THE PLANT JOURNAL, Issue 1 2009
Reetta Ahlfors
Summary Nitric oxide (NO) is involved together with reactive oxygen species (ROS) in the activation of various stress responses in plants. We have used ozone (O3) as a tool to elicit ROS-activated stress responses, and to activate cell death in plant leaves. Here, we have investigated the roles and interactions of ROS and NO in the induction and regulation of O3 -induced cell death. Treatment with O3 induced a rapid accumulation of NO, which started from guard cells, spread to adjacent epidermal cells and eventually moved to mesophyll cells. During the later time points, NO production coincided with the formation of hypersensitive response (HR)-like lesions. The NO donor sodium nitroprusside (SNP) and O3 individually induced a large set of defence-related genes; however, in a combined treatment SNP attenuated the O3 induction of salicylic acid (SA) biosynthesis and other defence-related genes. Consistent with this, SNP treatment also decreased O3 -induced SA accumulation. The O3 -sensitive mutant rcd1 was found to be an NO overproducer; in contrast, Atnoa1/rif1 (Arabidopsis nitric oxide associated 1/resistant to inhibition by FSM1), a mutant with decreased production of NO, was also O3 sensitive. This, together with experiments combining O3 and the NO donor SNP suggested that NO can modify signalling, hormone biosynthesis and gene expression in plants during O3 exposure, and that a functional NO production is needed for a proper O3 response. In summary, NO is an important signalling molecule in the response to O3. [source]

TRACING THE ORIGIN OF MULTI-DRUG RESISTANT (MDR) ESCHERICHIA COLI INFECTIONS FROM URINARY CATHETERS IN ICU CANINE PATIENTS

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue S1 2004
J Ogeer-Gyles
Introduction: Urinary tract infections (UTIs) in dogs with urinary catheters in intensive care units (ICUs) are frequent. Historically, multi-drug resistant (MDR) Escherichia coli account for about 10% of the UTIs. The objectives of this study were to determine the frequency of E. coli infections and of MDR E. coli in dogs with UTIs in our ICU, and to assess whether the MDR E. coli were community-acquired or nosocomial in origin. Methods: Over a 1-year period, rectal swabs were taken from all dogs in the ICU on the day of admission (D0) and on days 3 (D3), 6 (D6), 9 (D9) and 12 (D12). Urine was collected on these days from dogs with an indwelling urinary catheter (n=190). Rectal swabs and urine were routinely cultured. E. coli isolates were identified by biochemical tests. Using NCCLS guidelines, antibiotic susceptibility testing was done by disk diffusion method on fecal and urinary E. coli isolates. Twelve antimicrobial agents were used: nalidixic acid, enrofloxacin, cephalothin, cefoxitin, cefotaxime, ceftiofur, trimethoprim-sulfa, chloramphenicol, gentamicin, tetracycline, ampicillin, and amoxicillin/clavulanate. Pulsed-field gel electrophoresis (PFGE) was used to compare MDR E. coli UTI strains with fecal E. coli strains from the same patient and with MDR fecal E. coli from patients that were adjacent to, or housed in the same cages. Results: E. coli was cultured from 12 (48%) of 25 UTIs. Two of the E. coli were MDR. For one dog, PFGE showed no similarities among fecal E. coli and the urinary MDR E. coli isolates from the patient or between these isolates and fecal E. coli from a dog housed in the same kennel on the previous day. The MDR E. coli UTI was likely acquired prior to admission to the ICU, as it was present on D0. For the other dog, PFGE showed genetic similarity but not complete identity between the D3 MDR E. coli urinary isolate and the D3, D6, D9 fecal MDR isolates. This suggests that the UTI originated with the fecal E. coli. Using selective plates, fecal MDR E. coli were not found on D0. Selection of the MDR strain in the intestine by the use of antibiotics occurred while the dog was in the ICU and possibly led to the UTI. Conclusions: Multi-drug resistant E. coli accounted for 2 of 12 E. coli UTIs in dogs in the ICU over a 1-year period. Genotyping showed that one of the two MDR E. coli infections could possibly be of nosocomial origin. [source]

ARE HIGHLY STRUCTURED JOB INTERVIEWS RESISTANT TO DEMOGRAPHIC SIMILARITY EFFECTS?

PERSONNEL PSYCHOLOGY, Issue 2 2010
JULIE M. McCARTHY
This study examines the extent to which highly structured job interviews are resistant to demographic similarity effects. The sample comprised nearly 20,000 applicants for a managerial-level position in a large organization. Findings were unequivocal: Main effects of applicant gender and race were not associated with interviewers' ratings of applicant performance nor was applicant,interviewer similarity with regard to gender and race. These findings address past inconsistencies in research on demographic similarity effects in employment interviews and demonstrate the value of using highly structured interviews to minimize the potential influence of applicant demographic characteristics on selection decisions. [source]

Over expression of a Cytochrome P450 (CYP6P9) in a Major African Malaria Vector, Anopheles Funestus, Resistant to Pyrethroids

INSECT MOLECULAR BIOLOGY, Issue 1 2008
D. A. Amenya
Abstract Anopheles funestus Giles is one of the major African malaria vectors. It has previously been implicated in a major outbreak of malaria in KwaZulu/Natal, South Africa, during the period 1996 to 2000. The re-emergence of this vector was associated with monooxygenase-based resistance to pyrethroid insecticides. We have identified a gene from the monooxygenase CYP6 family, CYP6P9, which is over expressed in a pyrethroid resistant strain originating from Mozambique. Quantitative Real-Time PCR shows that this gene is highly over expressed in the egg and adult stages of the resistant strain relative to the susceptible strain but the larval stages showed almost no difference in expression between strains. This gene is genetically linked to a major locus associated with pyrethroid resistance in this A. funestus population. [source]

