bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stones in the lacrimal gland: a rare condition
Authors: Halborg Jakob , Prause Jan Ulrik , Toft Peter Bjerre , Skjødt Karen , Tommerup Niels Rath , Nielsen Ole Faurskov , Heegaard Steffen 
Published: August 2008

Abstract.Purpose:  Stones (dacryoliths) in the lacrimal drainage system are relatively common. However, stones in the lacrimal gland itself are very rare. We present three cases of lacrimal gland stones and describe the clinical and histopathological characteristics and composition of the stones.Methods:  Three patients presented with swelling in the lateral canthal region of several months’ duration. Clinical examination in each case revealed a mass adjacent to the lacrimal gland. We carried out surgical excision, histological examination and Raman spectroscopy.Results:  Histopathological examination of the excised material showed an eosinophilic, amorphic material organized in lamellae and localized in a ductule. The findings were consistent with a stone in the lacrimal gland in all three cases. All stones were composed of proteins of similar types. After surgery, the three patients healed without complications.Conclusions:  Lacrimal gland stones represent a very rare but relevant differential diagnosis when a patient presents with unilateral persistent conjunctivitis or with a tumour in the lateral canthus. Treatment is excision under local anaesthesia.
Stability and antibacterial potency of ceftazidime and vancomycin eyedrops reconstituted in BSS® against Pseudomonas aeruginosa and Staphylococcus aureus
Authors: Karampatakis Vasileios , Papanikolaou Theoharis , Giannousis Michael , Goulas Antonis , Mandraveli Kaliopi , Kilmpasani Maria , Alexiou‐Daniel Stella , Mirtsou‐Fidani Vassiliki 
Published: August 2008

Abstract.Purpose:  We aimed to study the stability and the in vitro antibacterial potency of ceftazidime and vancomycin eyedrops against Pseudomonas aeruginosa and Staphylococcus aureus, respectively, under different storage temperatures and light conditions.Methods:  Solutions of ceftazidime 50 mg/ml and vancomycin 50 mg/ml were prepared by reconstituting with balanced salt solution (BSS®) and stored at 4 °C and at 24 °C with and without exposure to light. The minimum bactericidal concentrations against P. aeruginosa and S. aureus were measured to evaluate the antimicrobial potency over a 4‐week period. Changes in the pH values and physical characteristics of the solutions were recorded over the same period of time.Results:  The antibacterial potency of ceftazidime decreased significantly from days 3 and 7 onwards at storage temperatures of 24 °C and 4 °C, respectively, but was not affected by light exposure. The pH value progressed from acidic to alkaline, peaking at day 3, in all solutions. The antibacterial potency of vancomycin remained stable during the 4‐week period, but its pH showed a slight progression from acidic to less acidic, in all solutions.Conclusions:  Ceftazidime eyedrops in BSS® appear to remain effective against P. aeruginosa for ≥ 7 days when stored at 4 °C, but were less effective when stored at 24 °C. Loss of antibacterial potency coincides with the appearance of visual and olfactory signs of degradation. The transient rise in pH at day 3 is a matter of possible concern, however, as it may affect patient tolerance. By contrast, vancomycin eyedrops in BSS® can be safely used for ≥ 4 weeks, stored at either 4 °C or 24 °C.
Activity of Hydroxyurea against
Leishmania mexicana
Authors: Martinez-Rojano Hugo , Mancilla-Ramirez Javier , Quiñonez-Diaz Laura , Galindo-Sevilla Norma 
Published: August 2008

ABSTRACT

Leishmania mexicana
is a protozoan parasite that causes a disease in humans with frequent relapses after treatment. It is also highly resistant to the currently available drugs. For this reason, there is an urgent need for more effective antileishmanial drugs. Hydroxyurea, an anticancer drug, is toxic to replicating eukaryotic cells and has been proven to be effective in arresting the
Leishmania major
cell cycle. In this study, hydroxyurea was tested in an in vitro model of intracellular
Leishmania
infection in macrophages. The parasite density in infected macrophages was measured by microscopy after incubation for various times and treatment with hydroxyurea at different concentrations. Viable parasites that could be transformed into promastigotes by shifting the temperature to 26°C were counted every other day after the replacement of hydroxyurea with fresh medium. Meglumine antimoniate, the standard drug treatment for
Leishmania mexicana
, was used as a reference drug under the same experimental conditions. Hydroxyurea completely eliminated
Leishmania
parasites when it was used at a dosage of 10 or 100 μg/ml. Differences in the length of treatment needed to achieve elimination were as follows: the 10-μg/ml doses required 9 days, while 3 days was sufficient when 100 μg/ml was used. Hydroxyurea had a 50% effective dose of 0.015 μg/ml in vitro, which was observed on day 6 after exposure. Hydroxyurea is highly effective in killing intracellular amastigotes in vitro.
Metronidazole Lacks Antibacterial Activity in Guinea Pigs Infected with
Mycobacterium tuberculosis
Authors: Hoff Donald R. , Caraway Megan L. , Brooks Elizabeth J. , Driver Emily R. , Ryan Gavin J. , Peloquin Charles A. , Orme Ian M. , Basaraba Randall J. , Lenaerts Anne J. 
Published: August 2008

