A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay.

Objective: Length of stay (LOS) and hospitalization costs were compared among patients admitted for community-acquired pneumonia (CAP) and initially treated with either levofloxacin 750 mg intravenous (IV) or with moxifloxacin 400 mg IV. Hospital-related complications and relationship of LOS and comorbidities were descriptively examined.

Methods: A retrospective database study was conducted of adult patients admitted for CAP and given levofloxacin 750 mg IV or moxifloxacin 400 mg IV through the first 3 days of hospitalization, using the Premier Perspective comparative database.

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer.

Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1, HLA-A2, or HLA-A3, were eligible to enroll in a phase 1 study designed to assess the safety and immunogenicity of a peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus a class II major histocompatibility complex-restricted synthetic helper peptide derived from tetanus toxoid protein. The vaccines were administered with granulocyte macrophage-colony stimulating factor in Montanide ISA-51 adjuvant over a 7-week period.

A mycoplasma peptide elicits heteroclitic CD4+ T cell responses against tumor antigen MAGE-A6.

Purpose: Although T-helper (Th) epitopes have been previously reported for many tumor antigens, including MAGE-A6, the relevant HLA-DR alleles that present these peptides are expressed by only a minority of patients. The identification of tumor antigenic epitopes presented promiscuously by many HLA-DR alleles would extend the clinical utility of these peptides in vaccines and for the immunomonitoring of cancer patients.

Experimental Design: A neural network algorithm and in vitro sensitization assays were employed to screen candidate peptides for their immunogenicity.

Antibodies for HIV treatment and prevention: window of opportunity?

Monoclonal antibodies are routinely used as therapeutics in a number of disease settings and have thus also been explored as potential treatment for human immunodeficiency virus (HIV)-1 infection. Antibodies targeting viral antigens, and those directed to the cellular receptors, have been considered for use in prevention and therapy. For virus-targeted antibodies, attention has focused primarily on their neutralizing activity, but such antibodies also have the potential to exert antiviral effects via effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), opsonization, or complement activation.

HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs) in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s) (MCLR).

Feature extraction using molecular planes for fuzzy relational clustering of a flexible dopamine reuptake inhibitor.

Six rigid-body parameters (Shift, Slide, Rise, Tilt, Roll, Twist) are commonly used to describe the relative displacement and orientation of successive base pairs in a nucleic acid structure. The present work adapts this approach to describe the relative displacement and orientation of any two planes in an arbitrary molecule-specifically, planes which contain important pharmacophore elements. Relevant code from the 3DNA software package (Nucleic Acids Res.

Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection.

Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells through the trans- and cis-infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we compare cis- and trans-infections of HIV-1 mediated by immature DCs (iDCs) and mature DCs (mDCs), using replication-competent and single-cycle HIV-1. Monocyte-derived iDCs were differentiated into various types of mDCs by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and CD40 ligand (CD40L).

Ease of care with patient controlled analgesia systems: questionnaire development and validation.

Aim: This paper is a report of the development and validation of two questionnaires assessing ease of caring for patients receiving patient controlled analgesia from the perspectives of nurses and physical therapists.

Background: While studies have assessed patient satisfaction with and preference for patient controlled analgesia modalities, no instruments have been developed to assess the ease of providing care (ease of care) for patients receiving patient controlled analgesia from nurses' and physical therapists' perspectives.

Method: Nurses and physical therapists participated in focus groups during 2003 to identify concepts associated with caring for patients receiving intravenous patient controlled analgesia.

Clinical staff resource use with intravenous patient-controlled analgesia in acute postoperative pain management: results from a multicenter, prospective, observational study.

The purpose of this study was to evaluate hospital resource utilization associated with intravenous patient-controlled analgesia (IV-PCA), with a focus on nursing, pharmacy, and central supply/engineering time spent from a hospital perspective. Data were collected during a multicenter (29 sites), prospective observational study in the United States of subjects who underwent total knee replacement (TKR), total hip replacement (THR), or abdominal hysterectomy (AH) and were administered analgesia through IV PCA for the management of acute postoperative pain. Nursing staff recorded the IV PCA-related tasks they performed for a subject and the duration of time required to perform each task from initial IV PCA set-up to discontinuation.

Time course of adverse events most commonly associated with topiramate for migraine prevention.

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period.

A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses.

Purpose: Prostate-specific membrane antigen (PSMA) is an attractive target for active immunotherapy. Alphavirus vaccines have shown promise in eliciting immunity to tumor antigens. This study investigated the immunogenicity of alphavirus vaccine replicon particles (VRP) that encode PSMA (PSMA-VRP).

Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers.

HIV type 1 (HIV-1) envelope is a noncovalent trimer of gp120-gp41 heterodimers, and its lability has hindered structural studies. SOSIP gp140 is a soluble, proteolytically mature form of the HIV-1 envelope wherein gp120-gp41 interactions are stabilized via a disulfide bond and gp41 contains an additional trimer-stabilizing point mutation. We describe the isolation of a substantially pure preparation of SOSIP gp140 trimers derived from KNH1144, a subtype A isolate.

A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning.