Resistant Pathogens in Urinary Tract Infections

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2002
Lindsay E. Nicolle MD
Antimicrobial susceptibility of bacteria causing urinary tract infection (UTI) has evolved over several decades as antimicrobial exposure has repeatedly been followed by emergence of resistance. Older populations in the community, long-term care facilities, or acute care facilities have an increased prevalence of resistant bacteria isolated from UTI. Resistant isolates are more frequent in long-term care populations than the community. Resistant isolates include common uropathogens, such as Escherichia coli or Proteus mirabilis, and organisms with higher levels of intrinsic resistance, such as Pseudomonas aeruginosa or Providencia stuartii. Isolation of resistant organisms is consistently associated with prior antimicrobial exposure and higher functional impairment. The increased likelihood of resistant bacteria makes it essential that a urine specimen for culture and susceptibility testing be obtained before instituting antimicrobial therapy. Therapy for the individual patient must be balanced with the possibility that antimicrobial use will promote further resistance. Antimicrobial therapy should be avoided unless there is a clear clinical indication. In particular, asymptomatic bacteriuria should not be treated with antimicrobials. Where symptoms are mild or equivocal, urine culture results should be obtained before initiating therapy. This permits selection of specific therapy for the infecting organism and avoids empiric, usually broad-spectrum, therapy. Where empirical therapy is necessary, prior infecting organisms should be isolated, and recent antimicrobial therapy, as well as regional or facility susceptibility patterns, should be considered in antimicrobial choice. Where empirical therapy is used, it should be reassessed 48 to 72 hours after initiation, once pretherapy cultures are available. [source]

Nisin-resistant (Nisr) Listeria monocytogenes and Nisr Clostridium botulinum Are Not Resistant to Common Food Preservatives

JOURNAL OF FOOD SCIENCE, Issue 5 2000
A.S. MAZZOTTA
ABSTRACT Nisin-resistant (Nisr) strains of Clostridium botulinum and Listeria monocytogenes may arise as nisin becomes more widely used as an additional safety barrier in minimally-processed foods. The sensitivity of Nisr L. monocytogenes ATCC 700301 and ATCC 700302 and toxigenic Nisr C. botulinum 169B to low pH, salt, sodium nitrite, and potassium sorbate was assayed using discontinuous gradients in broth and compared to the parental wild-type strains. The nisin-resistant strains did not have intrinsic resistance to low pH, sodium chloride, potassium sorbate, or sodium nitrite. In no case were the Nisr L. monocytogenes and C. botulinum strains examined more resistant to inhibitors than the parental strains. [source]

Motivation for Alcohol Becomes Resistant to Quinine Adulteration After 3 to 4 Months of Intermittent Alcohol Self-Administration

ALCOHOLISM, Issue 9 2010
Frederic W. Hopf
Background:, Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (>8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. Methods:, Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose,response for quinine taste preference in IAA and continuous-access animals was determined. Results:, Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in animals with continuous access to alcohol. Finally, no changes in quinine taste preference after 3 to 4 months IAA or continuous access to alcohol were observed. Conclusions:, We have developed a novel and technically simple hybrid operant/IAA model in which quinine-resistant motivation for alcohol is evident after an experimentally tractable period of time (3 to 4 months vs. 8 months). Quinine dramatically reduced sucrose and water intake by IAA rats, indicating that continued responding for alcohol in IAA rats despite adulteration with the normally aversive quinine might reflect maladaptive or compulsive motivation for alcohol. This model could facilitate identification of novel therapeutic interventions for pathological alcohol seeking in humans. [source]

Characterization of Reactions to Powdery Mildew (Podosphaera pannosa) in Resistant and Susceptible Rose Genotypes

JOURNAL OF PHYTOPATHOLOGY, Issue 5 2007
A. Dewitte
Abstract Fungal development of powdery mildew Podosphaera pannosa (Wallr.: Fr.) de Bary on rose leaves depends on constitutive or induced resistance mechanisms present in attacked rose genotypes. The relationship between fungal development and plant resistance was investigated microscopically on young greenhouse leaves of four rose genotypes with different levels of resistance: Rosa wichuraiana, R. laevigata anemoides and R. hybrida cultivars ,Excelsa' and ,Gomery'. Induced plant reactions, hydrogen peroxide production and cross sections through infected leaves were examined. The variation in development of the fungus on these rose genotypes depended on the relative presence of normal haustoria, abnormal haustoria, induced cell reactions, papilla formation or physical barriers. Formation of papillae could arrest up to one third of the successful penetrations. Papillae formation was often succeeded by total cell reaction. Abnormal haustoria were detected as rudimentary haustoria, haustoria with abnormal shape or haustoria without extra haustorial matrix. Post-haustorial cell reactions, with and without cell collapse, were detected. In non-collapsed cells, appositions were directed to both cell wall and haustorium. This was followed by accumulation of non-identified, probably antifungal compounds. Both single and multicell reactions occurred. Hydrogen peroxide was detected during papilla formation and induced cell reactions. [source]

