucose intolerance, male ␤ 2 -microglobulin knockout (KO) mice lacking NKT cells and C57BL/6J (wild-type) mice were fed with a high-fat diet (HFD) for 13 weeks. Body weight and visceral obesity were comparable between wild-type and KO mice. However, macrophage infiltration was reduced in adipose tissue and glucose intolerance was significantly ameliorated in KO mice.To further confirm that NKT cells are involved in these abnormalities, ␣-galactosylceramide, 0.1 g/g body weight, which specifically activates NKT cells, was administered after 13 weeks of HFD feeding. ␣-Galactosylceramide significantly exacerbated glucose intolerance and macrophage infiltration as well as cytokine gene expression in adipose tissue. O besity, specifically visceral obesity, increases the risk for metabolic disorders, such as type 2 diabetes mellitus, dyslipidemia, and hypertension as well as atherosclerotic cardiovascular diseases. Previous studies have demonstrated that the accumulation of macrophages within adipose tissue is well documented in obese individuals and that adipose tissue inflammation plays an important role in the pathogenesis of these metabolic disorders. 1,2 Macrophages are attracted by chemokines, such as monocyte chemoattractant protein 1 (MCP-1), and contribute to local inflammation through the release of other inflammatory cytokines, such as tumor necrosis factor (TNF) ␣. In high-fat diet (HFD)-fed obese mice, it has been shown that infiltration of macrophages into adipose tissue coincides with the occurrence of obesitymediated metabolic disorders. 2 The important role of adipose tissue macrophages in the pathogenesis of metabolic disorders has further been supported by recent data in C-C motif chemokine receptor 2 (CCR2)-deficient mice. 3 The CCR2 Ϫ/Ϫ mice exhibited a reduction in adipose tissue macrophages in association with an improvement of glucose homeostasis and insulin sensitivity. However, the abolished monocyte and macrophage recruitment into peripheral tissue via interaction with MCP-1 could not completely inhibit HFD-mediated metabolic disorders, suggesting that other inflammatory cells may play a role in this context. Wu et al 4 and Rocha et al 5 demonstrated that CD3-positive T lymphocytes are present in human adipose tissue; and regulated upon activation, normal T cell expressed secreted (RANTES), a T-cell-specific chemokine, and its respective receptor CCR5 are expressed in adipose tissue from obese patients. However, the role of other types of lymphocytes in adipose tissue inflam...

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Summary:Reverse seroconversion of hepatitis B virus (HBV) after allogeneic BMT is rare. We present a case of HBV reactivation late after allogeneic BMT which responded well to lamivudine therapy. A 35-year-old woman with CML received an allogeneic BMT. Before BMT, the patient had immunity to HBV, with serum antibodies against hepatitis B surface antigen (HBsAb), and the donor was completely negative for HBV. Four years after BMT, acute hepatitis occurred with a detectable level of HBV-DNA. Lamivudine rapidly reduced transaminase and bilirubin levels, and serum HBV-DNA decreased to negative. Retrospective analysis revealed that there had been a gradual decrease in serum HBsAb titers after BMT. Administration of lamivudine immediately after HBV replication may be more effective than vaccination of hepatitis B surface antigen-negative donors before BMT. Bone Marrow Transplantation (2002) 29, 361-363. DOI: 10.1038/sj/bmt/1703387 Keywords: allogeneic BMT; hepatitis B virus; lamivudine; immunosuppression It has been suggested that hepatitis B virus (HBV) in a dormant state may persist in the setting of BMT and this has been termed 'latent' infection. Reactivation of such a latent infection has been suspected in patients who had evidence of HBV immunity and who showed positive test results for hepatitis B surface antigen (HBsAg) with or without hepatitis after BMT. 1 Lamivudine, a nucleotide analogue that specifically inhibits viral reverse transcriptase, while suppressing HBV replication, is now being used widely in patients with chronic hepatitis B. 2 Lamivudine has also been administered to patients with HBV to prevent progression to fulminant hepatitis following BMT. 3,4 We report a case of reverse seroconversion from a hepa- Case reportIn June 1996, a 35-year-old woman with chronic myelogenous leukemia received a fully HLA-matched and minor ABO-mismatched (from A to AB) allogeneic BMT in the first chronic phase from an unrelated healthy donor. The conditioning regimen consisted of ranimustine, cyclophosphamide and total body irradiation. