Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

Effect of proton pump inhibitors on the development of hypomagnesemia induced by panitumumab.

Panitumumab, a therapeutic agent for unresectable advanced/recurrent colorectal cancer, is a human IgG2 monoclonal antibody that binds to and inhibits the activity of the epidermal growth factor receptor (EGFR). The onset of hypomagnesemia is a known side effect of anti-EGFR inhibitors, including panitumumab, and it is thought that inhibition of reabsorption of Mg in renal tubules is one of the causes. In addition, recent reports have shown that long-term administration of proton pump inhibitors (PPIs) reduces serum magnesium levels. Therefore, in this study, 102 patients who received oral PPIs treated with panitumumab were classified into a PPI combination group and a PPI non-combination group, and the effect of PPIs on the development of grade 2 or higher hypomagnesemia was investigated. The incidence of hypomagnesemia in the PPI combination group (46.9%, 15/32) was higher than that in the PPI non-combination group (25.7%, 18/70). A comparison of the backgrounds of the two groups of patients showed a significant difference in serum albumin levels. PPI administration was significantly associated with panitumumab-induced hypomagnesemia development when adjusted for known risk factors, serum albumin level, renal function, and oral magnesium oxide tablets in Cox proportional hazards regression analysis (hazard ratio 2.09; 95% confidence interval 1.03-4.22; P =0.040). These results indicate that detailed monitoring of serum magnesium levels is recommended for patients treated with panitumumab and co-administration of PPIs.

Effect of therapeutic plasma exchange on phenytoin plasma concentration in patients receiving intravenous fosphenytoin therapy.

We report for patients with encephalitis treated with plasma exchange (PE) and fosphenytoin. In patient 1, phenytoin levels decreased on the maintenance dose, and the phenytoin concentration was <10 µg/mL on day 12 of administration. In patient 2, the phenytoin levels was <10 µg/mL on day 4. Increasing the fosphenytoin dose pushed the phenytoin level into therapeutic range. There were no differences between the areas under the concentration-time curve of phenytoin with and without PE. We previously reported a decline in phenytoin levels after prolonged use of fosphenytoin. Therefore, dose adjustment of fosphenytoin in patients undergoing PE may be unnecessary.

Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean.

Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new 'aduncus' type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Eculizumab Salvage Therapy for Antibody-Mediated Rejection in a Desensitization-Resistant Intestinal Re-Transplant Patient.

The presence of elevated calculated panel reactive antibody (cPRA) and anti-HLA donor specific antibodies (DSA) are high risk factors for acute antibody-mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization-resistant intestinal re-transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut-off value of 3000 MFI and remains rejection free with a 2-year follow-up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization-resistant patients.

Molecular dynamics analysis of multiphase interfaces based on in situ extraction of the pressure distribution of a liquid droplet on a solid surface.

Molecular dynamics simulations of a nanoscale liquid droplet on a solid surface are carried out in order to examine the pressure tensor field around the multiphase interfaces, and to explore the validity of Young's equation. By applying the virial theorem to a hemicylindrical droplet consisting of argon molecules on a solid surface, two-dimensional distribution of the pressure tensor is obtained. Tensile principal pressure tangential to the interface is observed around the liquid-vapor transition layer, while both tensile and compressive principal pressure tangential to the interface exists around the solid-liquid transition layer due to the inhomogeneous density distribution. The two features intermix inside the overlap region between the transition layers at the contact line. The contact angle is evaluated by using a contour line of the maximum principal pressure difference. The interfacial tensions are calculated by using Bakker's equation and Young-Laplace equation to the pressure tensor distribution. The relation between measured contact angle and calculated interfacial tensions turns out to be consistent with Young's equation, which is known as the description of the force balance at the three-phase interface.

Citrulline level is a potent indicator of acute rejection in the long term following pediatric intestinal/multivisceral transplantation.

