Successful infusion of obinutuzumab by desensitization: a case of anaphylactic shock during desensitization

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Simultaneous control of the Dzyaloshinskii-Moriya interaction and magnetic anisotropy in nanomagnetic trilayers.

Magneto-optical Kerr effect (MOKE) microscopy measurements of magnetic bubble domains demonstrate that Ar^{+} irradiation around 100 eV can tune the Dzyaloshinskii-Moriya interaction (DMI) in Pt/Co/Pt trilayers. Varying the irradiation energy and dose changes the DMI sign and magnitude separately from the magnetic anisotropy, allowing tuning of the DMI while holding the coercive field constant. This simultaneous control emphasizes the different physical origins of these effects. To accurately measure the DMI, we propose and apply a physical model for a poorly understood peak in domain wall velocity at zero in-plane field. The ability to tune the DMI with the spatial resolution of the Ar^{+} irradiation enables new fundamental investigations and technological applications of chiral nanomagnetics.

Theory of Kondo suppression of spin polarization in nonlocal spin valves.

We theoretically analyze contributions from the Kondo effect to the spin polarization and spin diffusion length in all-metal nonlocal spin valves. Interdiffusion of ferromagnetic atoms into the normal metal layer creates a region in which Kondo physics plays a significant role, giving discrepancies between experiment and existing theory. We start from a simple model and construct a modified spin drift-diffusion equation which clearly demonstrates how the Kondo physics not only suppresses the electrical conductivity but even more strongly reduces the spin diffusion length. We also present an explicit expression for the suppression of spin polarization due to Kondo physics in an illustrative regime. We compare this theory to previous experimental data to extract an estimate of the Elliot-Yafet probability for Kondo spin flip scattering of 0.7 ± 0.4, in good agreement with the value of 2/3 derived in the original theory of Kondo.

Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis

BACKGROUND: Thymus and activation-regulated chemokine (TARC), a member of the CC chemokine family, plays a crucial role in Th2-specific inflammation. We aimed to determine the concentration of sputum TARC in children with asthma and eosinophilic bronchitis (EB) and its relation with eosinophilic inflammation, pulmonary function, and bronchial hyper-responsiveness. METHODS: In total, 90 children with asthma, 38 with EB, and 45 control subjects were enrolled. TARC levels were measured in sputum supernatants using an ELISA. We performed pulmonary function tests and measured exhaled fractional nitric oxide, eosinophil counts in blood, and sputum and serum levels of total IgE in all children. RESULTS: Sputum TARC levels were significantly higher in children with asthma than in either children with EB (p = 0.004) or the control subjects (p = 0.014). Among patients with asthma, sputum TARC concentration was higher in children with sputum eosinophilia than in those without sputum eosinophilia (p = 0.035). Sputum TARC levels positively correlated with eosinophil counts in sputum, serum total IgE levels, exhaled fractional nitric, and the bronchodilator response. Negative significant correlations were found between sputum TARC and FEV1/FVC (the ratio of forced expiratory volume in one second and forced expiratory vital capacity) or PC20 (the provocative concentration of methacholine causing a 20% decrease in the FEV1). CONCLUSION: Elevated TARC levels in sputum were detected in children with asthma but not in children with EB. Sputum TARC could be a supportive marker for discrimination of asthma from EB in children showing characteristics of eosinophilic airway inflammation

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Effects of dietary recombinant chlorella supplementation on growth performance, meat quality, blood characteristics, excreta microflora, and nutrient digestibility in broilers.

