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Background: Definitions of regional lymph nodes for gallbladder cancer differ according to staging system. Hence, the appropriate extent of lymph node dissection has not yet been standardized. Methods: Pathological stages and disease‐specific survival (DSS) of patients who had undergone surgical resection of gallbladder cancer between 1990 and 2016 were reviewed. Patients with nodal metastases limited to the hepatoduodenal ligament or common hepatic artery, extending to the posterosuperior pancreatic head lymph nodes (PSPLNs), or in nodes along the coeliac axis or superior mesenteric vessels were grouped as having Na, Nb and Nc disease respectively. Metastases beyond these regions were defined as distant metastases (M1). Absence of distant metastasis was expressed as M0. Results: A total of 259 patients were evaluated. There were 74, 31 and nine patients respectively in the Na, Nb and Nc groups. Twenty‐five, nine and four patients in the respective groups had M1 disease (P = 0·682). The 5‐year DSS rate was comparable between patients with Na M0 and those with Nb M0 disease (36 versus 34 per cent respectively; P = 0·950), whereas the rate in patients with Nc M0 status (0 per cent) was worse than that of patients with Nb M0 (P = 0·017) and comparable to that of patients with M1 disease (14 per cent; P = 0·590). Among 22 patients with Nb M0 disease, the 5‐year DSS rate did not differ between those who had undergone pancreatoduodenectomy and those who had had dissection of PSPLNs without pancreatoduodenectomy (50 versus 30 per cent respectively; P = 0·499). Conclusion: PSPLNs and nodes along the hepatoduodenal ligament and hepatic artery should be considered regional nodes for gallbladder cancer, and should be resected. Standardized lymphadenectomy is important [ABSTRACT FROM AUTHOR]

A triclinic polymorph Dy(t) and a monoclinic polymorph Dy(m) of [Dy(tta)3(L)] with L = 4-[6-(1,3-benzothiazol-2-yl)pyridin-3-yl]-4′,5′-bis(methylthio)tetrathiafulvene behave as Single-Molecule Magnets with hysteresis loops opened at zero field. Magnetic properties were enhanced through magnetic dilution and 164Dy isotopic enrichment which definitively support the importance of isotopes for the control of quantum magnets. [ABSTRACT FROM AUTHOR]

The long cooling time during heat treatment of a large forging due to mass effect leads to the creep deformation at not only high temperature but also transformation temperature ranges. Therefore, both the transformation plasticity and the creep together with the phase transformation significantly affect the stress distribution of the forging after the heat treatment. In this study, a FEM model considering both the transformation plasticity and creep was developed. Proposed model was integrated into commercial FEM codes ANSYS via user subroutines. The material properties of the transformation plasticity and creep were also measured experimentally. For experimental verification, the residual stress measurements of the large forged shaft are compared with those of the simulations. The simulations show that the residual stresses were mainly caused by the phase transformation stress. In particular, it is found that both the transformation plastic strain and the creep strain play important roles in simulating the residual stress during heat treatment of a large forged shaft. [ABSTRACT FROM AUTHOR]

Highlights: [•] The role of chromatin modification in NPC sequential fate switches. [•] The role of chromatin modification in neuronal differentiation. [•] Chromatin structure and DNA/histone modifications change during development. [•] Some modifications not only occur at specific gene loci, but also on a global scale. [ABSTRACT FROM AUTHOR]

Background: Anatomical resection of segment VIII (SVIII) is technically demanding. Only two small studies have published short-term outcomes. The aim of the present study was to evaluate short- and long-term outcomes after anatomical resection involving SVIII for hepatocellular carcinoma (HCC), and to compare long-term outcomes with those after non-anatomical resection of SVIII. Methods: Outcomes after anatomical resection of SVIII or its subsegments for HCC were compared with those in patients who underwent primary non-anatomical resection of SVIII during the same period. Results: A total of 154 patients underwent anatomical resection involving SVIII and 122 had non-anatomical resection. In patients undergoing anatomical resection, the preoperative indocyanine green retention rate at 15 min ranged from 2·9 to 32·2 (median 13·6) per cent, and was 10 per cent or more in 109 patients (70·8 per cent). Median duration of operation and blood loss were 378 min and 705 ml respectively. There were no postoperative deaths, but major adverse events occurred in ten patients (6·5 per cent). The cumulative 5-year recurrence-free and overall survival rates were 28·5 and 79·6 per cent, which were significantly better than rates of 19·4 and 64·8 per cent respectively after non-anatomical resection ( P = 0·036 and P < 0·001). Conclusion: Complete resection of SVIII or its subsegments can be performed safely and the long-term outcomes seem acceptable. This can be a curative procedure for HCC, especially in patients with limited liver function reserve, in whom right hepatectomy or right paramedian sectorectomy might otherwise be needed. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Japan's educational policy has encouraged efforts to integrate lifelong learning education into a variety of community settings, including schools. However, such integrated practices have been scarcely carried out throughout Japan. Gakusha yugo (unity of schools and community) is a concept that has emerged from experimental practices in the Akitsu community in Narasino City, Chiba Prefecture, Japan. Activities based on the Gakusha yugo concept are intergenerational in nature insofar as there is an integration of the elementary school curriculum with lifelong learning pursuits for adults in the community. There is also an emphasis on engaging adults and children together in meaningful activities for community development. This article explains the Gakusha yugo concept and introduces the model established in the Akitsu community. The history, contents and effects of the 'Akitsu Model' are described, and implications for the future development of the Gakusha yugo concept and practices are considered. [ABSTRACT FROM AUTHOR]

Abstract: Microstructures and martensitic transformation behavior have been examined as for CoNiGa ferromagnetic shape memory alloy (FMSMA) ribbons rapidly solidified by a single-roll melt spinning. Transmission electron microscopy (TEM) bright-field images revealed dense striations in the martensite variants. These striations are identified to be thin twins, as in other FMSMAs. The analysis of a pair of Kikuchi lines in a selected-area electron diffraction pattern indicates that the b/a and c/a axial ratios of the orthorhombic martensite are 1.01 and 0.961, respectively. Crossings of fully twinned martensite variants are frequently observed in the TEM bright-field images, and the internal twins disappear in the crossing regions, that is, the regions are subjected to detwinning. In addition to the crossing of martensite variants, checkers and straight bands of martensite variants are observed in the crystal grains of the ribbon surface. These typical morphologies are supposed to be caused by some self-accommodation of martensitic transformation stress. [Copyright &y& Elsevier]

Abstract: Background: Differentiating between acute cellular rejection (ACR) and recurrent hepatitis C virus after liver transplantation in hepatitis C virus–positive patients is difficult, but vital for preventing graft loss. Methods: The blood eosinophil counts 3 days before or on the day of biopsy were retrospectively reviewed to evaluate their value for predicting ACR in 91 biopsy samples from 45 patients. Results: Eosinophil counts on the day of biopsy were significantly higher in the ACR group (n = 20) than in the non-ACR (n = 71) group, although the difference was negligible 3 days before the biopsy. A relative eosinophil count of 2% or an absolute eosinophil count of 200 cells/mm3 predicted ACR with a specificity of 94% or 96%, respectively. Conclusions: Blood eosinophil count on the day of biopsy can be helpful in the diagnosis of ACR in patients who underwent living donor liver transplantation for hepatitis C virus–related cirrhosis. [Copyright &y& Elsevier]