Citrulline has been advocated as a marker for acute cellular rejection (ACR) in intestinal transplantation; however, its significance as a forewarning in the long-term follow-up remains unknown. This study aimed to investigate the association between citrulline levels and the grading of ACR to establish a cutoff point that accurately predicts ACR beyond 3 months posttransplant in the pediatric patient population. During a 16-year period (1995-2011), a total of 13 499 citrulline samples were prospectively collected from 111 consecutive pediatric intestinal/multivisceral transplant recipients: 2155 were obtained concurrently with intestinal biopsies. There were 185 ACR episodes observed among 74/111 (67%) patients (median follow-up: 4.4 years). Citrulline levels were inversely proportional to the severity of ACR. Negative predictive values for any type of ACR (cutoff, 20 µmol/L) and moderate/severe ACR (cutoff, 10 µmol/L) were 95% and 99%, respectively. When patients were divided according to graft size, diagnostic accuracy using the same cutoff was identical. Similarly, subgroup analysis by the timing of citrulline measurement prior to biopsy varying from 1 to 7 days demonstrated comparable results. Citrulline is a potent indicator as a danger signal for ACR, being an exclusionary, noninvasive biomarker with excellent negative predictive values in the long term after pediatric intestinal/multivisceral transplant.

MicroRNA signature of intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.

Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents.

Predisposing factors of diminished survival in simultaneous liver/kidney transplantation.

Since the adoption of the Model for End-Stage Liver Disease, simultaneous liver/kidney transplants (SLKT) have substantially increased. Recently, unfavorable outcomes have been reported yet contributing factors remain unclear. We retrospectively reviewed 74 consecutive adult SLKT performed at our center from 2000 to 2010 and compared with kidney transplant alone (KTA, N = 544). In SLKT, patient and death-censored kidney graft survival rates were 64 ± 6% and 81 ± 5% at 5 years, respectively (median follow-up, 47 months). Multivariable analyses revealed three independent risk factors affecting patient survival: hepatitis C virus positive (HCV+, hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1-7.9), panel reactive antibody (PRA) > 20% (HR 2.8, 95% CI 1.1-7.2) and female donor gender (HR 2.9, 95% CI 1.1-7.9). For death-censored kidney graft survival, delayed graft function was the strongest negative predictor (HR 8.3, 95% CI 2.5-27.9), followed by HCV+ and PRA > 20%. The adjusted risk of death-censored kidney graft loss in HCV+ SLKT patients was 5.8 (95% CI 1.6-21.6) compared with HCV+ KTA (p = 0.008). Recurrent HCV within 1 year after SLKT correlated with early kidney graft failure (p = 0.004). Careful donor/recipient selection and innovative approaches for HCV+ SLKT patients are critical to further improve long-term outcomes.

Combination treatment with statins and bezafibrate induces myotoxicity via inhibition of geranylgeranyl pyrophosphate biosynthesis and Rho activation in L6 myoblasts and myotube cells.

Statins and fibrates are frequently used to treat hyperlipidemia; however, these drugs may have adverse effects such as rhabdomyolysis. The incidence of rhabdomyolysis due to fibrates and statins is low (0.0028-0.0096%) when administered as monotherapy, however it increases to 0.015-0.021% when the drugs are used in combination. The mechanism underlying myotoxicity induced by the combination of statins and fibrates is yet unclear. Here, we investigated the mechanisms underlying induced myotoxicity in rat myoblasts L6 and differentiated L6 cells (myotubes) using a combination of statins and fibrates. We found that cell death induced by a combination of fluvastatin or simvastatin with bezafibrate or fenofibrate in L6 myoblasts and myotubes was mediated by inhibition of geranylgeranyl pyrophosphate (GGPP) production. Additionally, the drug combination inhibited Rho activation in L6 myoblasts and myotube cells. In L6 myoblasts, the combination of statins and bezafibrate enhanced p27 expression and induced G1 arrest and apoptosis. Furthermore, combined treatment suppressed Akt activation and enhanced Bim expression in L6 myotubes but did not affect extracellular regulated protein kinase 1/2 activation. These results suggested that combined administration of statins and fibrates induced death of L6 myoblasts and myotube cells by inhibiting GGPP biosynthesis and Rho pathway activation. Supplementation with GGPP may be therapeutically beneficial for preventing myotoxicity associated with combined statin and fibrates treatment.