How eukaryotic genomes encode the folding of DNA into nucleosomes and how this intrinsic organization of chromatin guides biological function are questions of wide interest. The physical basis of nucleosome positioning lies in the sequence-dependent propensity of DNA to adopt the tightly bent configuration imposed by the binding of the histone proteins. Traditionally, only DNA bending and twisting deformations are considered, while the effects of the lateral displacements of adjacent base pairs are neglected.

Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells.

Dendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear.

Effect of programmed number of intervals to detect ventricular fibrillation on implantable cardioverter-defibrillator aborted and unnecessary shocks.

Introduction: Detection of self-terminating arrhythmias by implantable cardioverter-defibrillators (ICDs) causes unnecessary battery depletion and unnecessary shocks. Our goal was to estimate the effect of the programmed number of intervals to detect (NID) ventricular fibrillation (VF) on ICD temporal episode rate, unnecessary shocks, and delay in detection of VF.

Methods And Results: We analyzed 773 ICD-detected VF episodes in 875 patients.

CD4 coexpression regulates DC-SIGN-mediated transmission of human immunodeficiency virus type 1.

Dendritic cells (DCs) potently stimulate the cell-cell transmission of human immunodeficiency virus type 1 (HIV-1). However, the mechanisms that underlie DC transmission of HIV-1 to CD4(+) T cells are not fully understood. DC-SIGN, a C-type lectin, efficiently promotes HIV-1 trans infection.

A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120.

The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex.

Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1.

The chemokine receptor CCR5 provides a portal of entry for human immunodeficiency virus type 1 (HIV-1) into susceptible CD4(+) cells. Both monoclonal antibody (MAb) and small-molecule CCR5 inhibitors have entered human clinical testing, but little is known regarding their potential interactions. We evaluated the interactions between CCR5 MAbs, small-molecule CCR5 antagonists, and inhibitors of HIV-1 gp120, gp41, and reverse transcriptase in vitro.

L-SIGN (CD209L) isoforms differently mediate trans-infection of hepatoma cells by hepatitis C virus pseudoparticles.

L-SIGN is a C-type lectin that is expressed on liver sinusoidal endothelial cells. Capture of Hepatitis C virus (HCV) by this receptor results in trans-infection of hepatoma cells. L-SIGN alleles have been identified that encode between three and nine tandem repeats of a 23 residue stretch in the juxtamembrane oligomerization domain.

Construction and characterization of soluble, cleaved, and stabilized trimeric Env proteins based on HIV type 1 Env subtype A.

The generation of an antibody response capable of neutralizing a broad range of clinical isolates remains an important goal of human immunodeficiency virus type 1 (HIV-1) vaccine development. Envelope glycoprotein (Env)-based vaccine candidates will also need to take into account the extensive genetic diversity of circulating HIV-1 strains. We describe here the generation of soluble, stabilized, proteolytically cleaved, trimeric forms of Env (SOSIP gp140 proteins) based on contemporary Env subtype A viruses from East Africa.

Modeling the Lac repressor-operator assembly: the influence of DNA looping on Lac repressor conformation.

Repression of transcription of the Escherichia coli Lac operon by the Lac repressor (LacR) is accompanied by the simultaneous binding of LacR to two operators and the formation of a DNA loop. A recently developed theory of sequence-dependent DNA elasticity enables one to relate the fine structure of the LacR-DNA complex to a wide range of heretofore-unconnected experimental observations. Here, that theory is used to calculate the configuration and free energy of the DNA loop as a function of its length and base-pair sequence, its linking number, and the end conditions imposed by the LacR tetramer.

Immunity to melanoma antigens: from self-tolerance to immunotherapy.

The development of effective immune therapy for cancer is a central goal of immunologists in the 21st century. Our laboratories have been deeply involved in characterization of the immune response to melanoma and translation of laboratory discoveries into clinical trials. We have identified a cohort of peptide antigens presented by Major Histocompatibility Complex (MHC) molecules on melanoma cells and widely recognized by T cells from melanoma patients.

Sequence-Dependent Effects in the Cyclization of Short DNA.

A new, computationally efficient Monte Carlo approach has been developed to estimate the ring-closure properties of short, realistically modeled DNA chains. The double helix is treated at the level of base-pair steps using an elastic potential that accounts for the sequence-dependent variability in the intrinsic structure and elastic moduli of the base-pair steps, including the known coupling of conformational variables. Rather than using traditional Metropolis-Monte Carlo techniques to generate representative configurations, a Gaussian sampling method is introduced to construct three-dimensional structures from linear combinations of the rigid-body parameters defining the relative orientation and displacement of successive base pairs.

IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen-derived peptides or recombinant protein effectively stimulate specific Type-1 CD4+ T-cell responses from normal donors and melanoma patients in vitro.

Although CD4(+) Type-1T helper (Th1) cells secreting interferon-gamma (IFN-gamma) appear to play an essential role in promoting durable antitumor immunity, we have previously shown that patients with cancer exhibit dysfunctional Th1-type responses against epitopes derived from tumor antigens, such as MAGE-A6. Here, we engineered human dendritic cells (DCs) to secrete high levels of the IFN-gamma-inducing cytokines, interleukin (IL)-12p70 and IL-18, via recombinant adenoviral infection to generate an in vitro stimulus capable of promoting previously deficient patient Th1-type responses. Dendritic cells co-infected with Ad.