bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Aminoglycoside 6′-
N
-Acetyltransferase Type Ib-Mediated Amikacin Resistance by Antisense Oligodeoxynucleotides
Authors: Sarno Renee , Ha Hongphuc , Weinsetel Natalia , Tolmasky Marcelo E. 
Published: September 2003

ABSTRACT

Amikacin has been very useful in the treatment of infections caused by multiresistant bacteria because it is refractory to the actions of most modifying enzymes. However, the spread of AAC(6′)-I-type acetyltransferases, enzymes capable of catalyzing inactivation of amikacin, has rendered this antibiotic all but useless in some parts of the world. The aminoglycoside 6′-
N
-acetyltransferase type Ib, which is coded for by the
aac
(
6′
)-
Ib
gene, mediates resistance to amikacin and other aminoglycosides. RNase H mapping and computer prediction of the secondary structure led to the identification of five regions accessible for interaction with antisense oligodeoxynucleotides in the
aac
(
6′
)
-Ib
mRNA. Oligodeoxynucleotides targeting these regions could bind to native mRNA with different efficiencies and mediated RNase H digestion. Selected oligodeoxynucleotides inhibited AAC(6′)-Ib synthesis in cell-free coupled transcription-translation assays. After their introduction into an
Escherichia coli
strain harboring
aac
(
6′
)
-Ib
by electroporation, some of these oligodeoxynucleotides decreased the level of resistance to amikacin. Our results indicate that use of antisense compounds could be a viable strategy to preserve the efficacies of existing antibiotics to which bacteria are becoming increasingly resistant.
Sensitization ofStaphylococcus aureusandEscherichia colito Antibiotics by the Sesquiterpenoids Nerolidol, Farnesol, Bisabolol, and Apritone
Authors: Brehm-Stecher Byron F. , Johnson Eric A. 
Published: September 2003

ABSTRACTThe sesquiterpenoids nerolidol, farnesol, bisabolol, and apritone were investigated for their abilities to enhance bacterial permeability and susceptibility to exogenous antimicrobial compounds. Initially, it was observed by flow cytometry that these sesquiterpenoids promoted the intracellular accumulation of the membrane-impermeant nucleic acid stain ethidium bromide by live cells ofLactobacillus fermentum, suggesting that enhanced permeability resulted from disruption of the cytoplasmic membrane. The ability of these sesquiterpenoids to increase bacterial susceptibility to a number of clinically important antibiotics was then investigated. In disk diffusion assays, treatment with low concentrations (0.5 to 2 mM) of nerolidol, bisabolol, or apritone enhanced the susceptibility ofStaphylococcus aureusto ciprofloxacin, clindamycin, erythromycin, gentamicin, tetracycline, and vancomycin. Nerolidol and farnesol also sensitizedEscherichia colito polymyxin B. Our results indicate the practical utility of sensitizing bacteria to antimicrobials with sesquiterpenoids that have traditionally been used as flavorants and aroma compounds in the food and perfume industries.
In Vitro Interaction of Flucytosine with Conventional and New Antifungals against
Cryptococcus neoformans
Clinical Isolates
Authors: Schwarz Patrick , Dromer Françoise , Lortholary Olivier , Dannaoui Eric 
Published: September 2003

ABSTRACT

Combinations of flucytosine with conventional and new antifungals were evaluated in vitro against 30 clinical isolates of
Cryptococcus neoformans
. Synergy determined by checkerboard analysis was observed with combinations of fluconazole, itraconazole, voriconazole, amphotericin B, and caspofungin with flucytosine against 77, 60, 80, 77, and 67% of the isolates, respectively. Antagonism was never observed. Killing curves showed indifferent interactions between triazoles and flucytosine and synergy between amphotericin B and flucytosine.
Activity of Megazol, a Trypanocidal Nitroimidazole, Is Associated with DNA Damage
Authors: Enanga Bertin , Ariyanayagam Mark R. , Stewart Mhairi L. , Barrett Michael P. 
Published: September 2003

ABSTRACT

DNA damage associated with the trypanocidal activity of megazol [2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] was shown in experiments in which DNA repair-deficient RAD51
−/−
Trypanosoma brucei
mutants were found to be hypersensitive to the drug. Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance.
Health status as a potential effect modifier of the relation between noise annoyance and incidence of ischaemic heart disease
Authors: Babisch W , Ising H , Gallacher J E J 
Published: September 2003