Fusarium eumartii Growth in Resistant and Susceptible Oak Species

JOURNAL OF PHYTOPATHOLOGY, Issue 9 2001
A. Ragazzi
Fusarium eumartii is a fungus associated with declining Quercus robur, in which it is found in the vessels. The response of oak species to infection is known to vary: Q. robur is susceptible, but Quercus cerris and Quercus pubescens are resistant. An experiment was carried out in 1996 and repeated in 1997, to examine how F. eumartii colonization differed in oak species that were susceptible or resistant to the fungus by counting the number of vessels with mycelium at various distances from the inoculation site in infected seedlings and by determining the amount of viable fungus in infected tissue. Infected vessels with mycelium were counted on sections (10 ,m thick) cut at 0, 2, 4, 6, 8 and 10 cm from the inoculation site on 1-year-old inoculated seedlings as well as on sections cut every 2 cm to the seedling tip. The amount of viable fungus was determined by counting the colony forming units (CFUs) in stem segments from the same seedlings. Quercus robur seedlings had the greatest number of infected vessels and the greatest number of CFUs. Forty days after inoculation, the extent of vertical fungal spread was 28.12 cm in Q. robur, 3.15 cm in Q. cerris and 3.00 cm in Q. pubescens. The greatest number of CFUs was found in Q. robur at day 5 after inoculation. Analysis of variance confirmed the results. [source]

Selected Line Difference in the Effects of Ethanol Dependence and Withdrawal on Allopregnanolone Levels and 5,-Reductase Enzyme Activity and Expression

ALCOHOLISM, Issue 12 2009
Michelle A. Tanchuck
Background:, Allopregnanolone (ALLO) is a progesterone derivative that rapidly potentiates ,-aminobutyric acidA (GABAA) receptor-mediated inhibition and modulates symptoms of ethanol withdrawal. Because clinical and preclinical data indicate that ALLO levels are inversely related to symptoms of withdrawal, the present studies determined whether ethanol dependence and withdrawal differentially altered plasma and cortical ALLO levels in mice selectively bred for differences in ethanol withdrawal severity and determined whether the alterations in ALLO levels corresponded to a concomitant change in activity and expression of the biosynthetic enzyme 5,-reductase. Methods:, Male Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice were exposed to 72 hours ethanol vapor or air and euthanized at select times following removal from the inhalation chambers. Blood was collected for analysis of ALLO and corticosterone levels by radioimmunoassay. Dissected amygdala, hippocampus, midbrain, and cortex as well as adrenals were examined for 5,-reductase enzyme activity and expression levels. Results:, Plasma ALLO was decreased significantly only in WSP mice, and this corresponded to a decrease in adrenal 5,-reductase expression. Cortical ALLO was decreased up to 54% in WSP mice and up to 46% in WSR mice, with a similar decrease in cortical 5,-reductase activity during withdrawal in the lines. While cortical gene expression was significantly decreased during withdrawal in WSP mice, there was a 4-fold increase in expression in the WSR line during withdrawal. Hippocampal 5,-reductase activity and gene expression was decreased only in dependent WSP mice. Conclusions:, These results suggest that there are line and brain regional differences in the regulation of the neurosteroid biosynthetic enzyme 5,-reductase during ethanol dependence and withdrawal. In conjunction with the finding that WSP mice exhibit reduced sensitivity to ALLO during withdrawal, the present results are consistent with the hypothesis that genetic differences in ethanol withdrawal severity are due, in part, to modulatory effects of GABAergic neurosteroids such as ALLO. [source]

Differential Effects of Ethanol on Insulin-Like Growth Factor-I Receptor Signaling

ALCOHOLISM, Issue 2 2000
Andrea E.M. Seiler
Background: Activation of the insulin-like growth factor I receptor (IGF-IR) by its ligands IGF-I and IGF-II induces cell proliferation and protects against apoptosis. Ethanol inhibits IGF-IR tyrosine autophosphorylation, which subsequently interferes with the activation of key downstream signaling mediators including insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and mitogen-activated protein (MAP) kinase. The ethanol-induced inhibition of IGF-IR signaling reduces mitogenesis and enhances apoptosis. In the current study, we demonstrate that the antiproliferative action of ethanol can be modulated by differential sensitivity of the autophosphorylation of the IGF-IR to ethanol. Methods: A series of subclones was generated from 3T3 cells that express the human IGF-IR. Results: There was considerable variability in the ability of ethanol to inhibit IGF-I-dependent IGF-IR tyrosine autophosphorylation and MAP kinase activation, despite equivalent IGF-IR expression. The IGF-IR was completely resistant to a high concentration of ethanol (150 mM) in several subclones. The sensitivity of IGF-IR autophosphorylation to ethanol correlated directly with the inhibition of IGF-I-mediated MAP kinase activation and cell proliferation. Resistant subclones exhibited features of the transformed phenotype including high MAP kinase activity, partial loss of contact inhibition, and the development of foci at confluency. The IGF-IR isolated from ethanol-resistant cells was similarly resistant to ethanol in autophosphorylation reactions in vitro, whereas ethanol inhibited the autophosphorylation of IGF-IR obtained from sensitive cells. Conclusions: Our findings are the first to demonstrate the modulation of ethanol sensitivity of a tyrosine kinase receptor, and they provide a molecular basis for differential effects of ethanol on cell proliferation. [source]

Arbuscular mycorrhizal fungi confer enhanced arsenate resistance on Holcus lanatus

