Anti-α-galactosidase A antibody response to agalsidase beta treatment: data from the Fabry Registry.

Agalsidase beta, a form of recombinant human α-galactosidase A (αGAL), is approved for use as enzyme replacement therapy (ERT) for Fabry disease. An immunogenic response against a therapeutic protein could potentially impact its efficacy or safety. The development of anti-αGAL IgG antibodies was evaluated in 571 men and 251 women from the Fabry Registry who were treated with agalsidase beta.

Incorporation of the HIV-1 microbicide cyanovirin-N in a food product.

An urgent need exists for HIV-1 microbicides. Here, we describe the in vivo testing of lactic acid bacteria bioengineered to secrete cyanovirin-N. We fed pigtail macaques a yogurt formulation that used bioengineered strains as a starter culture.

Reducing selection bias in case-control studies from rare disease registries.

Background: In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry.

Characterization of the retrocyclin analogue RC-101 as a preventative of Staphylococcus aureus nasal colonization.

Nasal colonization of Staphylococcus aureus is a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization of S. aureus has become a major consideration for the prevention of nosocomial infection.

Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation.

Background: The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta.

Methods: Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment.

Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide.

Background: RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF), enabling the efficient design of a safe and effective microbicide product.

Retrocyclins and their activity against HIV-1.

Primate theta-defensins are physically distinguished as the only known fully-cyclic peptides of animal origin. Humans do not produce theta-defensin peptides due to a premature stop codon present in the signal sequence of all six theta-defensin pseudogenes. Instead, since the putative coding regions of human theta-defensin pseudogenes have remained remarkably intact, their corresponding peptides, called "retrocyclins", have been recreated using solid-phase synthetic approaches.

Exoproteome of Staphylococcus aureus reveals putative determinants of nasal carriage.

Due to the increasing prevalence of nosocomial and community-acquired antibiotic resistant Staphylococcus aureus (SA), understanding the determinants of SA nasal carriage has become a major imperative. Previous research has revealed many host and bacterial factors that contribute to SA nasal carriage. To assess bacterial factors that facilitate nasal carriage, we compared the exoproteome of a nasal carrier strain of SA to a genetically similar noncarrier strain.

HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma.

We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called "SEVI" and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP.

Evolutionary analyses of Staphylococcus aureus identify genetic relationships between nasal carriage and clinical isolates.

Nasal carriage of Staphylococcus aureus has long been hypothesized to be a major vector for the transmission of virulent strains throughout the community. To address this hypothesis, we have analyzed the relatedness between a cohort of nasal carriage strains and clinical isolates to understand better the genetic conformity therein. To assess the relatedness between nasal carriage and clinical isolates of S.

Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin.

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties.

The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques.

Background: RC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported is active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, and is non-toxic and non-inflammatory in cervicovaginal cell culture. Herein, film-formulated RC-101 was assessed for its antiviral activity in vitro, safety in vivo, retention in the cervix and vagina, and ability to remain active against HIV-1 and SHIV after intravaginal application in macaques.

Methodology/principal Findings: RC-101 was formulated as a quick-dissolving film (2000 µg/film), retained complete activity in vitro as compared to unformulated peptide, and was applied intravaginally in six pigtailed macaques daily for four days.

Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescents and adults.

Background: In Gaucher disease (GD), acid-β-glucosidase (GBA1) gene mutations result in defective glucocerebrosidase and variable combinations of hematological, visceral, and diverse bone disease. Osteopenia is highly prevalent, but its age of onset during the natural course of GD is not known. It is also unclear if the degree of improvement in osteopenia, secondary to imiglucerase enzyme therapy, differs by the age of the patient.

The incidence of Parkinsonism in patients with type 1 Gaucher disease: data from the ICGG Gaucher Registry.

Purpose: Investigate the incidence of Parkinsonism among patients with Gaucher disease type 1 (GD1) and describe demographics, genotypes, and Gaucher disease (GD)-related characteristics for affected and non-affected patients.

Study Type: Cohort study with age- and gender-matched nested case-control analysis. Calculation of event incidence, standardized morbidity ratio, and event-free survival (Kaplan-Meier).

Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry.

Objective: To describe demographic, genetic, and clinical characteristics of patients with neuronopathic Gaucher disease (NGD).

Methods: All patients enrolled in the Neurological Outcomes Subregistry of the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of June 2007 were identified.

Results: The study cohort comprised 131 patients from 17 countries who were enrolled in the Neurological Outcomes Subregistry.

Staphylococcus aureus nasal carriage and its contributing factors.

Staphylococcus aureus is a medically important pathogen that is often acquired from hospital settings (nosocomial) as well as from the community (community acquired). Bacteria that reside in anterior nares of hosts serve as reservoirs for both the spread of the pathogen and predispose the host to subsequent infections. Here, we will review the extent and variability of nasal carriage, and the possible causative factors--both from the host and the bacterium.

Subversion of interleukin-1-mediated host defence by a nasal carrier strain of Staphylococcus aureus.

Staphylococcus aureus, a major source of nosocomial and community-acquired infections, has a nasal carriage rate exceeding 25% in the human population. To elucidate host-pathogen interactions pertaining to nasal carriage, we examined the role of interleukin-1 (IL-1) in the colonization of human nasal epithelial cells (NEC) by a nasal carrier strain and a non-carrier strain of S. aureus.

Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis.

Data from the International Collaborative Gaucher Group Gaucher Registry were analysed to assess the relationship between enzyme replacement therapy with imiglucerase (ERT) and incidence of avascular necrosis (AVN) in type 1 Gaucher disease (GD1), and to determine whether the time interval between diagnosis and initiation of ERT influences the incidence rate of AVN. All patients with GD1 enrolled in the Gaucher Registry who received ERT and did not report AVN prior to starting therapy (n = 2700) were included. The incidence rate of AVN following initiation of ERT was determined.

Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma.

Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold.

Reawakening retrocyclins: ancestral human defensins active against HIV-1.

Human alpha and beta defensins contribute substantially to innate immune defenses against microbial and viral infections. Certain nonhuman primates also produce theta-defensins-18 residue cyclic peptides that act as HIV-1 entry inhibitors. Multiple human theta-defensin genes exist, but they harbor a premature termination codon that blocks translation.

Pathogenesis gene families in the common minimal genome of Staphylococcus aureus are hypervariable.

Staphylococcus aureus is a versatile pathogen that shows high levels of inter-strain genetic variability and positive evolution in certain pathogenesis-related genes. Apart from gene content differences, variability in shared genes may affect pathogenicity. Studying such variability requires that the common minimal genome (CMG) be identified.

Reciprocal responsiveness to interleukin-12 and interferon-alpha specifies human CD8+ effector versus central memory T-cell fates.

Multiple innate signals regulate the genesis of effector and memory CD8+ T cells. In this study, we demonstrate that the innate cytokines interleukin (IL)-12 and interferon (IFN)-alpha/beta regulate distinct aspects of effector and memory human CD8+ T-cell differentiation. IL-12 exclusively promoted the development of IFN-gamma- and tumor necrosis factor (TNF)-alpha-secreting T effector memory (T(EM)) cells, whereas IFN-alpha drove the development of T central memory (T(CM)) cells.

Snitching, lies and computer crashes: an experimental investigation of secondary confessions.

Two laboratory studies with 332 student participants investigated secondary confessions (provided by an informant instead of the suspect). Participants allegedly caused or witnessed a simulated computer crash, then were asked to give primary or secondary confessions during interrogation. Study 1 replicated the false evidence effect for primary confessions.

Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1.

Purpose: To determine whether enzyme therapy with imiglucerase/alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients.

Methods: Analyses included all patients with Gaucher disease type 1 on enzyme therapy and with intact spleens in the large observational database of the International Collaborative Gaucher Group Gaucher Registry. Propensity scoring was used to match patients between enzyme therapy dose groups categorized as Group A (5 U to <29 U/kg/2 weeks), Group B (29 U to <48 U/kg/2 weeks), Group C (48 U to <75 U/kg/2 weeks).

Genome sequencing and analysis reveals possible determinants of Staphylococcus aureus nasal carriage.

Background: Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown.