Cryptococcus gattii Genotype VGIIa Infection in Man, Japan, 2007

We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America

Japan's Lost Decades and a Women-led Socio-solidarity Economy

Yoko Kitazawa examines the solidarity economies in Japan as a needed alternative to the failures of both government and neo-liberal capitalism. She describes the activities of different groups that are undertaking solidarity, with a focus on female farming entrepreneurs, consumers and non-profit organizations.

Xeno-Free Materials for Stabilizing Basic Fibroblast Growth Factor and Enhancing Cell Proliferation in Human Pluripotent Stem Cell Cultures

Induced pluripotent stem cells (iPSCs) are widely considered important for developing novel regenerative therapies. A major challenge to the growth and proliferation of iPSCs is the maintenance of their undifferentiated status in xeno- and feeder-free conditions. Basic fibroblast growth factor (bFGF) is known to contribute to the expansion of stem cells; however, bFGF is notoriously heat-labile and easily denatured. Here, we investigate the effects of a series of synthetic sulfated/sulfonated polymers and saccharides on the growth of iPSCs. We observed that these materials effectively prevented the reduction of bFGF levels in iPSC culture media during storage at 37 °C. Some of the tested materials also suppressed heat-induced decline in medium performance and maintained cell proliferation. Our results suggest that these sulfated materials can be used to improve the expansion culture of undifferentiated iPSCs and show the potential of cost effective, chemically defined materials for improvement of medium performance while culturing iPSCs

Pacing Lead-Induced Granuloma in the Atrium: A Foreign Body Reaction to Polyurethane

We described a case of an 82-year-old male who presented with a granuloma entrapping the polyurethane-coated pacing lead at the site of contact on the atrium. He had been paced for 8 years without symptoms or signs suggestive of an allergic reaction to the pacemaker system and died from thrombosis of the superior mesenteric artery and heart failure. A histological examination of the nodule showed an incidental granuloma with multinucleated giant cells. No granuloma was found in the heart or the lung

Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial

Abstract Currently, ERY974, a humanized IgG4 bispecific T cell-redirecting antibody recognizing glypican-3 and CD3, is in phase I clinical trials. After a first-in-human clinical trial of an anti-CD28 agonist monoclonal antibody resulting in severe life-threatening adverse events, the minimal anticipated biological effect level approach has been considered for determining the first-in-human dose of high-risk drugs. Accordingly, we aimed to determine the first-in-human dose of ERY974 using both the minimal anticipated biological effect level and no observed adverse effect level approaches. In the former, we used the 10% effective concentration value from a cytotoxicity assay using the huH-1 cell line with the highest sensitivity to ERY974 to calculate the first-in-human dose of 4.9 ng/kg, at which maximum drug concentration after 4 h of intravenous ERY974 infusion was equal to the 10% effective concentration value. To determine the no observed adverse effect level, we conducted a single-dose study in cynomolgus monkeys that were intravenously infused with ERY974 (0.1, 1, and 10 μg/kg). The lowest dose of 0.1 μg/kg was determined as the no observed adverse effect level, and the first-in-human dose of 3.2 ng/kg was calculated, considering body surface area and species difference. For the phase I clinical trial, we selected 3.0 ng/kg as a starting dose, which was lower than the first-in-human dose calculated from both the no observed adverse effect level and minimal anticipated biological effect level. Combining these two methods to determine the first-in-human dose of strong immune modulators such as T cell-redirecting antibodies would be a suitable approach from safety and efficacy perspectives. Clinical trial registration: JapicCTI-194805/NCT05022927