Copy Number Variation of KIR Genes Influences HIV-1 Control

The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control

Clot Formation in Canine Whole Blood as Measured by Rotational Thromboelastometry Is Influenced by Sample Handling and Coagulation Activator

The objective of the present study was to systematically evaluate the impact of methodology on thromboelastometry with canine whole blood. Thromboelastometry was performed on citrated blood using a variety of combinations of clotting activators [ex-tem (tissue factor or TF), in-tem (ellagic acid), diluted TF from Innovin, or Ca (recalcification only)] and storage times. Thromboelastometry was also performed using diluted TF from Innovin on blood collected into a contact inhibitor. Ex-vivo contact activation was compared between canine and human blood. Clotting activator had a marked impact on coagulation time, a minor impact on alpha angle, and no impact on clot formation time or maximum clot firmness. When ex-tem or in-tem was the clotting activator, sample storage up to 30 min did not affect results. With diluted TF from Innovin or Ca, sample storage was associated with the development of increased coagulability (as indicated by shorter coagulation time and clot formation time and higher alpha angle) due to ex-vivo contact activation. Canine blood underwent markedly more ex-vivo contact activation than did human blood. Canine blood undergoes significant ex-vivo contact activation during and after collection, which influences thromboelastometry results when a weak clotting activator (such as low TF or recalcification) is used. Thromboelastometry with a strong activator (such as ex-tem or in-tem) is less influenced by ex-vivo changes, and, therefore, likely to be more reflective of in-vivo hemostatic capabilities and to provide consistently interpretable and comparable results

Original Study Serial plasma lactate concentrations in 68 puppies aged 4 to 80 days

Abstract Objective: To determine a reference range for venous blood lactate concentrations in healthy neonatal dogs. Design: A prospective cohort study. Setting: All work was conducted at the College of Veterinary Medicine, Texas A&M University. Animals: Clinically healthy dogs: 68 puppies and 30 adults. Measurements and main results: A blood sample was collected from each puppy into lithium heparin via jugular venipuncture at 4, 10, 16, 28, 70, and 80 days of age. A single venous sample was collected from each adult dog. Lactate concentration in each sample was measured immediately using an automated analyzer. Two hundred seventy-seven blood samples were analyzed. Blood lactate concentrations of adult dogs were 1.80 AE 0.84 mmol/L (mean AE SD). Mean blood lactate concentrations of puppies were significantly higher at 4, 10, 16, and 28 days of age compared with those of adult dogs. The reference range for lactate concentration for puppies at 4 days of age was 1.07-6.59, and for the puppies from 10 to 28 days of age was 0.80-4.60. Conclusions: Assessment of perfusion can be challenging in neonates due to normal physiologic variation and small size. Measurement of lactate is rapid, minimally invasive, and has potential to be a useful marker of perfusion in neonatal dogs. However, lactate concentrations of neonatal dogs in this study were significantly higher than those of adult dogs. Reference ranges for venous lactate concentrations in adult dogs should not be used for puppies younger than 70 days of age

Epistatic Interaction Between KIR3DS1 and HLA-B Delays the Progression to AIDS

Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells. KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4+ T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection