Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice.

Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains.

Fluid-structure interaction study of hemodynamics and its biomechanical influence on carotid artery atherosclerotic plaque deposits.

Atherosclerotic plaque deposits are common causes of blood flow disruption in the carotid artery bifurcation and the associated fluid mechanics has been extensively studied using Computational Fluid Dynamics (CFD) and Fluid Structure Interaction (FSI). However, the elastic responses of plaques to hemodynamics in the carotid artery bifurcation has not been deeply studied using either of the above-mentioned numerical techniques. In this study, a two-way FSI study was coupled with CFD technique, using Arbitrary-Lagrangian-Eulerian method, to study the biomechanics of blood flow on nonlinear and hyperelastic calcified plaque deposits in a realistic geometry of the carotid sinus.

Blocking common γ chain cytokine signaling ameliorates T cell-mediated pathogenesis in disease models.

The common γ chain (γc; IL-2RG) is a subunit of the interleukin (IL) receptors for the γc cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The lack of appropriate neutralizing antibodies recognizing IL-2RG has made it difficult to thoroughly interrogate the role of γc cytokines in inflammatory and autoimmune disease settings. Here, we generated a γc cytokine receptor antibody, REGN7257, to determine whether γc cytokines might be targeted for T cell-mediated disease prevention and treatment.

IL-4 and IL-13, not eosinophils, drive type 2 airway inflammation, remodeling and lung function decline.

Rationale: Type 2 (T2) asthma is characterized by airflow limitations and elevated levels of blood and sputum eosinophils, fractional exhaled nitric oxide, IgE, and periostin. While eosinophils are associated with exacerbations, the contribution of eosinophils to lung inflammation, remodeling and function remains largely hypothetical.

Objectives: To determine the effect of T2 cytokines IL-4, IL-13 and IL-5 on eosinophil biology and compare the impact of depleting just eosinophils versus inhibiting all aspects of T2 inflammation on airway inflammation.

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality.

Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine.

Deficiency in interleukin-36R (IL-36R) antagonist caused by loss-of-function mutations in leads to DITRA (deficiency of IL-36 receptor antagonist), a rare inflammatory human disease that belongs to a subgroup of generalized pustular psoriasis (GPP). We report a functional genetic mouse model of DITRA with enhanced IL-36R signaling analogous to that observed in patients with DITRA, which provides new insight into our understanding of the IL-36 family of molecules in regulating barrier integrity across multiple tissues. Humanized DITRA-like mice displayed increased skin inflammation in a preclinical model of psoriasis, and in vivo blockade of IL-36R pathway using anti-human IL-36R antibody ameliorated imiquimod-induced skin pathology as both prophylactic and therapeutic treatments.

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets.

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks.

REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters.

An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease.

A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies.

T cell activation is initiated upon binding of the T cell receptor (TCR)/CD3 complex to peptide-major histocompatibility complexes ("signal 1"); activation is enhanced by engagement of a second "costimulatory" receptor, such as the CD28 receptor on T cells binding to its cognate ligand(s) on the target cell ("signal 2"). CD3-based bispecific antibodies act by replacing conventional signal 1, linking T cells to tumor cells by binding a tumor-specific antigen (TSA) with one arm of the bispecific and bridging to TCR/CD3 with the other. Although some of these so-called TSAxCD3 bispecifics have demonstrated promising antitumor efficacy in patients with cancer, their activity remains to be optimized.

A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys.

Bispecific antibodies, while showing great therapeutic potential, pose formidable challenges with respect to their assembly, stability, immunogenicity, and pharmacodynamics. Here we describe a novel class of bispecific antibodies with native human immunoglobulin format. The design exploits differences in the affinities of the immunoglobulin isotypes for Protein A, allowing efficient large-scale purification.

Ocular changes after photodynamic therapy.

Purpose: The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina.

Methods: As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT.

Cellular and cytokine responses in the circulation and tissue reactions in the lung of rhesus monkeys (Macaca mulatta) pretreated with cyclosporin A and challenged with staphylococcal enterotoxin B.

Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice against staphylococcal enterotoxin B (SEB) intoxication. To determine whether CsA treatment would work in a species closer to humans. 4 rhesus monkeys were given 50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of SEB.

Trace element levels in plasma/serum and erythrocytes of Keteku and white Fulani cattle.

