bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role for Cell Density in Antifungal Drug Resistance in
Candida albicans
Biofilms
Authors: Perumal Palani , Mekala Satish , Chaffin W. LaJean 
Published: May 2007

ABSTRACT

Biofilms of
Candida albicans
are less susceptible to many antifungal drugs than are planktonic yeast cells. We investigated the contribution of cell density to biofilm phenotypic resistance. Planktonic yeast cells in RPMI 1640 were susceptible to azole-class drugs, amphotericin B, and caspofungin at 1 × 10
3
cells/ml (standard conditions) using the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt] assay. As reported by others, as the cell concentration increased to 1 × 10
8
cells/ml, resistance was observed with 10- to 20-fold-greater MICs. Biofilms that formed in microtiter plate wells, like high-density planktonic organisms, were resistant to drugs. When biofilms were resuspended before testing, phenotypic resistance remained, but organisms, when diluted to 1 × 10
3
cells/ml, were susceptible. Drug-containing medium recovered from high-cell-density tests inhibited low-cell-density organisms. A fluconazole-resistant strain showed greater resistance at high planktonic cell density, in biofilm, and in resuspended biofilm than did low-density planktonic or biofilm organisms. A strain lacking drug efflux pumps
CDR1
,
CDR2
, and
MDR1
, while susceptible at a low azole concentration, was resistant at high cell density and in biofilm. A strain lacking
CHK1
that fails to respond to the quorum-sensing molecule farnesol had the same response as did the wild type. FK506, reported to abrogate tolerance to azole drugs at low cell density, had no effect on tolerance at high cell density and in biofilm. These observations suggested that cell density has a role in the phenotypic resistance of biofilm, that neither the drug efflux pumps tested nor quorum sensing through Chk1p contributes to resistance, and that azole drug tolerance at high cell density differs mechanistically from tolerance at low cell density.
Purine Salvage Pathways among
Borrelia
Species
Authors: Pettersson Jonas , Schrumpf Merry E. , Raffel Sandra J. , Porcella Stephen F. , Guyard Cyril , Lawrence Kevin , Gherardini Frank C. , Schwan Tom G. 
Published: May 2007

ABSTRACT

Genome sequencing projects on two relapsing fever spirochetes,
Borrelia hermsii
and
Borrelia turicatae
, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete
Borrelia burgdorferi
. The relapsing fever spirochetes contained six open reading frames that are absent from the
B. burgdorferi
genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (
hpt
), adenylosuccinate synthase (
purA
), adenylosuccinate lyase (
purB
), auxiliary protein (
nrdI
), the ribonucleotide-diphosphate reductase alpha subunit (
nrdE
), and the ribonucleotide-diphosphate reductase beta subunit (
nrdF
). Southern blot assays with multiple
Borrelia
species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in
B. burgdorferi
and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (
hpt
,
purA
, and
purB
) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general,
B. hermsii
exhibited significantly higher activity than did the
B. burgdorferi
cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates.
B. burgdorferi
showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the
hpt
gene in the relapsing fever spirochetes.
B. hermsii
incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did
B. burgdorferi
. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood.
Unique Gene Expression Profiles in Infants Vaccinated with Different Strains ofMycobacterium bovisBacille Calmette-Guérin
Authors: Wu Bo , Huang Chunhong , Garcia Lourdes , de Leon Alfredo Ponce , Osornio Jose Sifuentes , Bobadilla-del-Valle Miriam , Ferreira Leticia , Canizales Sergio , Small Peter , Kato-Maeda Midori , Krensky Alan M. , Clayberger Carol 
Published: May 2007

