Gait Pattern Alterations during Walking, Texting and Walking and Texting during Cognitively Distractive Tasks while Negotiating Common Pedestrian Obstacles.

Objectives: Mobile phone texting is a common daily occurrence with a paucity of research examining corresponding gait characteristics. To date, most studies have participants walk in a straight line vs. overcoming barriers and obstacles that occur during regular walking.

Censoring of autoreactive B cell development by the pre-B cell receptor.

Antibody diversity occurs randomly as B cells recombine their immunoglobulin (Ig) heavy- and light-chain genes during development. This process inevitably generates reactivity against self structures, and several mechanisms prevent the development of autoreactive B cells. We report here a role for the pre-B cell receptor, composed of Ig heavy and surrogate light chains, in the negative selection of cells expressing Ig heavy chains with the potential to generate autoantibodies.

Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion.

The process of allelic exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of allelic exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division.

The pre-B-cell receptor.

The pre-B-cell receptor (pre-BCR) is composed of two immunoglobulin mu heavy chains and two surrogate light chains, which associate with the signaling molecules Igalpha and Igbeta (Igalpha/beta). The production of a functional pre-BCR is the first checkpoint in the current model of B-cell development. The pre-BCR mediates signals resulting in heavy chain allelic exclusion, down-regulation of the recombination machinery, developmental progression, V(H) repertoire selection, proliferation and down-regulation of the surrogate light chain genes.

Only VpreB1, but not VpreB2, is expressed at levels which allow normal development of B cells.

The surrogate light chain (SLC) consists of the polypeptides lambda5 and, in the mouse, either VpreB1 or VpreB2. SLC associates with BILL-Cadherin and other glycoproteins to form the pro-B cell receptor (pro-BCR) at the pre-BI cell stage, and with the immunoglobulin mu heavy chain to form the pre-BCR at the pre-BII cell stage. The function of the pro-BCR, if any, is unknown, whereas the pre-BCR is crucial for proliferative expansion of pre-BII cells.

Both the pre-BCR and the IL-7Ralpha are essential for expansion at the pre-BII cell stage in vivo.

During B cell development, proliferative expansion takes place after expression of the pre-BCR. At this pre-BII cell stage, the IL-7Ralpha is also expressed. Some in vitro studies suggest that pre-BCR-dependent expansion relies on the IL-7Ralpha, and others that it does not.

Impaired B-1 and B-2 B cell development and atypical splenic B cell structures in IL-7 receptor-deficient mice.

The cytokine IL-7 and its receptor are essential for normal B and T lymphopoiesis. We have analyzed the role of this receptor in B cell development throughout ontogeny in IL-7 receptor alpha-deficient mice. We demonstrate that the IL-7 receptor becomes progressively more important with age.

The VpreB1 enhancer drives developmental stage-specific gene expression in vivo.

In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro-) and precursor (pre-) B cells. As part of the pre-B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage- and developmental-stage-specific VpreB1 enhancer.

The pre-B cell receptor and its role in proliferation and Ig heavy chain allelic exclusion.

The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy (microH) chain and the surrogate light chain encoded by VpreB and lambda5. The pre-BCR has been implicated in precursor B cell proliferation, differentiation and IgH chain allelic exclusion. B cell development in mice lacking the transmembrane form of microH chain is blocked at the precursor B cell stage: the cells cannot proliferate or differentiate further and the IgH locus is allelically included.

VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but functional allelic exclusion of the IgH locus.

At the precursor B cell stage during bone marrow B cell development, Ig muH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1, VpreB2, and lambda 5, to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and allelic exclusion of the IgH locus. Mice which lack either VpreB1/VpreB2 or lambda 5 show a lack of precursor B cell expansion but normal IgH allelic exclusion.

Loss of precursor B cell expansion but not allelic exclusion in VpreB1/VpreB2 double-deficient mice.

The pre-B cell receptor consists of immunoglobulin (Ig) mu heavy chains and surrogate light chain, i.e., the VpreB and lambda5 proteins.

Leucocyte entry and endothelial E-selectin expression following intradermal Propionibacterium acnes administration.

Immune responses in porcine skin to intradermal inoculation of heat-killed Propionibacterium acnes (HKPA), the major bacterial agent associated with human inflammatory acne, were studied. Pigs were chosen as experimental animals because their skin is similar in structure and composition to that of man and because the use of genetically inbred pigs enables leucocytes to be transferred between animals without eliciting rejection responses. Two pigs were sensitized intradermally with 10 mg of HKPA and were challenged 2 weeks later with doses ranging from 1-100 microg of HKPA in various intradermal sites on the ventral aspect of the abdomen.

DNA profiling reveals remarkably low genetic variability in a herd of SLA homozygous pigs.

Inbred strains of rodents have become indispensable for a wide range of biological studies. It has generally been accepted that genetic uniformity is unlikely to be achieved before 20 generations of brother x sister matings discouraging attempts to inbreed larger mammals. Nevertheless, pigs, homozygous for the swine MHC haplotype SLA b/b, have been inbred at the Babraham Institute for almost thirty years and used for immunological studies.

Analysis of monoclonal antibodies that recognize gamma delta T/null cells.

Thirty two monoclonal antibodies (mAbs) from the first round of analysis in the Second International Swine CD Workshop were placed together with additional mAb derived from the first workshop in the null cell panel for further evaluation. Preparations of peripheral blood leukocytes, concanavalin A stimulated peripheral blood mononuclear cells, and spleen cells were used in flow cytometric analyses. Nineteen mAbs identified molecules that were not expressed on null cells, not lineage specific, or recognized activation molecules.

Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens.

The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products.

Pig lymphocytes utilise mouse MAdCAM-1 to enter fetal gut xenografts in SCID mice.