Abstract: Martensitic transformation behavior, magnetic properties and microstructures of Co–Ni–Ga alloy ribbons are investigated and contrasted with those of Co–Ni–Ga bulk alloy. The rapidly solidified 40–60μm-thickness ribbons of the alloy were prepared by an electro-magnetically controlled single-rolled melt-spinning apparatus. Martensitic transformation characteristics of the Co–Ni–Ga ribbons resemble those of bulk samples. However, transformation temperatures in the ribbons are higher than those of the bulk, suggesting the formation of stress-induced martensites. Coercive force of the Co–Ni–Ga ribbons strongly depend on the direction of the applied magnetic field. Maximum coercive force is obtained at θ =70° (θ is the angle between the magnetic field and the ribbon plane). This anisotropy of the magnetic properties is considered to be characteristics of the rapidly solidified ribbons. Microstructures of the martensitic phase in the ribbons are similar to those in the bulk samples, that is, optical and scanning electron microscopies reveal a typical lenticular shape and transmission electron microscopy shows internal twins and specific streaks on selected area electron diffraction patterns. [Copyright &y& Elsevier]

Abstract: Background: The relationship between hepatitis C virus (HCV) infection and new-onset diabetes mellitus (NODM) after liver transplantation is a controversial issue. Methods: A total of 223 adult living donor liver transplantation (LDLT) recipients followed for more than 6 months were analyzed for the prevalence of NODM. The prevalence was compared between 62 HCV-positive and 161 HCV-negative patients. All the HCV-positive patients underwent preemptive antiviral treatment with interferon α2b and ribavirin. Results: Preoperative diabetes mellitus was more frequently observed in HCV-positive patients (18% vs 4%, P = .001). NODM occurred more frequently in HCV-positive patients (41% vs 22%, P = .003). Multivariate analysis, however, revealed that HCV was not a predictor for NODM. A comparison of 14 HCV-positive patients with persistent NODM and 48 patients without persistent NODM indicated that there was no significant difference in the frequency of the viral response to antiviral therapy nor in HCV-RNA levels. Impaired glucose tolerance did not impact postoperative survival after LDLT. Conclusions: HCV was not associated with the prevalence of NODM after LDLT. NODM did not influence patient survival. [Copyright &y& Elsevier]

Summary:Since the introduction of reduced-intensity stem-cell transplantation (RIST), allogeneic stem-cell transplantation has become available for elderly patients. While pharmacokinetics of cyclosporine might differ according to age or other factors, cyclosporine is uniformly started at an oral dose of 6?mg/kg/day. We retrospectively reviewed medical records of 35 patients aged between 32 and 65 (median 52) years who had undergone RIST. Doses of cyclosporine were adjusted to the target blood trough level of 150-250?ng/ml. Cyclosporine dosages were changed in 33 patients (94%). Dose reduction was required in 32 patients because of high blood levels (n=25), renal dysfunction (n=3), hepatic dysfunction (n=2), and hypertension (n=2). Cyclosporine doses were increased in one because of the suboptimal level. The median of the achieved stable doses was 3.1?mg/kg/day (range, 1.0-7.4). Five patients sustained Grade III toxicities according to NCI-CTC version 2.0: renal dysfunction (n=4), hyperbilirubinemia (n=2), and hypertension (n=2). No patients developed grade IV toxicity. There was no statistically significant difference in the frequency and severity of cyclosporine toxicities between patients aged 50 years and above and those below 50 years. The initial oral cyclosporine dose of 6?mg/kg/day was unnecessarily high irrespective of age. The possible overdose of cyclosporine might have aggravated regimen-related toxicities.Bone Marrow Transplantation (2005) 35, 1079-1082. doi:10.1038/sj.bmt.1704960 Published online 4 April 2005 [ABSTRACT FROM AUTHOR]

Summary. To evaluate the diagnostic value of a halo on computed tomography (CT) in the diagnosis of invasive pulmonary aspergillosis (IPA), we retrospectively reviewed chest CT scans and autopsy reports for patients who had been admitted to our hospitals for the treatment of hematological malignancy. Pulmonary complications were suspected in all patients and chest CT scans were taken within a month of death. We examined the association between autopsy and CT findings in 48 patients who were diagnosed as IPA (n = 17), candidosis (n = 4), zygomycosis (n = 2), infiltration of hematological malignancy (n = 12), bacterial pneumonia (n = 6), cytomegalovirus pneumonia (n = 2), pulmonary hemorrhage (n = 2), or pulmonary congestion (n = 1). Patients with IPA showed a variety of CT findings, including halo (n = 13), nodules (n = 14), granular shadows (n = 3), masses (n = 6), consolidations (n = 9), wedge-shaped consolidations (n = 1), and cavitation (n = 2). In contrast, 0, 11 and two of the 31 patients without IPA showed halo, nodules and masses, respectively. These signs were more frequently observed in IPA patients than in non-IPA patients. The CT halo, especially, seemed to be specific for IPA in hospitalized neutropenic patients with hematological malignancies who developed antibiotic-resistant fever. For CT findings other than these three signs, there were no significant differences between IPA- and non-IPA patients. [ABSTRACT FROM AUTHOR]