NEW PHYTOLOGIST, Issue 1 2002
C. Gonzalez-Chavez
Summary ,,The role of arbuscular mycorrhizal fungi (AMF) in arsenate resistance in arbuscular mycorrhizal associations is investigated here for two Glomus spp. isolated from the arsenate-resistant grass Holcus lanatus. ,,Glomus mosseae and Glomus caledonium were isolated from H. lanatus growing on an arsenic-contaminated mine-spoil soil. The arsenate resistance of spores was compared with nonmine isolates using a germination assay. Short-term arsenate influx into roots and long-term plant accumulation of arsenic by plants were also investigated in uninfected arsenate resistant and nonresistant plants and in plants infected with mine and nonmine AMF. ,,Mine AMF isolates were arsenate resistant compared with nonmine isolates. Resistant and nonresistant G. mosseae both suppressed high-affinity arsenate/phosphate transport into the roots of both resistant and nonresistant H. lanatus. Resistant AMF colonization of resistant H. lanatus growing in contaminated mine spoil reduced arsenate uptake by the host. ,,We conclude that AMF have evolved arsenate resistance, and conferred enhanced resistance on H. lanatus. [source]

Termination of Persistent Atrial Fibrillation Resistant to Cardioversion by a Single Radiofrequency Application

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2003
BENGT HERWEG
This report describes the termination of persistent AF refractory to multiple cardioversions and antiarrhythmic therapy in a patient without structural heart disease, with a single radiofrequency application delivered in the left upper pulmonary vein. The observations and failure of repeated internal and external cardioversion suggest a rapidly firing arrhythmia focus sustaining atrial fibrillation amenable to curative pulmonary vein ablation. (PACE 2003; 26:1420,1423) [source]

Analysis of Gene Polymorphisms Associated with K+ Ion Circulation in the Inner Ear of Patients Susceptible and Resistant to Noise-induced Hearing Loss

ANNALS OF HUMAN GENETICS, Issue 4 2009
Malgorzata Pawelczyk
Summary Noise-induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise-exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we replicated associations that were previously reported in a Swedish sample set, hence confirming that they are NIHL susceptibility genes. Additionally we report significant associations in GJB1, GJB2, GJB4, KCNJ10 and KCNQ1, however due to the lack of replication in the Swedish sample set, these results should be seen as suggestive. [source]

Astrocytes are More Resistant to Focal Cerebral Ischemia Than Neurons and Die by a Delayed Necrosis

BRAIN PATHOLOGY, Issue 4 2009
Günfer Gürer
Abstract Several recent reports proposed that astrocyte death might precede neuronal demise after focal ischemia, contrary to the conventional view that astrocytes are more resistant to injury than neurons. Interestingly, there are findings supporting each of these opposing views. To clarify these controversies, we assessed astrocyte viability after 2-h middle cerebral artery occlusion in mice. In contrast to neighboring neurons, astrocytes were alive and contained glycogen across the ischemic area 6 h after reperfusion, and at the expanding outer border of the infarct at later time points. These glycogen-positive astrocytes had intact plasma membranes. Astrocytes lost plasmalemma integrity much later than neurons: 19 ± 22 (mean ± standard deviation), 58 ± 14 and 69 ± 3% of astrocytes in the perifocal region became permeable to propidium iodide (PI) at 6, 24, 72 h after ischemia, respectively, in contrast to 81 ± 2, 96 ± 3, 97 ± 2% of neurons. Although more astrocytes in the cortical and subcortical core regions were PI-positive, their numbers were considerably less than those of neurons. Lysosomal rupture (monitored by deoxyribonuclease II immunoreactivity) followed a similar time course. Cytochrome-c immunohistochemistry showed that astrocytes maintained mitochondrial integrity longer than neurons. EM confirmed that astrocyte ultrastructure including mitochondria and lysosomes disintegrated much later than that of neurons. We also found that astrocytes died by a delayed necrosis without significantly activating apoptotic mechanisms although they rapidly swelled at the onset of ischemia. [source]

Deletion Mutants of Human Deoxycytidine Kinase mRNA in Cells Resistant to Antitumor Cytosine Nucleosides

CANCER SCIENCE, Issue 7 2001
Tohru Obata
We studied mutational events in deoxycytidine (dCyd) kinase mRNA expression, focusing on aberrant dCyd kinase mRNA, which has been frequently observed in established cell lines resistant to antitumor dCyd nucleoside analogues such as 1-,-D-arabinofuranosyl cytosine (Ara-C), gemcita-bine (dFdC) and 2,-C-cyano-2,-deoxy-l-,-D-arabinofuranosylcytosine (CNDAC). We describe here the expression of aberrant dCyd kinase mRNAs identified as splicing mutants. These mutants included deletions of the fifth exon in CNDAC-resistant cells (originating from HT-1080 cells), of the third exon in Ara-C-resistant cells (originating from SK-MEL-28 cells) and of the fourth exon in 2,-deoxy-2,-methylidenecytidine (DMDC)-resistant cells (originating from SK-MEL-28 cells). Various nucleoside-resistant cells originating from the same parental HT-1080 cells were established. The resulting cells expressed the same mRNA with deletion of the fifth exon, and the location of splicing was independent of the type of nucleosides used for the establishment of resistant cells. The deletion of the fifth exon in dCyd kinase seems to be a target for acquisition of resistance to antitumor cytosine nucleosides. However, distinct mutations in the dCyd kinase gene seem to be associated with acquisition of resistance to different antitumor cytosine nucleosides. [source]

ChemInform Abstract: Synthesis and Analysis of Structural Features of Phenoxazine Analogues Needed to Reverse Vinblastine Resistance in Multidrug Resistant (MDR) Cancer Cells.

