bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Activity of the Histatin Derivative P-113 against Multidrug-Resistant Pathogens Responsible for Pneumonia in Immunocompromised Patients
Authors: Giacometti Andrea , Cirioni Oscar , Kamysz Wojciech , D'Amato Giuseppina , Silvestri Carmela , Prete Maria Simona Del , Licci Alberto , Riva Alessandra , Łukasiak Jerzy , Scalise Giorgio 
Published: February 2005

ABSTRACT

The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113.
S. aureus
showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.
Emergence of Resistance to Rifampin and Rifalazil in
Chlamydophila pneumoniae
and
Chlamydia trachomatis
Authors: Kutlin Andrei , Kohlhoff Stephan , Roblin Patricia , Hammerschlag Margaret R. , Riska Paul 
Published: February 2005

ABSTRACT

Although rifamycins have excellent activity against
Chlamydophila pneumoniae
and
Chlamydia trachomatis
in vitro, concerns about the possible development of resistance during therapy have discouraged their use for treatment of chlamydial infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is the most active antimicrobial against
C. pneumoniae
and
C. trachomatis
in vitro, indicating its potential for treatment of acute and chronic
C. pneumoniae
and
C. trachomatis
infections. We investigated the effect of serial passage of two
C. pneumoniae
isolates and two serotypes of
C. trachomatis
in subinhibitory concentrations of rifalazil and rifampin on the development of phenotypic and genotypic resistance.
C. trachomatis
developed resistance to both antimicrobials within six passages, with higher level resistance to rifampin (128 to 256 μg/ml) and lower level resistance to rifalazil (0.5 to 1 μg/ml).
C. pneumoniae
TW-183 developed only low-level resistance to rifampin (0.25 μg/ml) and rifalazil (0.016 μg/ml) after 12 passages.
C. pneumoniae
CWL-029 failed to develop resistance to either drug. Two unique mutations emerged in the
rpoB
gene of rifampin (L456I) and rifalazil (D461E)-resistant
C. pneumoniae
TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil-resistant
C. trachomatis
UW-3/Cx/D, and a unique mutation (V136F) was found in rifalazil-resistant BU-434/L
2
. No mutations were detected in the entire
rpoB
gene of rifampin-resistant BU-434/L
2
. This is the first description of antibiotic resistance-associated mutations in
C. pneumoniae
and of rifampin resistance in
C. trachomatis
not associated with mutations in the
rpoB
gene.
Biological Characterization of Novel Inhibitors of the Gram-Positive DNA Polymerase IIIC Enzyme
Authors: Kuhl Alexander , Svenstrup Niels , Ladel Christoph , Otteneder Michael , Binas Annegret , Schiffer Guido , Brands Michael , Lampe Thomas , Ziegelbauer Karl , Rübsamen-Waigmann Helga , Haebich Dieter , Ehlert Kerstin 
Published: February 2005

ABSTRACT
Novel N-3-alkylated 6-anilinouracils have been identified as potent and selective inhibitors of bacterial DNA polymerase IIIC, the enzyme essential for the replication of chromosomal DNA in gram-positive bacteria. A nonradioactive assay measuring the enzymatic activity of the DNA polymerase IIIC in gram-positive bacteria has been assembled. The 6-anilinouracils described inhibited the polymerase IIIC enzyme at concentrations in the nanomolar range in this assay and displayed good in vitro activity (according to their MICs) against staphylococci, streptococci, and enterococci. The MICs of the most potent derivatives were about 4 μg/ml for this panel of bacteria. The 50% effective dose of the best compound (6-[(3-ethyl-4-methylphenyl)amino]-3-{[1-(isoxazol-5-ylcarbonyl)piperidin-4-yl]methyl}uracil) was 10 mg/kg of body weight after intravenous application in a staphylococcal sepsis model in mice, from which in vivo pharmacokinetic data were also acquired.
High bone mineral density in loaded skeletal regions of former professional football (soccer) players: what is the effect of time after active career?
Authors: Uzunca K , Birtane M , Durmus-Altun G , Ustun F 
Published: February 2005