We describe two patients who developed respiratory syncytial virus (RSV) pneumonia after BMT. One died of RSV pneumonia after three courses of steroid pulse therapy. Surprisingly, RSV antigen was identified in the bronchoalveolar lavage fluid (BALF) obtained post mortem. Steroid pulse therapy might have suppressed anti-RSV immunity, leading to persistent RSV infection for more than 1 month. The other patient received donor lymphocyte infusions (DLI) for relapsed plasma cell leukemia, while having active RSV pneumonia. His respiratory condition improved after DLI, and RSV antigen disappeared in BALF and nasal swabs. DLI might be effective in cases of life-threatening RSV pneumonia. Bone Marrow Transplantation (2000) 26, 573–576. [ABSTRACT FROM AUTHOR]

Presents the letter to the editor about an article on graft-versus-host disease, published in a previous issue of the journal.

Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation has been described as ocurring in 40% to 60% of cases. Although this type of recurrence was considered a benign condition for a long time, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney transplantation. In case 1, renal function remained stable with a creatinine level of 1.2 mg/dL at 5 months after diagnosis and 61 months after transplantation. In case 2, the patient lost his graft and returned to regular hemodialysis at 36 months after diagnosis and 125 months after kidney transplantation. [Copyright &y& Elsevier]

For a given odd integer n > 1 , we provide some families of imaginary quadratic number fields of the form Q ( x 2 − t n ) whose ideal class group has a subgroup isomorphic to Z / n Z . [ABSTRACT FROM AUTHOR]

This article discusses a new technique called "Loop9" for closing mucosal defects after colorectal endoscopic submucosal dissection (ESD). The study included 109 lesions in 106 patients who underwent colorectal ESD. The Loop9 method achieved a high success rate of 96.3% for complete closure of the defects, with a median closure time of 15 minutes. The technique was found to be feasible, effective, and cost-effective, eliminating the need for expensive devices or double-channel endoscopes. However, further studies are needed to validate these findings. [Extracted from the article]

To develop silicon-based spintronic devices, we have explored high-quality ferromagnetic Fe3Si/silicon (Si) structures. Using low-temperature molecular beam epitaxy at 130 °C, we realize the epitaxial growth of ferromagnetic Fe3Si layers on Si(111) with an abrupt interface, and the grown Fe3Si layer has the ordered DO3 phase. Measurements of magnetic and electrical properties for the Fe3Si/Si(111) yield a magnetic moment of ∼3.16μB/f.u. at room temperature and a rectifying Schottky-diode behavior with the ideality factor of ∼1.08, respectively. [ABSTRACT FROM AUTHOR]

Abstract: The vast amount of experience with deceased donor liver transplantation allows for the evaluation of the causes underlying late graft loss and the adoption of strategies for its prevention. In contrast, the long-term results or causes of late graft loss after adult-to-adult living donor liver transplantation have not been fully examined. Thus, we analyzed 176 adult recipients who survived at least 1 year after living donor liver transplantation. The median follow-up period was 33 months. Of the 176 recipients, eight died and three others underwent retransplantation. The most common cause of graft loss in our series was cholangitis (n = 4), which might be due partly to technical problems. The 3-year and 5-year patient survival rates of the subjects were 95% and 90%, respectively. Long-term survival after living donor liver transplantation was satisfactory in our series. Further improvement of surgical techniques for biliary reconstruction may reduce late graft loss. [Copyright &y& Elsevier]

Reports on the guidelines proposed by the French-American-British cooperative group for diagnosis of acute myeloid leukemia (AML-MO) to standardize the diagnostic criteria. Diagnosis of a patient with AML-MO; Characteristics of leukemic cells; Examination of bone marrow specimen.