The use of chlorella as an immune stimulant to enhance nonspecific host defense mechanisms or as an antimicrobial to inhibit bacterial growth has been reported. Thus, the aim of the present study was to clarify the effect of recombinant chlorella supplementation on growth performance, meat quality, and the blood profile, excreta microflora, and nutrient digestibility in broilers. A total of 375 one-day-old ROSS 308 broilers (male and female) were allotted to 5 dietary treatments using 5 cages with 15 chicks per cage. Treatments were: 1) NC, basal diet supplemented with 1.0% E. coli fermented liquor (EFL); 2) PC1, 0.2% EFL with chlorella; 3) PC2, 1.0% EFL with chlorella; 4) T1, 0.2% EFL with chlorella (anti-viral); and 5) T2, 1.0% EFL with chlorella (anti-viral). The broilers in the T2 treatment groups showed higher body weight gain (BGW) by 2.55% (P < 0.01) and lower feed conversion ratio (FCR) by 2.75% (P < 0.05) compared with those fed the control NC treatment group. Moreover, the blood contents of blood urea nitrogen (BUN), creatinine, and IgA in the broilers of the T2 treatment group were significantly increased by 28.12, 23.07, and 29.72%, respectively -more than those found in the broilers of the NC treatment group (P < 0.01). In contrast, the LDL/C in the blood from the animals in the T2 treatment group was significantly decreased by 23.23% - more than that in the blood from the NC broilers (P < 0.05). Based on these results, we suggest that the dietary supplementation of broilers with recombinant chlorella could improve their growth performance, increase the concentration of IgA and apparently metabolizable nitrogen in the blood, and decrease ammonia emissions. Therefore, our findings have important implications for the effect of recombinant chlorella supplementation through increasing the concentration of IgA and the level of metabolizable nitrogen.

The colour of paternity: extra-pair paternity in the wild Gouldian finch does not appear to be driven by genetic incompatibility between morphs.

In socially monogamous species, individuals can use extra-pair paternity and offspring sex allocation as adaptive strategies to ameliorate costs of genetic incompatibility with their partner. Previous studies on domesticated Gouldian finches (Erythrura gouldiae) demonstrated a genetic incompatibility between head colour morphs, the effects of which are more severe in female offspring. Domesticated females use differential sex allocation, and extra-pair paternity with males of compatible head colour, to reduce fitness costs associated with incompatibility in mixed-morph pairings. However, laboratory studies are an oversimplification of the complex ecological factors experienced in the wild and may only reflect the biology of a domesticated species. This study aimed to examine the patterns of parentage and sex ratio bias with respect to colour pairing combinations in a wild population of the Gouldian finch. We utilized a novel PCR assay that allowed us to genotype the morph of offspring before the morph phenotype develops and to explore bias in morph paternity and selection at the nest. Contrary to previous findings in the laboratory, we found no effect of pairing combinations on patterns of extra-pair paternity, offspring sex ratio or selection on morphs in nestlings. In the wild, the effect of morph incompatibility is likely much smaller, or absent, than was observed in the domesticated birds. Furthermore, the previously studied domesticated population is genetically differentiated from the wild population, consistent with the effects of domestication. It is possible that the domestication process fostered the emergence (or enhancement) of incompatibility between colour morphs previously demonstrated in the laboratory.

IgE cross-reactivity of peanut with walnut and soybean in children with food allergy

BACKGROUND: Peanut allergies are common and can be life-threating for sensitised individuals. Peanut allergens share significant amino acid homology with those of other legumes and tree nuts, but their cross-reactivity still remains unclear. OBJECTIVE: We sought to determine the clinical significance of the cross-reactivity of peanut allergens with those of walnut and soybean. METHODS: Pooled sera from eight subjects with both peanut and walnut specific IgE were investigated in an inhibition test. After the sera were incubated with either peanut or walnut protein extracts, the quantity of IgE antibodies against the peanut and walnut was measured using an immunoCAP test. Likewise, pooled sera from 18 subjects with both peanut and soybean specific IgE antibodies were incubated with either peanut or soybean protein extracts and evaluated with a peanut and soybean immunoCAP test. SDS-PAGE and immunoblotting were also performed with peanut, walnut and soybean protein extracts and relevant sera. RESULTS: Peanut specific IgE was inhibited up to 20% and 26% by walnut and soybean protein extracts, respectively. In reverse, walnut and soybean specific IgE were inhibited up to 21% and 23% by peanut protein extracts, respectively. In the immunoblot analysis, pooled serum from the subjects with peanut specific IgE antibodies reacted with walnut protein extracts significantly. CONCLUSION: Although the clinical significance of the cross-reactivity of peanut specific IgE with walnut and soybean protein extracts has not been established, we believe that individuals who are allergic to peanuts need to be cautious about consuming walnuts and soybeans

