A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumab.

A 68-year-old man, who was a patient with established rheumatoid arthritis (RA) with RA-associated interstitial lung disease (RA-ILD) and pulmonary emphysema, began taking tocilizumab. Subsequently, he developed dyspnea parallel to improvement of RA. At 10 months after the administration of tocilizumab, he was urgently admitted because of exacerbation of ILD. He died despite receiving steroid pulse therapy and antibiotic therapy on a respirator. This is the first case report to describe the exacerbation of ILD during treatment with tocilizumab in the postmarketing surveillance (PMS) period

Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

BACKGROUND: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway. METHODS: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. RESULTS: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. CONCLUSIONS: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs

Control of the pore size distribution and its spatial homogeneity in particulate activated carbon

There are circumstances where it is desirable to achieve a particular, optimal, pore size distribution (PSD) in a carbon, including in the molecular sieving, gas storage, CO2-capture and electrochemical energy storage. Activation protocols that cycle a carbon a number of times between a low-temperature oxygen chemisorption process and a higher temperature pyrolysis process have been proposed as a means of yielding such desired PSDs. However, it is shown here that for PFA-based char particles of ∼100 μm in size, only the super-micropores are substantially developed under such an activation protocol, with the ultra-micropores being substantially un-touched. It is also shown that a typical CO2-activation process yields similar control over PSD development. As this process is nearly 15 times faster than the cyclic-O2 protocol and yields larger pore volumes and areas for a given level of conversion, it is to be preferred unless spatial homogeneous porosity within the particles is also desired. If such homogeneity is desired, it is shown here that CO2 activation should continue to be used but at a rate of around one-tenth the typical; this slow rate also has the advantage of producing pore volumes and areas substantially greater than those obtained using the other activation protocols.CH acknowledges a joint scholarship provided by China Scholarship Council (CSC) and the University of Adelaide. SS acknowledges the award of International Postgraduate Research Scholarship (IPRS) from the University of Adelaide. SHM acknowledges the award of a President’s Scholarship from the University of South Australia. The support of the Australian Research Council Discovery Program (DP110101293) is also gratefully acknowledged

Effects of continuous passive motion on the expression of membrane type 1-matrix metalloproteinase in rat immobilized muscles

We examined the effects of continuous passive motion（ CPM） on membrane type 1-matrix metalloproteinase（ MT1-MMP） expression in rat immobilized muscles. Eight-week-old male Wister rats were used for each of two trials, one with 2 weeks, and another one with 4 weeks of immobilization with/without CPM. In each trial, rats were immobilized（ immobilization group）, and immobilized and simultaneously given CPM （CPM group）. The soleus muscle of each rat was evaluated by gelatin zymography, western blotting and reverse transcription-polymerase chain reaction（ RT-PCR）. Gelatin zymography revealed a greater level of gelatinase activity in the extract of the muscles of the immobilization group than in those of the control and CPM group. The expressions of matrix metalloproteinase 2 （MMP-2） and MT1-MMP mRNA in the muscle extract of the immobilization group were also greater than those in the control and CPM group. Our results suggested that joint immobilization induces expression of MT1-MMP, a cleavage enzyme of MMP-2 in muscles, resulting in muscular degeneration, and that CPM can prevent these changes

Hepatitis E Virus Transmission from Wild Boar Meat

We investigated a case of hepatitis E acquired after persons ate wild boar meat. Genotype 3 hepatitis E virus (HEV) RNA was detected in both patient serum and wild boar meat. These findings provided direct evidence of zoonotic foodborne transmission of HEV from a wild boar to a human

Characteristics of plasma parameters and turbulence in the isotope-mixing and the non-mixing states in hydrogen–deuterium mixture plasmas in the large helical device

Characteristics of plasma parameters and turbulence in the isotope-mixing and the non-mixing states in hydrogen-deuterium mixture plasmas in the large helical device are discussed. The isotope mixing state is characterized by the uniform isotope ratio profile regardless of the location of the particle source of each species in the isotope mixture plasma. The isotope non-mixing state is identified by the non-uniform isotope ratio profile measured with bulk charge exchange spectroscopy when the beam fueling isotope species differs from the recycling isotope species. The effect of collisionality, $T_e/T_i$ ratio, sign of density gradient on transition between isotope mixing and non-mixing is discussed. The plasma parameters preferable for the non-mixing state are found to be lower collisionality, higher $T_e/T_i$, and negative or zero density gradient (peaked or flat density profile). The time scale of transition from non-mixing to mixing is evaluated by the hydrogen and deuterium pellet injection near the plasma edge and is found to be less than 5 ms, which is much shorter than the particle confinement time. The strong correlation between isotope mixing and turbulence characteristics is observed. This strong correlation suggests the change in turbulence is a strong candidate for the mechanism causing the transition between uniform and non-uniform isotope density ratio profiles