TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).

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Hepcidin, a key regulator of iron metabolism, is expressed in the liver, distributed in blood, and excreted in urine. However, to date, no reliable and practical method for measuring the bioactive form of hepcidin in serum has been developed. Here, we used surface-enhanced laser desorp-

In response to the subduction of the young Shikoku Basin of the Philippine Sea Plate, arc magmas erupted in SW Japan throughout the late Cenozoic. Many magma types are present including ocean island basalt (OIB), shoshonite (SHO), arc-type alkali basalt (AB), typical subalkalic arc basalt (SAB), high-Mg andesite (HMA), and adakite (ADK). OIB erupted since the Japan Sea back-arc basin opened, whereas subsequent arc magmas accompanied subduction of the Shikoku Basin. However, there the origin of the magmas in relation to hot subduction is debated. Using new major and trace element and Sr-Nd-Pb-Hf isotope analyses of 324 lava samples from seven Quaternary volcanoes, we investigated the genetic conditions of the magma suites using a geochemical mass balance model, Arc Basalt Simulator version 4 (ABS4), that uses these data to solve for the parameters such as pressure/temperature of slab dehydration/melting and slab flux fraction, pressure, and temperature of mantle melting. The calculations suggest that those magmas originated from slab melts that induced flux melting of mantle peridotite. The suites differ mostly in the mass fraction of slab-melt flux, increasing from SHO through AB, SAB, HMA, to ADK. The pressure and temperature of mantle melting decreases in the same order. The suites differ secondarily in the ratio of altered oceanic crust to sediment in the source of the slab melt. The atypical suites associated with hot subduction result from unusually large mass fractions of slab melt and unusually cool mantle temperatures.

Hereditary hemochromatosis (HH) is a common genetic disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. The vast majority of individuals with HH are homozygous for mutations in the HFE gene. Recently a second transferrin receptor (TFR2) was discovered, and a previously uncharacterized type of hemochromatosis (HH type 3) was identified in humans carrying mutations in the TFR2 gene. To characterize the role for TFR2 in iron homeostasis, we generated mice in which a premature stop codon (Y245X) was introduced by targeted mutagenesis in the murine Tfr2 coding sequence. This mutation is orthologous to the Y250X mutation identified in some patients with HH type 3. The homozygous Tfr2 Y245X mutant mice showed profound abnormalities in parameters of iron homeostasis. Even on a standard diet, hepatic iron concentration was several-fold higher in the homozygous Tfr2 Y245X mutant mice than in wild-type littermates by 4 weeks of age. The iron deposition in the mutant mice was predominantly hepatocellular and periportal. The mean splenic iron concentration in the homozygous Tfr2 Y245X mutant mice was significantly less than that observed in the wild-type mice. The homozygous Tfr2 Y245X mutant mice also demonstrated elevated transferrin saturations. There were no significant differences in parameters of erythrocyte production including hemoglobin levels, hematocrits, erythrocyte indices, and reticulocyte counts. Heterozygous Tfr2 Y245X mice did not differ in any measured parameter from wild-type mice. This study confirms the important role for TFR2 in iron homeostasis and provides a tool for investigating the excess iron absorption and abnormal iron distribution in iron-overload disorders.iron ͉ liver ͉ gene targeting T ransferrin receptor (TFR)2 is a recently identified type II membrane protein with significant homology to the classical transferrin receptor (TFR1). Both TFR1 and TFR2 are capable of transporting transferrin-bound iron into the cell (1) and supporting cell growth (2). However, their properties differ in several critical ways. TFR2 has a lower affinity for holotransferrin than does TFR1 (1, 3). The expression pattern of TFR2 mRNA is quite distinct from TFR1 as well (4, 5). In particular, the TFR2 gene is expressed at much higher levels in liver compared with other tissues, whereas the TFR1 gene demonstrates little hepatic expression. TFR1 and TFR2 differ also in their response to changes in cellular iron status. The TFR1 transcript contains multiple iron-responsive elements in the 3Ј-untranslated region. These elements stabilize the TFR1 transcript under conditions of low cellular iron. The TFR2 transcript does not contain these elements, and TFR2 message and TFR2 protein levels vary little with changes in iron status (4, 5). The observation that hepatic expression of Tfr2 persists despite iron overload in a murine Hfe gene knockout model of hereditary hemochromatosis (HH) led us to suggest that Tfr2-mediated iron uptake contributes...