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Low Hemoglobin A1c Increases the Risk of Disability in Community-dwelling Older Non-diabetics Adults.

OBJECTIVE: To describe the health characteristics of individuals with low HbA1c levels and evaluate the association between HbA1c level and disability or all-cause mortality in non-diabetic older adults. DESIGN: Prospective observational cohort study. SETTING: Seongnam, Gyeongi Province, Korea. PARTICIPANTS: Among the 1,000 community-dwelling Koreans ≥ 65 years of age who were followed for 5 years, 760 non-diabetic individuals were analyzed. MEASUREMENTS: Activities of Daily Living (ADL) and Instrumental ADL (IADL) were evaluated and mortality data were obtained from the National Statistics Office of Korea. RESULTS: The mean age was 76.3 (SD 9.0) years, and 319 subjects (42.0%) were male. Lower level of HbA1c was associated with less frequent hypertension and less frequent use of aspirin or statin, and lower values of body mass index, hematocrit, total iron-binding capacity, albumin, and cholesterol level. The participants were categorized into 3 groups according to their HbA1c (group I, < 5.5%; group II, 5.5~5.9%; and group III, 6.0 ~ 6.4%). Although, there was no significant difference in functional status according to baseline HbA1c level, disability was more frequently observed as the HbA1c level decrease (18.3% in group I, 12.5% in group II, and 5.3% in group III, p=0.029) at the 5-year follow-up evaluation. There were 172 deaths (22.6%) during the follow-up period. There was no significant difference in mortality among the groups, however, group I had a 2.071-fold higher risk for the incident disability or mortality over group III after adjusting age, gender, and possible confounder (95% CI: 1.040 ~ 4.124, p=0.038). CONCLUSIONS: Lower level of HbA1c was associated with an increased risk of disability in non-diabetic older adults.

Linkage mapping of a polymorphic plumage locus associated with intermorph incompatibility in the Gouldian finch (Erythrura gouldiae).

Colour polymorphism is known to facilitate speciation but the genetic basis of animal pigmentation and how colour polymorphisms contribute to speciation is poorly understood. Restricted recombination may promote linkage disequilibrium between the colour locus and incompatibility genes. Genomic rearrangement and the position of relevant loci within a chromosome are important factors that influence the frequency of recombination. Therefore, it is important to know the position of the colour locus, gene order and recombination landscape of the chromosome to understand the mechanism that generates incompatibilities between morphs. Recent studies showed remarkable pre- and postzygotic incompatibilities between sympatric colour morphs of the Gouldian finch (Erythrura gouldiae), in which head feather colour is genetically determined by a single sex-linked locus, Red. We constructed a genetic map for the Z chromosome of the Gouldian finch (male-specific map distance=131 cM), using 618 captive-bred birds and 34 microsatellite markers, to investigate the extent of inter- and intraspecific genomic rearrangements and variation in recombination rate within the Z chromosome. We refined the location of the Red locus to a ~7.2-cM interval in a region with a moderate recombination rate but outside the least-recombining, putative centromeric region. There was no evidence of chromosome-wide genomic rearrangements between the chromosomes carrying the red or black alleles with the current marker resolution. This work will contribute to identifying the causal gene, which will in turn enable alternative explanations for the association between incompatibility and colouration, such as fine-scale linkage disequilibrium, genomic rearrangements and pleiotropy, to be tested.

Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts.

Bone marrow-derived early endothelial progenitor cells (BM-EPCs) are a clinical tool for enhancing revascularization. However, the therapeutic efficacy of co-transplantation of BM-EPC with islets has not been investigated. In this study, marginal mass islets were co-transplanted with or without BM-EPCs under the kidney capsules of syngeneic streptozotocin-induced diabetic mice. Using green fluorescent protein transgenic (GFP-Tg) mice as BM-EPC and islet donors or recipients, the role of EPCs in revascularization was assessed for graft morphology, vascular density and fate of EPCs by immunohistochemistry. Islet-EPC co-transplantation improved the outcome of islet transplantation as measured by glucose tolerance, serum insulin level and diabetes reversal rate, compared with transplantation of islets alone. Between groups, the morphology of islet grafts showed significant differences in size and composition of grafted endocrine tissues. Significantly more vessel density derived from donors and recipients was detected with islet-EPC co-transplantation. Abundant GFP-Tg mice-derived BM-EPCs (GFP-EPCs) were observed in or around islet grafts and incorporated into CD31-positive capillaries. Remaining GFP-EPCs expressed VEGF. In conclusion, co-transplantation of islets with BM-EPCs could improve the outcome of marginal mass islet transplantation by promoting revascularization and preserving islet morphology.

Effects of dietary supplementation of citrus by-products fermented with a probiotic microbe on growth performance, innate immunity and disease resistance against Edwardsiella tarda in juvenile olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

Two consecutive studies were conducted to evaluate the dietary supplementation of citrus by-products (CB) fermented with probiotic bacteria on growth performance, feed utilization, innate immune responses and disease resistance of juvenile olive flounder. In Experiment I, five diets were formulated to contain 0% (control) or 3% four different CB fermented with Bacillus subtilis (BS), Enterococcus faecium (EF), Lactobacillus rhamnosus (LR) and L. plantarum (LP) (designated as CON, CBF-BS, CBF-EF, CBF-LR and CBF-LP, respectively). During 10 weeks of a feeding trial, growth performance and feed efficiency were not significantly different among all the fish groups. However, fish fed CBF containing diets had significantly higher survivals than the CON group. Disease resistance of fish against Edwardsiella tarda was increased by the fermentation of CB. In Experiment II, we chose the BS as a promising probiotic and formulated five diets to contain 0%, 2%, 4%, 6% and 8% CBF-BS. Growth performance was not significantly affected by the CBF-BS supplementation during 6 weeks of a feeding trial. Innate immunity of fish was significantly enhanced by CBF-BS supplementation. Myeloperoxidase and lysozyme activities were increased in a dose-dependent manner by dietary CBF-BS inclusions. In a consecutive challenge test against E. tarda, an increased disease resistance was found by CBF-BS supplementation. These studies indicate that the fermentation process of CB with probiotic has beneficial effects on innate immunity and thereby increases disease resistance of olive flounder against E. tarda. Bacillus subtilis can be used as a promising probiotic microbe for by-product fermentation in fish feeds.

Plasmon-exciton hybridization in ZnO quantum-well Al nanodisc heterostructures.

We demonstrate the formation of a hybridized plasmon-exciton state exhibiting strong exciton-plasmon coupling in ZnO/Zn(0.85)Mg(0.15)O single quantum wells capped with arrays of Al nanodiscs. Tuning the quantum-well width and the diameter and pitch of the Al nanodisc arrays facilitates a transition from the weak-coupling regime into the strong coupling regime. Finite-difference time-domain simulations substantiate the localization of the plasmonic quadrupole moment within the ZnO quantum-well layer, resulting in a hybridized plasmonexciton state demonstrating a Rabi splitting of roughly 15 meV in heterostructures that exhibit a prominent plasmon quadrupole mode. The significant tunability offered by quantum-well heterostructures like those discussed here provides a flexible system for controlling exciton plasmon coupling in a device-compatible thin-film architecture.

