Left Ventrolateral Prefrontal Cortical Activity During Reward Expectancy and Mania Risk.

Importance: Mania/hypomania is the pathognomonic feature of bipolar disorder (BD). As BD is often misdiagnosed as major depressive disorder (MDD), replicable neural markers of mania/hypomania risk are needed for earlier BD diagnosis and pathophysiological treatment development.

Objective: To replicate the previously reported positive association between left ventrolateral prefrontal cortex (vlPFC) activity during reward expectancy (RE) and mania/hypomania risk, to explore the effect of MDD history on this association, and to compare RE-related left vlPFC activity in individuals with and at risk of BD.

Psychological Assessment and Intervention at the Boston Marathon.

The Boston Marathon is a highly regarded event in the running world, not just for its prestige and challenging course, but also for its implementation of a psychology team to support runners. The 2013 Boston Marathon bombings underscored the essential role that mental health support plays at this event, prompting the development and expansion of its innovative care model. This review critically outlines, evaluates, and analyzes the approach and effectiveness of the psychological care model provided to runners on race day as part of the Boston Marathon medical team, including the standard of care, how it functions, and best practices for other marathons.

Narrative-based autobiographical memory interventions for PTSD: a meta-analysis of randomized controlled trials.

Introduction: The aim of this systematic review and meta-analysis is to evaluate the efficacy of narrative-based interventions (NBIs) for individuals with post-traumatic stress disorder (PTSD). Investigating the efficacy of NBIs should yield insight on autobiographical memory (AM) phenomena implicated in PTSD onset and recovery, leading to improved intervention protocols. Furthermore, by analyzing how NBIs influence maladaptive AM distortions, we hope to shed light on the theorized narrative architecture of AM more generally.

Natural anti-galactose alpha1,3 galactose antibodies delay, but do not prevent the acceptance of extracellular matrix xenografts.

Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To examine in detail the potential role of the alpha gal epitope in immune recognition of this acellular, avascular biomaterial, we have used mice which have a genetic disruption in the alpha1,3 galactosyltransferase gene (alpha gal(-/-)mice) and thus express natural anti-alpha gal antibodies in a manner similar to humans.

Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response.

Background: Porcine small intestinal submucosa (SIS) is an acellular, naturally derived extracellular matrix (ECM) that has been used for tissue remodeling and repair in numerous xenotransplantations. Although a vigorous immune response to xenogeneic extracellular matrix biomaterials is expected, to date there has been evidence for only normal tissue regeneration without any accompanying rejection. The purpose of this study was to determine the reason for a lack of rejection.

IL-12-mediated increases in protection elicited by pneumococcal and meningococcal conjugate vaccines.

Interleukin-12 (IL-12) may be a beneficial adjuvant for augmenting vaccine efficacy against encapsulated bacteria such as Streptococcus pneumoniae and Neisseria meningitidis since it can stimulate production of interferon-gamma (IFN-gamma) and secretion of antibody isotypes that are efficient at mediating complement fixation and opsonophagocytosis. In this study, we demonstrate the ability of IL-12 to enhance murine antibody responses, particularly IgG2a levels, to both pneumococcal and meningococcal conjugate vaccines. Transfer of immune serum from mice immunized with the meningococcal conjugate vaccine and IL-12 resulted in increased survival times, whereas transfer of serum from mice immunized with the pneumococcal conjugate and IL-12 resulted in protection from death upon bacterial challenge.

IgA immunodeficiency leads to inadequate Th cell priming and increased susceptibility to influenza virus infection.

IgA is considered to be the principal Ab involved in defense against pathogens in the mucosal compartment. Using mice with a targeted disruption in IgA gene expression (IgA(-/-) mice), we have examined the precise role of IgA in protective anti-influenza responses after intranasal vaccination. IgA(-/-) mice immunized intranasally with soluble hemagglutinin (hemagglutinin subtype 1) and neuraminidase (neuraminidase subtype 1) vaccine in the absence of adjuvant were found to be more susceptible to influenza virus infection than IgA(+/+) mice (13 vs 75% survival after virus challenge).

A pivotal role for interferon-gamma in protection against group A streptococcal skin infection.

Administration of exogenous recombinant interleukin-12 (rIL-12) either prophylactically or therapeutically provides significant protection against lethal group A streptococcal skin infection in a mouse model. Treatment of mice with rIL-12 before infection with group A streptococci induced expression of interferon-gamma (IFN-gamma) at the infection site. In vivo neutralization of IFN-gamma increased susceptibility to lethal infection and completely abrogated the protective effects of rIL-12.