ABSTRACT

Metronidazole, which is used for the treatment of infections caused by anaerobic organisms, was evaluated in
Mycobacterium tuberculosis
-infected guinea pigs.
M. tuberculosis
can adapt to hypoxia, which is present in the primary lesions of infected guinea pigs. Metronidazole treatment (for 6 weeks at 100 mg/kg of body weight) resulted in no reduction in the bacillary burden and significantly worsened lesion inflammation.
Fluoroquinolone Enhances the Mutation Frequency for Meropenem-Selected Carbapenem Resistance in
Pseudomonas aeruginosa
, but Use of the High-Potency Drug Doripenem Inhibits Mutant Formation
Authors: Tanimoto Koichi , Tomita Haruyoshi , Fujimoto Shuhei , Okuzumi Katsuko , Ike Yasuyoshi 
Published: August 2008

ABSTRACT

The mutation frequency for carbapenem resistance in
Pseudomonas aeruginosa
strains that were selected with carbapenems was enhanced in the presence of subinhibitory concentrations of fluoroquinolones. The mutants showed either a loss of OprD activity or increased
mexAB
-
oprM
expression. The highest mutant isolation frequency was obtained by selection with meropenem, while doripenem inhibited mutant growth.
Development of Intergenotypic Chimeric Replicons To Determine the Broad-Spectrum Antiviral Activities of Hepatitis C Virus Polymerase Inhibitors
Authors: Herlihy Koleen J. , Graham Joanne P. , Kumpf Robert , Patick Amy K. , Duggal Rohit , Shi Stephanie T. 
Published: August 2008

ABSTRACT
To address the need for broad-spectrum antiviral activity characterization of hepatitis C virus (HCV) polymerase inhibitors, we created a panel of intergenotypic chimeric replicons containing nonstructural (NS) protein NS5B sequences from genotype 2b (GT2b), GT3a, GT4a, GT5a, and GT6a HCV isolates. Viral RNA extracted from non-GT1 HCV patient plasma was subjected to reverse transcription. The NS5B region was amplified by nested PCR and introduced into the corresponding region of the GT1b (Con-1) subgenomic reporter replicon by Splicing by Overlap Extension (SOEing) PCR. Stable cell lines were generated with replication-competent chimeras for in vitro antiviral activity determination of HCV nonnucleoside polymerase inhibitors (NNIs) that target different regions of the protein. Compounds that bind to the NNI2 (thiophene carboxylic acid) or NNI3 (benzothiadiazine) allosteric sites showed 8- to >1,280-fold reductions in antiviral activity against non-GT1 NS5B chimeric replicons compared to that against the GT1b subgenomic replicon. Smaller reductions in susceptibility, ranging from 0.2- to 33-fold, were observed for the inhibitor binding to the NNI1 (benzimidazole) site. The inhibitor binding to the NNI4 (benzofuran) site showed broad-spectrum antiviral activity against all chimeric replicons evaluated in this study. In conclusion, evaluation of HCV NNIs against intergenotypic chimeric replicons showed differences in activity spectrum for inhibitors that target different regions of the enzyme, some of which could be associated with specific residues that differ between GT1 and non-GT1 polymerases. Our study demonstrates the utility of chimeric replicons for broad-spectrum activity determination of HCV inhibitors.
RamA Confers Multidrug Resistance in
Salmonella enterica
via Increased Expression of
acrB
, Which Is Inhibited by Chlorpromazine
Authors: Bailey Andrew M. , Paulsen Ian T. , Piddock Laura J. V. 
Published: August 2008

ABSTRACT

Salmonella enterica
serovar Typhimurium SL1344, in which efflux pump genes (
acrB
,
acrD
,
acrF
,
tolC
) or regulatory genes thereof (
marA
,
soxS
,
ramA
) were inactivated, was grown in the presence of 240 antimicrobial and nonantimicrobial agents in the Biolog Phenotype MicroArray. Mutants lacking
tolC
,
acrB
, and
ramA
grew significantly worse than other mutants in the presence of 48 agents (some of which have not previously been identified as substrates of AcrAB-TolC) and particularly poorly in the presence of phenothiazines, which are human antipsychotics. MIC testing revealed that the phenothiazine chlorpromazine had antimicrobial activity and synergized with common antibiotics against different
Salmonella
serovars and SL1344. Chlorpromazine increased the intracellular accumulation of ethidium bromide, which was ablated in mutants lacking
acrB
, suggesting an interaction with AcrB. High-level but not low-level overexpression of
ramA
increased the expression of
acrB
; conferred resistance to chloramphenicol, tetracycline, nalidixic acid, and triclosan and organic solvent tolerance; and increased the amount of ethidium bromide accumulated. Chlorpromazine induced the modest overproduction of
ramA
but repressed
acrB
. These data suggest that phenothiazines are not efflux pump inhibitors but influence gene expression, including that of
acrB
, which confers the synergy with antimicrobials observed.
Mouse Model of Hemolytic-Uremic Syndrome Caused by Endotoxin-Free Shiga Toxin 2 (Stx2) and Protection from Lethal Outcome by Anti-Stx2 Antibody
Authors: Sauter Kristin A. D. , Melton-Celsa Angela R. , Larkin Kay , Troxell Megan L. , O'Brien Alison D. , Magun Bruce E. 
Published: August 2008

ABSTRACTHemolytic-uremic syndrome (HUS) results from infection by Shiga toxin (Stx)-producingEscherichia coliand is the most common cause of acute renal failure in children. We have developed a mouse model of HUS by administering endotoxin-free Stx2 in multiple doses over 7 to 8 days. At sacrifice, moribund animals demonstrated signs of HUS: increased blood urea nitrogen and serum creatinine levels, proteinuria, deposition of fibrin(ogen), glomerular endothelial damage, hemolysis, leukocytopenia, and neutrophilia. Increased expression of proinflammatory chemokines and cytokines in the sera of Stx2-treated mice indicated a systemic inflammatory response. Currently, specific therapeutics for HUS are lacking, and therapy for patients is primarily supportive. Mice that received 11E10, a monoclonal anti-Stx2 antibody, 4 days after starting injections of Stx2 recovered fully, displaying normal renal function and normal levels of neutrophils and lymphocytes. In addition, these mice showed decreased fibrin(ogen) deposition and expression of proinflammatory mediators compared to those of Stx2-treated mice in the absence of antibody. These results indicate that, when performed during progression of HUS, passive immunization of mice with anti-Stx2 antibody prevented the lethal effects of Stx2.
IONIZATION IN A 1-DIMENSIONAL DIPOLE MODEL
Authors: COSTIN O. , LEBOWITZ J. L. , STUCCHIO C. 
Published: August 2008

We study the evolution of a one-dimensional model atom with δ-function binding potential, subjected to a dipole radiation field E(t)x with E(t) a 2π/ω-periodic real-valued function. We prove that when E(t) is a trigonometric polynomial, complete ionization occurs, i.e. the probability of finding the electron in any fixed region goes to zero as t → ∞. For ψ(x, t = 0) compactly supported and general periodic fields, we decompose ψ(x, t) into uniquely defined resonance terms and a remainder. Each resonance is 2π/ω periodic in time and behaves like the exponentially growing Green's function near x = ±∞. The remainder is given by an asymptotic power series in t-1/2 with coefficients varying with x.
An adaptive automatically tuning intrusion detection system
Authors: Yu Zhenwei , Tsai Jeffrey J. P. , Weigert Thomas 
Published: August 2008

An intrusion detection system (IDS) is a security layer to detect ongoing intrusive activities in computer systems and networks. Current IDS have two main problems: The first problem is that typically so many alarms are generated as to overwhelm the system operator, many of these being false alarms. The second problem is that continuous tuning of the intrusion detection model is required in order to maintain sufficient performance due to the dynamically changing nature of the monitored system. This manual tuning process relies on the system operators to work out the updated tuning solution and to integrate it into the detection model.
In this article, we present an automatically tuning intrusion detection system, which controls the number of alarms output to the system operator and tunes the detection model on the fly according to feedback provided by the system operator when false predictions are identified. This system adapts its behavior (i) by throttling the volume of alarms output to the operator in response to the ability of the operator to respond to these alarms, and (ii) by deciding how aggressively the detection model should be tuned based on the accuracy of earlier predictions. We evaluated our system using the KDDCup'99 intrusion detection dataset. Our results show that an adaptive, automatically tuning intrustion detection system will be both practical and efficient.
Predicting Clinical Outcome through Molecular Profiling in Stage III Melanoma
Authors: John Thomas , Black Michael A. , Toro Tumi T. , Leader Debbie , Gedye Craig A. , Davis Ian D. , Guilford Parry J. , Cebon Jonathan S. 
Published: August 2008

Abstract
Purpose: Patients with macroscopic stage III melanoma represent a heterogeneous cohort with average 5-year overall survival rates of &lt;30%. With current algorithms, it is not possible to predict which patients will achieve longer-term survival. We hypothesized that molecular profiling could be used to identify prognostic groups within patients with stage III melanoma while also providing a greater understanding of the biological programs underpinning these differences.
Experimental Design: Lymph node sections from 29 patients with stage IIIB and IIIC melanoma, with divergent clinical outcome including 16 “poor-prognosis” and 13 “good-prognosis” patients as defined by time to tumor progression, were subjected to molecular profiling using oligonucleotide arrays as an initial training set. Twenty-one differentially expressed genes were validated using quantitative PCR and the 15 genes with strongest cross-platform correlation were used to develop two predictive scores, which were applied to two independent validation sets of 10 and 14 stage III tumor samples.
Results: Supervised analysis using differentially expressed genes was able to differentiate the prognostic groups in the training set. The developed predictive scores correlated directly with clinical outcome. When the predictive scores were applied to the two independent validation sets, clinical outcome was accurately predicted in 90% and 85% of patients, respectively.
Conclusion: We describe a gene expression profile that is capable of distinguishing clinical outcomes in a previously homogeneous group of stage III melanoma patients.
Effect of Rapamycin Alone and in Combination with Sorafenib in an Orthotopic Model of Human Hepatocellular Carcinoma
Authors: Wang Zheng , Zhou Jian , Fan Jia , Qiu Shuang-Jian , Yu Yao , Huang Xiao-Wu , Tang Zhao-You 
Published: August 2008

Abstract
Purpose: Novel therapeutic strategies are needed to prevent the tumor recurrence or metastasis after liver transplantation for hepatocellular carcinoma (HCC). This study was to investigate the effect of rapamycin, alone and in combination with sorafenib, on HCC in vivo.
Experimental Design: Xenograft of a highly metastatic human HCC tumor (LCI-D20) was used to evaluate primary tumor growth and lung metastasis after treatment with rapamycin alone or in combination with sorafenib. Tumor cell proliferation was determined by Ki-67 immunostaining. To detect tumor cell apoptosis, the terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling assay was used. Tumor angiogenesis was investigated by using a monoclonal anti-CD31 antibody. A vascular endothelial growth factor ELISA kit was used to measure vascular endothelial growth factor protein levels in the mice serum.
Results: Rapamycin, alone and in combination with sorafenib, strongly inhibited primary tumor growth and lung metastases in LCI-D20 model. Furthermore, the combination therapy significantly enhanced the effect of antitumor on primary tumor growth compared with single treatment with either rapamycin (P &lt; 0.001) or sorafenib (P &lt; 0.001). Rapamycin alone inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Nevertheless, the combination therapy showed a significant inhibition of tumor cell proliferation (P &lt; 0.05). Additionally, the combination therapy also further enhanced suppression of tumor cell angiogenesis compared with rapamycin treatment (P &lt; 0.01). However, the induction of apoptosis in combination therapy group was not significantly higher than in the rapamycin-treated group (P &gt; 0.05).
Conclusions: The combination therapy of rapamycin and sorafenib could be a new and promising therapeutic approach to the treatment of HCC and prevention of HCC recurrence after liver transplantation.
Vascular Endothelial Growth Factor Receptor-1 Contributes to Resistance to Anti–Epidermal Growth Factor Receptor Drugs in Human Cancer Cells
Authors: Bianco Roberto , Rosa Roberta , Damiano Vincenzo , Daniele Gennaro , Gelardi Teresa , Garofalo Sonia , Tarallo Valeria , De Falco Sandro , Melisi Davide , Benelli Roberto , Albini Adriana , Ryan Anderson , Ciardiello Fortunato , Tortora Giampaolo 
Published: August 2008