CHEMINFORM, Issue 2 2001
G. B. Eregowda
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

N -Linked Glycosylated , -Peptides Are Resistant to Degradation by Glycoamidase A

CHEMISTRY & BIODIVERSITY, Issue 12 2005
Matthew
, -Peptides are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural , -peptides. This is one of many characteristics that make , -peptides an attractive class of compounds for drug discovery efforts. To further understand the molecular recognition properties of , -peptides and the ability of enzymes to degrade them, we have synthesized a series of N- linked glycosylated , - and , -peptides, and tested their stability towards a glycosidase. We found that glyco- , -peptides that contain N- acetylglucosamine (1) or N,N -diacetylchitobiose (2) are completely stable to degradation by glycoamidase A. In comparison, the glyco- , -peptides 3 and 4 containing N -acetylglucosamine or N,N -diacetylchitobiose are degraded. Inhibition experiments using increasing concentrations of a glyco- , -peptide fail to inhibit degradation of the corresponding glyco- , -peptide, even when the glyco- , -peptide is at a 128-fold higher concentration than the glyco- , -peptide. Evidently, the glyco- , -peptides have a much weaker affinity for the active site of the glycosidase than the corresponding glyco- , -peptide. These and the results with proteolytic enzymes suggest that the additional CH2 group introduced into the , -amino acid residues causes , -peptides not to be recognized by hydrolytic enzymes. The results described herein suggest the potential of , -peptides that are functionalized with carbohydrates for biological and biomedical investigations, without having to be concerned about the carbohydrate being removed. [source]

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease: analysis of nationwide experience in Scotland (2004,2008)

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
G. T. HO
Summary Background, Adalimumab is a second generation humanized anti-tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn's disease (CD). Aims, To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting. Methods, We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4-year period (2004,2008). Results, A total of 98 patients received adalimumab - 100.5 patient follow-up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1-year follow-up, with 30% and 55% requiring dose escalation to weekly therapy at 1-and 2-year follow-up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively). Conclusions, Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy- and disease-related risks of serious complications. [source]

Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996,1998

ACTA PAEDIATRICA, Issue 2000
E Miller
The results of enhanced national surveillance of pneumococcal disease in children <15y of age in England and Wales are reported for the period 1996,1998. Of the 1985 cases of laboratory-confirmed invasive disease (annual incidence 6.6 per 100000 overall and 39.7 per 100000 in infants <1 y of age), 485 (24%) were meningitis (annual incidence of 1.6 per 100000 overall and 15.7 per 100000 in infants <1 y of age). Fifty-nine deaths in children with invasive disease were identified-3% of the total reports. Thirty-one different serogroups/types were identified, with organisms in the 7-valent conjugate vaccine responsible for 69% of the infections in children <5 y of age; this rose to 77% and 82%, respectively, for the 9-and 11-valent vaccines. Resistance to penicillin varied from 2.3% to 6.2% in different years, but erythromycin resistance remained constant at 17%. The vast majority of resistant isolates were in vaccine serotype/groups. Computerized hospital admission records for all children <15 y of age with a discharge diagnosis code indicating probable pneumococcal disease were also analysed for 1997. The annual incidence for cases with a code specifically mentioning S. pneumoniae was 9.9 per 100000 compared with 71.2 per 100000 for lobar pneumonia; the mean duration of stay for both was < 1 wk. The incidence of admission for pneumococcal meningitis (1.9 overall and 19.6 for infants < 1 y of age) was similar to that derived from laboratory reports and resulted in an average duration of stay of 2 wk. Conclusion: This surveillance has confirmed the substantial burden of morbidity attributable to pneumococcal disease in British children and the potential public health benefits that could be achieved by the use of pneumococcal conjugate vaccines. [source]

Induction of apoptosis by A3 adenosine receptor agonist N6 -(3-iodobenzyl)-adenosine-5,- N -methylcarboxamide in human leukaemia cells: a possible involvement of intracellular mechanism

ACTA PHYSIOLOGICA, Issue 2 2010
P. Mlejnek
Abstract Aim:, The sensitivity of cancer cells which exhibit multi-drug resistance phenotype to A3 adenosine receptor (A3AR) agonist N6 -(3-iodobenzyl)-adenosine-5,- N -methylcarboxamide (IB-MECA) was studied. Methods:, To establish direct relationship between P-glycoprotein (P-gp, ABCB1 and MDR1) expression and IB-MECA induced cell death, a straightforward method for precise estimation of intracellular level of this A3AR agonist was developed. Results:, We subjected three human leukaemia cell lines HL-60, K562 and K562/HHT to treatment with micromolar concentrations of IB-MECA. Although all cell lines used expressed A3AR, there was a large difference in their sensitivity to IB-MECA. While HL-60 and K562 cells were almost equally sensitive, the K562/HHT cells, which exhibit a multi-drug resistance phenotype because of overexpression of P-gp, were significantly more resistant. We found that the intracellular level of IB-MECA in K562/HHT cells was approx. 10 times lower than those in HL-60 or K562 cells. Inhibitors of P-gp, including cyclosporine A (CsA) and verapamil (Vpa), increased the intracellular level of IB-MECA and reversed the resistance of K562/HHT cells to this drug. Accordingly, shRNA-mediated down-regulation of P-gp significantly increased the intracellular level of IB-MECA in K562/HHT cells which simultaneously exhibited reduced resistance to this A3AR agonist. In addition, an in vitro enzyme-based assay provided evidence that IB-MECA might serve as a substrate for P-gp. Conclusion:, Our results suggest that P-gp overexpression prevents cells from IB-MECA induced apoptosis despite the A3AR expression. Pro-apoptotic effect of IB-MECA seemed to strongly depend on its intracellular accumulation rather than on its interaction with A3AR. [source]

