bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Efficacies of Two Antimony Regimens To Treat
Leishmania braziliensis
-Induced Cutaneous Leishmaniasis in Rhesus Macaques (
Macaca mulatta
)
Authors: Grimaldi G. , Porrozzi R. , Friedrich K. , Teva A. , Marchevsky R. S. , Vieira F. , Miekeley N. , Paumgartten F. J. R. 
Published: October 2009

ABSTRACT

This study compared the efficacies of two
N
-methylglucomine antimoniate (MA) dose regimens for treating macaques with
Leishmania braziliensis
-induced chronic skin disease. Whereas all animals treated with the full dose (20 mg MA/kg/day) were cured, 50% of the monkeys receiving a low-dose regimen (5 mg MA/kg/day) relapsed. The antimony concentrations in macaque plasma and tissue samples were greater in the full-dose group than in that receiving a subtherapeutic MA regimen. Our data also suggest the presence of drug-induced hepatic pathology.
Allelic Exchange and Mutant Selection Demonstrate that Common Clinical
embCAB
Gene Mutations Only Modestly Increase Resistance to Ethambutol in
Mycobacterium tuberculosis
Authors: Safi Hassan , Fleischmann Robert D. , Peterson Scott N. , Jones Marcus B. , Jarrahi Behnam , Alland David 
Published: October 2009

ABSTRACT

Mutations within codon 306 of the
Mycobacterium tuberculosis embB
gene modestly increase ethambutol (EMB) MICs. To identify other causes of EMB resistance and to identify causes of high-level resistance, we generated EMB-resistant
M. tuberculosis
isolates in vitro and performed allelic exchange studies of
embB
codon 406 (
embB
406) and
embB
497 mutations. In vitro selection produced mutations already identified clinically in
embB
306,
embB
397,
embB
497,
embB
1024, and
embC
13, which result in EMB MICs of 8 or 14 μg/ml, 5 μg/ml, 12 μg/ml, 3 μg/ml, and 4 μg/ml, respectively, and mutations at
embB
320,
embB
324, and
embB
445, which have not been identified in clinical
M. tuberculosis
isolates and which result in EMB MICs of 8 μg/ml, 8 μg/ml, and 2 to 8 μg/ml, respectively. To definitively identify the effect of the common clinical
embB
497 and
embB
406 mutations on EMB susceptibility, we created a series of isogenic mutants, exchanging the wild-type
embB
497 CAG codon in EMB-susceptible
M. tuberculosis
strain 210 for the
embB
497 CGG codon and the wild-type
embB
406 GGC codon for either the
embB
406 GCC,
embB
406 TGC,
embB
406 TCC, or
embB
406 GAC codon. These new mutants showed 6-fold and 3- to 3.5-fold increases in the EMB MICs, respectively. In contrast to the
embB
306 mutants, the isogenic
embB
497 and
embB
406 mutants did not have preferential growth in the presence of isoniazid or rifampin (rifampicin) at their MICs. These results demonstrate that individual
embCAB
mutations confer low to moderate increases in EMB MICs. Discrepancies between the EMB MICs of laboratory mutants and clinical
M. tuberculosis
strains with identical mutations suggest that clinical EMB resistance is multigenic and that high-level EMB resistance requires mutations in currently unknown loci.
Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population
Authors: Stark D. , Barratt J. L. N. , van Hal S. , Marriott D. , Harkness J. , Ellis J. T. 
Published: October 2009

SUMMARYGlobally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such asGiardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites.
Delusional Infestation
Authors: Freudenmann Roland W. , Lepping Peter 
Published: October 2009

SUMMARYThis papers aims at familiarizing psychiatric and nonpsychiatric readers with delusional infestation (DI), also known as delusional parasitosis. It is characterized by the fixed belief of being infested with pathogens against all medical evidence. DI is no single disorder but can occur as a delusional disorder of the somatic type (primary DI) or secondary to numerous other conditions. A set of minimal diagnostic criteria and a classification are provided. Patients with DI pose a truly interdisciplinary problem to the medical system. They avoid psychiatrists and consult dermatologists, microbiologists, or general practitioners but often lose faith in professional medicine. Epidemiology and history suggest that the imaginary pathogens change constantly, while the delusional theme “infestation” is stable and ubiquitous. Patients with self-diagnosed “Morgellons disease” can be seen as a variation of this delusional theme. For clinicians, clinical pathways for efficient diagnostics and etiology-specific treatment are provided. Specialized outpatient clinics in dermatology with a liaison psychiatrist are theoretically best placed to provide care. The most intricate problem is to engage patients in psychiatric therapy. In primary DI, antipsychotics are the treatment of choice, according to limited but sufficient evidence. Pimozide is no longer the treatment of choice for reasons of drug safety. Future research should focus on pathophysiology and the neural basis of DI, as well as on conclusive clinical trials, which are widely lacking. Innovative approaches will be needed, since otherwise patients are unlikely to adhere to any study protocol.
Passage through
Ixodes scapularis
Ticks Enhances the Virulence of a Weakly Pathogenic Isolate of
Borrelia burgdorferi
Authors: Adusumilli Sarojini , Booth Carmen J. , Anguita Juan , Fikrig Erol 
Published: October 2009

ABSTRACT

Lyme disease is the most common tick-borne illness in the United States. In this paper we explore the contribution of
Ixodes scapularis
ticks to the pathogenicity of
Borrelia burgdorferi
in mice. Previously we demonstrated that an isolate of
B. burgdorferi
sensu stricto (designated N40), passaged 75 times in vitro (N40-75), was infectious but was no longer able to cause arthritis and carditis in C3H mice. We now show that N40-75 spirochetes can readily colonize
I. scapularis
and multiply during tick engorgement. Remarkably, tick-transmitted N40-75 spirochetes cause disease in mice. N40-75 spirochetes isolated from these animals also retained their pathogenicity when subsequently administered to mice via syringe inoculation. Array analysis revealed that several genes associated with virulence, including
bba25
,
bba65
,
bba66
,
bbj09
, and
bbk32
, had higher expression levels in the tick-passaged N40-75 spirochete. These data suggest that transmission of a high-passage attenuated isolate of
B. burgdorferi
by the arthropod vector results in the generation of spirochetes that have enhanced pathogenesis in mice.
Partial Protection againstHelicobacter pyloriin the Absence of Mast Cells in Mice
Authors: Ding Hua , Nedrud John G. , Wershil Barry , Redline Raymond W. , Blanchard Thomas G. , Czinn Steven J. 
Published: October 2009

ABSTRACTThe goal of this study is to evaluate the contribution of mast cells toHelicobacter pyloriimmunity in a model of vaccine-induced protection. Mast cell-deficientKitlSl/KitlSl-dand control mice were immunized withH. pylorisonicate plus cholera toxin and challenged withH. pylori, and the bacterial loads, inflammatory infiltrates, and cytokine responses were evaluated and compared at 1, 2, and 4 weeks postchallenge. In vitro stimulation assays were performed using bone marrow-derived mast cells, and recall assays were performed with spleen cells of immunized mast cell-deficient and wild-type mice. Bacterial clearance was observed by 2 weeks postchallenge in mast cell-deficient mice. The bacterial load was reduced by 4.0 log CFU in wild-type mice and by 1.5 log CFU in mast cell-deficient mice. Neutrophil numbers in the gastric mucosa of immuneKitlSl/KitlSl-dmice were lower than those for immune wild-type mice (P< 0.05). Levels of gastric interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) were also significantly lower in immuneKitlSl/KitlSl-dmice than in wild-type mice (P< 0.001). Immunized mast cell-deficient and wild-type mouse spleen cells produced IFN-γ and IL-17 in response toH. pyloriantigen stimulation. TNF-α and CXC chemokines were detected in mast cell supernatants after 24 h of stimulation withH. pyloriantigen. The results indicate that mast cells are not essential for but do contribute to vaccine-induced immunity and that mast cells contribute to neutrophil recruitment and inflammation in response toH. pylori.
12/15-Lipoxygenase-Dependent Myeloid Production of Interleukin-12 Is Essential for Resistance to Chronic Toxoplasmosis
Authors: Middleton Melissa K. , Zukas Alicia M. , Rubinstein Tanya , Kinder Michelle , Wilson Emma H. , Zhu Peijuan , Blair Ian A. , Hunter Christopher A. , Puré Ellen 
Published: October 2009

ABSTRACTInterleukin-12 (IL-12) is critical for resistance toToxoplasma gondiiduring both the acute and chronic stages of infection. However, the cellular and molecular pathways that regulate IL-12 production during chronic toxoplasmosis are incompletely defined. We recently discovered that 12/15-lipoxygenase (12/15-LOX), which oxidizes unsaturated lipids in macrophages, is a novel and selective regulator of IL-12 production. We now demonstrate the essential role of this enzyme in the chronic phase of toxoplasmosis. Although 12/15-LOX-deficient mice were resistant to acuteT. gondiiinfection, 80% of 12/15-LOX-deficient mice died during chronic toxoplasmosis, compared to no deaths in wild-type controls. The morbidity of chronically infected 12/15-LOX mice was associated with an increase in brain inflammation and parasite burden. These data suggest that the evolution of the immune response toT. gondiiis accompanied by an increasing requirement for 12/15-LOX-mediated signaling. Consistent with this conclusion, 12/15-LOX activity was enhanced during chronic, but not acute, toxoplasmosis. Furthermore, the enhanced susceptibility of 12/15-LOX-deficient mice to chronic toxoplasmosis was associated with reduced production of IL-12 and gamma interferon (IFN-γ) that was not evident during acute infection. Importantly, ex vivo IFN-γ production by 12/15-LOX-deficient splenocytes could be rescued by the addition of recombinant IL-12. These data establish that 12/15-LOX is a critical mediator of the chronic type 1 inflammatory response and that immune mediators can be subject to distinct cellular and/or molecular mechanisms of regulation at different stages of inflammation.
SuperantigenicStaphylococcus aureusStimulates Production of Interleukin-17 from Memory but Not Naive T Cells
Authors: Islander Ulrika , Andersson Annica , Lindberg Erika , Adlerberth Ingegerd , Wold Agnes E. , Rudin Anna 
Published: October 2009

ABSTRACTT-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible toStaphylococcus aureusinfections compared to individuals having Th17 cells.S. aureusis part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killedS. aureuswould be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producingS. aureusbut not nonsuperantigenicS. aureusor other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation withS. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenicS. aureusare particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.
A Histidine-to-Arginine Substitution in Panton-Valentine Leukocidin from USA300 Community-Acquired Methicillin-Resistant
Staphylococcus aureus
Does Not Impair Its Leukotoxicity
Authors: Besseyre des Horts Timothée , Dumitrescu Oana , Badiou Cédric , Thomas Damien , Benito Yvonne , Etienne Jerome , Vandenesch François , Lina Gerard 
Published: October 2009

ABSTRACT

Panton-Valentine leukocidin (PVL) is a synergohymenotropic toxin (SHT) produced by
Staphylococcus aureus
. At present, there are conflicting reports on the leukotoxic activity of PVL and its consequent role as a virulence factor in USA300. In this work, we compared the cytolytic effects induced by wild-type PVL and those of PVL harboring a histidine-to-arginine substitution at amino acid 176 in the
S. aureus
USA300 strain. We also investigated the capacity of wild-type and H176R LukS-PV to recruit and form pores with the F components of other SHTs. For this purpose, we assayed polymorphonuclear neutrophils for leukotoxicity after incubation with either culture supernatants from strains bearing different PVL haplotypes or recombinant toxins from different types of SHT. We show here that the H176R variation in the PVL sequence causes no change in leukotoxicity and that the R variant is as efficient as wild-type PVL at inducing pore formation in leukocytes.
Histamine Plays an Essential Regulatory Role in Lung Inflammation and Protective Immunity in the Acute Phase ofMycobacterium tuberculosisInfection
Authors: Carlos D. , Fremond C. , Samarina A. , Vasseur V. , Maillet I. , Ramos S. G. , Erard F. , Quesniaux V. , Ohtsu H. , Silva C. L. , Faccioli L. H. , Ryffel B. 
Published: October 2009

ABSTRACTThe course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Recent data suggest a regulatory role of histamine not only in the innate but also in the adaptive immune response. We used a model of pulmonaryMycobacterium tuberculosisinfection in histamine-deficient mice lacking histidine decarboxylase (HDC−/−), the histamine-synthesizing enzyme. To confirm that mycobacterial infection induced histamine production, we exposed mice toM. tuberculosisand compared responses in C57BL/6 (wild-type) and HDC−/−mice. Histamine levels increased around fivefold above baseline in infected C57BL/6 mice at day 28 of infection, whereas only small amounts were detected in the lungs of infected HDC−/−mice. Blocking histamine production decreased both neutrophil influx into lung tissue and the release of proinflammatory mediators, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), in the acute phase of infection. However, the accumulation and activation of CD4+T cells were augmented in the lungs of infected HDC−/−mice and correlated with a distinct granuloma formation that contained abundant lymphocytic infiltration and reduced numbers of mycobacteria 28 days after infection. Furthermore, the production of IL-12, gamma interferon, and nitric oxide, as well as CD11c+cell influx into the lungs of infected HDC−/−mice, was increased. These findings indicate that histamine produced afterM. tuberculosisinfection may play a regulatory role not only by enhancing the pulmonary neutrophilia and production of IL-6 and TNF-α but also by impairing the protective Th1 response, which ultimately restricts mycobacterial growth.
Benthic bioturbator enhances CH4 fluxes among aquatic compartments and atmosphere in experimental microcosms
Authors: Figueiredo-Barros Marcos Paulo , Caliman Adriano , Leal João J. F. , Bozelli Reinaldo L. , Farjalla Vinicius F. , Esteves Francisco A. 
Published: October 2009

We utilized laboratory microcosms to evaluate the effects of a benthic sediment bioturbator ( Heteromastus similis ; Polychaeta; conveyor-belt deposit feeder) on vertical distributions of CH4 in sediment and net CH4 fluxes across sediment–water–air interfaces. The effect of H. similis on sediment CH4 concentration ([CH4]) varied depending on sediment depth and was strongest at higher animal densities. In comparison with defaunated controls, microcosms with the highest density of H. similis exhibited an increase in [CH4] of 3.7-fold, on average, at the sediment surface (0–2 cm), but these concentrations decreased by ~2-fold in deeper sediment layers (2–8 cm). However, irrespective of sediment depth, the density of H. similis resulted in an overall nonlinear reduction of bulk sediment [CH4]. Most of the observed CH4 losses from the sediment were due to CH4 oxidation, but the bioturbatory activities of H. similis also promoted significant increases in [CH4] in both the water column and the microcosm headspace. These results suggest that benthic invertebrates can mediate CH4 turnover between compartments in aquatic ecosystems, with further consequences for the coupling between benthic–pelagic food chains via the methanotrophic-mediated microbial loop, as well as increase CH4 emissions to the atmosphere.
Algorithmic aspects of bandwidth trading
Authors: Bhatia Randeep , Chuzhoy Julia , Freund Ari , Naor Joseph (Seffi) 
Published: October 2009

We study algorithmic problems that are motivated by bandwidth trading in next-generation networks. Typically, bandwidth trading involves sellers (e.g., network operators) interested in selling bandwidth pipes that offer to buyers a guaranteed level of service for a specified time interval. The buyers (e.g., bandwidth brokers) are looking to procure bandwidth pipes to satisfy the reservation requests of end-users (e.g., Internet subscribers). Depending on what is available in the bandwidth exchange, the goal of a buyer is to either spend the least amount of money so as to satisfy all the reservations made by its customers, or to maximize its revenue from whatever reservations can be satisfied.
We model this as a real-time nonpreemptive scheduling problem in which machine types correspond to bandwidth pipes and jobs correspond to end-user reservation requests. Each job specifies a time interval during which it must be processed, and a set of machine types on which it can be executed. If necessary, multiple machines of a given type may be allocated, but each must be paid for. Finally, each job has associated with it a revenue, which is realized if the job is scheduled on some machine.
There are two versions of the problem that we consider. In the cost minimization version, the goal is to minimize the total cost incurred for scheduling all jobs, and in the revenue maximization version the goal is to maximize the revenue of the jobs that are scheduled for processing on a given set of machines. We consider several variants of the problems that arise in practical scenarios, and provide constant factor approximations.
Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes
Authors: Mumenthaler Shannon M. , Ng Patricia Y.B. , Hodge Amanda , Bearss David , Berk Gregory , Kanekal Sarath , Redkar Sanjeev , Taverna Pietro , Agus David B. , Jain Anjali 
Published: October 2009

Abstract
The serine/threonine family of Pim kinases function as oncogenes and have been implicated in prostate cancer progression, particularly in hormone-refractory prostate disease, as a result of their antiapoptotic function. In this study, we used a pharmacologic inhibitor targeting the Pim family members, SGI-1776, to determine whether modulation of Pim kinase activity could alter prostate cancer cell survival and modulate chemotherapy resistance. Extensive biochemical characterization of SGI-1776 confirmed its specificity for the three isoforms of the Pim family. Treatment of prostate cancer cells with SGI-1776 resulted in a dose-dependent reduction in phosphorylation of known Pim kinase substrates that are involved in cell cycle progression and apoptosis (p21Cip1/WAF1 and Bad). Consequently, SGI-1776 compromised overall cell viability by inducing G1 cell cycle arrest and triggering apoptosis. Overexpression of recombinant Pim-1 markedly increased sensitivity of SGI-1776–mediated prostate cancer cell apoptosis and p21Cip1/WAF1 phosphorylation inhibition, reinforcing the specificity of SGI-1776. An additional cytotoxic effect was observed when SGI-1776 was combined with taxane-based chemotherapy agents. SGI-1776 was able to reduce cell viability in a multidrug resistance 1 protein–based taxane-refractory prostate cancer cell line. In addition, SGI-1776 treatment was able to resensitize chemoresistant cells to taxane-based therapies by inhibiting multidrug resistance 1 activity and inducing apoptosis. These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. [Mol Cancer Ther 2009;8(10):2882–93]
Development and Evaluation of a Novel Solution, Somah, for the Procurement and Preservation of Beating and Nonbeating Donor Hearts for Transplantation
Authors: Thatte Hemant S. , Rousou Laki , Hussaini Bader E. , Lu Xiu-Gui , Treanor Patrick R. , Khuri Shukri F. 
Published: October 2009

Background—Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage.Methods and Results—Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah.Conclusions—The Celsior preservation solution in clinical use today has led to a profound decline in cardiomyocyte and endothelial cell viability, whereas the newly designed Somah solution has safeguarded myocyte and endothelial integrity and function during organ storage. Use of Somah as a storage medium may lead to optimized graft function and long-term patient survival after transplantation.