Aims:Traffic noise is a psychosocial stressor. Epidemiological studies suggest chronic noise stress to be a risk factor for cardiovascular disorders.Methods:In a prospective cohort study, the association between annoyance and disturbances due to road traffic noise and the incidence of ischaemic heart disease (IHD) was studied in 3950 middle aged men.Results:Depending on the questionnaire item, non-significant odds ratios for IHD incidence ranging from 0.9 to 1.4 were found for the highly noise annoyed/disturbed subjects when compared with the less annoyed/disturbed subjects, over the six year follow up period. However, this relation was strongly modified by the prevalence of pre-existing chronic diseases. In subjects free of any chronic disease at the beginning of the follow up, significant odds ratios between 1.7 and 3.0 were seen. In the subgroup with chronic diseases no such noise effects were seen. This surprising result of no effect in the group of people with a potential risk, due to pre-existing health problems, may be because of the dilution of the true effect due to recall bias.Conclusions:Annoyance and disturbance due to road traffic noise is associated with a higher incidence of IHD. Prevalence of disease can be an important effect modifier of the relation between noise annoyance and health outcomes.
Time To Pregnancy and occupational lead exposure
Authors: Joffe M , Bisanti L , Apostoli P , Kiss P , Dale A , Roeleveld N , Lindbohm M-L , Sallmén M , Vanhoorne M , Bonde J P 
Published: September 2003

Background:Lead exposure is known to be harmful to the male reproductive system, including impairment of fertility. However, it is unclear whether currently existing low levels of exposure have this effect.Aims:To study retrospectively current workers in lead using industries (battery manufacture, smelting, etc), and in non-lead using control industries, in four European countries, with Time To Pregnancy as the outcome variable, as part of the EU funded Asclepios Project.Methods:Exposure assessment was mainly by blood lead values, which were available from the late 1970s, supplemented by imputed values where necessary. Three exposure models were studied: (1) short term (recent) exposure; (2) total duration of work in a lead using industry; and (3) cumulative exposure. A Cox proportional hazards model with discrete ties was used for the statistical analysis, with covariates for both partners.Results:A total of 1104 subjects took part, of whom 638 were occupationally exposed to lead at the relevant time. Blood lead levels were mainly less than 50 μg/dl. No consistent association of Time To Pregnancy with lead exposure was found in any of the exposure models, although reduced fertility was observed in one category each in models (2) and (3).Conclusions:This basically negative result is unlikely to be due to the misclassification of key variables, to insufficient statistical power, or to bias, for example, response bias. If any impairment of male reproductive function exists at the levels of occupational lead exposure now current, it does not appear to reduce biological fertility.
Synergistic effect of hepatitis virus infection and occupational exposures to vinyl chloride monomer and ethylene dichloride on serum aminotransferase activity
Authors: Hsieh H-I , Wang J-D , Chen P-C , Cheng T-J 
Published: September 2003

Aims:To study the synergistic effect of occupational chemical exposure and hepatitis virus infection on serum aminotransferase activity.Methods:A total of 568 male workers who were employed in five polyvinyl chloride (PVC) or four vinyl chloride monomer (VCM) manufacturing factories were studied. Information relating to current job title, alcohol consumption, and cigarette smoking was obtained. Exposure level of chemical mixtures was classified by hygienic effect (a summation of personal time weighted average/reference permissible exposure level of each chemical) into high, moderate, and low exposure groups. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-hepatitis C antibody were assayed.Results:Hepatitis virus infection and increased body mass index were associated with abnormal serum aminotransferase activity. In workers with hepatitis virus infection, those with high exposure had a higher prevalence of abnormal AST and ALT compared to low exposure; among those without hepatitis virus infection, the differences of prevalence of abnormal AST and ALT were not significant between different chemical exposure groups. There was a significant trend of increasing risks of increased AST and ALT in moderate and high exposure groups with hepatitis virus infection. Such a synergistic effect was more prominent among HBeAg-positive workers.Conclusions:Mixed exposures to 1,2-ethylene dichloride and VCM have a positive synergistic effect with hepatitis virus infection on liver damage. Assessment of fitness for work should be considered in workers with hepatitis B and C infection, when they have potential exposure to hepatotoxins in the workplace.
Cancer risk in offspring of male pesticide applicators in agriculture in Sweden
Authors: Rodvall Y , Dich J , Wiklund K 
Published: September 2003