Ileocecal junction (ICJ) and proximal intestine (PI) fragments from CD45(323-) allovariant fetal pigs were grafted subcutaneously into SCID mice. The xenografts were examined 8-12 weeks later using two-color immunohistology and the ICJ, but not PI, xenografts were found to contain three types of vessels. The first (the majority) was lined with mouse endothelium (mAb 9F1+), the second was lined with pig endothelium, and the third was chimeric.

Constitutive and inflammatory lymphocyte trafficking.

Here we provide a brief overview of lymphocyte trafficking with particular emphasis on the current state of knowledge in the pig. We discuss how the emphasis of research has changed since early studies in the 1960s and outline the current hypothesis of a multistep cascade for lymphocyte migration through specialized endothelia. During the last several years our research has focused mainly on lymphocyte migration in vivo.

The role of E-selectin in lymphocyte and polymorphonuclear cell recruitment into cutaneous delayed hypersensitivity reactions in sensitized pigs.

We have studied the role of E-selectin in leukocyte accumulation into Ag-specific cutaneous delayed-type hypersensitivity reactions in pigs sensitized to the topical application of 2,4-dinitro-1-fluorobenzene or to the intradermal injection of bacillus Calmette-Guérin. The delayed-type hypersensitivity reactions were shown to be specific for the sensitizing Ag and characterized by the up-regulation of E-selectin, as demonstrated by the uptake of tracer 99mTc-labeled monoclonal anti-E-selectin mAb and entry of 51Cr-labeled PBL and (111)In-labeled polymorphonuclear cells (PMN). Intravenous injection of 5 mg/kg of a F(ab')2 preparation of a monoclonal anti-E-selectin Ab at peak times of leukocyte entry resulted in a significant inhibition of entry of both PMN and lymphocytes.

Lymphocyte subsets and adhesion molecules in cutaneous inflammation induced by inflammatory agonists: correlation between E-selectin and gamma delta TcR+ lymphocytes.

Kinetic and phenotypic heterogeneity in leukocyte subsets and adhesion-molecule expression is characteristic of many inflammatory conditions. We have studied the effect of various cytokines and inflammatory agonists on the type of leukocyte present and the adhesion molecules expressed in acute lesions (up to 3 days old) in porcine skin by immunohistology. Four major histocompatability complex-homozygous inbred pigs received replicate intradermal injections of IL-1 alpha, TNF-alpha, PMA, or PHA.

In vivo E-selectin upregulation correlates early with infiltration of PMN, later with PBL entry: MAbs block both.

The endothelial molecule E-selectin binds most leukocyte subsets in vitro. Yet its role in regulating the very different kinetics of inflammatory infiltration of different leukocyte subsets in vivo is unclear. The kinetics of E-selectin upregulation and polymorphonuclear leukocyte (PMN) and blood lymphocyte (PBL) localization in inflammation induced by interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) were investigated in a well-established inbred pig trafficking model.

Transfer of T-cell-mediated, antigen-specific delayed type hypersensitivity reactions to naive recipient inbred pigs.

Using inbred major histocompatibility complex-homozygous SLAb/b pigs, delayed-type hypersensitivity (DTH) reactions against either intradermal tuberculin (PPD) or topical 2,4-dinitro-1-fluorobenzene (DNFB) were transferred specifically by the intravenous injection of approximately 6 x 10(8) blood lymphocytes kg-1 bodyweight from donors sensitised, respectively, either with BCG or with DNFB into three-week-old piglets from an inbred litter. This antigen-specific, passively acquired sensitivity was revealed by three measures of DTH reactivity: first, macroscopic inflammation, which developed at the rate and intensity expected for actively acquired sensitivity to DNFB or PPD in older pigs; secondly, similarly enhanced local specific uptake of intravenously injected 51Cr-labelled normal lymphocytes (more than 35-fold for each); and, thirdly, histological evidence of markedly increased local infiltration of CD45+ lymphocytes and polymorphs, endothelial activation and the expression of adhesion molecules.

Genetically determined CD45 variant of value in leucocyte tracing in vivo in the pig.

This paper describes a monoclonal antibody (mAb), anti-pig CD45 (MAC323), that is directed against a polymorphic determinant. A monomorphic anti-pig CD45 mAb (K252.1E4) bound strongly to leucocytes from both MAC323+ and MAC323- pigs, demonstrating the absence of the epitope rather than the CD45 molecule.

The behaviour of monoclonal antibodies in the First International Pig CD Workshop reacting with gamma delta/Null T lymphocytes in the blood of SLAb/b line pigs.

Further studies were carried out on the monoclonal antibodies (mAbs) from the First International Swine CD Workshop which react with gamma delta Null T-lymphocytes, defined by the binding of mAb w020/141 (MAC320) as Swine Workshop Cluster number SWC6. Studies were also carried out on several other mAbs from the same workshop which identify other CD antigens, but whose binding is not restricted exclusively to gamma delta Null T-lymphocytes. The first group consists of 11 mAbs (w021, w022, w059-w065, w105 and w117) and the second group of 18 mAbs (w008, w026, w056, w067-w071, w080, w091-w094, w110, w111, w118, w119 and w121).

Major long-term changes in gamma delta T-cell receptor-positive and CD2+ T-cell subsets after neonatal thymectomy in the pig: a longitudinal study lasting nearly 2 years.

Blood leucocyte subsets in neonatally (20-day-old) thymectomized (Tx) and sham-thymectomized (STx) pigs were analysed 13 times over nearly 2 years. Tx piglets showed a persistent selective leucopenia, due mainly to a approximately 95% reduction in gamma delta null T cells which fell, with a circulating half-life of approximately 2 weeks, to approximately 0.3 x 10(6)/ml.