Genetic evaluation of health costs in US organic Holstein calves and cows.

Minimizing the incidence of disease on organic dairy farms is important for both economic and animal welfare purposes. The objective of this study was to estimate genetic parameters for total disease treatment costs using producer-recorded treatments in organic Holstein dairy calves and cows. Individual cow and calf health data were collected from 16 USDA certified organic farms from across the United States.

Allergy: Evaluation of 16 years (2007-2022) results of the shared external quality assessment program in Belgium, Finland, Portugal and The Netherlands.

Objectives: This paper evaluates 16 year results of the Allergy EQA program shared by EQA organisers in Belgium, Finland, Portugal, and The Netherlands.

Methods: The performance of Thermo Fisher and Siemens user groups (in terms of concordance between both groups, between laboratory CV, prevalence of clinically significant errors) and suitability of samples (stability and validity of dilution of patient samples) are evaluated using data of 192 samples in the EQA programs from 2007 to 2022. Measurands covered are total IgE, screens and mixes, specific IgE extracts and allergen components.

Genetic parameters and association of national evaluations with breeding values for health traits in US organic Holstein cows.

Among other regulations, organic cows in the United States cannot receive antibiotics and preserve their organic status, emphasizing the importance of prevention of illness and benefit of high genetic merit for disease resistance. At the same time, data underlying national genetic evaluations primarily come from conventional cows, drawing concern to the possibility of a genotype by environment interaction whereby the value of a genotype varies depending on the environment, and potentially limits the relevance of these evaluations to organic cows. The objectives of this study were to characterize the genetics of and determine the presence of genotype by environment interaction for health traits in US organic dairy cows.

Genetic parameters of calf morbidity and stayability for US organic Holstein calves.

The objectives of this study were to estimate genetic parameters of calf health in organic US Holstein calves. Calves were born on farms across the United States from 2006 to 2019. Three calf health traits were evaluated in the study: calf respiratory disease until 365 d of age, calf scours until 60 d of age, and heifer stayability until 365 d of age.

Genetic parameters of passive transfer of immunity for US organic Holstein calves.

Passive transfer of immunity is important for calf health and survival. The objectives of this study were to estimate genetic parameters for calf passive transfer of immunity through producer-recorded serum total protein (STP) and to determine associations with other routinely evaluated traits in organic Holstein calves (n = 16,725) that were born between July 2013 to June 2018; a restricted subset (n = 7,518) of calves with known Holstein maternal grandsires was analyzed separately. Producers measured STP on farm, and STP was extracted from farm management software.

Analytical and clinical performance of the fully-automated LIAISONXL calprotectin immunoassay from DiaSorin in IBD patients.

Objectives: Distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) based on clinical symptoms is often difficult. In this study we assessed the performance of the fully-automated calprotectin immunoassay from DiaSorin in IBD diagnosis and follow-up and compared it to the EliA calprotectin 2 immunoassay.

Design: and Methods: The calprotectin immunoassay from DiaSorin run on the LIAISONXL was analytically and clinically validated and compared to the EliA calprotectin 2 immunoassay from Thermo Fisher Scientific run on the ImmunoCAP250.

Genomic predictions for crossbred dairy cattle.

Genomic evaluations are useful for crossbred as well as purebred populations when selection is applied to commercial herds. Dairy farmers had already spent more than $1 million to genotype over 32,000 crossbred animals before US genomic evaluations became available for those animals. Thus, new tools were needed to provide accurate genomic predictions for crossbreds.

NUMBER: standardized reference intervals in the Netherlands using a 'big data' approach.

Background External quality assessment (EQA) programs for general chemistry tests have evolved from between laboratory comparison programs to trueness verification surveys. In the Netherlands, the implementation of such programs has reduced inter-laboratory variation for electrolytes, substrates and enzymes. This allows for national and metrological traceable reference intervals, but these are still lacking.

Analytical validation of the Hevylite assays for M-protein quantification.

Background: The heavy/light chain (HLC) immunoassay quantifies the different heavy chain/light chain combinations of each immunoglobulin (Ig) class. This makes the HLC assay suited to quantify monoclonal immunoglobulins (M-protein) and for monitoring of patients with monoclonal gammopathies. This method is particularly advantageous for those samples in which electrophoretic quantification of the M-protein is not possible.

Can serum L-lactate, D-lactate, creatine kinase and I-FABP be used as diagnostic markers in critically ill patients suspected for bowel ischemia.

Background: The prognostic value of biochemical tests in critically ill patients with multiple organ failure and suspected bowel ischemia is unknown.

Methods: In a prospective observational cohort study intensive care patients were included when the attending intensivist considered intestinal ischemia in the diagnostic workup at any time during intensive care stay. Patients were only included once.

Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression.

PU.1 as an essential activator for the expression of gp91(phox) gene in human peripheral neutrophils, monocytes, and B lymphocytes.