Aims:To explore cancer risk from date of birth until 1994 in children, born 1958 or later, of Swedish male pesticide applicators.Methods:Records of male pesticide applicators licensed 1965–76 were linked to the Multigeneration Register. The records of their offspring were then linked to the Swedish Cancer Registry and the Cause of Death Register.Results:In total 51 cases of cancer were observed, which is significantly lower than the expected 73.0 (standardised incidence ratio (SIR) 0.70, 95% CI 0.52 to 0.92). Tumours of the nervous system was most common, amounting to 20 cases, 39% of all cancer cases (SIR 1.01, 95% CI 0.62 to 1.56). A statistically significant reduced risk for leukaemia was found (SIR 0.43, 95% CI 0.19 to 0.86). For non-Hodgkin’s lymphoma, three cases were observed and 4.8 expected (SIR 0.63, 95% CI 0.13 to 1.83). For Hodgkin’s disease, five cases were observed versus 3.7 expected (SIR 1.36, 95% CI 0.44 to 3.17). Two cases of testicular cancer were observed and 1.7 expected (SIR 1.19, 95% CI 0.13 to 4.28).Conclusions:None of the a priori hypotheses of increased risk of tumours of the nervous system, kidney cancer, leukaemia, lymphoma, soft tissue sarcoma, and testicular cancer in children of male pesticide applicators could be confirmed.
Reason, Society and Religion
Authors: Wallace Andy 
Published: September 2003

I have two main objectives in this essay: (1) to situate the events of 11 September within the context of the impact of modernization on religious consciousness and institutions; and (2) to suggest, albeit without adequate empirical support, that militant Islamic opposition to the West in general and the United States in particular is itself an effect of the peculiar path of modernization that has unfolded in the Gulf region of the Middle East over the last 200 years. To develop my argument, I draw upon Habermas's theory of social evolution. Since this strategy requires explaining the key components of that theory, I devote a good part of the article to this task. The paper has five parts. In parts one and two, I criticize competing explanations of the events of 11 September from left, right and center. All these positions fail in one way or another to take seriously the religious significance of those events. In part three, I explain the six central dimensions of Habermas's theory of social evolution: (1) communicative rationality; (2) communicative action; (3) life-world; (4) system; (5) social typology; and (6) the systemic colonization of the life-world. In part four, I examine the relation between religion and modernity. In part five, I examine the modernization processes in the Gulf region of the Middle East. Empirical evidence tentatively suggests that such a process has been one-dimensional, focusing on systemic complexity to the detriment of the communicative rationalization of the life-world. Such evidence also indicates the existence of widespread systemic colonization of the life-world. If the empirical data are correct, then we can explain the emergence of extreme militant Islamic fundamentalism as an effect of a retarded development of those socio-political structures necessary for the realization of communicative rationality.
The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia
Authors: Cook Mark A. , Milligan Donald W. , Fegan Christopher D. , Darbyshire Philip J. , Mahendra Premini , Craddock Charles F. , Moss Paul A. H. , Briggs David C. 
Published: September 2003

AbstractKiller immunoglobulin–like receptors (KIRs) regulate cell activity of natural killer (NK) cells and some T cells. The predominant ligand for inhibitory KIRs is HLA-C, which subdivides into 2 groups based on the specificity of inhibitory KIRs. The ligands for activatory KIRs are unknown. Following hematopoietic stem cell transplantation (HSCT), recipient tissues may not express a ligand for KIRs present within the graft, and the combination of donor KIR and recipient HLA-C types could influence outcome. HLA and KIR genotypes were determined in 220 donor-recipient pairs from HLA-matched sibling HSCTs performed for myeloid (n = 112) and lymphoid (n = 108) diseases. In HSCTs performed for myeloid disease, overall survival was worse in patients homozygous for group 2 HLA-C (C2) than in patients who carried a group 1 HLA-C (C1) allele (P &lt; .005). Moreover, this effect is seen only when the donor additionally carries the activating KIR gene KIR2DS2 (P = .045). No effect was seen in patients with lymphoid disease. Thus, in HLA-matched sibling HSCT for myeloid leukemia, patients homozygous for C2 alleles receiving a graft from a donor carrying the KIR gene KIR2DS2 have a significantly reduced chance of survival.
Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype–identical sibling selected using preimplantation genetic diagnosis
Authors: Grewal Satkiran S. , Kahn Jeffrey P. , MacMillan Margaret L. , Ramsay Norma K. C. , Wagner John E. 
Published: September 2003

