bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Polymorphisms of CD14, Toll‐like Receptor 4, and Caspase‐Recruitment Domain 15 Are Not Associated with Necrotizing Enterocolitis in Very Low Birth Weight Infants
Authors: Szebeni Beáta , Szekeres Roxána , Rusai Krisztina , Vannay Ádám , Veres Gábor , Treszl András , Arató András , Tulassay Tivadar , Vásárhelyi Barna 
Published: December 2005

ABSTRACTObjectives:Inadequate response of the innate immune system to bacterial antigens present in the intestinal flora may play a role in the development of necrotizing enterocolitis (NEC). Pattern recognition receptors such as CD14, toll‐like receptor (TLR) 4, and caspase‐recruitment domain (CARD) 15 bind bacterial lipopolysaccharide and peptidoglycan, and their activation leads to production of inflammatory cytokines. Our aim was to evaluate whether single nucleotide polymorphisms (SNPs) of CD14, TLR4, and CARD15 are associated with the risk of NEC in very low birth weight (VLBW) infants.Patients and Methods:We determined the CD14 C−260T, TLR4 A + 896G, C + 1196T, and CARD15 G + 2722C, C + 2104T, 3020insC functional SNPs in dried blood samples from 118 VLBW infants (of those, 41 developed NEC) and from 146 healthy term newborns using polymerase chain reaction and restriction fragment length polymorphism methods. We tested the association between genotype and risk of NEC.Results:No significant differences were found in the prevalence of CD14 −260T, TLR4 +896G, +1196T, and CARD15 +2722C, +2104T, 3020insC alleles between VLBW infants and healthy term newborns (P = NS). The frequencies of investigated genotypes were similar in infants with and without NEC (P = NS). Furthermore, we did not find any association between genotype and prematurity or sepsis, which are important risk factors of NEC.Conclusions:Carrier state of the tested CD14, TLR4, and CARD15 SNPs is not associated with NEC risk in VLBW infants.
Positive Association of Macrophage Migration Inhibitory Factor Gene‐173G/C Polymorphism with Biliary Atresia
Authors: Arikan Cigdem , Berdeli Afig , Ozgenc Funda , Tumgor Gokhan , Yagci Rasit V , Aydogdu Sema 
Published: December 2005

ABSTRACTBackground:Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Its expression was increased in several inflammatory diseases, and MIF gene polymorphisms have an effect on disease outcome and response to glucocorticoid treatment.Aim:To investigate the role of the 173G/C polymorphism of the MIF gene for susceptibility to biliary atresia (BA).Method:Between February 2002 and November 2004, 18 patients (mean age 1 ± 0.4 years) diagnosed as having BA were studied. After informed consent, blood was collected, and DNA was obtained. MIF 173C/G polymorphism was detected using the polymerase chain reaction‐restriction fragment length polymorphism based method. BA patients were compared with a group of chronic liver disease patients (CLD) (n = 36) and a group of unrelated healthy controls (n = 103).Results:MIF‐173C allele frequency was significantly higher than both the CLD and healthy control groups (P = 0.03, odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3‐15.1; P = 0.000, OR 4.1, 95% CI 2.3‐7.6, respectively). Univariate analysis showed that MIF‐173G/C polymorphism was significantly associated with BA (for GC genotype, OR = 6, 95 % CI 2.8‐11.5, P = 0.000). There was no significant correlation between pediatric end stage liver disease score and MIF genotypes both in BA and CLD groups.Conclusion:Our results suggest that the ‐173C allele of the MIF gene might be associated with the susceptibility to BA.
Novel Gyrase Mutations in Quinolone-Resistant and -Hypersusceptible Clinical Isolates of
Mycobacterium tuberculosis
: Functional Analysis of Mutant Enzymes
Authors: Aubry Alexandra , Veziris Nicolas , Cambau Emmanuelle , Truffot-Pernot Chantal , Jarlier Vincent , Fisher L. Mark 
Published: December 2005