We have reported a deficiency of a 91-kDa glycoprotein component of the phagocyte NADPH oxidase (gp91(phox)) in neutrophils, monocytes, and B lymphocytes of a patient with X chromosome-linked chronic granulomatous disease. Sequence analysis of his gp91(phox) gene revealed a single-base mutation (C --> T) at position -53. Electrophoresis mobility-shift assays showed that both PU.

Performance of CD3xCD19 bispecific monoclonal antibodies in B cell malignancy.

Bispecific monoclonal antibodies, with a dual specificity for tumor associated antigens on target cells and for surface markers on immune effector cells, have been shown (in vitro) to be effective in directing and triggering effector cells to kill target cells resulting in target cell lysis. Bispecific monoclonal antibodies (BsAb) against the CD3 antigen on T cells and the CD19 antigen on B cell were developed. Data obtained by in vitro experiments might indicate that clinical responses in BsAb immunotherapy, will only be obtained in patients with minimal tumor load, and may need additional T cell stimulation via cytokines such as IL-2.

Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies.

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells.

CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma.

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found.

The efficacy of CD3 x CD19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2.

To evaluate the potency by which human T cells are targeted and activated by bispecific monoclonal antibodies (BsAbs) to lyse tumor cells, a clonogenic assay was developed. The efficacy of a CD3 x CD19 BsAb binding to both the CD3 T-cell antigen and the CD19 B-cell antigen was already proven in 51Cr-release assays and in 3-day activation cultures. To achieve more quantitative results, a 14-day clonogenic assay, based on limiting-dilution, was performed for the determination of the initial and residual number of clonogenic units obtained with a CD19+ pre-pre-B acute lymphoblastic leukemia (ALL-B) cell line.

Interaction of human monocyte Fc gamma receptors with rat IgG2b. A new indicator for the Fc gamma RIIa (R-H131) polymorphism.

Rat mAbs receive considerable interest for immunologic intervention in man. The rat IgG2b isotype has previously been found to be optimally active both in vivo and in vitro. We found that both a rat IgG2b CD3 mAb and a monovalent hybrid rat IgG2b-mouse IgG1 bispecific Ab triggered T cell activation in PBMC.

Unprimed CD4+ and CD8+ T cells can be rapidly activated by a CD3 x CD19 bispecific antibody to proliferate and become cytotoxic.

We previously reported that a CD3 x CD19 bispecific antibody (bsAb) can induce efficient killing of tumour cells by preactivated T cells isolated from patients with B cell malignancy. For future intravenous application we investigated whether resting T cells from peripheral blood can be stimulated to proliferate and become cytotoxic with the CD3 x CD19 bsAb alone. Indeed peripheral blood mononuclear cells, isolated from healthy donors or patients with B cell malignancy, started to proliferate within 1 day in response to CD3 x CD19 bsAb.

Evaluation of Fc gamma receptor mediated T-cell activation by two purified CD3 x CD19 bispecific monoclonal antibodies with hybrid Fc domains.

Two bispecific monoclonal antibodies (BsAb), differing in H chain isotype combination, were made for treatment of B-cell leukaemia/lymphoma; QAI-2, CD3-mouse-IgG1 x CD19-mouse-IgG2a and QAI-3, CD3-mouse-IgG1 x CD19-mouse-IgG2b. Both purified BsAb proved equally effective for their ability to target pre-activated T cells towards CD19 positive tumour cells. In T-cell proliferation assays, the capacity of Fc gamma RIa (CD64), Fc gamma RIIa-R131 and Fc gamma RIIa-H131 (CD32) transfected fibroblasts was tested to present the BsAb.

Killing of autologous B-lineage malignancy using CD3 x CD19 bispecific monoclonal antibody in end stage leukemia and lymphoma.

To develop an effective tumor immunotherapy for B-lineage non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL), a bispecific monoclonal antibody (BsAb) has been generated with the first specificity for the CD3 epsilon-chain and the second for the CD19 antigen. Peripheral blood mononuclear cells (PBMCs) isolated from patients with NHL or ALL during remission or relapse rapidly proliferated (up to 179-fold increase) on in vitro activation combining phytohemagglutinin or CD3 monoclonal antibody with interleukin-2. After 3 weeks of stimulation, more than 90% of the PBMCs was CD3+ and CD8+, even when cultures were started with only 5% CD3+ cells.

Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19).

Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb.

No expansion of the pre-B and B-cell compartments in the bone marrow of patients with multiple myeloma.

We have recently demonstrated that the CD24 antigen density of bone marrow (BM) lymphoid cells discriminates between pre-B cells and mature B-cells. Using this new method, we evaluated the B-cell lineage in the BM and peripheral blood (PB) of 18 patients with multiple myeloma (MM). First, the percentage of pre-B cells was significantly reduced by 40% in the BM of patients with MM: 2.