Objectives:Physical exercise is an important factor in the acceleration and maintenance of bone mineral density (BMD). Football is an impact loading sport and some studies demonstrate its site specific, bone mass increasing effect. We compared BMD at different skeletal regions in a group of former professional football players and in normal control subjects and evaluated the effect of demographic factors and time after active career on BMD.Methods:Twenty four former football players <70 years old who had retired from professional football at least 10 years previously and 25 non-athletic controls were recruited. The demographic characteristics, activity levels, and dietary habits of all subjects and the chronological history of the footballers’ professional careers were noted. BMD was measured by DEXA at the calcaneus and distal tibia and at the lumbar spine, proximal femur, and distal and proximal radius, and compared between groups. Stepwise multiple linear regression analysis was used to determine the probable predictors of BMD in former football players.Results:In former players BMD values were found to be significantly higher at the lumbar spine, femur neck, femur trochanter, distal tibia, and calcaneus, but not at Ward’s triangle (femur) or the distal and proximal radius regions compared with controls. Time after active career was the only independent predictor of BMD at the lumbar spine, proximal femur (neck, trochanter, and Ward’s triangle), and distal tibia.Conclusions:Former footballers had higher BMD at weight loaded sites and time after active career seemed to be an important factor in determining BMD.
Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome
Authors: Näslund J E , Odenbring S , Näslund U-B , Lundeberg T 
Published: February 2005

Objectives:Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The aims of this study were to determine whether bone scintigrams of patients suffering from patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony compartment of the knee uptake, if any, was localised.Methods:Fifty eight patients with chronic PFPS were examined. All patients underwent a detailed clinical history and a thorough physical examination of the knee. Anterior and lateral static images of both knees were made using a gamma camera 3 h after injection of 550 MBq of99mTc-HMDP. Two experienced radiologists visually evaluated the scans blindly and separately. As 51 patients had bilateral pain, 109 painful knees are included in the results.Results:Diffuse uptake on bone scintigrams was found in 48 knees in 30 of the patients. In 33 knees the uptake was localised to only one bone compartment, in 10 knees diffuse uptake was found in two of the bones forming the knee joint, and in six knees all three bone compartments (the distal femur, the patella, and the proximal tibia) exhibited diffuse uptake.Conclusions:Scintigrams of approximately half of the patients with PFPS will show diffuse uptake in one or more of the bony compartments of the knee joint and radioactive tracer accumulation will occur as often in the proximal tibia as in the patella.
Segregated Microstructure and Crystal Structure in Sputter-Deposited Co–Cr Carbon-Added Films
Authors: Masuya Haruko , Awano Haruo 
Published: February 2005

The compositionally segregated microstructure and the crystal structure of sputter-deposited Co–Cr films to which various percentages of carbon were added are studied by transmission electron microscopy. The results are as follows:
(1) The degree of segregation in the microstructure increases as amount of carbon added increases. The segregated pattern is changed by the amount of carbon added.
(2) The saturation magnetization increases as the degree of the segregation increases. The perpendicular coercivity depends on the perpendicular magnetic anisotropy, and magnetic anisotropy is related to the degree of segregation and the refinement of the segregated pattern.
(3) The plane defects perpendicular to the C-axis in sputter-deposited Co–Cr films are grown by carbon addition.
Epitaxial Growth of InN by Halogen Transport Method
Authors: Osamu Igarashi Osamu Igarashi 
Published: February 2005

InN was epitaxially grown on (0001) α-Al2O3 substrates by the halogen transport method. Surface treatment of the substrate by a H2+Br2 gas (passed over In) just before the growth was essential for obtaining the epitaxial layers of InN. Arrays of extra spots were observed in the reflection electron-diffraction patterns of thin InN films. The extra spot arrays could be explained from the viewpoint that the crystal film was composed of twins. In these twin structures, the twinning planes were (7̄ 12 5̄ 0) and (1̄ 1̄ 20 9̄ 0). These extra spots ultimately disappeared with prolonged growth time. This result shows that as the growth proceeds, crystallites having a predominant orientation overwhelm other crystallites.
Farnesyltransferase inhibitor R115777 (Zarnestra, Tipifarnib) synergizes with paclitaxel to induce apoptosis and mitotic arrest and to inhibit tumor growth of multiple myeloma cells
Authors: Zhu Kuichun , Gerbino Elvira , Beaupre Darrin M. , Mackley Paul A. , Muro-Cacho Carlos , Beam Craig , Hamilton Andrew D. , Lichtenheld Mathias G. , Kerr William G. , Dalton William , Alsina Melissa , Sebti Saïd M. 
Published: February 2005

