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Localized secretion of ATP and opioids revealed through single Ca2+ channel modulation in bovine chromaffin cells.

In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are effectively inhibited by ATP and opioids that are coreleased with catecholamines during cell activity. This autocrine loop causes a delay in Ca2+ channel activation that is quickly removed by preceding depolarizations. Changes in Ca2+ channel gating by secreted products thus make it possible to correlate Ca2+ channel activity to secretory events. Here, using cell-attached patch recordings, we found a remarkable correlation between delayed Ca2+ channel openings and neurotransmitter secretion induced by either local or whol

Editorial: The Role of Complement in Health and Disease.

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… Pertussis (whooping cough), caused by Bordetella pertussis , is still one of the most deadly childhood diseases. Hovingh et al. focused on the interaction of Vag8, one of its virulence factors, with C1-inhibitor (C1-INH). …

Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies.

BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proport

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… The proportion of participants with seroprotection was lowest for mumps (50%; 95% CI, 33%–67%), hepatitis A virus (HAV; 43%; 95% CI, 27%–61%), hepatitis B virus (HBV; 39%; 95% CI, 24%–58%), Hib (15%; 95% CI, 6%–32%), S . pneumoniae (0%; 95% CI, 0%–13%), and Bordetella pertussis ( B . pertussis ; 0%; …

ECC-4 Abstracts

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Chimeric antigen receptors: "CARs" in the fast lane for rheumatology.

PURPOSE OF REVIEW: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease. RECENT FINDINGS: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease.

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… However, in a recent abstract report, a panel of infectious disease-associated antibodies showed minimal impact of anti-CD19 4-1BBz CAR T therapy on preexisting pathogen humoral immunity including Streptococcus Pneumoniae, Influenza A (H1N1), SARS CoV-2, Bordetella Pertussis, Hepatitis B, and Diphtheria …

Respiratory Tract Infections: Sinusitis, Bronchitis, and Pneumonia

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… Bacteria, particularly atypical organisms, can also cause acute bronchitis; commonly implicated pathogens include Bordetella pertussis , Chlamydophila pneumoniae , and Mycoplasma pneumonia . …

OCA-B promotes pathogenic maturation of stem-like CD4+ T cells and autoimmune demyelination.

Stem-like T cells selectively contribute to autoimmunity, but the activities that promote their pathogenicity are incompletely understood. Here, we identify the transcription coregulator OCA-B as a driver of the pathogenic maturation of stem-like CD4+ T cells to promote autoimmune demyelination. Using 2 human multiple sclerosis (MS) datasets, we show that POU2AF1, the gene encoding OCA-B, is elevated in CD4+ T cells from patients with MS. We show that T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection

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… We induced EAE in C57BL/6 female Ocab fl/fl ;CD4-Cre mice and littermate Ocab fl/fl controls through s.c. injection of MOG 35–55 peptide in CFA followed by i.p. injections of Bordetella pertussis toxin. …

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNFα) by target populations, mainly Th17 and IL-17-secreting TCRγδ cells (Tγδ17). Due to their pivotal role in inflammatory diseases, IL-23 and

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… The IL-23/IL-17 axis is essential in the resolution of infection by Candida albicans [ 232 , 233 ], Staphylococcus aureus [ 234 ], and Bordetella pertussis [ 235 ], and IL-23-induced IL-22 production is involved in the clearance of lymphocytic choriomeningitis virus (LCMV) infection [ 236 ]. …

Иммунорегулирующий амфипатический песптид, полученный из молекулы защиты фасиолы гепатики (FhHDM-1.C2), демонстрирует мощную биотерапевтическую активность в мусриновой модели множественного склероза.

Молекулярные защитные молекулы (HDM) — семейство иммунных регуляционных пептидов, которые выражаются исключительно триматодными червями. Ранее мы продемонстрировали, что в vivo FhHDM-1, архетипный член HDM, регулировала макрофагическую реакцию на подстрекательские лиганды, тем самым облегчая процесс повреждения иммунной ткани в нескольких мусриновых моделях воспалительных заболеваний. Соответственно, мы исходили из того, что понимание взаимосвязи между структурой и функцией НДМ облегчило бы идентификацию минимального биоактивного пептида, который представлял бы собой более синтезируемый, эконо

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… Each mouse received 300 ng of Bordetella pertussis toxin (Sapphire Biosciences) intravenously (iv) on days 0 and 3. Clinical assessment (weight and observation) was conducted daily from day 7 post‐injection. …

20 Years of Legislation - How Australia Has Responded to the Challenge of Regulating Genetically Modified Organisms in the Clinic.

•In contrast to the prior voluntary system, since 2001, gene technology in Australia has been regulated under a legislated national Gene Technology Regulatory Scheme which is administered by the Gene Technology Regulator.•The Scheme provides science-based assessment of the potential risks of gene technology to the health and safety of people and the environment.•It complements the role of the Australian Therapeutic Goods Administration which regulates all therapeutic products in Australia to ensure they are safe and effective.•Recent reforms to the Scheme contribute to, and anticipate, the con

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… Adeno-associated virus of various serotypes; Adenovirus , includes various human, chimpanzee, and ovine serotypes; Poxviridae, includes various strains of Vaccinia virus and Fowlpox virus ; Herpesviridae, includes Herpes simplex virus 1 and Human cytomegalovirus ; Bacterium, includes Bifidobacterium longum, Bordetella …

Disorders of the Spinal Cord

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… MRI findings in a dog with diskospondylitis caused by Bordetella species. J Small Anim Pract. 2004;45:417. doi: 10.1111/j.1748-5827.2004.tb00259.x. Coates JR. Intervertebral disk disease. Vet Clin North Am Small Anim Pract. 2000;30:77. doi: 10.1016/s0195-5616(00)50004-7. …

Моноклональные антитела: от волшебной пули до точного оружия.