Gastrointestinal Bacterial Transmission among Humans, Mountain Gorillas, and Livestock in Bwindi Impenetrable National Park, Uganda

CONSERVATION BIOLOGY, Issue 6 2008
INNOCENT B. RWEGO
ecología de enfermedades; Escherichia coli; primates; salud del ecosistema; zoonosis Abstract:,Habitat overlap can increase the risks of anthroponotic and zoonotic pathogen transmission between humans, livestock, and wild apes. We collected Escherichia coli bacteria from humans, livestock, and mountain gorillas (Gorilla gorilla beringei) in Bwindi Impenetrable National Park, Uganda, from May to August 2005 to examine whether habitat overlap influences rates and patterns of pathogen transmission between humans and apes and whether livestock might facilitate transmission. We genotyped 496 E. coli isolates with repetitive extragenic palindromic polymerase chain reaction fingerprinting and measured susceptibility to 11 antibiotics with the disc-diffusion method. We conducted population genetic analyses to examine genetic differences among populations of bacteria from different hosts and locations. Gorilla populations that overlapped in their use of habitat at high rates with people and livestock harbored E. coli that were genetically similar to E. coli from those people and livestock, whereas E. coli from gorillas that did not overlap in their use of habitats with people and livestock were more distantly related to human or livestock bacteria. Thirty-five percent of isolates from humans, 27% of isolates from livestock, and 17% of isolates from gorillas were clinically resistant to at least one antibiotic used by local people, and the proportion of individual gorillas harboring resistant isolates declined across populations in proportion to decreasing degrees of habitat overlap with humans. These patterns of genetic similarity and antibiotic resistance among E. coli from populations of apes, humans, and livestock indicate that habitat overlap between species affects the dynamics of gastrointestinal bacterial transmission, perhaps through domestic animal intermediates and the physical environment. Limiting such transmission would benefit human and domestic animal health and ape conservation. Resumen:,El traslape de hábitats puede incrementar los riesgos de transmisión de patógenos antroponótica y zoonótica entre humanos, ganado y simios silvestres. Recolectamos bacterias Escherichia coli de humanos, ganado y gorilas de montaña (Gorilla gorilla beringei) en el Parque Nacional Bwindi Impenetrable, Uganda, de mayo a agosto 2005 para examinar sí el traslape de hábitat influye en las tasas y patrones de transmisión de patógenos entre humanos y simios y sí el ganado facilita esa transmisión. Determinamos el genotipo de 496 aislados de E. coli con marcaje de reacción en cadena de polimerasa palindrómica extragénica (rep-PCR) y medimos la susceptibilidad a 11 antibióticos con el método de difusión de disco. Realizamos análisis de genética poblacional para examinar las diferencias genéticas entre poblaciones de bacterias de huéspedes y localidades diferentes. Las poblaciones de gorilas con alto grado de traslape en el uso de hábitat con humanos y ganado presentaron E. coli genéticamente similar a E. coli de humanos y ganado, mientras que E. coli de gorilas sin traslape en el uso hábitat con humanos y ganado tuvo relación lejana con las bacterias de humanos y ganado. Treinta y cinco porciento de los aislados de humanos, 27% de los aislados de ganado y 17% de los aislados de gorilas fueron clínicamente resistentes a por lo menos un antibiótico utilizado por habitantes locales, y la proporción de gorilas individuales con presencia de aislados resistentes declinó en las poblaciones proporcionalmente con la disminución en el grado de traslape con humanos. Estos de patrones de similitud genética y resistencia a antibióticos entre E. coli de poblaciones de simios, humanos y ganado indican que el traslape de hábitat entre especies afecta la dinámica de transmisión de bacterias gastrointestinales, probablemente a través de animales domésticos intermediarios y el ambiente físico. La limitación de esa transmisión beneficiaría a la salud de humanos y animales domésticos y a la conservación de simios. [source]

