Central Venous Catheter Complications during Home Parenteral Nutrition: A Prospective Pilot Study of 481 Patients with More than 30,000 Catheter Days

Background: Home parenteral nutrition (HPN) has been shown to delay deterioration in cancer patients with malnutrition. Its risk-benefit ratio, however, is determined by the threat of central venous catheter (CVC) complications. Only few prospective studies on this subject exist, most of them based on small samples. The objective of this study was to provide reliable estimates of incidence rates of CVC complications in everyday HPN patient care in Germany. Patients and Methods: Aiming for a large prospective cohort study, we cooperated with a service provider caring for HPN patients nationwide. Between July 1 and November 30, 2006, all consecutive adult patients with more than 10 infusion days and no previous history of HPN were recruited. Follow-up ended on January 31, 2007. Data were collected in a standardised way by the provider's staff. To prevent underreporting, we used computer-assisted telephone interviews with medical caregivers as a provider-independent data source. Results: 481 patients met the inclusion criteria, contributing a total of 31,337 catheter days. 52 patients experienced a total of 63 CVC complications, resulting in an incidence rate of 2.01 CVC complications per 1,000 catheter days including 1.02 CVC infections per 1,000 catheter days. Conclusion: HPN administration can be safely performed with a relatively low rate of CVC complications

Systemically Administered TLR7/8 Agonist and Antigen-Conjugated Nanogels Govern Immune Responses against Tumors

[Image: see text] The generation of specific humoral and cellular immune responses plays a pivotal role in the development of effective vaccines against tumors. Especially the presence of antigen-specific, cytotoxic T cells influences the outcome of therapeutic cancer vaccinations. Different strategies, ranging from delivering antigen-encoding mRNAs to peptides or full antigens, are accessible but often suffer from insufficient immunogenicity and require immune-boosting adjuvants as well as carrier platforms to ensure stability and adequate retention. Here, we introduce a pH-responsive nanogel platform as a two-component antitumor vaccine that is safe for intravenous application and elicits robust immune responses in vitro and in vivo. The underlying chemical design allows for straightforward covalent attachment of a model antigen (ovalbumin) and an immune adjuvant (imidazoquinoline-type TLR7/8 agonist) onto the same nanocarrier system. In addition to eliciting antigen-specific T and B cell responses that outperform mixtures of individual components, our two-component nanovaccine leads in prophylactic and therapeutic studies to an antigen-specific growth reduction of different tumors expressing ovalbumin intracellularly or on their surface. Regarding the versatile opportunities for functionalization, our nanogels are promising for the development of highly customized and potent nanovaccines

Pointlike structure for super p-branes

We present an efficient method to understand the p-brane dynamics in a unified framework. For this purpose, we reformulate the action for super p-branes in the form appropriate to incorporate the pointlike (parton) structure of higher dimensional p-branes and intend to interpret the p-brane dynamics as the collective dynamics of superparticles. In order to examine such a parton picture of super p-branes, we consider various superparticle configurations that can be reduced from super p-branes, especially, a supermembrane, and study the partonic structure of classical p-brane solutions.Comment: 22 pages, corrected typos, to appear in Phys. Rev. D58, 085018 (1998

The Heat Shock Response of Mycobacterium Tuberculosis: Linking Gene Expression, Immunology and Pathogenesis

The regulation of heat shock protein (HSP) expression is critically important to pathogens such as Mycobacterium tuberculosis and dysregulation of the heat shock response results in increased immune recognition of the bacterium and reduced survival during chronic infection. In this study we use a whole genome spotted microarray to characterize the heat shock response of M. tuberculosis. We also begin a dissection of this important stress response by generating deletion mutants that lack specific transcriptional regulators and examining their transcriptional profiles under different stresses. Understanding the stimuli and mechanisms that govern heat shock in mycobacteria will allow us to relate observed in vivo expression patterns of HSPs to particular stresses and physiological conditions. The mechanisms controlling HSP expression also make attractive drug targets as part of a strategy designed to enhance immune recognition of the bacterium

Antigen loading of MHC class I molecules in the endocytic tract

Major histocompatibility complex (MHC) class I molecules bind antigenic peptides that are translocated from the cytosol into the endoplasmic reticulum by the transporter associated with antigen processing. MHC class I loading independent of this transporter also exists and involves peptides derived from exogenously acquired antigens. Thus far, a detailed characterization of the intracellular compartments involved in this pathway is lacking. In the present study, we have used the model system in which peptides derived from measles virus protein F are presented to cytotoxic T cells by B-lymphoblastoid cells that lack the peptide transporter. Inhibition of T cell activation by the lysosomotropic drug ammoniumchloride indicated that endocytic compartments were involved in the class I presentation of this antigen. Using immunoelectron microscopy, we demonstrate that class I molecules and virus protein F co-localized in multivesicular endosomes and lysosomes. Surprisingly, these compartments expressed high levels of class II molecules, and further characterization identified them as MHC class II compartments. In addition, we show that class I molecules co-localized with class II molecules on purified exosomes, the internal vesicles of multivesicular endosomes that are secreted upon fusion of these endosomes with the plasma membrane. Finally, dendritic cells, crucial for the induction of primary immune responses, also displayed class I in endosomes and o

Candida albicans Possesses Sap7 as a Pepstatin A-Insensitive Secreted Aspartic Protease

BACKGROUND: Candida albicans, a commensal organism, is a part of the normal flora of healthy individuals. However, once the host immunity is compromised, C. albicans opportunistically causes recurrent superficial or fatal systemic candidiasis. Secreted aspartic proteases (Sap), encoded by 10 types of SAP genes, have been suggested to contribute to various virulence processes. Thus, it is important to elucidate their biochemical properties for better understanding of the molecular mechanisms that how Sap isozymes damage host tissues. METHODOLOGY/PRINCIPAL FINDINGS: The SAP7 gene was cloned from C. albicans SC5314 and heterogeneously produced by Pichia pastoris. Measurement of Sap7 proteolytic activity using the FRETS-25Ala library showed that Sap7 was a pepstatin A-insensitive protease. To understand why Sap7 was insensitive to pepstatin A, alanine substitution mutants of Sap7 were constructed. We found that M242A and T467A mutants had normal proteolytic activity and sensitivity to pepstatin A. M242 and T467 were located in close proximity to the entrance to an active site, and alanine substitution at these positions widened the entrance. Our results suggest that this alteration might allow increased accessibility of pepstatin A to the active site. This inference was supported by the observation that the T467A mutant has stronger proteolytic activity than the wild type. CONCLUSIONS/SIGNIFICANCE: We found that Sap7 was a pepstatin A-insensitive protease, and that M242 and T467 restricted the accessibility of pepstatin A to the active site. This finding will lead to the development of a novel protease inhibitor beyond pepstatin A. Such a novel inhibitor will be an important research tool as well as pharmaceutical agent for patients suffering from candidiasis