ABSTRACT

Mutations in the DNA gyrase GyrA
2
GyrB
2
complex are associated with resistance to quinolones in
Mycobacterium tuberculosis
. As fluoroquinolones are being used increasingly in the treatment of tuberculosis, we characterized several multidrug-resistant clinical isolates of
M. tuberculosis
carrying mutations in the genes encoding the GyrA or GyrB subunits associated with quinolone resistance or hypersusceptibility. In addition to the reported putative quinolone resistance mutations in GyrA, i.e., A90V, D94G, and D94H, we found that the GyrB N510D mutation was also associated with ofloxacin resistance. Surprisingly, several isolates bearing a novel combination of
gyrA
T80A and A90G changes were hypersusceptible to ofloxacin.
M. tuberculosis
GyrA and GyrB subunits (wild type [WT] and mutants) were overexpressed in
Escherichia coli
, purified to homogeneity, and used to reconstitute highly active gyrase complexes. Mutant proteins were produced similarly from engineered
gyrA
and
gyrB
alleles by mutagenesis. MICs, enzyme inhibition, and drug-induced DNA cleavage were determined for moxifloxacin, gatifloxacin, ofloxacin, levofloxacin, and enoxacin. Mutant gyrase complexes bearing GyrA A90V, D94G, and D94H and GyrB N510D were resistant to quinolone inhibition (MICs and 50% inhibitory concentrations [IC
50
s] at least 3.5-fold higher than the concentrations for the WT), and all, except the GyrB mutant, were less efficiently trapped as a quinolone cleavage complex. In marked contrast, gyrase complexes bearing GyrA T80A or A90G were hypersusceptible to the action of many quinolones, an effect that was reinforced for complexes bearing both mutations (MICs and IC
50
s up to 14-fold lower than the values for the WT). This is the first detailed enzymatic analysis of hypersusceptibility and resistance in
M. tuberculosis
.
Two Cathelicidin Genes Are Present in both Rainbow Trout (
Oncorhynchus mykiss
) and Atlantic Salmon (
Salmo salar
)
Authors: Chang Chin-I , Zhang Yong-An , Zou Jun , Nie Pin , Secombes Christopher J. 
Published: December 2005

ABSTRACT

Further to the previous finding of the rainbow trout
rt
CATH_1 gene, this paper describes three more cathelicidin genes found in salmonids: two in Atlantic salmon, named
as
CATH_1 and
as
CATH_2, and one in rainbow trout, named
rt
CATH_2. All the three new salmonid cathelicidin genes share the common characteristics of mammalian cathelicidin genes, such as consisting of four exons and possessing a highly conserved preproregion and four invariant cysteines clustered in the C-terminal region of the cathelin-like domain. The
as
CATH_1 gene is homologous to the rainbow trout
rt
CATH_1 gene, in that it possesses three repeat motifs of TGGGGGTGGC in exon IV and two cysteine residues in the predicted mature peptide, while the
as
CATH_2 gene and
rt
CATH_2 gene are homologues of each other, with 96% nucleotide identity. Salmonid cathelicidins possess the same elastase-sensitive residue, threonine, as hagfish cathelicidins and the rabbit CAP18 molecule. The cleavage site of the four salmonid cathelicidins is within a conserved amino acid motif of QKIRTRR, which is at the beginning of the sequence encoded by exon IV. Two 36-residue peptides corresponding to the core part of
rt
CATH_1 and
rt
CATH_2 were chemically synthesized and shown to exhibit potent antimicrobial activity.
rt
CATH_2 was expressed constitutively in gill, head kidney, intestine, skin and spleen, while the expression of
rt
CATH_1 was inducible in gill, head kidney, and spleen after bacterial challenge. Four cathelicidin genes have now been characterized in salmonids and two were identified in hagfish, confirming that cathelicidin genes evolved early and are likely present in all vertebrates.
In Vivo and In Vitro Studies of Antibiotic Release from and Bacterial Growth Inhibition by Antibiotic-Impregnated Polymethylmethacrylate Hip Spacers
Authors: Kelm Jens , Regitz Thilo , Schmitt Eduard , Jung Werner , Anagnostakos Konstantinos 
Published: December 2005

ABSTRACT
The antimicrobial properties and the elution characteristics of gentamicin-vancomycin-loaded hip spacers were studied in vivo and in vitro. Vancomycin elution was greater than gentamicin elution. The antibiotic concentrations in vivo were less than those in vitro. Not dependent on implantation duration, growth inhibition by spacers in vitro was observed for 2 weeks. The reason for protracted wound healing cannot be insufficient antibiotic release.
Anucleate Cell Blue Assay: a Useful Tool for Identifying Novel Type II Topoisomerase Inhibitors
Authors: Oyamada Yoshihiro , Ito Hideaki , Fujimoto-Nakamura Mika , Tanitame Akihiko , Iwai Noritaka , Nagai Kazuo , Yamagishi Jun-ichi , Wachi Masaaki 
Published: December 2005

ABSTRACT

About 95,000 compounds were screened by the anucleate cell blue assay. Fifty-one of the hit compounds had various structures and showed inhibitory activity against DNA gyrase and/or topoisomerase IV. Moreover, the compounds exhibited antibacterial activity against a fluoroquinolone- and novobiocin-resistant strain of
Staphylococcu
s
aureus
. The anucleate cell blue assay is therefore a useful tool for finding novel type II topoisomerase inhibitors.
Heterogeneous Macrolide Resistance and Gene Conversion in the Pneumococcus
Authors: Wolter Nicole , Smith Anthony M. , Farrell David J. , Klugman Keith P. 
Published: December 2005