ABSTRACTVaccination withMycobacterium bovisbacille Calmette-Guérin (BCG) has variable efficacy in preventing tuberculosis. We hypothesized that some of this variation might be due to differences among BCG strains. To test this, neonates in Orizaba, Mexico, were vaccinated with one of three different BCG strains (BCG-Brazil [BBCG], BCG-Denmark [DBCG], or BCG-Japan [JBCG]). One year after vaccination, peripheral blood mononuclear cells (PBMC) were obtained and recall immune responses to culture filtrate proteins (CFP) ofMycobacterium tuberculosiswere evaluated using quantitative real-time PCR. CFP-activated PBMC from BBCG- and DBCG-immunized children expressed high levels of cytokines characteristic of an adaptive immune response (gamma interferon, interleukin-2β [IL-12β], and IL-27), while those from children immunized with JBCG did not. In contrast, vaccination with JBCG resulted in significantly greater expression of cytokines characteristic of a proinflammatory immune response (IL-1α, IL-1β, IL-6, and IL-24) in PBMC activated with CFP compared to PBMC from children vaccinated with BBCG or DBCG. Thus, different strains of BCG can activate different immune pathways, which may affect long-term vaccine efficacy.
Possible Correlates of Long-Term Protection againstHelicobacter pylorifollowing Systemic or Combinations of Mucosal and Systemic Immunizations
Authors: Taylor Jennifer M. , Ziman Melanie E. , Fong Julie , Solnick Jay V. , Vajdy Michael 
Published: May 2007

ABSTRACTThe ability to induce long-term immunity toHelicobacter pyloriis necessary for an effective vaccine. This study was designed to establish the most efficient route(s) (systemic, mucosal, or a combination) of immunization for induction of long-term immunity and to define correlates of protection. Mice were immunized orally alone (oral group), intramuscularly (i.m.) alone (i.m. group), orally followed by i.m. (oral/i.m. group), or i.m. followed by orally (i.m./oral group). Long-term protective immunity to oralH. pylorichallenge was observed 3 months after immunization through the i.m. or oral/i.m. route. Protection correlated with an increase inH. pylori-specific interleukin-12 and both immunoglobulin G1 (IgG1) and IgG2a serum titers following challenge. Mice that were not protected (oral or i.m./oral) had increased levels of IgA in both sera and Peyer's patches. This study demonstrates the ability to induce long-term immunity againstH. pylori, provides correlates of protection, and illustrates the crucial role of the immunization route(s).
Survival ofChlamydia muridarumwithin Dendritic Cells
Authors: Rey-Ladino Jose , Jiang Xiaozhou , Gabel Brent R. , Shen Caixia , Brunham Robert C. 
Published: May 2007

ABSTRACTImmune responses toChlamydia trachomatisunderlay both immunity and immunopathology. Immunopathology in turn has been attributed to chronic persistent infection with persistence being defined as the presence of organisms in the absence of replication. We hypothesized that dendritic cells (DCs) play a central role inChlamydiaimmunity and immunopathology by favoring the long-term survival ofC. muridarum. This hypothesis was examined based on (i) direct staining ofChlamydiain infected DCs to evaluate the development of inclusions, (ii) titration of infected DCs on HeLa cells to determine cultivability, and (iii) transfer ofChlamydia-infected DCs to naive mice to evaluate infectivity. The results show thatChlamydiasurvived within DCs and developed both typical and atypical inclusions that persisted in a subpopulation of DCs for more than 9 days after infection. Since the cultivability ofChlamydiafrom DCs onto HeLa was lower than that estimated by the number of inclusions in DCs, this suggests that the organisms may be in state of persistence. Intranasal transfer of long-term infected DCs or DCs purified from the lungs of infected mice caused mouse lung infection, suggesting that in addition to persistent forms, infectiveChlamydiaorganisms also developed within chronically infected DCs. Interestingly, after in vitro infection withChlamydia, most DCs died. However,Chlamydiaappeared to survive in a subpopulation of DCs that resisted infection-induced cell death. Surviving DCs efficiently presentedChlamydiaantigens toChlamydia-specific CD4+T cells, suggesting that the bacteria are able to both direct their own survival and still allow DC antigen-presenting function. Together, these results raise the possibility thatChlamydia-infected DCs may be central to the maintenance of T-cell memory that underlies both immunity and immunopathology.
Differential Stability and Trade-Off Effects of Pathoadaptive Mutations in the
Escherichia coli
FimH Adhesin
Authors: Weissman Scott J. , Beskhlebnaya Viktoriya , Chesnokova Veronika , Chattopadhyay Sujay , Stamm Walter E. , Hooton Thomas M. , Sokurenko Evgeni V. 
Published: May 2007