Absence of SpeB production in virulent large capsular forms of group A streptococcal strain 64.

Passage in human blood of group A streptococcal isolate 64p was previously shown to result in the enhanced expression of M and M-related proteins. Similarly, when this isolate was injected into mice via an air sac model for skin infection, organisms recovered from the spleens showed both increased expression of M and M-related proteins and increased skin-invasive potential. We show that these phenotypic changes were not solely the result of increased transcription of the mRNAs encoding the M and M-related gene products.

A secreted streptococcal cysteine protease can cleave a surface-expressed M1 protein and alter the immunoglobulin binding properties.

Previous studies of recent clinical isolates of serotype M1 group A streptococci indicated that they display two patterns of non-immune human IgG subclass binding reactivity associated with their M1 protein. One group reacted with all four IgG subclasses (type IIo), while the second group expressed an M1 protein reacting preferentially with human IgG3 (type IIb). In this study, we have demonstrated that a cysteine protease, SpeB, present in culture supernatants of M1 serotype group A streptococcal isolates expressing type IIb IgG binding protein, can convert a recombinant Emm1 protein from a type IIo functional profile to a type IIb profile by removal of 24 amino acids from the N-terminus of the mature M1 protein.

Role of emm and mrp genes in the virulence of group A streptococcal isolate 64/14 in a mouse model of skin infection.

The virulence of group A streptococcal isolate 64/14 and paired isogenic mutants in which either the emm or mrp gene had been insertionally inactivated was compared in mice. Loss of expression of the emm gene product resulted in a significant loss of virulence when the isolate was injected into the skin but had no significant difference when injected intraperitoneally. By contrast, inactivation of the mrp gene caused the organism to be more virulent in the skin, while having no significant effect intraperitoneally.

Do chickens immunized with bacterial immunoglobulin G-binding proteins produce rheumatoid factor-like antibodies?

An association between the production of rheumatoid factor (RF)-like antibodies in animals immunized with bacterial immunoglobulin (Ig)G-binding proteins has been noted. Three potential explanations have been proposed: (1) altered host IgG due to binding of the immunogen; (2) B-cell superantigenic properties of the binding proteins; and (3) idiotype-anti-idiotype response leading to an antibody which acts as an antigen mimic. In order to distinguish among these possibilities, it is necessary to carry out studies in animals whose IgG does not react with the IgG-binding protein immunogen.

Inactivation of single genes within the virulence regulon of an M2 group A streptococcal isolate result in differences in virulence for chicken embryos and for mice.

An M2 streptococcal isolate and isogenic mutants in which either the emm or mrp gene was insertionally inactivated were tested for virulence using either a mouse model or a chicken embryo model. The results of the studies using the mouse model demonstrated that neither the emm nor mrp gene products had a significant effect on virulence when mice were challenged via the i.p.

Detection of streptococcal class I M protein in psoriasis by confocal immunofluorescent microscopy.

Epidemiological evidence implicates Streptococcus pyogenes (group A) infection as a common triggering stimulus for psoriasis. Unequivocal demonstration of streptococcal antigens in psoriatic skin has been difficult due to cross-reactive antigens in both normal human tissue and group A streptococci, which complicate immunohistological analysis. In this study cryostat sections of involved psoriatic skin were stained with monoclonal antibody 111-15504 to group A streptococci.

Identification of key gene products required for acquisition of plasmin-like enzymatic activity by group A streptococci.

Group A streptococci incubated in human plasma can acquire a plasmin-like enzymatic activity. This process involves at least two bacterial proteins and two human protein cofactors. In this study, the key bacterial proteins were identified by using a series of isogenic mutants of group A isolate, CS101.

Properties of IgG-binding proteins expressed by Streptococcus pyogenes isolates are predictive of invasive potential.

Recent clinical Streptococcus pyogenes isolates of the M1 serotype can be grouped according to the IgG-binding properties of their M proteins. One group expressed an IgG-binding M1 protein reactive with human IgG1, IgG2, IgG3, and IgG4 (type IIo); the other expressed a protein with predominant reactivity with human IgG3 alone (type IIb). Both IgG-binding protein phenotypes were equally resistant to phagocytosis in human blood; however, when they were injected into a skin air sac on outbred CD1 mice, all mice injected with M1 isolates of the type IIo phenotype were dead within 70 h, while only 40% of those injected with M1 isolates of the type IIb phenotype died within the same period.

Analysis of immunoglobulin G-binding-protein expression by invasive isolates of Streptococcus pyogenes.