In order to determine the probable role of trace elements in the maintenance of trypanotolerance in tropical cattle, the levels of zinc (Zn), copper (Cu), manganese (Mn) and iron (Fe) in plasma/serum and erythrocytes of trypanotolerant Keteku (Kt) and trypanosusceptible White Fulani (WF) cattle were measured by atomic absorption spectrophotometry (AAS) and compared by breed or sex. Trypanotolerance was associated with significantly higher (P < 0.05) erythrocyte levels of Zn and Mn.

The immune response of Trypanosoma gambiense-infected mice to Schistosoma whole worm antigens.

Heterologous humoral and cellular immune response to Schistosoma mansoni and S. bovis antigens were investigated in Tryponosoma gambiense-infected mice in order to understand the concurrent immune response to both parasites. Immune response as measured by the Indirect Haemagglutination Test (IHA), Spontaneous sheep red blood cell rosette formation with B-lymphocytes and the mean number of T-lymphocytes forming rosettes with AET-treated SRBC to the schistosome antigens, was significantly depressed in the trypanosome-infected mice.

Application of molecular biological techniques for detection of epizootic hemorrhagic disease virus (EHDV-318) recovered from a sentinel calf in central Sudan.

Epizootic hemorrhagic disease virus (EHDV), isolate 318 (EHDV-318), an untyped virus recovered from a sentinel calf herd at the Khartoum University farm in central Sudan, was characterized using molecular biological techniques. With dot blot hybridization technique, a cDNA probe derived from genome segment 6 of EHDV-2 (Alberta strain) hybridized with RNA from EHDV-318. Application of serogroup-specific EHDV polymerase chain reaction (PCR) to EHDV-318 RNA resulted in specific amplification of a 387 bp PCR product.

Toxicity of raw limabeans (Phaseolus lunatus L.) and limabean fractions for growing chicks.

1. In a 4-week feeding trial, raw limabeans Phaseolus lunatus and extracted limabean fractions were tested as dietary ingredients in broiler starter diets. During the study, parameters such as body weight, lengths of intestinal sections as well as weights and histopathology of some organs (liver, kidney, heart, adrenals, spleen, brain, pancreas and small intestine) were investigated.

Inactivated oil emulsion vaccines from selected clones of Newcastle disease virus.

The immunogenicity of oil emulsion (OE) vaccines prepared from two selected clones of a Nigerian strain of Newcastle disease virus and two commercial vaccine strains were compared. Geometric mean haemagglutination inhibition titre was lowest in OE-Lasota, although all four vaccines gave 100% protection against clinical Newcastle disease. The use of OE vaccines is recommended for commercial use in Nigeria.

Correlation of humoral immune response with clinical presentation, pulmonary lesions and mortality patterns of goats experimentally infected with peste des petits ruminants virus.

The patterns of humoral immune response, measured by enzyme-linked immunosorbent assay and the development of clinical signs, pulmonary lesions and mortality patterns were studied in goats experimentally infected with peste des petits ruminants virus (PPRV) or Kata virus. It was possible to classify the animals into high and low responders according to the pattern of humoral immune response. The high responders had a prolonged, chronic infection characterized by a giant cell pneumonia which was sometimes complicated by bronchopneumonia.

Prevalence of aflatoxin B1 in commercial poultry rations in Nigeria.

122 samples of commercial poultry feed from 5 southern states of the Republic of Nigeria were investigated for their content of aflatoxin B1.57.4% of all samples examined contained aflatoxin B1.

The prevalence of antibodies of Brucella abortus, Dermatophilus congolensis and bovine leukaemia virus in Nigerian slaughter cattle.

In a pilot survey to compare the relative prevalence of three diseases in apparently healthy White Fulani Zebu (WFZ) cattle slaughtered in Nigeria, sera from 80 randomly selected animals with no significant gross lesions on ante mortem and post mortem inspection were examined for antibodies to Brucella abortus, Dermatophilus congolensis and bovine leukaemia virus. Of the samples screened, 5.0, 8.

Quantitation of natural antibodies to infectious bursal disease in Nigerian indigenous chickens.

Serum samples collected from 687 indigenous chickens located in small scattered groups in four states of Nigeria were examined for antibodies to infectious bursal disease (IBD) virus by the agar-gel precipitation (AGPT) and counterimmunoelectrophoresis (CIEOP) tests. 51 of the positive samples were further titrated by each of the two techniques. CIEOP detected more positive reactors (74.