Abstract
Despite major advances, multiple myeloma (MM) remains an incurable malignancy. Recently we have found that disease stabilization was achieved in 64% of patients with advanced MM treated with the farnesyltransferase inhibitor R115777 (Zarnestra) in a phase 2 clinical trial. In order to enhance R115777 antitumor activity in MM, we examined the combination of this novel agent with other anticancer drugs in MM cell lines. In this study, R115777 was found to synergize with paclitaxel and docetaxel, but not with other chemotherapy agents, including doxorubicin, 5-fluorouracil, cisplastin, melphalan, mitoxantrone, and dexamethasone. R115777 synergized with paclitaxel to inhibit MM cell proliferation and to induce apoptosis. Synergism in the induction of apoptosis was accompanied by increase in cytochrome c release and caspase-3 activation. Furthermore, flow cytometry analysis also showed that paclitaxel and R115777 synergized to induce G2/M cell-cycle arrest. Importantly, synergism was observed in taxane- and R115777-resistant MM cells. In the human severe combined immunodeficient (SCID-hu) bone model of myeloma growth, the ability of paclitaxel to inhibit tumor growth in vivo was enhanced by R115777. Combination of paclitaxel or docetaxel with R115777 in the treatment of MM cells from patients with multiple myeloma was more beneficial than treatment with single agents. Our results provide the basis for combination therapy clinical trials with paclitaxel or docetaxel with R115777 in MM patients. (Blood. 2005;105:4759-4766)
An inducible caspase 9 safety switch for T-cell therapy
Authors: Straathof Karin C. , Pulè Martin A. , Yotnda Patricia , Dotti Gianpietro , Vanin Elio F. , Brenner Malcolm K. , Heslop Helen E. , Spencer David M. , Rooney Cliona M. 
Published: February 2005

Abstract
The efficacy of adoptive T-cell therapy as treatment for malignancies may be enhanced by genetic modification of infused cells. However, oncogenic events due to vector/transgene integration, and toxicities due to the infused cells themselves, have tempered enthusiasm. A safe and efficient means of removing aberrant cells in vivo would ameliorate these concerns. We describe a “safety switch” that can be stably and efficiently expressed in human T cells without impairing phenotype, function, or antigen specificity. This reagent is based on a modified human caspase 9 fused to a human FK506 binding protein (FKBP) to allow conditional dimerization using a small molecule pharmaceutical. A single 10-nM dose of synthetic dimerizer drug induces apoptosis in 99% of transduced cells selected for high transgene expression in vitro and in vivo. This system has several advantages over currently available suicide genes. First, it consists of human gene products with low potential immunogenicity. Second, administration of dimerizer drug has no effects other than the selective elimination of transduced T cells. Third, inducible caspase 9 maintains function in T cells overexpressing antiapoptotic molecules. These characteristics favor incorporation of inducible caspase 9 as a safety feature in human T-cell therapies.
The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum
Authors: Tiffert Teresa , Lew Virgilio L. , Ginsburg Hagai , Krugliak Miriam , Croisille Laure , Mohandas Narla 
Published: February 2005

