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Importance of integrin LFA-1 deactivation for the generation of immune responses

The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen-1 (LFA-1) alpha(L) subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1(d/d) mutant mice

Restricted variable region gene usage and possible rheumatoid factor relationship among human monoclonal antibodies specific for the AD-1 epitope on cytomegalovirus glycoprotein B

The nucleotide sequences of the variable region genes encoding five different human, high affinity antibodies, specific for the major neutralization determinant (AD-1) expressed by human cytomegalovirus glycoprotein B (gp58/116), have been determined. Three of the five heavy chain variable regions belonged to the small VHV-family, although they combined with a diverse set of light chains (V kappa

New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis

Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics many clinical and histopathological aspects of multiple sclerosis. Non-MHC quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced EAE have previously been identified in the EAE-permissive strain, DA, on rat chromosomes 4,10,15, a

Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display: implications for autoimmunity and molecular mimicry

Two monoclonal antibodies (mAb) CB268 and CII-C1 to type 11 collagen (CII) react with precisely the same conformational epitope constituted by the residues ARGLT on the three chains of the CII triple helix. The antibodies share structural similarity, with most differences in the complementarity determining region 3 of the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by s

Limits of colour vision in dim light

Humans and most vertebrates have duplex retinae with multiple cone types for colour vision in bright light, and one single rod type for achromatic vision in dim light. Instead of comparing signals from multiple spectral types of photoreceptors, such species use one highly sensitive receptor type thus improving the signal-to-noise ratio at night. However, the nocturnal hawkmoth Deilephila elpenor,

The Antimicrobial Peptide LL-37 Alters Human Osteoblast Ca Handling and Induces Ca(2+)-Independent Apoptosis.

The human antimicrobial peptide cathelicidin LL-37 has, besides its antimicrobial properties, also been shown to regulate apoptosis in a cell type-specific manner. Mechanisms involved in LL-37-regulated apoptotic signaling are not identified. Here, we show that LL-37 reduces the human osteoblast-like MG63 cell number and cell viability in the micromolar concentration range with an IC(50) value of

Collagen type II is recognized by a pathogenic antibody through germline encoded structures

Collagen type II (CII) is a cartilage-specific target of pathologic humoral autoimmune responses in rheumatoid arthritis as well as in the collagen-induced arthritis model. The aim of the present study is to investigate the critical amino acid residues conferring CII epitope specificity of the prototypic arthritogenic murine mAb CIIC1. A homology model of the CIIC1 single-chain antibody fragment (

Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis

Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridom

Galiellalactone is a novel therapeutic candidate against hormone-refractory prostate cancer expressing activated Stat3.

BACKGROUND: Signal transducer and activator of transcription 3 (Stat3) is constitutively active (phosphorylated) in several forms of cancer, including prostate cancer (PCa). Stat3 signaling may be an interesting target for cancer therapy since inhibition of this pathway mediates growth inhibition and apoptosis of these cells. In this study we investigated the in vitro and in vivo effects of the fu

Activation of latent protease function of pro-hK2, but not pro-PSA, involves autoprocessing

BACKGROUND: Human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) are members of an extensive kallikrein family of proteases. Both proteases are secreted as zymogens or proenzymes containing a seven amino acid propeptide that must be proteolytically removed for enzymatic activation. The physiological proteases that activate pro-hK2 and pro-PSA are not known. METHODS: The pro-hK2 p

B cell activation by outer membrane vesicles--a novel virulence mechanism.

Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent B cell response by the immunoglobulin (Ig) D-binding superantigen MID. Here we

Radiative lifetimes and transition probabilities in Rh I

Radiative lifetimes of 17 high-lying excited states in Rh I aremeasured using the time-resolved laser-induced fluorescence method. Out of these lifetimes, 13 are new and the remaining four confirm previous measurements. Furthermore, we report the first theoretical investigation of Rh I, where the radiative decay properties of all experimentally known levels below 47 000 cm(-1) are calculated using

Transcription factor c-Rel plays a crucial role in driving anti-CD40-mediated innate colitis.

Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of g

Comorbidity and health-related quality of life in patients with severe chronic obstructive pulmonary disease attending Swedish secondary care units

Introduction: Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement. The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT). Methods: Infor

Unveiling systematic biases in the 1D LTE excitation-ionization balance of Fe for FGK stars: a novel approach to determination of stellar parameters

We present a comprehensive analysis of different techniques available for the spectroscopic analysis of FGK stars and provide a recommended methodology which efficiently estimates accurate stellar atmospheric parameters for large samples of stars. Our analysis includes a simultaneous equivalent width analysis of Fe I and Fe II spectral lines, and for the first time, utilizes on-the-fly non-local t

Wireless Positioning using Ellipsoidal Constraints

Indoor location-based positioning systems have attracted notable interest during recent years for a wide range of personal and commercial applications. As is well known, the GPS systems does not allow for accurate positioning indoors, resulting in the development of various forms of indoor positioning techniques, mostly being based on radio frequency measurements. In this paper, we examine a novel