Treatment of autoimmune diabetes in NOD mice by Toll-like receptor 2 tolerance in conjunction with dipeptidyl peptidase 4 inhibition.

AIMS/HYPOTHESIS: We have shown that chronic administration of the Toll-like receptor 2 (TLR2) agonist Pam3CSK(4) prevents diabetes in NOD mice by inducing TLR2 tolerance of dendritic cells (DCs). We have also reported that a novel dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1229, could increase beta cell mass. Here we investigated whether a combination of DPP4 inhibition, with beneficial effects on beta cell mass, and TLR2 tolerisation, protecting beta cells from autoimmune destruction, could treat a model of established type 1 diabetes. METHODS: Diabetic NOD mice were treated with 100 µg Pam3CSK(4), administered three times a week for 3 weeks, in combination with feeding with chow containing 0.3% DA-1229. Beta cell mass and proliferation were studied by immunohistochemistry. DC tolerance was assessed by studying diabetogenic CD4(+) T cell priming after adoptive transfer and expression of costimulatory molecules on DCs by flow cytometry. RESULTS: We observed reversal of diabetes in NOD mice by Pam3CSK(4)+DA-1229 but not by either Pam3CSK(4) or DA-1229 alone. Beta cell mass and the number of proliferating beta cells were significantly enhanced by Pam3CSK(4)+DA-1229, but not by either Pam3CSK(4) or DA-1229 alone. Diabetogenic T cell priming by DCs and upregulation of costimulatory molecules after ex vivo stimulation were attenuated in mice treated with Pam3CSK(4)+DA-1229, indicating DC tolerance. The relative proportions of CD4(+) T cells, CD8(+) T cells, B cells, DCs, macrophages and regulatory T cells, and T-helper polarisation were unchanged by treatment with Pam3CSK(4)+DA-1229. CONCLUSIONS/INTERPRETATION: These data demonstrate that a combination of TLR2 tolerisation and DPP4 inhibition can reverse early-onset diabetes in NOD mice.

Counting small hypointense spots confounds the quantification of functional islet mass based on islet MRI.

Iron-containing fragmented islets or free iron released from dying cells could confound the interpretation of MRI of iron nanoparticle-labeled islets. Exclusion of small hypointense spots could be a useful strategy to avoid such artifact. We investigated whether this strategy could improve the estimation of functioning islet mass after islet transplantation. Using a rat syngeneic intraportal islet transplantation model, we quantitatively assessed the relationships between total area, number of hypointense spots on MRI that belong to each size quartile and glycemic control of the recipients. The total area of hypointense spots on MRI was greater in the recipients that achieved diabetes reversal (p = 0.002), whereas the total number of hypointense spots was not different (p = 0.757). Exclusion of small hypointense spots improved the association between the number of hypointense spots and the blood glucose level of the recipients (p < 0.001). Ex-vivo imaging and histologic study confirmed that some small hypointense spots represent the phagocytosed free iron. Exclusion of small hypointense spots improved the quantification of the functional islet mass based on islet MRI. This would be a useful principle in the development of an algorithm to estimate functioning islet mass based on islet MRI.

Hepatocellular carcinoma in patients with chronic liver disease: a comparison of gadoxetic acid-enhanced MRI and multiphasic MDCT.