AbstractThe only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLA-identical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient underwent transplantation with her newborn sibling donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed. (Blood. 2004;103:1147-1151)
Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations
Authors: Damle Rajendra N. , Batliwalla Franak M. , Ghiotto Fabio , Valetto Angelo , Albesiano Emilia , Sison Cristina , Allen Steven L. , Kolitz Jonathan , Vinciguerra Vincent P. , Kudalkar Prasad , Wasil Tarun , Rai Kanti R. , Ferrarini Manlio , Gregersen Peter K. , Chiorazzi Nicholas 
Published: September 2003

AbstractPatients with B-cell chronic lymphocytic leukemia (B-CLL) segregate into subgroups with very different survival times. Because clinical observations suggest that leukemic cells accumulate at different rates, we measured telomere length and telomerase activity in B-CLL cells to distinguish differences in cellular replication. Our data indicate that the telomeres of B-CLL cells are shorter than telomeres of B cells from healthy subjects, indicating that the leukemic cells have a prolonged proliferative history. Leukemic cells of the immunoglobulin V gene mutation subgroups differ in telomere length and telomerase activity. B lymphocytes from the subgroup with poor outcome and with limited IgV gene mutations have uniformly shorter telomeres and more telomerase activity than those from the subgroup with better outcome and with considerable mutations. Differences in telomere length appear to largely reflect the proliferative histories of precursors of the leukemic cells, although differences in cell division, masked by the action of telomerase, cannot be excluded. These results may provide insight into the stages of maturation and the activation pathways of the cells that give rise to B-CLL. In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories.
CD44-hyaluronic acid interactions mediate shear-resistant binding of lymphocytes to dermal endothelium in acute cutaneous GVHD
Authors: Milinkovic Mirjana , Antin Joseph H. , Hergrueter Charles A. , Underhill Charles B. , Sackstein Robert 
Published: September 2003

AbstractFor circulating lymphocytes to migrate to inflammatory sites, they must first adhere to the target tissue endothelium with sufficient strength to overcome the shear forces of blood flow. We previously reported that dermal papillary vessels in acute graft-versus-host disease (aGVHD) support shear-resistant lymphocyte adherence. We now identify the relevant adhesion molecule(s) directing this binding, showing that interactions between lymphocyte CD44 and hyaluronic acid (HA) expressed on dermal vessels in aGVHD alone confer this shear-resistant attachment. Native HA deposits on vascular endothelium support lymphocyte adherence, whereas HA immobilized on plastic does not. HA expressed at dermal endothelium in aGVHD is thus specialized to support lymphocyte adherence under flow conditions, and CD44-HA interactions may contribute to lymphocytotropism to skin in aGVHD.
Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation
Authors: Pitchford Simon C. , Riffo-Vasquez Yanira , Sousa Ana , Momi Stefania , Gresele Paolo , Spina Domenico , Page Clive P. 
Published: September 2003

AbstractAsthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)–sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with shamsensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.
Cyclophosphamide metabolism is affected by azole antifungals
Authors: Marr Kieren A. , Leisenring Wendy , Crippa Fulvio , Slattery John T. , Corey Lawrence , Boeckh Michael , McDonald George B. 
Published: September 2003

Abstract
We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT. After enrollment of the first 197 patients, a data and safety monitoring board reviewed potential drug-related toxicities. Patients who received itraconazole developed higher serum bilirubin and creatinine values in the first 20 days after SCT, with highest values in patients who received itraconazole concurrent with cyclophosphamide (CY) conditioning. Analysis of CY metabolism in a subset of patients demonstrated higher exposure to toxic metabolites among recipients of itraconazole compared with fluconazole. These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities.
Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency
Authors: Camerer Eric , Duong Daniel N. , Hamilton Justin R. , Coughlin Shaun R. 
Published: September 2003

Abstract
The availability of the relevant mutant mouse lines provided an opportunity to test the doctrine that platelet activation and fibrin formation account for the importance of thrombin for hemostasis. Prothrombin-deficient mice that survive to birth exsanguinate in the perinatal period. By contrast, protease-activated receptor 4 (PAR4)–deficient mice, which have platelets that fail to respond to thrombin, survive to adulthood with only a mild bleeding diathesis, and fibrinogen-deficient mice show perinatal bleeding but those that survive this period can have a relatively normal life expectancy. We now report that mice that lacked both PAR4 and fibrinogen exsanguinated at birth like prothrombin-deficient mice. However, while approximately half of prothrombindeficient embryos die during midgestation, mice lacking both PAR4 and fibrinogen developed normally. At face value, these results suggest that platelet activation and fibrin formation are together sufficient to account for the importance of thrombin for hemostasis but not for its importance for embryonic development.