Body Size and Risk of Extinction in Australian Mammals

CONSERVATION BIOLOGY, Issue 5 2001
Marcel Cardillo
For Australian terrestrial mammals this link is of particular interest because it is widely believed that species in the intermediate size range of 35,5500 g (the "critical weight range") have been the most prone to recent extinction. But the relationship between body size and extinction risk in Australian mammals has never been subject to a robust statistical analysis. Using a combination of randomization tests and phylogenetic comparative analyses, we found that Australian mammal extinctions and declines have been nonrandom with respect to body size, but we reject the hypothesis of a critical weight range at intermediate sizes. Small species appear to be the least prone to extinction, but extinctions have not been significantly clustered around intermediate sizes. Our results suggest that hypotheses linking intermediate body size with high risk of extinction in Australian mammals are misguided and that the focus of future research should shift to explaining why the smallest species are the most resistant to extinction. Resumen: El vínculo entre el tamaño del cuerpo y el riesgo de extinción ha sido el centro de mucha atención reciente. Para los mamíferos terrestres australianos este vínculo es de particular interés debido a que se cree ampliamente que las especies en un rango intermedio de tamaño de 35,5500 g (el rango de peso crítico) ha sido el más susceptible a extinciones recientes. Sin embargo, la relación entre extinciones, el tamaño y el riesgo de extinción en mamíferos australianos nunca ha sido sometida a un análisis estadístico robusto. Usando una combinación de pruebas aleatorizadas y análisis filogenéticos comparativos, encontramos que las extinciones y disminuciones de mamíferos australianos han sido no aleatorias con respecto al tamaño del cuerpo, pero rechazamos la hipótesis de un rango crítico a tamaños intermedios. Las especies pequeñas aparentan ser las menos susceptibles de extinción, pero las extinciones no se han agrupado significativamente alrededor de tamaños intermedios. Nuestros resultados sugieren que la hipótesis que vincula el tamaño intermedio de cuerpo con un alto riesgo de extinción en mamíferos australianos está mal planteada y que el centro de la investigación a futuro deberá enfocarse a explicar el porqué las especies más pequeñas son las más robustas a la extinción. [source]

ESTIMATING INTERVENTION EFFECTS IN VARYING RISK SETTINGS: DO POLICE RAIDS REDUCE ILLEGAL DRUG DEALING AT NUISANCE BARS?,

CRIMINOLOGY, Issue 2 2003
JACQUELINE COHEN
This paper investigates the effectiveness of police raids in reducing drug dealing in and around nuisance bars. We examine effects of both dosage (number of raids) and duration (months) of the intervention, as well as the conditioning effects of land use and population characteristics in shaping the underlying risk levels of drug dealing in the target and surrounding areas. Results indicate that the police intervention suppresses levels of drug dealing during periods of active enforcement, but the effects largely disappear when the intervention is withdrawn. Also, the effects of the intervention are mediated by risk characteristics in target and surrounding areas. Target areas characterized by higher levels of risk are more resistant to intervention effects than those with lower levels of risk. Risk factors in nearby areas are also significant. Bars with high levels of risk arising from land uses in surrounding areas are easier to treat, while bars with high levels of population-based risk in surrounding areas are harder to treat. [source]

Changes in the contractile properties of motor units in the rat medial gastrocnemius muscle after one month of treadmill training

ACTA PHYSIOLOGICA, Issue 4 2008
M. Pogrzebna
Abstract Aim:, The influence of 4 weeks treadmill training on the contractile properties of motor units (MUs) in the rat medial gastrocnemius muscle was investigated. Methods:, A population of 18 Wistar rats was divided into two groups: trained on a treadmill (n = 7, locomotion speed 27 cm s,1, 1 km daily, 5 days a week, for 4 weeks) and control (n = 11). The contractile properties of isolated MUs were studied. Functional isolation of units was achieved by electrical stimulation of filaments of the ventral roots. A total of 299 MUs were investigated (142 in the control group and 157 in the trained group). They were divided into fast fatigable (FF), fast resistant to fatigue (FR) and slow (S). Their proportions and parameters of contractions were analysed. Results:, Following training, the number of FF units decreased and the number of FR units increased. The distribution of the fatigue index changed within these two types of fast units. The twitch and tetanus forces increased considerably in fast MUs, mainly in those of the FF type. The contraction and relaxation times shortened in the FR and S MUs. The steep part of the force,frequency curves shifted towards higher stimulation frequencies in FR and S units, while in FF units the shift was in the opposite direction. Conclusion:, The significant change in the proportions of fast MUs following training indicates FF to FR transformation. The various effects of training seen in the different MU types help explain the rationale behind mixed training. [source]

AKAP-independent localization of type-II protein kinase A to dynamic actin microspikes

CYTOSKELETON, Issue 9 2009
Robert L. Rivard
Abstract Regulation of the cyclic AMP-dependent protein kinase (PKA) in subcellular space is required for cytoskeletal dynamics and chemotaxis. Currently, spatial regulation of PKA is thought to require the association of PKA regulatory (R) subunits with A-kinase anchoring proteins (AKAPs). Here, we show that the regulatory RII, subunit of PKA associates with dynamic actin microspikes in an AKAP-independent manner. Both endogenous RII, and a GFP-RII, fusion protein co-localize with F-actin in microspikes within hippocampal neuron growth cones and the leading edge lamellae of NG108-15 cells. Live-cell imaging demonstrates that RII,-associated microspikes are highly dynamic and that the coupling of RII, to actin is tight, as the movement of both actin and RII, are immediately and coincidently stopped by low-dose cytochalasin D. Importantly, co-localization of RII, and actin in these structures is resistant to displacement by a cell-permeable disrupter of PKA-AKAP interactions. Biochemical fractionation confirms that a substantial pool of PKA RII, is associated with the detergent-insoluble cytoskeleton and is resistant to extraction by a peptide inhibitor of AKAP interactions. Finally, mutation of the AKAP-binding domain of RII, fails to disrupt its association with actin microspikes. These data provide the first demonstration of the physical association of a kinase with such dynamic actin structures, as well as the first demonstration of the ability of type-II PKA to localize to discrete subcellular structures independently of canonical AKAP function. This association is likely to be important for microfilament dynamics and cell migration and may prime the investigation of novel mechanisms for localizing PKA activity. Cell Motil. Cytoskeleton 2009. © 2009 Wiley-Liss, Inc. [source]