AIM: To compare the diagnostic performances of gadoxetic acid-enhanced magnetic resonance imaging (MRI) and multiphasic multidetector computed tomography (MDCT) in the detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease. MATERIALS AND METHODS: Institutional review board approval was obtained for this study and informed consent was obtained from all patients. Fifty-one patients (43 men, eight women; age range 32-80 years) with 73 HCCs underwent gadoxetic acid-enhanced MRI and multiphasic MDCT. Two readers independently analysed each image in three separate reading sessions. The alternative free-response receiver operating characteristic (AFROC) method was used to analyse the diagnostic accuracy. Positive and negative predictive values and sensitivity were evaluated. RESULTS: A total of 73 HCCs were detected in 51 patients. Although not significant (p>0.05), the areas under the receiver operating characteristic curves were 0.877 and 0.850 for MDCT, 0.918 and 0.911 for dynamic MRI, and 0.905 and 0.918 for combined interpretation of dynamic and hepatobiliary phase MR images. Differences in sensitivity, specificity, and positive and negative predictive values between the readers were not statistically significant (p>0.05). Combined interpretation of dynamic and hepatobiliary phase MRI images was more useful than MDCT in the detection of HCC lesions ≤1cm in diameter for one reader (p=0.043). CONCLUSION: Gadoxetic acid-enhanced MRI and MDCT show similar diagnostic performances for the detection of HCC in patients with chronic liver disease. However, the combined interpretation of dynamic and hepatobiliary phase MRI images may improve diagnostic accuracy in the detection of HCC lesions ≤1cm in diameter.

Autophagy deficiency in beta cells leads to compromised unfolded protein response and progression from obesity to diabetes in mice.

AIMS/HYPOTHESIS: The unfolded protein response (UPR) in endoplasmic reticulum (ER) and autophagy are known to be related. We investigated the role of autophagy in UPR of pancreatic beta cells and the susceptibility of autophagy-deficient beta cells to the ER stress that is implicated in the development of diabetes. METHODS: Rat insulin promoter (RIP)-Cre(+);autophagy-related 7 (Atg7)(F/W) mice were bred with ob/w mice to derive RIP-Cre(+);Atg7(F/F)-ob/ob mice and to induce ER stress in vivo. GFP-LC3(+)-ob/ob mice were generated to examine in vivo autophagic activity. Real-time RT-PCR was performed to study the expression of the genes of the UPR machinery. Proteolysis was assessed by determining release of incorporated radioactive leucine. RESULTS: Production of UPR machinery was reduced in autophagy-deficient beta cells, which was associated with diminished production of p85α and p85ß regulatory subunits of phosphoinositide 3-kinase. Because of compromised UPR machinery, autophagy-deficient beta cells were susceptible to ER stressors in vitro. When mice with beta cell-specific autophagy deficiency, which have mild hyperglycaemia, were bred with ob/ob mice to induce ER stress in vivo, severe diabetes developed, which was accompanied by an increase in beta cell death and accumulation of reactive oxygen species. The increased demand for UPR present in obesity was unmet in autophagy-deficient beta cells. Autophagy level and autophagic activity were enhanced by lipid, while proteolysis was reduced. CONCLUSIONS/INTERPRETATION: These results suggest that autophagy is important for intact UPR machinery and appropriate UPR in response to lipid injury that increases demand for UPR. Autophagy deficiency in pancreatic beta cells may contribute to the progression from obesity to diabetes.

Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*).