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Cyclosporin A had been changed to tacrolimus because of encephalopathy. Hematopoietic engraftment was achieved, and the patient was treated with oral tacrolimus for acute hepatic GVHD. During follow-up after discharge, serum transaminase levels remained stable, and tacrolimus administration was stopped 11 months after BMT. Chronic GVHD of the skin and oral cavity with lichen planus was mild, needed no additional prednisolone, and disappeared 12 months after BMT. Thereafter, there was no clinical evidence of chronic GVHD. Before BMT, serological examination showed that the donor was negative for HBsAg and HBsAb, and had normal liver function, while the patient was positive for anti-HBs and had antibodies to hepatitis B core antigen and was negative for antibodies against hepatitis B e antigen (HBeAb). Tests conducted at the Japan Red Cross Hokkaido Blood Center showed that all of the patient...

Summary:A 21-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation from an HLA-identical sibling donor. The patient also had chronic hepatitis B and the donor was an HBV carrier. To decrease HBV and improve hepatic dysfunction before BMT, the patient had received lamivudine for 6 months. After marrow transfusion, administration of lamivudine was continued to inhibit replication of donor-derived HBV. The patient showed hematological engraftment on day 13 without any serious liver dysfunction. Eight months after BMT, she is now alive and well without chronic liver GVHD or reactivation of hepatitis B. HBV-DNA was not detected in the patient's serum. Administration of lamivudine to a BMT recipient with chronic hepatitis B may be a safe and promising way to prevent fatal liver dysfunction in the setting of allogeneic BMT, even in the event of BMT from an HBV-positive donor. Bone Marrow Transplantation (2002) 29, 269-271. DOI: 10.1038/sj/bmt/1703350 Keywords: allogeneic bone marrow transplantation; hepatitis B virus; lamivudine Allogeneic BMT has become one of the most effective treatment modalities for patients with hematological diseases. However, myeloablative and immunosuppressive conditioning, acute and chronic GVHD, and administration of immunosuppressive drugs for prophylaxis and treatment of GVHD enhance viral replication with a consequent increase in viral carriers. Reactivation of hepatitis B virus (HBV) infection after allogeneic BMT is well known in carriers. 1 Although hepatitis B surface antigen (HBsAg) positivity in the recipient is not generally considered to be a strict contraindication for BMT, patients with chronic HBV infection have a high risk of severe hepatic failure, leading to fulminant hepatitis with a fatal outcome, after transplantation due to reactivation of HBV. 2,3 Moreover, the use of HBsAg-positive donors, particularly if hepatitis B e antibody (anti-HBe) positive, has been shown to increase the risk of severe liver disease in BMT recipients, and hepatitis B surface antibody (anti-HBs) positivity has been shown to prevent severe liver damage. 4 Recently, lamivudine, which is one of the reverse transcriptase inhibitors of human immunodeficiency virus (HIV) and has been used to treat patients with HIV infection, has been administered to patients with chronic hepatitis B. 5,6 Several studies have shown the effectiveness of lamivudine for inhibition of HBV reactivation and for clinical and pathological improvement in hepatic dysfunction even in patients with hematological diseases after stem cell transplantation. 7,8 Here, we report a successful allogeneic BMT from an HBV-positive sibling donor (HBV carrier) into a patient with severe aplastic anemia complicated by chronic hepatitis B, using lamivudine. Case reportIn October 1996, a 21-year-old woman was diagnosed with severe aplastic anemia. She was treated with a combination of cyclosporin A, anti-thymocyte globulin (ATG), and granulocyte colony-stimulating factors, but her pancytopenia did not impro...