AbstractIn most inherited red blood cell (RBC) disorders with high gene frequencies in malaria-endemic regions, the distribution of RBC hydration states is much wider than normal. The relationship between the hydration state of circulating RBCs and protection against severe falciparum malaria remains unexplored. The present investigation was prompted by a casual observation suggesting that falciparum merozoites were unable to invade isotonically dehydrated normal RBCs. We designed an experimental model to induce uniform and stable isotonic volume changes in RBC populations from healthy donors by increasing or decreasing their KCl contents through a reversible K+ permeabilization pulse. Swollen and mildly dehydrated RBCs were able to sustain Plasmodium falciparum cultures with similar efficiency to untreated RBCs. However, parasite invasion and growth were progressively reduced in dehydrated RBCs. In a parallel study, P falciparum invasion was investigated in density-fractionated RBCs from healthy subjects and from individuals with inherited RBC abnormalities affecting primarily hemoglobin (Hb) or the RBC membrane (thalassemias, hereditary ovalocytosis, xerocytosis, Hb CC, and Hb CS). Invasion was invariably reduced in the dense cell fractions in all conditions. These results suggest that the presence of dense RBCs is a protective factor, additional to any other protection mechanism prevailing in each of the different pathologies. (Blood. 2005; 105:4853-4860)
CNS activity of Pokeweed Anti-viral Protein (PAP) in mice infected with Lymphocytic Choriomeningitis Virus (LCMV)
Authors: Uckun Fatih M , Rustamova Larisa , Vassilev Alexei O , Tibbles Heather E , Petkevich Alexander S 
Published: February 2005

Abstract
Background
Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV).

Methods
We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation.

Results
PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069).

Conclusion
Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.
Up-regulation of the interferon-inducible IFI16 gene by oxidative stress triggers p53 transcriptional activity in endothelial cells
Authors: Gugliesi Francesca , Mondini Michele , Ravera Raffaella , Robotti Andrea , de Andrea Marco , Gribaudo Giorgio , Gariglio Marisa , Landolfo Santo 
Published: February 2005

AbstractReactive oxygen species (ROS), including hydrogen peroxide (H2O2), induces injury of endothelium in a variety of pathophysiological conditions, such as inflammation, aging, and cancer. In our study, we characterized the signaling pathway linking oxidative stress induced by sublethal concentrations of H2O2 to p53 in primary human endothelial cells through the interferon (IFN)-inducible gene IFI16. Induction of IFI16 by H2O2 was concentration- and time-dependent (maximum at 50 μM, 6 h after treatment) and down-regulated by pretreatment with N-acetyl-L-cysteine, which acts as an antioxidant. This pathway is a general response to ROS and not specific to H2O2 treatment, as two other ROS-generating compounds, i.e., S-nitroso-N-acetylpenicillamine and tert-butyl hydroperoxide, were equally capable to induce IFI16. Moreover, IFI16 up-regulation is a result of protein accumulation, as expression of corresponding mRNA, assessed by real-time polymerase chain reaction, was not affected. To investigate the mechanism of IFI16 accumulation, cells were incubated for 6 h in the presence of H2O2 or IFN-β, and then cycloheximide was added to inhibit further protein synthesis. The half-life of IFI16 protein was found to be significantly increased in H2O2-treated cells compared with IFN-β-treated cells (t1/2=120 min vs. &gt;30 min in H2O2- vs. IFN-β-treated cells, respectively). An increase of IFI16 was accompanied by interaction with p53 phosphorylated at its N terminus, as shown by immunoprecipitation experiments. Moreover, binding to IFI16 resulted in its transcriptional activation as shown by an increase in the activity of a reporter gene driven by p53-responsive sequences derived from the p21WAF1 promoter, along with an increase in the p21 mRNA and protein levels. Altogether, these results demonstrate a novel role of IFI16 in the signal transduction pathway that leads to p53 activation by oxidative stress in endothelial cells.
Regulated recruitment of DC-SIGN to cell–cell contact regions during zymosan-induced human dendritic cell aggregation
Authors: de la Rosa Gonzalo , Yáñez-Mó María , Samaneigo Raphael , Serrano-Gómez Diego , Martínez-Muñoz Laura , Fernández-Ruiz Elena , Longo Natividad , Sánchez-Madrid Francisco , Corbí Ángel L , Sánchez-Mateos Paloma 
Published: February 2005