Моноклональные антитела (mAbs) используются для профилактики, обнаружения и лечения широкого спектра неинфекционных и инфекционных заболеваний. За последние несколько лет рынок МП рос экспоненциально, при этом ожидаемый совокупный годовой прирост (CAGR) составил 11.07% от 2024 (В тыс.237.64 млрд. долл. США на конец 2023) к 2033 (В тыс.679.03 млрд. долл. США к концу 2033). С момента появления технологии гибридомы 1975, терапия на базе антител была реализована с использованием муринных антител, которые стали еще более гуманизированными и полностью человеческими антителами, что уменьшило риск имм

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… When Bordetella pertussis ( B. pertussis ) initially interacts with epithelial cells, it is shown that the bacterial proliferation is accelerated [ 336 ]. …

Vaccine schedule recommendations and updates for patients with hematologic malignancy post-hematopoietic cell transplant or CAR T-cell therapy.

Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine-preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post-HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post-cellular therapies are less well defined. This review highlig

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… Bexsero, at 2 month intervals, from 6 months post‐HCT OR Three doses of Trumenba at 1 and 5‐month intervals, from 6 months post‐HCT Diphtheria and tetanus a : DT (full dose diphtheria) Td (reduced dose diphtheria) DTaP (higher dose of tetanus, diphtheria, pertussis toxoid) Tdap (lower dose formulation) Bordetella …

Overview of infectious complications among CAR T- cell therapy recipients.

Chimeric antigen receptor-modified T cell (CAR T-cell) therapy has revolutionized the management of hematological malignancies. In addition to impressive malignancy-related outcomes, CAR T-cell therapy has significant toxicity-related adverse events, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and opportunistic infections. Different CAR T-cell targets have different epidemiology and risk factors for infection, and these targets result in different long-term immunodeficiency st

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… Based on the epidemiology of infections after CAR T-cell therapy and known effects of B-cell aplasia and hypogammaglobulinemia, key vaccines to consider include annual influenza, Streptococcus pneumoniae , Haemophilus influenzae type b , Corynebacterium diphtheriae and Clostridium tetani toxins, Bordetella …

Глубинные пространственные омики MLADI-MS, управляемые квантовой каскадной лазерной микроскопией среднего инфракрасного изображения.

В пространственной "omics " высокоуверенные молекулярные идентификации необходимы для исследования сложной биологии и для пространственной биомаркировки. Однако нынешняя масс-спектрометрическая съемка (MSI) на основе пространственной "омики" должна скомпрометировать скорость получения данных и глубину биохимического профилирования. Здесь мы введём быструю, без этикеток квантовую каскадную лазерную микроскопию среднего инфракрасного изображения (QCL-MIR), чтобы направить MSI в высокоинтересные области тканей, такие маленькие, как гломерули почки, культурные многоклеточные сфероидные я

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… μg myelin oligodendrocyte glycoprotein (MOG) 35-55 (Charité Berlin, Germany) emulsified 1:1 in complete Freud’s adjuvant consisting of incomplete Freud’s adjuvant (Merck, #F5506-10X10ML) enriched with 10 mg/mL Mycobacterium tuberculosis (Difco/BD Pharmingen, #H37Ra). 150 ng Pertussis toxin from Bordetella …

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive ther

Roles of Microvesicles in Tumor Progression and Clinical Applications.

Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids ca

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… Moreover, TMVs can directly target cancer cells. 16 EV vaccines were first used to prevent infectious diseases, including diphtheria, Mycobacterium tuberculosis, and Bordetella pertussis. 132–134 Subsequently, investigators found that EV vaccines could be adapted for tumor therapy. 135 MVs released by …

Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

Клиническое представление лептоспироза: ретроспективное исследование 34 Пациенты поступили в одно учебное заведение во Франции.

Лептоспироз имеет весьма изменчивое клиническое представление, которое может быть связано с различными заражающими сероварами, факторами хост-компьютеров или их комбинацией. Это исследование проводилось ретроспективно 34 Число пациентов с серологическим подтвержденным лептоспирозом, принятых в течение отчетного периода 1992-2002. Наиболее частыми симптомами при поступлении в школу были лихорадка (см.100%), головная боль75%), миальгии55%), артхальгии45%) и рвотой (т.е.39%). Применяемые лабораторные исследования включали в себя лимфопенцию (см.85%), тромбоцитопенсия75%), повышенные ферменты пече

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… Making a specific diagnosis of pertussis in patients with clinical evidence of infection is one of the many challenges presented by Bordetella pertussis. …

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

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… Overview of clinical trials using nanoparticle‐based immunotherapy against cancer and infectious diseases BCG, Bacille Calmette Guerin tuberculosis vaccine; BIPCV, bivalent influenza peptide conjugate vaccine; CPA, cyclophosphamide; DLBCL, diffuse large B‐cell lymphoma; DTPaHibIPV, diphtheria, tetanus, bordetella …