Background Data on outcomes of left hepatic trisectionectomy ( LT) for perihilar cholangiocarcinoma are limited. The aim of this study was to clarify short- and long-term outcomes of LT for perihilar cholangiocarcinoma. Methods Patients with perihilar cholangiocarcinoma who underwent LT between January 2000 and October 2011 were analysed. Surgical variables, mortality, morbidity (Clavien grade I-V), recurrence sites and survival were compared between subjects who underwent LT, right hemihepatectomy or left hemihepatectomy. Results A total 214 patients underwent resection for perihilar cholangiocarcinoma, 25 (11·7 per cent) of whom underwent LT, 88 (41·1 per cent) right hemihepatectomy and 94 (43·9 per cent) left hepatectomy. There were no deaths among those who had LT, but 20 patients developed complications. The incidence of grade IIIa complications was significantly higher among patients who underwent LT than in patients who had right or left hemihepatectomy ( P = 0·001 and P < 0·001 respectively). Only one patient developed a grade IIIb or IV complication (liver failure) after LT. The overall 5-year survival rate after LT was 39 per cent and median survival was 45 months. There were no significant differences in survival between patients who underwent LT and those who had a right or left hemihepatectomy. Conclusion LT may provide a good outcome for advanced perihilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries. [ABSTRACT FROM AUTHOR]

Abstract: Background: An accurate estimation of preoperative volumetric measurements of the donor liver is essential in living donor liver transplantation. Methods: Three-dimensional (3-D) computed tomography (CT) was applied to 56 living donors. 3-D images of the liver were constructed using the region-growing method and the volume of each sector was measured. Results: The median volume ratios of the left liver, caudate lobe, right paramedian, and lateral sectors were 34%, 4%, 38%, and 25% of the total liver volume, respectively. The shape of the congestive area in the right paramedian sector was properly demonstrated by 3-D CT. The volume of the region corresponded to 32% of the right liver. The actual volume of the graft correlated well with the estimated graft volume (n = .86). Conclusions: The region-growing method was useful for graft selection and for determining the indication of middle hepatic vein reconstruction in right liver grafts. [Copyright &y& Elsevier]

Abstract: The right lateral sector is an alternative graft for living donor liver transplantation. Three-dimensional image reconstruction of right lateral sector grafts was performed to reveal vascular anatomy and volume using three-dimensional computed tomography software in three donors. There was a correlation between actual and estimated volume (r = .93), although actual graft volume tended to be larger than the preoperative estimated volume. In one donor, a portal branch of the right lateral sector was independently ramified. The branch was sacrificed in the operation because its territory volume was only 44 cm3. Three-dimensional images matched the shape of the right lateral sector graft. Three-dimensional computed tomography might be useful before donor hepatectomy, providing important information for decisions regarding the operative procedure. [Copyright &y& Elsevier]

Summary:To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25–2.97; P=0.003), performance status (2–4 vs 0–1) (2.50, 1.51–4.16; P<0.001), risk of underlying diseases (1.85, 1.21–2.83; P=0.004), acute GVHD (2.57, 1.72–3.84; P<0.001), and CML (0.38, 0.21–0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.Bone Marrow Transplantation (2005) 36, 667–674. doi:10.1038/sj.bmt.1705122; published online 22 August 2005 [ABSTRACT FROM AUTHOR]

Summary:Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n=6) or autopsy results (n=1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n=1), <10 mg/dl haptoglobin (n=1), and >200 IU/dl lactic dehydrogenase (LD) (n=4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n=4), fresh frozen plasma (n=1), and a reduction of immunosuppressive agents (n=1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.Bone Marrow Transplantation (2005) 36, 517–523. doi:10.1038/sj.bmt.1705099; published online 18 July 2005 [ABSTRACT FROM AUTHOR]