Personality disorders improve in patients treated for major depression

ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010
R. T. Mulder
Mulder RT, Joyce PR, Frampton CMA. Personality disorders improve in patients treated for major depression. Objective:, To examine the stability of personality disorders and their change in response to the treatment of major depression. Method:, 149 depressed out-patients taking part in a treatment study were systematically assessed for personality disorders at baseline and after 18 months of treatment using the SCID-II. Results:, Personality disorder diagnoses and symptoms demonstrated low-to-moderate stability (overall , = 0.41). In general, personality disorder diagnoses and symptoms significantly reduced over the 18 months of treatment. There was a trend for the patients who had a better response to treatment to lose more personality disorder symptoms, but even those who never recovered from their depression over the 18 months of treatment lost, on average, nearly three personality disorder symptoms. Conclusion:, Personality disorders are neither particularly stable nor treatment resistant. In depressed out-patients, personality disorder symptoms in general improve significantly even in patients whose response to their treatment for depressive symptoms is modest or poor. [source]

Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion

DEPRESSION AND ANXIETY, Issue 8 2007
John P. O'Reardon M.D.
Abstract Repetitive transcranial magnetic stimulation (rTMS) appears to be efficacious in the treatment of major depression based on the results of controlled studies, but little is known about its antidepressant mechanism of action. Mood sensitivity following rapid tryptophan depletion (RTD) has been demonstrated in depressed patients responding to SSRI antidepressants and phototherapy, but not in responders to electroconvulsive therapy (ECT). We sought to study the effects of RTD in patients with major depression responding to a course of treatment with rTMS. Twelve subjects treated successfully with rTMS monotherapy underwent both RTD and sham depletion in a double-blind crossover design. Depressive symptoms were assessed using both a modified Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The differential change in depression scores across the procedures was compared. No significant difference in mood symptoms was noted between RTD and the sham-depletion procedure on either continuous measures of depression, or in the proportions of subjects that met predefined criteria for a significant degree of mood worsening. Responders to rTMS are resistant to the mood perturbing effects of RTD. This suggests that rTMS does not depend on the central availability of serotonin to exert antidepressant effects in major depression. Depression Anxiety 24:537,544, 2007. © 2006 Wiley-Liss, Inc. [source]

The Treatment of Melasma with Fractional Photothermolysis: A Pilot Study

DERMATOLOGIC SURGERY, Issue 12 2005
Cameron K. Rokhsar MD
Background. Melasma is a common pigmentary disorder that remains resistant to available therapies. Facial resurfacing with the pulsed CO2 laser has been reported successful but requires significant downtime, and there is a risk of adverse sequelae. Objective. To determine if melasma will respond to a new treatment paradigm, fractional resurfacing. Methods. Ten female patients (Fitzpatrick skin types III,V) who were unresponsive to previous treatment were treated at 1- to 2-week intervals with the Fraxel laser (Reliant Technologies, Palo Alto, CA, USA). Wavelengths of 1,535 and 1,550 nm were both used, and 6 to 12 mJ per microthermal zone with 2,000 to 3,500 mtz/cm2 were the treatment parameters. Four to six treatment sessions were performed. Responses were evaluated according to the percentage of lightening of original pigmentation. Two physicians evaluated the photographs, and each patient evaluated her own response. Results. The physician evaluation was that 60% of patients achieved 75 to 100% clearing and 30% had less than 25% improvement. The patients' evaluations agreed, except for one patient, who graded herself as 50 to 75% improved as opposed to the physician grading of over 75%. There was one patient with postinflammatory hyperpigmentation and no patient with hypopigmentation. No downtime was necessary for wound healing. Conclusions. Fractional resurfacing affords a new treatment algorithm for the treatment of melasma that combines decreased risk and downtime with significant efficacy. This treatment modality deserves further exploration to maximize benefits. RELIANT technologies LOANED THE FRAXEL LASER FOR THE STUDY. RICHARD E. FITZPATRICK, MD, IS A PAID CONSULTANT FOR RELIANT AND A STOCKHOLDER. [source]

Pilonidal Sinus Disease Treated by Depilation Using an 800 nm Diode Laser and Review of the Literature

DERMATOLOGIC SURGERY, Issue 5 2005
Anthony V. Benedetto DO, FACP
background. Pilonidal sinus disease is a debilitating, disfiguring chronic ailment that is often resistant to therapy. Its etiology and treatment remain in question. objective. To assess the efficacy of an 800 nm diode laser in the treatment of recalcitrant pilonidal sinus disease. methods. Two patients with recalcitrant pilonidal sinus disease were treated in the lower back, buttocks, and perigluteal cleft area with an 800 nm diode laser with a spot size of 9 × 9 mm, fluences of 30 to 48 J/cm2, and pulse widths of 15 to 24 milliseconds. results. Long-term relief of pilonidal sinus disease was produced with as few as two treatments 2 months apart to as many as six treatments over a 2-year period. With each successive treatment, fewer pulses were needed and the interval between treatments increased. conclusion. The 800 nm diode laser may be an effective tool in the treatment of pilonidal sinus disease. By eliminating the source of hair and hair fragments that course along the surface of the lower back and buttocks, interruption of the etiologic source for pilonidal sinus disease can be accomplished. [source]