AIM: To assess and compare the efficacy and safety of liraglutide with those of glimepiride, both in combination with metformin for the treatment of type 2 diabetes in Asian population from China, South Korea and India. METHODS: A 16-week, randomized, double-blind, double-dummy, four-arm, active control trial was carried out. In total, 929 subjects with type 2 diabetes with a mean (±s.d.) age of 53.3 ± 9.5 years, HbA1(c) of 8.6 ± 1.0% and body weight of 68.1 ± 11.7 kg were randomized (liraglutide 0.6, 1.2 or 1.8 mg once daily or glimepiride 4 mg once daily all in combination with metformin: 1 : 1 : 1 : 1). One subject withdrew immediately after randomization and before exposure. RESULTS: HbA1(c) was significantly reduced in all groups compared with baseline. Treatment with liraglutide 1.2 and 1.8 mg was non-inferior to glimepiride (mean HbA1(c) reduction: 1.36% points, 1.45% points and 1.39% points, respectively). No significant difference was shown in the percentage of subjects reaching American Diabetes Association HbA1(c) target <7% or American Association of Clinical Endocrinologists target ≤6.5% between liraglutide 1.2 and 1.8 mg and glimepiride. Liraglutide was associated with a 1.8-2.4 kg mean weight reduction, compared with a 0.1 kg mean weight gain with glimepiride. Liraglutide led to a significantly greater reduction in systolic blood pressure (SBP) compared with glimepiride. Two subjects in the glimepiride group reported major hypoglycaemia while none in the liraglutide groups. Liraglutide was associated with about 10-fold lower incidence of minor hypoglycaemia than glimepiride. Gastrointestinal disorders were the most common adverse events (AEs) for liraglutide, but were transient and resulted in few withdrawals. CONCLUSIONS: In Asian subjects with type 2 diabetes, once-daily liraglutide led to improvement in glycaemic control similar to that with glimepiride but with less frequent major and minor hypoglycaemia. Liraglutide also induced a significant weight loss and reduced SBP and was generally well tolerated. The most frequently reported AE was transient nausea. The effect of liraglutide in this Asian population is comparable to the effects seen in Caucasian, African American and Hispanic populations in global liraglutide phase 3 trials.

Living-donor liver transplantation in patients with concurrent active tuberculosis at transplantation.

SETTING: Although active tuberculosis (TB) is a contraindication for liver transplantation (LT), LT may be the only possible treatment option in patients with irreversible liver failure and concurrent TB. OBJECTIVES: To assess the outcome of LT in patients with concurrent TB and liver failure. METHODS: We retrospectively evaluated the clinical outcomes of nine LT recipients with concurrent TB in Korea, an intermediate TB burden country. RESULTS: The primary causes of living-donor LT (LDLT) in nine patients were anti-tuberculosis drug-induced fulminant hepatic failure (n = 4) and end-stage liver disease (n = 5). The sites of active TB were the lungs (n = 5), lymph nodes (n = 3) and pleura (n = 1). After LDLT, most patients were treated with less hepatotoxic drugs, including fluoroquinolones, ethambutol and cycloserine; none was treated with pyrazinamide. One patient experienced acute rejection, probably attributable to an interaction between rifampicin and cyclosporine. All nine patients, including one taking rifabutin, successfully completed anti-tuberculosis treatment and have been followed up for a median of 926 days after LDLT, without relapse of TB. CONCLUSION: When properly managed, the prognosis of LDLT recipients with concurrently active TB at transplantation is very favourable. The current protocol, which considers active TB an absolute contraindication for LT, should be modified or relaxed, particularly for patients with LDLT.

Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development.

Developmental tissues go through regression, remodeling, and apoptosis. In these processes, macrophages phagocytize dead cells and induce apoptosis directly. In hyaloid vascular system (HVS), macrophages induce apoptosis of vascular endothelial cells (VECs) by cooperation between the Wnt and angiopoietin (Ang) pathways through cell-cell interaction. However, it remains unclear how macrophages are activated and interact with VECs. Here we show that Ninjurin1 (nerve injury-induced protein; Ninj1) was temporally increased in macrophages during regression of HVS and these Ninj1-expressing macrophages closely interacted with hyaloid VECs. Systemic neutralization using an anti-Ninj1 antibody resulted in the delay of HVS regression in vivo. We also found that Ninj1 increased cell-cell and cell-matrix adhesion of macrophages. Furthermore, Ninj1 stimulated the expression of Wnt7b in macrophages and the conditioned media from Ninj1-overexpressing macrophages (Ninj1-CM) decreased Ang1 and increased Ang2 in pericytes, which consequently switched hyaloid VEC fate from survival to death. Collectively, these findings suggest that macrophages express Ninj1 to increase the death signal through cell-cell interaction and raise the possibility that Ninj1 may act similarly in other developmental regression mediated by macrophages.