ABSTRACT

FimH is the tip adhesin of mannose-specific type 1 fimbriae of
Escherichia coli
, which are critical to the pathogenesis of urinary tract infections. Point FimH mutations increasing monomannose (1M)-specific uroepithelial adhesion are commonly found in uropathogenic strains of
E. coli
. Here, we demonstrate the emergence of a mixed population of clonally identical
E. coli
strains in the urine of a patient with acute cystitis, where half of the isolates carried a glycine-to-arginine substitution at position 66 of the mature FimH. The R66 mutation induced an unusually strong 1M-binding phenotype and a 20-fold advantage in mouse bladder colonization. However,
E. coli
strains carrying FimH-R66, but not the parental FimH-G66, had disappeared from the patient's rectal and urine samples collected from 29 to 44 days later, demonstrating within-host instability of the R66 mutation. No FimH variants with R66 were identified in a large (>600 strains) sequence database of
fimH
-positive
E. coli
strains. However, several strains carrying genes encoding FimH with either S66 or C66 mutations appeared to be relatively stable in the
E. coli
population. Relative to FimH-R66, the FimH-S66 and FimH-C66 variants mediated only moderate increases in 1M binding but preserved the ability to enhance binding under flow-induced shear conditions. In contrast, FimH-R66 completely lost shear-enhanced binding properties, with bacterial adhesion being inhibited by shear forces and lacking a rolling mode of binding. These functional trade-offs may determine the natural populational instability of this mutation or other pathoadaptive FimH mutations that confer dramatic increases in 1M binding strength.
Conjugated Polyunsaturated Oxacyclic Carbene Complexes: Synthesis, Structure, and Properties
Authors: Fischer Helmut , Rädler Michael , Mosbacher Alexander , Drexler Matthias , Hübner Eike , Weibert Bernhard , Heck Jürgen , Wittenburg Christian , Steffens Stefan 
Published: May 2007

The reaction of [(CO)5M(thf)] with but-3-yn-1-ols in the presence of NEt3 offers a convenient route to 2-oxacyclopentylidene complexes [(CO)5M=C-O-CH2CH2CH2] (M = Cr (1a), W (1b)) in yields up to 96%. Furthermore, the reaction of 1 with ω-(dimethylamino)- substituted enals, Me2N-(CH=CH)n-C(=O)H, activated by Me3SiCl/NEt3 or POCl3/NEt3 gives via aldol condensation the unsaturated oxacyclic push-pull carbene complexes [(CO)5M=C-O-CH2CH2C{=CH-(CH=CH)n-NMe2}] (n = 0 (2), 1 (3), 2 (4), 3 (5)). In 2-5, the amino group acts as an electron-donor unit and the oxacyclic carbene pentacarbonyl moiety as an electron acceptor. The aminometallaenes 2-5 have been characterized spectroscopically, the chromium complexes 2a-5a additionally by X-ray structure analysis. For some complexes, their nonlinear optical properties (second harmonic generation) have been studied and β values up to 58 × 10-30 esu have been determined. The results of DFT calculations on chromium complexes 2a-5a show that on lengthening of the unsaturated chain the influence of the carbonyl-metal fragment on the polyunsaturated chain strongly decreases.
OPTIMIZATION AND THE MIRANDA APPROACH IN DETECTING HORSESHOE-TYPE CHAOS BY COMPUTER
Authors: BÁNHELYI BALÁZS , CSENDES TIBOR , GARAY BARNABAS M. 
Published: May 2007

