Universal dark halo scaling relation for the dwarf spheroidal satellites

Motivated by a recently found interesting property of the dark halo surface density within a radius, $r_{\rm max}$, giving the maximum circular velocity, $V_{\rm max}$, we investigate it for dark halos of the Milky Way's and Andromeda's dwarf satellites based on cosmological simulations. We select and analyze the simulated subhalos associated with Milky Way-sized dark halos and find that the values of their surface densities, $\Sigma_{V_{\rm max}}$, are in good agreement with those for the observed dwarf spheroidal satellites even without employing any fitting procedures. This implies that this surface density would not be largely affected by any baryonic feedbacks and thus universal. Moreover, all subhalos on the small scales of dwarf satellites are expected to obey the relation $\Sigma_{V_{\rm max}}\propto V_{\rm max}$, irrespective of differences in their orbital evolutions, host halo properties, and observed redshifts. Therefore, we find that the universal scaling relation for dark halos on dwarf galaxy mass scales surely exists and provides us important clues to understanding fundamental properties of dark halos. We also investigate orbital and dynamical evolutions of subhalos to understand the origin of this universal dark halo relation and find that most of subhalos evolve generally along the $r_{\rm max}\propto V_{\rm max}$ sequence, even though these subhalos have undergone different histories of mass assembly and tidal stripping. This sequence, therefore, should be the key feature to understand the nature of the universality of $\Sigma_{V_{\rm max}}$.Comment: 12 pages, 5 figures and 3 tables, submitted to Ap

Hepatic Angiomyolipoma with Minimal Intratumoral Fat Content

We report a rare case of hepatic angiomyolipoma with minimal fat content. The low fat content led to an incorrect preoperative diagnosis. A 38-year-old man who was a carrier of hepatitis B virus infection incidentally presented with a hepatic tumor. His serum alpha-fetoprotein level was normal. Ultrasonography revealed a well-circumscribed, heterogeneous hypoechoic nonencapsulated liver tumor measuring 34 × 24 mm. Precontrast computed tomography (CT) did not reveal fatty attenuation in the lesion. Contrast-enhanced CT revealed a hypervascular nonencapsulated tumor in the arterial phase and moderate washing out of the contrast medium in the portal phase. A hypervascular tumor was observed on CT hepatic arteriography, and complete washing out of the contrast medium on CT during arterial portography. These findings are compatible with hepatocellular carcinoma. The tumor exhibited low signal intensity on T1-weighted images and high signal intensity on T2-weighted images; no hypointensity was observed on fat suppression images. The patient underwent left hemihepatectomy because of a preoperative diagnosis of hepatocellular carcinoma. The histopathological diagnosis was a hepatic angiomyolipoma with 5% fat content. Low fat content makes the diagnosis of this condition difficult. The absence of serum tumor markers and the presence of a nonencapsulated hypervascular tumor may facilitate the accurate preoperative diagnosis of hepatic angiomyolipomas that have a low fat content and mimic hepatocellular carcinoma

In Vivo Imaging of Transplanted Islets with ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 by Targeting GLP-1 Receptor

Glucagon-like peptide 1 receptor (GLP-1R) is highly expressed in pancreatic islets, especially on β-cells. Therefore, a properly labeled ligand that binds to GLP-1R could be used for in vivo pancreatic islet imaging. Because native GLP-1 is degraded rapidly by dipeptidyl peptidase-IV (DPP-IV), a more stable agonist of GLP-1 such as Exendin-4 is a preferred imaging agent. In this study, DO3A-VS-Cys^(40)-Exendin-4 was prepared through the conjugation of DO3A-VS with Cys^(40)-Exendin-4. The in vitro binding affinity of DO3A-VS-Cys^(40)-Exendin-4 was evaluated in INS-1 cells, which overexpress GLP-1R. After ^(64)Cu labeling, biodistribution studies and microPET imaging of ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 were performed on both subcutaneous INS-1 tumors and islet transplantation models. The subcutaneous INS-1 tumor was clearly visualized with microPET imaging after the injection of ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4. GLP-1R positive organs, such as pancreas and lung, showed high uptake. Tumor uptake was saturable, reduced dramatically by a 20-fold excess of unlabeled Exendin-4. In the intraportal islet transplantation models, ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 demonstrated almost two times higher uptake compared with normal mice. ^(64)Cu-DO3A-VS-Cys^(40)-Exendin-4 demonstrated persistent and specific uptake in the mouse pancreas, the subcutaneous insulinoma mouse model, and the intraportal human islet transplantation mouse model. This novel PET probe may be suitable for in vivo pancreatic islets imaging in the human

Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic stem cell transplantation (SCT). Because our previous trial of preemptive therapy with foscarnet sodium (phosphonoformic acid; PFA) failed to prevent HHV-6 encephalitis, we conducted a prospective study to examine the safety of prophylactic PFA administration and elucidate the changes in the plasma HHV-6 DNA levels in the early post-SCT period. Plasma HHV-6 DNA was measured thrice weekly from day 6. PFA, 90mg/kg/day, was administered from days 7 to 21 after bone marrow or peripheral blood SCT and to day 25 after umbilical cord blood transplantation. Of the 10 patients enrolled, 2 dropped out of the study, 1 because of early death, and 1 with a low glomerular filtration rate. Grade 3 or greater adverse events occurred in 9 of the 10 prophylactic PFA patients and in 7 of the 10 control patients who had clinical backgrounds similar to the study subjects and underwent SCT during the same period. Neurological disorders developed in none of the study subjects but in 4 of the 10 control patients, including 2 with HHV-6 encephalitis. HHV-6 reactivation occurred in 3 of the 10 study subjects. The prophylactic PFA regimen was thus safe and it may reduce the risk of limbic encephalitis, but is not considered to be potent enough to prevent HHV-6 reactivation. (C) 2011 John Wiley & Sons A/S

Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages

Mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene in hematopoietic stem cells (HSCs) results in the loss of glycosylphosphatidylinositol- anchored proteins (GPI-APs) on HSCs, but minimally affects their development, and thus can be used as a clonal maker of HSCs. We analyzed GPI-APs expression on six major lineage cells in a total of 574 patients with bone marrow (BM) failure in which microenvironment itself is thought to be unaffected, including aplastic anemia (AA) or myelodysplastic syndrome (MDS). GPI-APs-deficient (GPIAPs-) cells were detected in 250 patients. Whereas the GPIAPs- cells were seen in all six lineages in a majority of patients who had higher proportion ([dbmtequ]3%) of GPIAPs- cells, they were detected in only limited lineages in 92.9% of cases in the lower proportion (<3%) group. In all 250 cases, the same lineages of GPI-APs- cells were detected even after 6-18-month intervals, indicating that the GPIAPs- cells reflect hematopoiesis maintained by a self-renewing HSC in most of cases. The frequency of clones with limited lineages seen in mild cases of AA was similar to that in severe cases, and clones with limited lineages were seen even in two health volunteer cases. These results strongly suggest most individual HSCs produce only restricted lineages even in a steady state. While this restriction could reflect heterogeneity in the developmental potential of HSCs, we propose an alternative model in which the BM microenvironment is mosaic in supporting commitment of progenitors toward distinct lineages. Our computer simulation based on this model successfully recapitulated the observed clinical data. © AlphaMed Press

Hybrid Surgery for Portosystemic Encephalopathy in a Patient with Liver Cirrhosis: a case report

Regarding the treatment for a portosystemic shunt, surgical or interventional radiological closure of the shunt was established. Interventional radiology including balloon-occluded retrograde transvenous obliteration can worsen portal hypertension and create a large thrombus close to the major venous system in the case of a huge portosystemic shunt. In contrast, it is also difficult to treat some cases through surgery alone when huge complicated shunts exist very deep in the body. Herein, we report a successful case of surgical shunt ligation for portosystemic encephalopathy in a hybrid operation room that enabled intraoperative angiography and computed tomography. A 62-year-old woman with chronic hepatitis C was referred to our hospital due to high levels of serum ammonia and hepatic encephalopathy. She had a massive, complicated portosystemic shunt from the inferior mesenteric vein to the left renal vein but did not have esophageal or gastric varices. It was difficult to occlude the portosystemic shunt by interventional radiologic techniques because the shunt had an extremely large amount of blood flow and many collateral routes. We performed the shunt ligation in the hybrid operation room. Intraoperative angiography provided detailed information about the portosystemic shunt, such as direction or volume of blood flow and collateral routes in real time. Her encephalopathy disappeared completely and she remains healthy with improved liver functional reserve to date. In conclusion, this is a successful case of a hybrid operation for an extremely large and complicated portosystemic shunt, providing for intraoperative angiography as a safe and reliable surgical treatment for portosystemic encephalopathy in patients with liver cirrhosis

Successful treatment of Trichosporon fungemia in a patient with refractory acute myeloid leukemia using voriconazole combined with liposomal amphotericin B

Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML

Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia

To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number-neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA), we used a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes (HLA-LLs) in 144 AA patients. HLA-LLs, accounting for 0.2–99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patients and in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL+ patients were granulocytes (Gs), monocytes (Ms), B cells (Bs), and T cells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survival rate (100%) in 8 newly diagnosed HLA-LL+ patients were significantly higher than in 23 HLA-LL− patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients. © 2016 ISEH - International Society for Experimental HematologyEmbargo Period 12 month