Summary:We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12–10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08–20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090–0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.Bone Marrow Transplantation (2005) 36, 205–213. doi:10.1038/sj.bmt.1705027; published online 6 June 2005 [ABSTRACT FROM AUTHOR]

Summary:Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.Bone Marrow Transplantation (2005) 35, 549-546. doi:10.1038/sj.bmt.1704776 Published online 31 January 2005 [ABSTRACT FROM AUTHOR]

Summary:Bloodstream infection (BSI) is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). Corticosteroids mask inflammatory responses, delaying the initiation of antibiotics. We reviewed medical records of 69 allo-SCT patients who had been on>0.5?mg/kg prednisolone to investigate the efficacy of weekly surveillance blood cultures. A total of 36 patients (52%) had positive cultures, 25 definitive BSI and 11 probable BSI. Pathogens in definitive BSI were Staphylococcus epidermidis (n=7), S. aureus (n=4), Entrococcus faecalis (n=3), Pseudomonas aeruginosa (n=5), Acenitobacter lwoffii (n=4), and others (n=10). The median interval from the initiation of corticosteroids to the first positive cultures was 24 days (range, 1-70). At the first positive cultures, 15 patients with definitive BSI were afebrile. Four of them remained afebrile throughout the period of positive surveillance cultures. Patients with afebrile BSI tended to be older (P=0.063), and had in-dwelling central venous catheters less frequently than febrile patients (P<0.0001). Bloodstream pathogens were directly responsible for death in two patients with afebrile BSI. This study demonstrates that cortisosteroid frequently masks inflammatory reactions in allo-SCT recipients given conrticosteroids, and that surveillance blood culture is only diagnostic clue for‘occult’BSI.Bone Marrow Transplantation (2005) 35, 577-582. doi:10.1038/sj.bmt.1704830 Published online 24 January 2005 [ABSTRACT FROM AUTHOR]

Cryptococcosis is the third most common invasive fungal infection in solid organ transplantation, which usually occurs more than 6 months after the primary operation. In our series of 180 consecutive adult living-donor liver transplantation recipients, three (1.5%) had cryptococcosis and one of these patients died. The serum cryptococcal antigen examination was positive in all three patients who suffered from cryptococcosis. The serum cryptococcal antigen test might contribute to the early detection and treatment of cryptococcosis. [ABSTRACT FROM AUTHOR]

Summary:Acute regimen-related toxicity (RRT) is minimal in reduced-intensity stem-cell transplantation (RIST). However, the Seattle RRT grading (Bearman et al), developed in the context of conventional-intensity transplantation, is frequently applied to RIST. We compared the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 with the Seattle criteria after RIST in 86 patients. RRT within 30 days of transplant graded by both sets of criteria were significantly associated with the outcome confirming the predictive value of both the systems. A total of 15 patients died of disease progression, and 12 of transplant-related mortality: RRT (n=2), graft-versus-host disease (GVHD) (n=7), infection (n=1), and others (n=2). GVHD-related deaths primarily resulted from infections after steroid treatment (n=6) and bronchiolitis obliterans (n=1). This study shows that NCI-CTC is appropriate in toxicity evaluation of RIST, and that its application to RIST enables a toxicity comparison between RIST and other types of cancer treatments. Since GVHD is a significant problem in RIST, modifications are required to evaluate immunological complications following RIST.Bone Marrow Transplantation (2004) 34, 787-794. doi:10.1038/sj.bmt.1704673 Published online 13 September 2004 [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In this study, we examined the in vivo effect of FTY720 on rat thymus and spleen. Materials and methods: Inbred male Lewis (RT-Il) rats, 5-weeks-old, received FTY720 (0.1, 1, or 10 mg/kg) by intramuscular injection into 1 of 4 limbs daily for 7 days. The rats were humanely killedat 1, 3, 5, or 7 days after starting administration of FTY720. The thymus and spleen were obtained for hematoxylin and eosin (HE) as well as immunoperoxidase staining using the antibodies OX8 (CD8), W3/25 (CD4), and OX6 (major histocompatibility complex class II). Results: HE staining revealed marked atrophy in the cortical region of the thymus among rats administered FTY720 at the dose of 10 mg/kg. The atrophy extended to the whole cortex. On day 7 of administration of FTY 720 (10 mg/kg), the medulla of the thymus showed relative expansion due to cells accumulation. Also, the spleens of FTY720-treated rats revealed an obvious reduction in the T-cell–dependent areas around the central artery. In conclusion, the immunosuppressive effect of FTY720 may be due to an inhibitory effect on T-cell emigration from the thymus to the periphery. [Copyright &y& Elsevier]

