Identity of the elusive IgM Fc receptor (FcμR) in humans

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcμR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcμR in human B-lineage cDNA libraries. FcμR is defined as a transmembrane sialoglycoprotein of ∼60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcα/μR) but exhibits an exclusive Fcμ-binding specificity. The cytoplasmic tail of FcμR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcμR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcμR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcμR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcμR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis

The Efficacy of Bepotastine Besilate Compared With Hydroxyzine Pamoate for Preventing Infusion Reactions to the First Dose of Rituximab in Patients With Non-Hodgkin Lymphoma: Protocol for a Phase II, Double-Blind, Multicenter Randomized Trial

BackgroundRituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. ObjectiveThis study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. MethodsThis is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist–induced drowsiness using the visual analogue scale, with each patient providing their individual response. ResultsThis study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. ConclusionsThis study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. Trial RegistrationJapan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169 International Registered Report Identifier (IRRID)DERR1-10.2196/5488

Carcinomas in the remnant thyroid after thyroidectomy for Graves\u27 disease: report of a case

A 52-year-old female who had undergone subtotal thyroidectomy for Graves\u27 disease 20 years previously was referred to us with nodules in both lobes in her remnant thyroid. Although benign follicular tumors were most likely to be considered on further examinations, total remnant thyroidectomy was performed due to the increasing size of the nodules. Diagnoses of papillary carcinoma (follicular variant) and minimally invasive follicular carcinoma were strongly suspected based on the findings of the histological examination. In follow-up examinations after subtotal thyroidectomy for Graves\u27 disease, not only function but also structure of the remnant thyroid, should be focused on. Although rare, the possibility for carcinoma should be considered if nodules present in the remnant thyroid

Usefulness of C-11-methionine-positron emission tomography for the diagnosis of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disease of the brain caused by the JC virus that occurs mainly in immunocompromised patients. The prognosis is very poor. As the lesion looks like non- specific leukoencephalopathy, making a diagnosis at the early stage is very difficult. We report three PML cases in which there was a mismatch between C-11-methionine-positron emission tomography (MET-PET) uptake and F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake. All three cases demonstrated the hyper-uptake of MET around the white matter lesions and hypo-uptake of FDG inside the lesions. We speculate that the infection had ended inside the white matter lesions of these patients, while JC virus infection was ongoing around the lesions, resulting in the increase of methionine metabolism, and the glucose metabolism was reduced or intermediate because inflammatory cells infiltrate PML lesions rarely. Two patients who were diagnosed and treated with mefloquine while the JC virus was at a low level in the cerebrospinal fluid are still alive. We suggest the usefulness of MET-PET for the early diagnosis of PML and early treatment with mefloquine

Protective Effect of Chitin Urocanate Nanofibers against Ultraviolet Radiation

Urocanic acid is a major ultraviolet (UV)-absorbing chromophore. Chitins are highly crystalline structures that are found predominantly in crustacean shells. Alpha-chitin consists of microfibers that contain nanofibrils embedded in a protein matrix. Acid hydrolysis is a common method used to prepare chitin nanofibrils (NFs). We typically obtain NFs by hydrolyzing chitin with acetic acid. However, in the present study, we used urocanic acid to prepare urocanic acid chitin NFs (UNFs) and examined its protective effect against UVB radiation. Hos: HR-1 mice coated with UNFs were UVB irradiated (302 nm, 150 mJ/cm2), and these mice showed markedly lower UVB radiation-induced cutaneous erythema than the control. Additionally, sunburn cells were rarely detected in the epidermis of UNFs-coated mice after UVB irradiation. Although the difference was not as significant as UNFs, the number of sunburn cells in mice treated with acetic acid chitin nanofibrils (ANFs) tended to be lower than in control mice. These results demonstrate that ANFs have a protective effect against UVB and suggest that the anti-inflammatory and antioxidant effects of NFs influence the protective effect of ANFs against UVB radiation. The combination of NFs with other substances that possess UV-protective effects, such as urocanic acid, may provide an enhanced protective effect against UVB radiation