Lower osteocalcin and osteopontin contents of the femoral head in hip fracture patients than osteoarthritis patients.

UNLABELLED: In patients with femoral neck fracture, clinical factors, bone metabolism markers (in serum, urine, and bone), bone mineral density, radiographic parameters, and bone histomorphometric parameters were investigated to detect determinants of fragility fracture. The osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratio of cortical bone were selected as significant predictors. INTRODUCTION: Measurement of bone mineral density is widely used to assess bone strength, but this also depends on other bone components and on bone structure. The objective of this study was to investigate risk factors for fracture related to bone quality, the patient's history, and the patient's lifestyle. METHODS: Twenty-one patients with femoral neck fracture and 18 patients with osteoarthritis were enrolled. Blood and urine samples were collected on admission to hospital, and bone samples were obtained from femoral necks resected during surgery. Multivariate logistic regression analysis was performed using osteoarthritis and femoral neck fracture as combined variables to assess the influence of alcohol or coffee intake, eating natto (fermented soybeans), osteocalcin and calcium concentrations, the osteocalcin/deoxypyridinoline ratio and osteopontin/calcium ratios of cortical bone and cancellous bone, various bone histomorphometric parameters, the bone mineral density of the lumbar spine and the intact contralateral femoral neck, and various radiographic parameters of the spine RESULTS: By forward stepwise multivariate analysis, the osteocalcin/deoxypyridinoline and osteopontin/calcium ratios of cortical bone were selected as significant factors for fracture (the odds ratios were 0.493 and <0.001, respectively; both P<0.001). CONCLUSIONS: A decrease of osteopontin and osteocalcin in bone is important for promoting vulnerability to hip fracture.

Impact of intraperitoneal chemotherapy after gastrectomy with positive cytological findings in peritoneal washings.

BACKGROUND: There is no standard treatment available for gastric cancer patients whose sole 'non-curative factor' is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. METHODS: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. RESULTS: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. CONCLUSION: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells.

Successful treatment for a case of near-fatal secondary adrenal insufficiency.

A thirty-six-year old female with shock was found to be unconsciousness a few days after developing a respiratory infection. Her past medical history included autoimmune hypothyroidism. Her state of shock was not controlled by massive fluid resuscitation with a vasopressor and antibiotics. However an infusion of 250 mg methylprednisolone dramatically improved her shock state. Further examination indicated secondary acute adrenal insufficiency. Adrenal insufficiency may complicate other endocrine disorders. Accordingly, a physician should consider hypoadrenocorticism, when patients are in a state of refractory shock in spite of massive infusion with a vasopressor especially in patients with other endocrine disorders.

Combined pancreas and en bloc kidney transplantation using a bladder patch technique from very small pediatric donors.

Very small pediatric donors are underutilized for pancreas and kidney transplantation for the fear of inadequate islet mass and higher incidence of technical complications, and the lower age limit for such donors is not well defined. We present here two cases of combined pancreas and en bloc kidney transplantation from very small pediatric donors (14 and 18 months old) to adult type 1 diabetic and uremic patients. The conventional surgical procedure for simultaneous pancreas and kidney transplantation with systemic venous and bladder exocrine drainage was successfully applied to very small organs. For both, we utilized the recently described bladder patch technique for ureteral reconstruction. One patient developed venous thrombosis (partial thrombosis of the splenic and mesenteric veins) and the other urine leak (from a midportion of the medial ureter without compromising the bladder patch) after the transplants; both were successfully managed and the patients demonstrated immediate and sustained pancreas and kidney graft functions for 12 and 2 months posttransplantation. These cases illustrate the feasibility of combined pancreas and en bloc kidney transplantation from very small pediatric donors using a bladder patch technique to avoid small ureteral anastomosis.

CD49d and CD49e induce cell adhesion-mediated drug resistance through the nuclear factor-κB pathway in Burkitt lymphoma.

Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin's B-cell lymphoma. Currently, multi-agent chemotherapy regimens are being used to significantly improve cure rates and achieve complete remissions in BL patients. However, drug resistance can often occur within 6 months in BL patients, contributing to poor prognosis. Mounting evidence suggests that cell adhesion-mediated drug resistance (CAM-DR), caused by the interaction between the bone marrow microenvironment and tumour cells may play an important role in drug resistance to chemotherapy. However, the molecular mechanism underlying CAM-DR in BL has not been identified yet. In this study, we investigated the molecular mechanism responsible for CAM-DR in BL cells. We also examined the therapeutic targets of CAM-DR in BL cells and found CD49d and CD49e to be the important adhesion molecules involved. However, CD49a, CD49b, CD11a, CD29, CD18, and CD61 were not found to be associated with CAM-DR in BL cells. Furthermore, we clarified that CD49d- and CD49e-mediated CAM-DR could be attributed to an increase in the expression of B cell leukemia-xL (Bcl-xL) and survivin proteins, and a decrease in the expression of Bcl-2 associated X (Bax), Bcl-2 interacting mediator (Bim) and p53 upregulated modulator of apoptosis (PUMA) proteins via nuclear factor kappaB (NF-κB) activation. In addition, bortezomib was found to overcome CAM-DR in BL cells by inhibiting NF-κB. Thus, bortezomib may have potential clinical applications in the treatment of CD49d- and CD49e-mediated CAM-DR in BL patients.

Afterimage of perceptually filled-in surface.

An afterimage induced by prior adaptation to a visual stimulus is believed to be due to bleaching of photochemical pigments or neural adaptation in the retina. We report a type of afterimage that appears to require cortical adaptation. Fixating a neon-color spreading configuration led not only to negative afterimages corresponding to the inducers (local afterimages), but also to one corresponding to the perceptually filled-in surface during adaptation (global afterimage). These afterimages were mutually exclusive, undergoing monocular rivalry. The strength of the global afterimage correlated to a greater extent with perceptual filling-in during adaptation than with the strength of the local afterimages. Thus, global afterimages are not merely by-products of local afterimages, but involve adaptation at a cortical representation of surface.

Hyperinfection strongyloidiasis in a liver transplant recipient treated with parenteral ivermectin.

Severe strongyloidiasis, including hyperinfection and dissemination, is a recognized complication of solid organ transplantation. However, the development of strongyloidiasis in a liver transplant recipient has not been previously described. We present a case of severe strongyloidiasis occurring in a patient 4 months after liver transplantation and 1 month after receiving treatment for acute rejection. We assess the management challenges in this patient who remained symptomatic despite oral treatment with ivermectin and albendazole and eventual successful treatment with parenteral ivermectin. We review the published experience with alternative methods of ivermectin administration. We also investigate the possible source of infection, as the patient was not from an endemic area.

Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin recovery during preoperative autologous blood donation and after hip surgery.

OBJECTIVE: Preoperative autologous blood donation is a widely used alternative to allogenic transfusion in hip surgery. However, it has been reported that autologous blood donation may induce preoperative anemia. Juzentaihoto (TJ-48) (Tsumura Co., Tokyo, Japan) is a Japanese herbal medicine that has been used to alleviate anemia. We investigated the effect of TJ-48 on anemia in the perioperative period. PATIENTS AND METHODS: 18 hips of 18 female patients who underwent total hip arthroplasty or rotational acetabular osteotomy (RAO) were divided into two groups. Group A consisted of 9 hips of 9 patients who were treated with TJ-48 at a dose of 7.5 g per day from 21 days before surgery to the day before surgery. Group B consisted of 9 hips of 9 patients who did not take TJ-48. Preoperative autologous blood donation was performed 21, 14 and 7 days before surgery. All patients deposited 400 ml each time for a total of 1,200 ml. Hemoglobin level was recorded on preoperative Days 21, 14 and 7 and postoperative Days 1, 4, 7 and 14. RESULTS: During the preoperative period, repeated measures ANOVA showed a significant difference between the two groups in hemoglobin level (p = 0.04). Despite the lack of TJ-48 after surgery, the rate of hemoglobin decline in Group A was less than in Group B at all examination times. No patients with TJ-48 experienced side effects, including gastrointestinal symptoms and unusual laboratory data. CONCLUSION: TJ-48 is useful for treating anemia during preoperative autologous donation.

The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis.

The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.