We report on experiences with an adaptive subdivision method supported by interval arithmetic that enables us to prove subset relations of the form [Formula: see text], and thus check certain sufficient conditions for chaotic behavior of dynamical systems in a rigorous way. Our proof of the underlying abstract theorem avoids referring to any results of applied algebraic topology and relies only on the Brouwer fixed point theorem. The second novelty is that the process of gaining the subset relations to be checked is, to a large extent, also automatized. The promising subset relations come from solving a constrained optimization problem via the penalty function approach. Abstract results and computational methods are demonstrated by finding embedded copies of the standard horseshoe dynamics in iterates of the classical Hénon mapping.
Masquerader: High Mobility Group Box-1 and Cancer
Authors: Ellerman Jessica E. , Brown Charles K. , de Vera Michael , Zeh Herbert J. , Billiar Timothy , Rubartelli Anna , Lotze Michael T. 
Published: May 2007

Abstract
Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
Heat Shock Protein 27 Protects L929 Cells from Cisplatin-Induced Apoptosis by Enhancing Akt Activation and Abating Suppression of Thioredoxin Reductase Activity
Authors: Zhang Yong , Shen Xun 
Published: May 2007

Abstract
Purpose: Heat shock protein 27 (Hsp27) is up-regulated in multiple malignancies and implicated in cisplatin resistance. It is attempted to know how Hsp27 endues cell with cisplatin resistance by interfering with upstream of both apoptosis signal–regulating kinase 1 (ASK1)/p38 mitogen-activated protein kinase–activated apoptotic signaling and serine/threonine kinase Akt-dependent survival signaling.
Experimental Design: The mouse L929 cells stably transfected with human Hsp27 or its dominant-negative mutant and the human cervical cancer HeLa cells transfected with Hsp27 siRNA were used. The cisplatin-induced apoptosis and activation of ASK1, p38, and Akt were compared in control cells, cells overexpressing Hsp27, and cells with their endogenous Hsp27 knocked down.
Results: Hsp27 effectively protected the cells from cisplatin-induced DNA fragmentation. The p38 inhibitors obviously decreased whereas Akt inhibitors markedly increased the apoptotic fraction in cisplatin-treated cells. Overexpression of Hsp27 doubly enhanced the drug-induced Akt activation while substantially depressing the drug-induced activation of ASK1 and p38. Knockdown of the endogenous Hsp27 in HeLa cells resulted in the effects opposite to that observed in the Hsp27-overexpressing cells. Enhancement of Akt activation is associated with complex formation between Akt and Hsp27, whereas depression of ASK1/p38 activation is attributed to a reversion of the drug-induced inhibition of thioredoxin reductase activity and subsequent oxidation of thioredoxin.
Conclusions: Hsp27 endues cells with cisplatin resistance via depression of the drug-induced ASK1/p38 activation and enhancement of the drug-induced Akt activation. This study revealed the intervention of Hsp27 in upstream of both ASK1/p38 apoptotic signaling and phosphatidylinositol 3-kinase/Akt survival signaling. Therefore, the inhibition of Hsp27 may be a novel strategy of cancer chemotherapy.
Utility of Osteopontin and Serum Mesothelin in Malignant Pleural Mesothelioma Diagnosis and Prognosis Assessment
Authors: Grigoriu Bogdan-Dragos , Scherpereel Arnaud , Devos Patrick , Chahine Bachar , Letourneux Marc , Lebailly Pierre , Grégoire Marc , Porte Henri , Copin Marie-Christine , Lassalle Philippe 
Published: May 2007

Abstract
Purpose: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects.
Experimental Design: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival.
Results: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients.
Conclusions: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.
Spectral Fluorescence Molecular Imaging of Lung Metastases Targeting HER2/neu
Authors: Koyama Yoshinori , Hama Yukihiro , Urano Yasuteru , Nguyen Dao M. , Choyke Peter L. , Kobayashi Hisataka 
Published: May 2007

