Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement.

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget's disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, alpha-alpha CTX, and beta-beta CTX) were measured at baseline and 6 months after therapy.

A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia.

Group B Streptococcus (GBS) is a major cause of bacterial meningitis and neurological morbidity in newborn infants. The cellular and molecular mechanisms by which this common organism causes CNS injury are unknown. We show that both heat-inactivated whole GBS and a secreted proteinaceous factor from GBS (GBS-F) induce neuronal apoptosis via the activation of murine microglia through a TLR2-dependent and MyD88-dependent pathway in vitro.

Interobserver agreement for the diagnosis of venous thromboembolism on computed tomography chest angiography and indirect venography of the lower extremities in emergency department patients.

Objectives: To determine interobserver agreement between radiologists for computed tomography (CT) angiography and venography. CT venography of the lower extremities combined with standard CT angiography of the chest may result in an increased overall diagnosis rate of venous thromboembolism (pulmonary embolism or deep venous thrombosis).

Methods: The study had a retrospective cohort design.

Modulation of surgical fibrosis by microbial zwitterionic polysaccharides.

Bacterial carbohydrates have long been considered T cell-independent antigens that primarily induce humoral immune responses. Recently, it has been demonstrated that bacterial capsules that possess a zwitterionic charge motif can activate CD4(+) T cells after processing and presentation by antigen-presenting cells. Here we show that these zwitterionic polysaccharides can prevent T helper 1-mediated fibrosis by signaling for the release of IL-10 from CD4(+) T cells in vivo.

Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans.

Zwitterionic capsular polysaccharides: the new MHCII-dependent antigens.

The immune system has evolved the ability for T cells to recognize nearly any biological polymer, including peptides, protein superantigens, and glycolipids through presentation by the major histocompatibility complex (MHC) proteins such as MHC class I (MHCI), MHC class II (MHCII), and CD1. A recent and unexpected addition to this list is the zwitterionic capsular polysaccharide (ZPS). These bacterial molecules utilize MHCII presentation to activate T cells via recognition by alphabeta T cell receptor (alphabetaTCR) proteins.

Anchors away: contribution of a glycolipid anchor to bacterial invasion of host cells.

Group B Streptococcus (GBS) is an important cause of infections, including meningitis. The molecular events underlying its pathogenesis are poorly understood. A study in this issue of the JCI reports that the GBS invasion-associated gene (iagA) contributes to meningeal infection and virulence by facilitating invasion of the cells that compose the blood-brain barrier and of other host cells.

An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined.

Identification of a universal Group B streptococcus vaccine by multiple genome screen.

Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a major cause of life-threatening infections in newborns. To develop a broadly protective vaccine, we analyzed the genome sequences of eight GBS isolates and cloned and tested 312 surface proteins as vaccines. Four proteins elicited protection in mice, and their combination proved highly protective against a large panel of strains, including all circulating serotypes.

Role of lipoteichoic acid in the phagocyte response to group B streptococcus.

Group B Streptococcus (GBS) cell walls potently activate phagocytes by a largely TLR2-independent mechanism. In contrast, the cell wall component lipoteichoic acid (LTA) from diverse Gram-positive bacterial species has been shown to engage TLR2. In this study we examined the role of LTA from GBS in phagocyte activation and the requirements for TLR-LTA interaction.

Structural and genetic diversity of group B streptococcus capsular polysaccharides.

Group B Streptococcus (GBS) is an important pathogen of neonates, pregnant women, and immunocompromised individuals. GBS isolates associated with human infection produce one of nine antigenically distinct capsular polysaccharides which are thought to play a key role in virulence. A comparison of GBS polysaccharide structures of all nine known GBS serotypes together with the predicted amino acid sequences of the proteins that direct their synthesis suggests that the evolution of serotype-specific capsular polysaccharides has proceeded through en bloc replacement of individual glycosyltransferase genes with DNA sequences that encode enzymes with new linkage specificities.

Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration.

ClC-7 is a chloride channel of late endosomes and lysosomes. In osteoclasts, it may cooperate with H(+)-ATPases in acidifying the resorption lacuna. In mice and man, loss of ClC-7 or the H(+)-ATPase a3 subunit causes osteopetrosis, a disease characterized by defective bone resorption.