ABSTRACT

A macrolide-resistant clinical isolate of
Streptococcus pneumoniae
with 23S rRNA mutations showed a heterogeneous phenotype and genotype. The mutant 23S rRNA genes from this isolate transformed susceptible strain R6 to resistance. Culture of resistant strain R6 in the absence of antibiotic pressure showed gene conversion to occur between the four 23S rRNA alleles, resulting in reversion to susceptibility with the resistant phenotype showing a fitness cost. These data explain the disappearance on subculture of heterogeneous macrolide resistance in the pneumococcus.
Clonal Dissemination and
mupA
Gene Polymorphism of Mupirocin-Resistant
Staphylococcus aureus
Isolates from Long-Term-Care Facilities in South Korea
Authors: Yoo Jae Il , Shin Eun Shim , Cha Jeong Ok , Lee Jeom Kyu , Jung Young Hee , Lee Kyeong Min , Kim Bong Su , Lee Yeong Seon 
Published: December 2005

ABSTRACT

We identified 25 high-level mupirocin-resistant (MuH) and 21 low-level mupirocin-resistant (MuL)
Staphylococcus aureus
isolates from eight long-term-care facilities (LTCFs). The pulsed-field gel electrophoresis patterns of 19 MuH and 19 MuL isolates from two facilities were identical for 18 and 15 isolates, respectively. The most predominant
mupA
restriction fragment length polymorphism type was found in 21 MuH isolates. We conclude that clonal transmission of MuH and MuL
S. aureus
strains occurred in these LTCFs. This is the first report of clonal transfer of mupirocin resistance in LTCFs.
In Vitro Activity of Fosfomycin against Extended-Spectrum-β-Lactamase- Producing
Escherichia coli
and
Klebsiella pneumoniae
: Comparison of Susceptibility Testing Procedures
Authors: de Cueto M. , López L. , Hernández J. R. , Morillo C. , Pascual A. 
Published: December 2005

ABSTRACT

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
and
Klebsiella pneumoniae
to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for
E. coli
, whereas marked discrepancies were observed for
K. pneumoniae
.
Involvement of the Drug Transporters P Glycoprotein and Multidrug Resistance-Associated Protein Mrp2 in Telithromycin Transport
Authors: Yamaguchi Shoji , Zhao Ying Lan , Nadai Masayuki , Yoshizumi Hideo , Cen Xiaobo , Torita Shoko , Takagi Kenji , Takagi Kenzo , Hasegawa Takaaki 
Published: December 2005

ABSTRACTThe present study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin.
Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1
Authors: Anderson Gülsüm , Gries Margarete , Kurihara Noriyoshi , Honjo Tadashi , Anderson Judy , Donnenberg Vera , Donnenberg Albert , Ghobrial Irene , Mapara Markus Y. , Stirling David , Roodman David , Lentzsch Suzanne 
Published: December 2005

AbstractCC-4047, an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFκ-B ligand/macrophage colony-stimulating factor–stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for 3 weeks decreased osteoclast formation accompanied by complete inhibition of bone resorption. The inhibitory effect was similar when cultures were treated for 3 weeks or for only the first week (90% inhibition), indicating that CC-4047 inhibits early stages of osteoclast formation. Inhibition of osteoclastogenesis by CC-4047 was mediated by a shift of lineage commitment to granulocyte colony-forming units at the expense of granulocyte-macrophage colony-forming units. Further studies revealed that this shift in lineage commitment was mediated through down-regulation of PU.1. Treatment with thalidomide resulted in significantly less potent inhibition of osteoclast formation and bone resorption. These results provide evidence that CC-4047 blocks osteoclast differentiation during early phases of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug for targeting both tumors and osteoclastic activity in patients with multiple myeloma and other diseases associated with osteolytic lesions.
Insulin allergy and resistance successfully treated by desensitisation with Aspart insulin
Authors: Matheu Victor , Perez Eva , Hernández Marta , Díaz Elisa , Darias Ricardo , González Abel , García Jose C , Sánchez Inmaculada , Feliciano Laura , Caballero Agueda , Torre Fernando de la 
Published: December 2005