Background and aims: Many lines of evidence suggest that T helper cell type 1 (Th1) immune responses predominate in Crohn's disease (CD). Recently, a novel transcription factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1 development. This study was designed to investigate the role of T-bet and proinflammatory cytokines in Th1 mediated immunopathology in CD. Materials: CD4+ lamina propria mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n = 10; ulcerative colitis (UC), n = 10; normal controls (NL), n = 5). Methods: (1) T-bet expression of CD4+ LPMCs was examined by quantitative real time polymerase chain reaction and western blotting. (2) T-bet expression of LPMCs stimulated by interleukin (IL)-12/IL-18 was analysed by western blotting. (3) Interferon γ (IFN-γ) production and T-bet expression of CD4+ peripheral blood mononuclear cells (PBMCs) were examined with or without stimulation by anti-CD3/CD28 monoclonal antibodies and/or IL-12. RESULTS: (1) T-bet expression of CD4+ LPMCs was increased in CD compared with UC and NL. (2) Synergistically, augmentation of IFN-γ production by IL-12/IL-18 was independent of T-bet expression in LPMCs. (3) T-bet was induced by T cell receptor stimulation in CD4+ PBMCs. T-bet induction correlated with IFN-γ production and with augmentation of surface expressed IL-12 receptor β2. Conclusions: T-bet induction by antigenic stimulation and subsequent stimulation by macrophage derived IL-12/IL-18 are important for establishing Th1 mediated immunopathology in CD. [ABSTRACT FROM AUTHOR]

Summary:The purpose of this study was to evaluate the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen (RIST) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In all, 36 patients (median age 55 years) underwent RIST from an HLA-matched related donor between September 1999 and December 2002. The diagnoses included AML (n=14), leukemia evolving from MDS (n=10), and MDS (refractory anemia with excess blasts n=6, refractory anemia n=6). The RIST regimen consisted of purine analog (cladribine or fludarabine)/busulfan, with or without antithymocyte globulin. The regimen was well tolerated, and 34 patients achieved durable engraftment and most achieved remission after RIST. A total of 17 patients developed grade II-IV acute GVHD, and 27 developed chronic GVHD. Eight patients relapsed, and five of them received antithymocyte globulin (ATG) as part of the preparative regimen. A total of 12 patients died (four disease progression, six transplantation-related complications, and two others). Estimated 1-year disease-free survival (DFS) in low- and high-risk groups was 85 and 64%, respectively. We conclude that RIST can be performed safely in elderly patients with myeloid malignancies, and has therapeutic potential for those who fail conventional chemotherapy. In view of the significant association between GVHD or ATG and DFS, defined management of GVHD following RIST should become a major target of clinical research.Bone Marrow Transplantation (2004) 33, 891-900. doi:10.1038/sj.bmt.1704477 Published online 29 March 2004 [ABSTRACT FROM AUTHOR]

Summary:To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180?mg/m2, n=18) or cladribine-based (0.77?mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8?Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.Bone Marrow Transplantation (2004) 33, 697-702. doi:10.1038/sj.bmt.1704425 Published online 2 February 2004 [ABSTRACT FROM AUTHOR]