Residual immune dysregulation syndrome in treated HIV infection.

Antiretroviral therapy has revolutionized the course of HIV infection, improving immune function and decreasing dramatically the mortality and morbidity due to the opportunistic complications of the disease. Nonetheless, even with sustained suppression of HIV replication, many HIV-infected persons experience a syndrome characterized by increased T cell activation and evidence of heightened inflammation and coagulation. This residual immune dysregulation syndrome or RIDS is more common in persons who fail to increase circulating CD4+ T cells to normal levels and in several epidemiologic studies it has been associated with increased morbidity and mortality.

Genetic variation in 15-hydroxyprostaglandin dehydrogenase and colon cancer susceptibility.

Background: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a metabolic antagonist of COX-2, catalyzing the degradation of inflammation mediator prostaglandin E2 (PGE2) and other prostanoids. Recent studies have established the 15-PGDH gene as a colon cancer suppressor.

Methods: We evaluated 15-PDGH as a colon cancer susceptibility locus in a three-stage design.

IL-17 in psoriasis: implications for therapy and cardiovascular co-morbidities.

Psoriasis is a prevalent, chronic inflammatory disease of the skin mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes, including activated antigen presenting cells (APCs), monocytes/macrophages, and Th1 and Th17 cells. Increased proliferation of keratinocytes and endothelial cells in conjunction with immune cell infiltration leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Interaction of activated T cells with monocytes/macrophages occurs via the Th17/IL-23 axis and is crucial for maintaining the chronic inflammation.

Microbial contamination of hematopoietic progenitor and other regenerative cells used in transplantation and regenerative medicine.

Background: Microbial contamination of hematopoietic progenitor cells (HPCs) and other regenerative cells used in transplantation and regenerative medicine can occur during collection and after in vitro manipulation, including purging, cryopreservation, thawing, and infusion.

Study Design And Methods: Microbiologic culture findings on consecutive HPCs and other cell preparations at a single institution derived from peripheral blood, marrow, cord blood, and mesenchymal stromal cells during all phases of manipulation were retrospectively examined from 2005 through 2011. Results were classified as confirmed positive, false positive, and indeterminate.

Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.

Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR.

Exosomes: looking back three decades and into the future.

Exosomes are extracellular membrane vesicles whose biogenesis by exocytosis of multivesicular endosomes was discovered in 1983. Since their discovery 30 years ago, it has become clear that exosomes contribute to many aspects of physiology and disease, including intercellular communication. We discuss the initial experiments that led to the discovery of exosomes and highlight some of the exciting current directions in the field.

Simultaneous magnetic resonance angiography and perfusion (MRAP) measurement: initial application in lower extremity skeletal muscle.

Purpose: To obtain a simultaneous 3D magnetic resonance angiography and perfusion (MRAP) using a single acquisition and to demonstrate MRAP in the lower extremities. A time-resolved contrast-enhanced exam was used in MRAP to simultaneously acquire a contrast-enhanced MR angiography (MRA) and dynamic contrast-enhanced (DCE) perfusion, which currently requires separate acquisitions and thus two contrast doses. MRAP can be used to assess large and small vessels in vascular pathologies such as peripheral arterial disease.

Treatment of long term anterior dislocation of the TMJ.

Acute dislocation of the temporomandibular joint (TMJ) is a relatively common occurrence; chronic long-term dislocation is rare. Variance in the duration of dislocation and anatomical considerations make the treatment for long-standing dislocation complex and controversial. This paper attempts to review the literature associated with chronic TMJ dislocation treatment options and presents the authors' experience with a particularly long term dislocation.

Risk for ingestion of toxic substances in children with Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS) have several common findings that may predispose to ingestion of potentially dangerous items. This study examined whether individuals with PWS have an increased prevalence of toxic ingestions. A survey regarding history of ingestions in PWS individuals and sibling controls was designed, piloted, and distributed on-line.

From classification to epilepsy ontology and informatics.

The 2010 International League Against Epilepsy (ILAE) classification and terminology commission report proposed a much needed departure from previous classifications to incorporate advances in molecular biology, neuroimaging, and genetics. It proposed an interim classification and defined two key requirements that need to be satisfied. The first is the ability to classify epilepsy in dimensions according to a variety of purposes including clinical research, patient care, and drug discovery.

T-cell immune monitoring by the ELISPOT assay for interferon gamma.

The enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma has been available for more than twenty years and has been used for a number of applications, including the monitoring of T cell immunity in solid organ transplant recipients. Studies from single centers indicate that heightened T cell alloreactivity measured with this assay correlates with acute and chronic rejection and with poor long-term allograft function. The assay has been used not only to assess T cell reactivity after transplantation, but also as a tool for assessing immune risk prior to transplantation.

Bacterial colonization and beta defensins in the female genital tract in HIV infection.

Beta defensins are antimicrobial peptides that serve to protect the host from microbial invasion at skin and mucosal surfaces. Here we explore the relationships among beta defensin levels, total bacterial colonization, and colonization by bacterial vaginosis (BV)-related bacteria and lactobacilli in the female genital tract in HIV infected women and healthy controls. Cervicovaginal lavage (CVL) samples were obtained from 30 HIV-infected women and 36 uninfected controls.