AbstractPurpose: Surgical resection of pulmonary metastases is now a clinically accepted cancer therapy but its success depends on the accurate localization and removal of all tumor foci. To enhance the detection of pulmonary metastases during surgery, we developed an i.v. administered optical probe that uses a monoclonal antibody, Herceptin (trastuzumab), conjugated to a fluorophore, rhodamine green (RhodG), to specifically detect human epidermal growth factor receptor type 2 (HER2/neu)–expressing pulmonary lesions in an animal model of lung metastases.Experimental Design: Pulmonary metastases were induced by i.v. injection of gene-transfected murine embryonic fibroblasts (3T3) cells in a murine model to produce a mixed population of HER2+ and HER2− tumors. To image these tumors, an anti-HER2 (Herceptin) or a control (HUT) complementarity-determining region–grafted antibody was conjugated to RhodG and injected i.v. into mice. Spectral fluorescence imaging was done after thoracotomy and images were correlated with gross and microscopic pathology to assess sensitivity and specificity.Results: HER2+ tumors injected with Herceptin-RhodG were more fluorescent than either HER2− tumors or HER2+ tumors injected with HUT-RhodG at all time points. The maximal fluorescence signal in HER2+ tumors injected with Herceptin-RhodG was observed at 1 day postinjection. The tumors fluoresced primarily at the rim and not their center, reflecting the binding-site barrier that is commonly seen with high-affinity antibodies.Conclusion: A HER2-targeted optical imaging probe shows the ability to specifically enhance HER2+ pulmonary metastases but not HER2− pulmonary metastases. The high sensitivity and specificity of this probe is encouraging for the development of antigen-targeted optical probes to assist in the resection of pulmonary metastases.
Aurora-A and p16 Polymorphisms Contribute to an Earlier Age at Diagnosis of Pancreatic Cancer in Caucasians
Authors: Chen Jinyun , Li Donghui , Wei Chongjuan , Sen Subrata , Killary Ann M. , Amos Christopher I. , Evans Douglas B. , Abbruzzese James L. , Frazier Marsha L. 
Published: May 2007

Abstract
Purpose: Aurora-A and p16 play a major role in cell cycle checkpoint regulation. Both of them are important in the maintenance of centrosome duplication. Therefore, we hypothesized that polymorphisms in the two genes may interact or work together to influence the finely tuned mechanisms of cell cycle regulation that these proteins regulate. The purpose of this study was to investigate the association of the Aurora-A (T91A), and p16 (C540G and C580T) polymorphisms with age at diagnosis of pancreatic cancer.
Experimental Design: We genotyped 148 Caucasian patients with a diagnosis of pancreatic cancer for the Aurora-A and p16 polymorphisms using pyrosequencing. We tested the association between age at diagnosis and the Aurora-A and p16 genotypes by comparing Kaplan-Meier curves, evaluating the homogeneity of the curves using the log-rank test. We used Cox proportional hazard regression analysis to estimate the association between time to diagnosis and genotype, adjusting for gender.
Results: Patients with the Aurora-A polymorphic genotypes had a median age at diagnosis with pancreatic cancer that was 2.8 years earlier than those with the wild-type genotype [log-rank, P = 0.015; hazard ratio (HR), 1.55; 95% confidence intervals (95% CI), 1.09-2.20]. There was no significant association between the p16 genotypes and age at diagnosis. However, the Aurora-A and p16 C580T polymorphisms combined had a synergistic effect on age-associated risk for early diagnosis of pancreatic cancer. Compared with patients with wild-type genotypes for both genes, the median age at diagnosis for patients with one or two polymorphic alleles for both genes was 12.6 years earlier (log-rank, P = 0.0002; HR, 3.88; 95% CI, 1.94-7.76). No significant associations between the polymorphisms and the cancer metastatic status or survival after diagnosis were found.
Conclusions: Our findings suggest that the Aurora-A polymorphism contributes to a significantly earlier age at diagnosis of pancreatic cancer, and that Aurora-A and p16 C580T polymorphisms synergistically contribute to an earlier age at diagnosis of pancreatic cancer.