AbstractA 25-year-old, with type I Diabetes Mellitus with a previous diagnosis of Protamine Allergy but not to human Insulin, started to notice anaphylactic reactions inmmediatly after bolus with Insulin. Skin prick and intradermal test were positive to all insulins. Skin tests to other potential allergens resulted negative. Examination after bolus of Human Insulin revealed urticaria. Daily insulin requirement were around 2-2,4 U/Kg/day. Slow desensitisation with Aspart insulin, the insulin with lowest size of skin test, was performed using subcutaneous insulin pump. Six months after the end of desensitisation his daily insulin requirement decreased to 0.8 U/Kg/day and oral corticosteroids are being reduced with no symptoms.
Comparison of CA-125 and Standard Definitions of Progression of Ovarian Cancer in the Intergroup Trial of Cisplatin and Paclitaxel Versus Cisplatin and Cyclophosphamide
Authors: Rustin Gordon J.S. , Timmers Petra , Nelstrop Ann , Shreeves Gavin , Bentzen Soeren M. , Baron Benoit , Piccart Martine J. , Bertelsen Kamma , Stuart Gavin , Cassidy James , Eisenhauer Elizabeth 
Published: December 2005

Purpose A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated. Retrospectively, we determined whether the use of this CA-125 definition in a randomized trial would have shown the same magnitude of difference between the treatment arms as was shown when the standard progression definition was used. Patients and Methods A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma, of whom 628 were assessable according to CA-125. The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125. Results Of the 628 patients assessable for both definitions, 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition. There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm (TP) compared with the cyclophosphamide and cisplatin arm (CP) when either standard or CA-125 criteria were used to define progression (standard, P = .002; CA-125, P = .011). The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression. Conclusion The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or standard criteria were used to define progression.
First-Line Single Agent Treatment With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: A Phase II Study
Authors: Niho Seiji , Kubota Kaoru , Goto Koichi , Yoh Kiyotaka , Ohmatsu Hironobu , Kakinuma Ryutaro , Saijo Nagahiro , Nishiwaki Yutaka 
Published: December 2005

Purpose We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC) to assess its efficacy and toxicity. Patients and Methods Patients received 250 mg doses of gefitinib daily. Administration of gefitinib was terminated if partial response (PR) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks. In these cases, platinum-based doublet chemotherapy was given as a salvage treatment. We evaluated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples. Results Forty-two patients were enrolled between March and November 2003, with 40 of these patients being eligible. The response rate was 30% (95% CI, 17% to 47%). The most common toxicity included grade 1 or 2 acne-like rash (50%) and grade 1 diarrhea (18%). Grade 2 or 3 hepatic toxicity was observed in 8% of patients. Four patients developed grade 5 interstitial lung disease (ILD). Thirty patients received second-line chemotherapy. Median survival time was 13.9 months (95% CI, 9.1 to 18.7 months), and the 1-year survival rate was 55%. Tumor samples were available in 13 patients, including four cases of PR, six cases of stable disease, and three cases of progressive disease. EGFR mutations (deletions in exon 19 or point mutations [L858R or E746V]) were detected in four tumor tissues. All four patients with EGFR mutation achieved PR with gefitinib treatment. Conclusion Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.
Preoperative Serum Tissue Factor Levels Are an Independent Prognostic Factor in Patients With Ovarian Carcinoma
Authors: Han Liz Y. , Landen Charles N. , Kamat Aparna A. , Lopez Adriana , Bender David P. , Mueller Peter , Schmandt Rosemarie , Gershenson David M. , Sood Anil K. 
Published: December 2005

Purpose Tissue factor (TF) is a procoagulant that plays an important part in tumor angiogenesis. We sought to determine the role of preoperative serum TF levels in predicting clinical outcome in patients with ovarian cancer. Materials and Methods TF expression was determined by reverse transcriptase polymerase chain reaction in ovarian cell lines. Using enzyme-linked immunosorbent assay, we assessed preoperative serum TF levels in 98 women with invasive epithelial ovarian carcinoma, 30 with low malignant potential (LMP) tumors, 16 with benign tumors, and a separate validation group of 39 women with adnexal masses. Clinical information was gathered from chart review. Results TF was expressed in four of the five ovarian cancer cell lines, but absent in the nontransformed cells. Ovarian cancer patients had a median preoperative serum TF level of 85.2 pg/mL, which was significantly higher than in those with LMP tumors (12.8 pg/mL; P < .01) and benign adnexal disease (30.7 pg/mL; P < .01). TF ≥ 190 pg/mL was significantly associated with decreased patient survival (P < .01). After adjusting for other clinical variables in a multivariate Cox regression model, TF ≥ 190 pg/mL was an independent prognostic factor (P < .01). Analysis of serum TF levels from the validation set confirmed that high TF (≥190 pg/mL) was associated with a 3.4-fold increase in risk of death from disease (P = .02) and shorter survival (P = .01). Conclusion Preoperative serum TF levels are significantly elevated in patients with ovarian carcinoma. Elevated preoperative TF level is an independent prognostic factor for death from disease.