Invasive group A streptococcal isolates collected as part of a Centers for Disease Control and Prevention surveillance study were analyzed for expression of immunoglobulin G (IgG)-binding proteins. Two IgG-binding phenotypes of group A isolates of the M1 serotype were identified. The first group expressed a surface protein that bound all four human IgG subclasses (type IIo) and was recognized by rabbit anti-serotype M1-specific antiserum but not by normal rabbit serum.

Distinct profiles of immunoglobulin G-binding-protein expression by invasive serotype M1 isolates of Streptococcus pyogenes.

Analysis of immunoglobulin G (IgG)-binding-protein expression by invasive group A streptococcal isolates of the M1 serotype collected as part of a Centers for Disease Control and Prevention surveillance study revealed two distinct phenotypes. One group of type M1 isolates expressed a surface protein reactive with all four human IgG subclasses (type IIo), while a second group expressed a surface protein demonstrating significant reactivity only with human IgG3 (type IIb). The functional forms of IgG-binding protein were antigenically related, and both were recognized by a rabbit polyclonal antiserum to serotype M1 but not by normal rabbit serum.

Protection of mice from group A streptococcal skin infection by interleukin-12.

It has been shown that interleukin (IL)-12 induces cell-mediated immunity and provides significant protection against intracellular organisms. The ability of this cytokine to enhance immunity in a mouse model of group A streptococcal skin infection was studied. Outbred CD1 mice were injected for 3 consecutive days with 0.

Characterization of a gene coding for a type IIo bacterial IgG-binding protein.

Two antigenic classes of non-immune IgG-binding proteins can be expressed by group A streptococci. One antigenic group of proteins is recognized by an antibody prepared against the product of a cloned fcrA gene (anti-FcRA). In this study, the immunogen used to prepare the antibody that defines the second antigenic class was shown to be the product of the emm-like (emmL) gene of M serotype 55 group A isolate, A928.

Identification of two functional forms of immunoglobulin G3-binding protein expressed by group A streptococci.

Analysis of group A streptococcal immunoglobulin G (IgG)-binding protein reactivity with different human IgG3-myeloma proteins provided evidence for at least two functional forms of these molecules. Representative IgG3-binding molecules were isolated, biotinylated, and used as tracers in competitive binding assays. Cross-inhibition studies demonstrated the existence of two distinct patterns of IgG3-binding activity.

Analysis of genes encoding two unique type IIa immunoglobulin G-binding proteins expressed by a single group A streptococcal isolate.

An emm-like gene (emmL) and a fcrA gene from group A streptococcal strain 64/14 (emmL64/14 and fcrA64/14) were amplified by PCR and force cloned into the heat-inducible expression vector pJLA 602. The emmL gene encoded a recombinant protein that bound human IgG1, IgG2, and IgG4 in a nonimmune fashion. This is the reactivity profile of a type IIa IgG-binding protein.

Association of type II immunoglobulin G-binding protein expression and survival of group A streptococci in human blood.

Expression of immunoglobulin G (IgG)-binding proteins on group A streptococcus strain 64 was monitored on bacteria subjected to sequential passage in human blood. After approximately 10 cycles through human blood, strain 64 demonstrated enhanced levels of IgG-binding protein, including the expression of a type IIa binding molecule with an M(r) of approximately 47,000 present only at very low levels on the parent isolate. Changes in the expression of IgG-binding proteins after passage in human blood were similar to those observed when the same organism was passaged sequentially intraperitoneally in mice.

Association between expression of immunoglobulin G-binding proteins by group A streptococci and virulence in a mouse skin infection model.

In this study, we developed a mouse model of skin infection to test the association between expression of immunoglobulin-binding proteins by and infectivity of group A streptococci. Group A streptococci capable of crossing tissue barriers and establishing a lethal systemic infection in mice showed a higher level of immunoglobulin-binding protein expression. The group A streptococci recovered from the spleen of a mouse that died following a skin infection were found to be more virulent when injected into the skin of naive mice.

Functional and serological analysis of type II immunoglobulin G-binding proteins expressed by pathogenic group A streptococci.

Bacterial immunoglobulin-binding proteins expressed on the surface of group A streptococci represent a heterogeneous family of functionally related proteins. In this report, we describe efficient methods for extracting immunoglobulin-binding proteins and classifying them functionally and antigenically. A common characteristic of immunoglobulin-binding proteins expressed by group A streptococci appears to be the absence of internal methionine residues in the binding protein.