Background: More patients with moderate-to-severe plaque psoriasis achieved responses with JNJ-77242113, a targeted oral peptide inhibiting interleukin (IL)-23 receptor signaling, versus placebo at Week(W)16 of the phase 2 FRONTIER-1 study.
Objective: FRONTIER-2, a long-term extension of FRONTIER-1, evaluated JNJ-77242113 through 1 year.
Methods: FRONTIER-1 participants received JNJ-77242113 at doses from 25mg once daily (QD) to 100mg twice daily (BID) or placebo, through W16.
Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects.
View Article and Find Full Text PDFFood allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23IgG1 memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23IgG1 memory B cells correlated with circulating concentrations of IgE in children with peanut allergy.
View Article and Find Full Text PDFSide-chain-functionalized aliphatic polyesters are promising as functional biodegradable polymers. We have investigated ring-opening reactions of γ-carbonyl-substituted ε-caprolactones (gCCLs) to obtain poly(ε-caprolactone) (PCL) analogues. Organic catalysts and Sn(Oct) often used for the ring-opening polymerization (ROP) of ε-caprolactone (CL) have been explored to find the conditions for the formation of polymeric products of gCCLs.
View Article and Find Full Text PDFAn effective HIV vaccine likely requires the elicitation of neutralizing antibodies (NAbs) against multiple HIV-1 clades. The recently developed cleavage-independent native flexibly linked (NFL) envelope (Env) trimers exhibit well-ordered conformation and elicit autologous tier 2 NAbs in multiple animal models. Here, we investigated whether the fusion of molecular adjuvant C3d to the Env trimers can improve B- cell germinal center (GC) formation and antibody responses.
View Article and Find Full Text PDFUnlabelled: Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23 IgG1 memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These 'type2-marked' IgG1 memory B cells differentially express IL-4/IL-13 regulated genes / , and germline and carry highly mutated B cell receptors (BCRs).
View Article and Find Full Text PDFBackground: Brain abscess is a life-threatening event. Moreover, when Klebsiella pneumoniae is the cause, rapid diagnosis and appropriate treatment are required. Klebsiella invasive liver abscess syndrome, a bloodstream metastatic infection of potentially aggressive nature, has been recognized to cause infection in the central nervous system, and concern for Klebsiella liver abscess syndrome is increasing globally.
View Article and Find Full Text PDFCancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer-related muscle wasting and its mechanism using a colon-26 murine cachexia model.
View Article and Find Full Text PDFSMARCA4-deficient sarcoma was first reported in the chest and recently in the uterus, but not in the stomach. Here, we present a patient diagnosed with SMARCA4-deficient sarcoma of the stomach, using histochemistry. An emergency operation was performed due to perforation of the tumor.
View Article and Find Full Text PDFEpithelial‑mesenchymal transition (EMT) is considered a crucial event in the development of cancer metastasis. Metformin is a drug used in the treatment of type 2 diabetes. Recently, increasing evidence has indicated that metformin possesses anti‑tumor activities.
View Article and Find Full Text PDFMany tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12).
View Article and Find Full Text PDFThe patient was a 69-year-old woman.Upper gastrointestinal endoscopy showed a protruding tumor in the mid-thoracic esophagus, and biopsy revealed small cell carcinoma in November 2012. Four courses of neoadjuvant chemotherapy comprising CDDP and CPT-11 were administered, and radical resection was performed in March 2013.
View Article and Find Full Text PDFBackground: Fulminant type 1 diabetes is characterized by an intrinsic insulin deficiency resulting from the severe destruction of pancreatic β cells and it rapidly leads to ketoacidosis. However, the association between fulminant type 1 diabetes in pregnancy and specific viral infections has not been reported.
Case Presentation: The patient in this study was a 31-year-old Japanese woman, and at 30 weeks of pregnancy she was admitted with marked fatigue.
Along with the increase in consumption of raw animal meat, the prevalence of food poisoning is increasing. A 67-year-old Japanese man had eaten raw venison 4 hours prior to the beginning of vomiting. Many white cysts were discovered in the venison, with numerous bradyzoites being detected after the cysts were punctured.
View Article and Find Full Text PDFBackground And Aims: We examined the efficacy of the combined use of L-menthol spraying (L-mentholS) as an antispasmodic agent and carbon dioxide insufflation (CO2I) on the adenoma detection rate (ADR) in a prospective, single-center trial with a 2 × 2 factorial design.
Methods: We randomly assigned 611 patients scheduled to undergo colonoscopy to 4 groups: (1) the L-mentholS + CO2I (n = 153), (2) L-mentholS + air insufflation (AI; n = 156), (3) CO2I (n = 153), and (4) AI (n = 149) groups. We used 20 mL of 0.
Background: Immune-checkpoint inhibitors (ICIs) are novel promising agents for the treatment of malignant tumors. However, critical endocrine immune-related adverse events (irAEs) by ICIs often occur.
Case Report: A 63-year-old woman with advanced malignant melanoma had received anti-PD-1 antibody (nivolumab, 2 mg/kg every 3 weeks) for 8 cycles (from day 0 to day 147).
How precursor frequencies and antigen affinities impact interclonal B cell competition is a particularly relevant issue for candidate germline-targeting HIV vaccine designs because of the in vivo rarity of naive B cells that recognize broadly neutralizing epitopes. Knowing the frequencies and affinities of HIV-specific VRC01-class naive human B cells, we transferred B cells with germline VRC01 B cell receptors into congenic recipients to elucidate the roles of precursor frequency, antigen affinity, and avidity on B cell responses following immunization. All three factors were interdependently limiting for competitive success of VRC01-class B cells.
View Article and Find Full Text PDFWe developed a biodegradable polycarbonate that demonstrates antithrombogenicity and vascular cell adhesion via organocatalytic ring-opening polymerization of a trimethylene carbonate (TMC) analogue bearing a methoxy group. The monoether-tagged polycarbonate demonstrates a platelet adhesion property that is 93 and 89% lower than those of poly(ethylene terephthalate) and polyTMC, respectively. In contrast, vascular cell adhesion properties of the polycarbonate are comparable to those controls, indicating a potential for selective cell adhesion properties.
View Article and Find Full Text PDFWe have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation, and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimers via their C-terminal polyhistidine tails to nickel lipids integrated into the lipid bilayer. Despite favorable effects, concern remained over the potentially longer-term instability of noncovalent linkage of the trimers to the liposomes.
View Article and Find Full Text PDF22q11.2 Deletion Syndrome (22qDS) is often complicated by autoimmune diseases. To clarify the causal relationship, we examined the lymphocyte subset distribution and the human leucocyte antigen (HLA) in two female patients (one child and an elderly) with Graves' disease (GD) and 22qDS.
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