Abstract
Purpose: The resistance to selective EGFR inhibitors involves the activation of alternative signaling pathways, and Akt activation and VEGF induction have been described in EGFR inhibitor–resistant tumors. Combined inhibition of EGFR and other signaling proteins has become a successful therapeutic approach, stimulating the search for further determinants of resistance as basis for novel therapeutic strategies.
Experimental Design: We established human cancer cell lines with various degrees of EGFR expression and sensitivity to EGFR inhibitors and analyzed signal transducers under the control of EGFR-dependent and EGFR-independent pathways.
Results: Multitargeted inhibitor vandetanib (ZD6474) inhibited the growth and the phosphorylation of Akt and its effector p70S6 kinase in both wild-type and EGFR inhibitor–resistant human colon, prostate, and breast cancer cells. We found that the resistant cell lines exhibit, as common feature, VEGFR-1/Flt-1 overexpression, increased secretion of VEGF and placental growth factor, and augmented migration capabilities and that vandetanib is able to antagonize them. Accordingly, a new kinase assay revealed that in addition to VEGF receptor (VEGFR)-2, RET, and EGFR, vandetanib efficiently inhibits also VEGFR-1. The contribution of VEGFR-1 to the resistant phenotype was further supported by the demonstration that VEGFR-1 silencing in resistant cells restored sensitivity to anti-EGFR drugs and impaired migration capabilities, whereas exogenous VEGFR-1 overexpression in wild-type cells conferred resistance to these agents.
Conclusions: This study shows that VEGFR-1 contributes to anti-EGFR drug resistance in different human cancer cells. Moreover, vandetanib inhibits VEGFR-1 activation, cell proliferation, and migration, suggesting its potential utility in patients resistant to EGFR inhibitors.
Phenotype and Functional Characterization of Long-term gp100-Specific Memory CD8+ T Cells in Disease-Free Melanoma Patients Before and After Boosting Immunization
Authors: Walker Edwin B. , Haley Daniel , Petrausch Ulf , Floyd Kevin , Miller William , Sanjuan Nelson , Alvord Greg , Fox Bernard A. , Urba Walter J. 
Published: August 2008

AbstractPurpose: Effective cancer vaccines must both drive a strong CTL response and sustain long-term memory T cells capable of rapid recall responses to tumor antigens. We sought to characterize the phenotype and function of gp100 peptide-specific memory CD8+ T cells in melanoma patients after primary gp100209-2M immunization and assess the anamnestic response to boosting immunization.Experimental Design: Eight-color flow cytometry analysis of gp100-specific CD8+ T cells was done on peripheral blood mononuclear cells collected shortly after the primary vaccine regimen, 12 to 24 months after primary vaccination, and after boosting immunization. The anamnestic response was assessed by comparing the frequency of circulating gp100-specific T cells before and after boosting. Gp100 peptide-induced in vitro functional avidity and proliferation responses and melanoma-stimulated T-cell CD107 mobilization were compared for cells from all three time points for multiple patients.Results: The frequency of circulating gp100-specific memory CD8+ T cells was comparable with cytomegalovirus-specific and FLU-specific T cells in the same patients, and the cells exhibited anamnestic proliferation after boosting. Their phenotypes were not unique, and individual patients exhibited one of two distinct phenotype signatures that were homologous to either cytomegalovirus-specific or FLU-specific memory T cells. Gp100-specific memory T cells showed some properties of competent memory T cells, such as heightened in vitro peptide-stimulated proliferation and increase in central memory (TCM) differentiation when compared with T-cell responses measured after the primary vaccine regimen. However, they did not acquire enhanced functional avidity usually associated with competent memory T-cell maturation.Conclusions: Although vaccination with class I–restricted melanoma peptides alone can break tolerance to self-tumor antigens, it did not induce fully competent memory CD8+ T cells—even in disease-free patients. Data presented suggest other vaccine strategies will be required to induce functionally robust long-term memory T cells.