Coming of age: carbohydrates and immunity.

Adaptive immune responses have long been considered the "territory" of antigenic proteins, whereas carbohydrates are characterized as T-cell-independent antigens that are not typically recognized by the complete adaptive machinery. The current modus operandi when searching for dominant epitopes is the use of synthetic peptides designed from the primary structure of interesting target proteins; however, there is growing evidence that sugars can also play a critical role in immune recognition. Findings reported in this issue of the European Journal of Immunology begin to shed light on the differences in protein glycosylation that can occur in association with disorders like rheumatoid arthritis and the effect these changes have on collagen recognition by the immune system.

Regulation of virulence by a two-component system in group B streptococcus.

Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes.

Electrocardiographic findings in Emergency Department patients with pulmonary embolism.

To assess the pre-study, null hypothesis that there is no difference in the electrocardiogram (EKG) findings for Emergency Department (ED) patients who rule in vs. rule out for suspected pulmonary embolism, a retrospective review of a cohort of patients with pulmonary embolism and their controls was conducted in an academic, suburban ED. Patients who were evaluated in the ED during a one-year study period for symptoms suggestive of pulmonary embolism were eligible for inclusion.

Polysaccharide processing and presentation by the MHCII pathway.

The adaptive immune system functions through the combined action of antigen-presenting cells (APCs) and T cells. Specifically, class I major histocompatibility complex antigen presentation to CD8(+) T cells is limited to proteosome-generated peptides from intracellular pathogens while the class II (MHCII) endocytic pathway presents only proteolytic peptides from extracellular pathogens to CD4(+) T cells. Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria can activate CD4(+) T cells.

Immune response of healthy women to 2 different group B streptococcal type V capsular polysaccharide-protein conjugate vaccines.

Background: Infections caused by group B streptococcal (GBS) type V are increasingly common. Capsular polysaccharide (CPS)-protein conjugate GBS vaccines are immunogenic in healthy adults, but type V vaccines have not previously been tested.

Methods: Thirty-five healthy, nonpregnant women were randomized to receive an intramuscular dose of GBS type V CPS-tetanus toxoid (TT) vaccine (n=15), GBS type V CPS-cross-reactive material (CRM(197)) conjugate vaccine (n=15), or placebo (n=5) (double-masked design).

Biological chemistry of immunomodulation by zwitterionic polysaccharides.

Capsular polysaccharides isolated from pathogenic bacteria are comprised typically of many repeating units from one to eight or more monosaccharides in length. These polysaccharides stimulate the murine humoral immune system to elicit primarily IgM antibody responses. Studies conducted primarily in the mouse have characterized these polymers as T cell-independent antigens.

Glycoconjugate vaccines to prevent group B streptococcal infections.

Group B Streptococcus (GBS) is an opportunistic pathogen of humans. At-risk populations include neonates born to colonised mothers, peripartum women, diabetics, and the elderly with underlying illnesses. Vaccines to prevent GBS disease have been developed by coupling purified capsular polysaccharide (CPS) antigen of GBS with an immunogenic protein carrier.

Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments.

Recent reports suggest that physicians in non-ambulatory settings can use indirect CT venography (CTV) of the lower extremities immediately following spiral CT angiography (CTA) of the chest to identify patients with a negative CTA who have thromboembolic disease identified on CTV. We sought to determine the frequency of isolated deep venous thrombosis (DVT) discovered on CTV in emergency department (ED) patients with complaints suggestive of pulmonary embolism (PE) yet having a negative CTA. This study was conducted in a suburban and urban ED where patients with symptoms suspicious for PE were primarily evaluated with CTA and CTV.

Safety and immunogenicity of a bivalent group B streptococcal conjugate vaccine for serotypes II and III.

To determine whether 2 monovalent group B streptococcus (GBS) serotype II or III capsular polysaccharide (CPS)-tetanus toxoid (TT) conjugate vaccines combined in a single intramuscular dose would elicit immune responses comparable to those of monovalent vaccines, 75 healthy adults were randomized to receive GBS II-TT (3.6 micro g of CPS), GBS III-TT (12.5 micro g of CPS), or a bivalent mixture of GBS II-TT/III-TT vaccine (double-masked design).