AbstractZymosan is a β-glucan, mannan-rich yeast particle widely used to activate the inflammatory response of immune cells. We studied the zymosan-binding potential of human dendritic cells (hDCs) by using specific carbohydrate inhibitors and blocking monoclonal antibodies. We show that DC-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN) is a major nonopsonic recognition receptor for zymosan on hDCs. Indeed, blocking of DC-SIGN inhibited the inflammatory response of DCs to zymosan. We compared the zymosan-binding capacity of hDC-SIGN to that of Dectin-1 and complement receptor 3 (CR3), which are receptors involved in the nonopsonic recognition of these yeast-derived particles. Dectin-1- and DC-SIGN-K562 cells bound to zymosan particles, whereas CR3-K562 cells did not. DC-SIGN and Dectin-1 were also expressed in COS cells to compare their ability to trigger particle internalization in a nonphagocytic cell line. DC-SIGN transfectants were unable to internalize bound particles, indicating that DC-SIGN is primarily involved in recognition but not in particle internalization. Zymosan induced a rapid DC aggregation that was accompanied by a dramatic change of DC-SIGN distribution in the plasma membrane. Under resting conditions, DC-SIGN was diffusely distributed through the cell surface, displaying clusters at the free leading edge. Upon zymosan treatment, DC-SIGN was markedly redistributed to cell–cell contacts, supporting an adhesion role in DC–DC interactions. The mechanism(s) supporting DC-SIGN-mediated intercellular adhesion were further investigated by using DC-SIGN-K562 aggregation. DC-SIGN was highly concentrated at points of cell–cell contact, suggesting a role for enhanced avidity during DC-SIGN-mediated intercellular adhesion.
The expression and roles of Toll-like receptors in the biology of the human neutrophil
Authors: Parker Lisa C , Whyte Moira K B , Dower Steven K , Sabroe Ian 
Published: February 2005

AbstractNeutrophils are amongst the first immune cells to arrive at sites of infection, where they initiate antimicrobial and proinflammatory functions, which serve to contain infection. Sensing and defeating microbial infections are daunting tasks as a result of their molecular heterogeneity; however, Toll-like receptors (TLRs) have emerged as key components of the innate-immune system, activating multiple steps in the inflammatory reaction, eliminating invading pathogens, and coordinating systemic defenses. Activated neutrophils limit infection via the phagocytosis of pathogens and by releasing antimicrobial peptides and proinflammatory cytokines and generating reactive oxygen intermediates. Through the production of chemokines, they additionally recruit and activate other immune cells to aid the clearance of the microbes and infected cells and ultimately, mount an adaptive immune response. In acute inflammation, influx of neutrophils from the circulation leads to extremely high cell numbers within tissues, which is exacerbated by their delayed, constitutive apoptosis caused by local inflammatory mediators, potentially including TLR agonists. Neutrophil apoptosis and safe removal by phagocytic cells limit tissue damage caused by release of neutrophil cytotoxic granule contents. This review addresses what is currently known about the function of TLRs in the biology of the human neutrophil, including the regulation of TLR expression, their roles in cellular recruitment and activation, and their ability to delay apoptotic cell death.
Particle separation using ultrasound can be used with human shed mediastinal blood
Authors: Jönsson Henrik , Nilsson Andreas , Petersson Filip , Allers Mats , Laurell Thomas 
Published: February 2005

Background: Shed mediastinal blood collected by cardiotomy suction has been shown to be a large contributor to lipid microemboli ending up in different organs. The aim of this study was to test the separation efficiency on human shed blood of a new separation method developed to meet this demand. Methods: Shed mediastinal blood collected from the pericardial cavity of 13 patients undergoing cardiac surgery with cardiopulmonary bypass was collected. The blood was processed in an eight-channel parallel PARSUS separator, and separation efficiency was determined. Results: Erythrocyte recovery, in terms of a separation ratio, varied between 68% and 91%. Minor electrolyte changes took place, where levels of sodium increased and levels of potassium and calcium decreased. Conclusion: This study demonstrates that PARSUS technology can be used on human shed mediastinal blood with good separation efficiency. The technology is, thereby, suggested to have future clinical relevance.