Mycobacterium tuberculosis ManLAM inhibits T-cell-receptor signaling by interference with ZAP-70, Lck and LAT phosphorylation.

Immune evasion is required for Mycobacterium tuberculosis to survive in the face of robust CD4(+) T cell responses. We have shown previously that M. tuberculosis cell wall glycolipids, including mannose capped lipoarabinomannan (ManLAM), directly inhibit polyclonal murine CD4(+) T cell activation by blocking ZAP-70 phosphorylation.

Regulation generation: the suppressive functions of human regulatory T cells.

Proper regulation of immune homeostasis is necessary to limit inflammation and prevent autoimmune and chronic inflammatory diseases. Many autoimmune diseases, such as psoriasis, are driven by vicious cycles of activated T cells that are unable to be suppressed by regulatory T cells. Effective suppression of auto-reactive T cells by regulatory T cells (Treg) is critical for the prevention of spontaneous autoimmune disease.

Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease.

Nitric oxide participates in cellular signal transduction largely through S-nitrosylation of allosteric and active-site cysteine thiols within proteins, forming S-nitroso-proteins (SNO-proteins). S-nitrosylation of proteins has been demonstrated to affect a broad range of functional parameters including enzymatic activity, subcellular localization, protein-protein interactions, and protein stability. Analogous to other ubiquitous posttranslational modifications that are regulated enzymatically, including phosphorylation and ubiquitinylation, accumulating evidence suggests the existence of enzymatic mechanisms for regulating protein S-nitrosylation.

Disseminated Mycobacterium chelonae infection in a patient receiving an epidermal growth factor receptor inhibitor for advanced head and neck cancer.

We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.

Development of a 96-well catheter-based microdilution method to test antifungal susceptibility of Candida biofilms.

Background: Candida biofilms, which are often associated with device-related infections, including catheter-related bloodstream infections, are resistant to commonly used antifungal agents. Current microtitre (96-well) plate-based methods to determine the antifungal susceptibility of these biofilms do not involve clinically relevant substrates (e.g.

Detection of bacterial contamination in prestorage culture-negative apheresis platelets on day of issue with the Pan Genera Detection test.

Background: Bacterial contamination is currently the most important infectious risk associated with transfusion of platelet (PLT) products. Prestorage culture has reduced but not eliminated this problem.

Study Design And Methods: Eighteen hospitals studied the Pan Genera Detection (PGD) test, a rapid, lateral-flow immunoassay for the detection of Gram-positive and Gram-negative bacteria.

S-Nitrosylation at the interface of autophagy and disease.

In this issue of Molecular Cell, Sarkar et al. (2011) provide the first evidence for involvement of nitric oxide bioactivity in autophagy and suggest new insight into the role of aberrant S-nitrosylation in the pathogenesis of neurodegeneration.

Phase I Clinical Trials in Patients ≥80.

Phase I clinical trials play a crucial role in development of therapeutics for cancer patients. During phase I clinical trials common toxicities are delineated, dose limiting toxicities (DLT) are determined and a dose for phase II studies is recommended. However, reviews of the phase I population indicate a younger group of participants with a median age of 50-55.

Activity of TDT 067 (terbinafine in Transfersome) against agents of onychomycosis, as determined by minimum inhibitory and fungicidal concentrations.

TDT 067 is a novel carrier-based dosage form (liquid spray) of 15 mg/ml of terbinafine in Transfersome that has been developed to deliver terbinafine to the nail bed to treat onychomycosis. In this study, we report the in vitro activities of TDT 067 against dermatophytes, compared with those of the Transfersome vehicle, naked terbinafine, and commercially available terbinafine (1%) spray. The MICs of TDT 067 and comparators against 25 clinical strains each of Trichophyton rubrum, T.

Time to detection of Mycobacterium tuberculosis as an alternative to quantitative cultures.

Testing new drugs is critical to improving the treatment of tuberculosis. Quantitative cultures of Mycobacterium tuberculosis on solid media have been used in Phase 1 and 2 trials, but are time and resource intensive. Time to detection (TTD) of growth of M.

Brain volumes in adolescents with very low birth weight: effects on brain structure and associations with neuropsychological outcomes.

The aims of this study were to examine abnormalities in brain structure in adolescents and young adults with very low birth weight (VLBW, <1,500 g) and associations of these abnormalities with neuropsychological outcomes. The sample of 108 participants from 14 to 19 years of age included 37 participants with <750 g birth weight, 35 with 750-1,499 g birth weight, and 36 normal birth weight (NBW) controls. One or both of the VLBW groups had smaller brain volumes, larger lateral ventricles, and a small surface area of the corpus callosum than the NBW controls.

Novel bis-indole agents active against multidrug-resistant Acinetobacter baumannii.

The in vitro activity of 5 novel Microbiotix bis-indole agents (MBXs) (Microbiotix, Worcester, MA) against 30 multidrug-resistant (MDR) Acinetobacter baumannii (including 18 resistant to carbapenems) was evaluated. Overall, MIC(90)'s ranged from 1 to 8 μg/mL, whereas those for imipenem were >64 μg/mL. MBX 1196 was the most potent (MIC(90), 1 μg/mL).