A synthetic analog of Shiga toxin (Stx) receptor (Synsorb Pk) was quantitatively assessed to determine whether it can protect human renal adenocarcinoma cells (ACHN cells) from the cytotoxicity of Stx1 and Stx2 by coincubation experiments. Coincubation of 100 and 20 ng of Stx1 and Stx2 with 50 mg of Synsorb Pk for 1 hr at 37 C in 1 ml of Eagle's Minimum Essential Medium supplemented with 1% (v/v) nonessential amino acid and 10% (v/v) fetal calf serum protected 50% of the cells from the cytotoxic effect. Chromosorb P, an inert matrix control, did not absorb the Stxs at all. Heat‐treatment (boiled for 10 min) to Synsorb Pk caused a 50% decrease in Stx2‐binding activity, but did not effect the Stx1 binding. Further, Stxs bound to Synsorb Pk could be demonstrated. When 20 mg of Synsorb Pk was coincubated for 30 min at 37 C in 1 ml of phosphate‐buffered saline with 1 and 10 ng or more of Stx1 or Stx2, respectively, the toxins could be detected on the surface when the bound toxins on Synsorb Pk were used as the solid phase in enzyme immunoassay. The amount of 100 ng/ml of both Stx1 and Stx2 appeared to saturate 20 mg/ml of Synsorb Pk after coincubating for 30 min at 37 C. While assessing the Stxs' binding activity to Synsorb Pk, it was demonstrated that Stx1 had a higher affinity to Pk trisaccharide than Stx2. These observations provide useful information on the effectiveness of Synsorb Pk to trap and eliminate free Stxs produced in the gut of patients infected by Stx‐producing Escherichia coli, and to prevent the progression of hemorrhagic colitis to hemolytic uremic syndrome.

Background:The most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8.Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by genetic form, particularly biallelic mutations in KATP channel genes. A few reports indicated marked clinical heterogeneity in siblings with identical biallelic mutations in ABCC8. The clinical heterogeneity in biallelic KATP CHI was speculated to be caused by epigenetic and environmental factors or related to differences in splicing factor machinery.Objective: To elucidate the clinical pathophysiology, especially heterogeneity, among three cases with CHI caused by a homogenous novel mutation. Patients and Methods:We report a case series that includes two siblings and one unrelated individual with CHI caused by a homogenous 1-bp deletion around the splice acceptor site at the exon 35 mutation of ABCC8, which exhibited markedly distinct phenotypes. To assess the effect of the mutation on splicing, we performed digital droplet polymerase chain reaction (ddPCR) on normal pancreas tissue and a patient's lymphocytes.Results: ddPCR of ABCC8 cDNA revealed that expression of exon 35 and its upstream and downstream regions did not differ. These data suggested that clinical heterogeneity may not be caused by differences in splicing factor machinery. Conclusion:The phenotypic variation in homozygotes could not be explained by splicing abnormalities. Though early genetic diagnosis of KATP CHI could contribute to selecting appropriate therapeutic options, more deliberate selection of therapeutic options in diffuse CHI due to biallelic ABCC8 mutations may be required.

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Immune checkpoint inhibitors, such as nivolumab, have been recognized that the enhanced immune responses often lead to immune-related adverse events (irAEs) in various organs. Although cutaneous toxicity is one of the most common irAEs, bullous pemphigoid (BP) with immune checkpoint inhibitors is rare. Herein, the authors report a case of BP in a patient of the metastatic malignant melanoma of the brain under the treatment of nivolumab. It is notable that this case showed the clear correlation between the status of using of nivolumab and serum levels of anti-BP180 antibody. In addition, the skin eruptions in the case were mainly pruritic erosive or crusted papules and these clinical features may be the clinical characteristics of BP induced by nivolumab.

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