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PubMed2001

Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate.

Glycopeptide resistance in Staphylococcus aureus is poorly understood. The diversity of change documented in cell walls of clinical glycopeptide-intermediate S. aureus (GISA) isolates is evidence that a single genetic or biochemical change cannot account for resistance in all isolates described to date. Therefore, identification of new GISA clinical isolates provides an opportunity to gain insight into the range of adaptive strategies employed by staphylococci to survive in the presence of glycopeptides. In April 1999, a GISA isolate was obtained from the blood of a 63-year-old dialysis patient in Illinois. This isolate was one of six clonally identical MRSA isolates (A-F) serially obtained from the blood of this patient who was receiving vancomycin therapy. All isolates were resistant to oxacillin (MIC > 256 mg/L). The initial isolate had an MIC of vancomycin of 1 mg/L. However, the presence of a subpopulation that could grow in the presence of 5 mg/L of vancomycin indicated that this isolate was predisposed to the acquisition of the GISA phenotype (MIC of vancomycin 10-12 mg/L), which occurred 13 days later, associated with an increased MIC of the endopeptidase lysostaphin and slightly increased cell wall thickness. The first and last isolates in the series, A and F, resisted killing when incubated in vancomycin 2 mg/L, resisted autolysis when incubated in Triton X-100 and had a decreased expression of a c. 116 kDa autolytic band, properties that were different from glycopeptide-susceptible control isolates. Lysostaphin resistance was not accompanied by alterations in the peptidoglycan pentaglycine cross-bridge or a decrease in oxacillin MIC. These data, when taken together with the demonstration of increased cross-linking in isolate F compared with isolate A, demonstrate that vancomycin resistance in these isolates probably occurred by a mechanism different from that of other GISA isolates described to date.

Anti-Bacterial Agents↗
PubMed1980

Methionine synthesis, aminoimidazole carboxamide excretion and folate levels in pregnant rats.

The capacity for tetrahydrofolate regeneration through folate-linked methionine synthesis and for purine-ring closure through formylation of aminoimidazole carboxamide ribotide was studied in pregnant female rats fed diets containing either methionine or homocystine with or without folic acid. Plasma and liver folates, serine transhydroxymethylase, 5,10-methylene tetrahydrofolate dehydrogenase and glutamate formiminotransferase activities were also assayed. Pregnancy proceeded normally in all groups. Hypotrophic fetuses were observed only with the diet containing homocystine and no folic acid. Plasma folates were severely depleted at the end of pregnancy even when folic acid was present in the diet. Hepatic stores of folate were twice as high in the methionine as in the homocystine-fed pregnant females supplemented with folic acid. This favorable effect of methionine was not observed in folic acid-deficient females. No change in levels of serine transhydroxymethylase, 5,10-methylenetetrahydrofolate dehydrogenase, glutamate formimino-transferase activities was observed. Pregnancy did not stimulate methionine synthetase activity, the level of which was primarily affected by the nutritional conditions. Because of its low output and narrow range of adaptativity, methionine synthetase cannot be the sole regulatory factor of THF regeneration. Urinary excretion of aminoimidazole carboxamide was enhanced in folic acid-deficient pregnant females and was not prevented by supplying methionine.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2004

Improving crop salt tolerance.

Salinity is an ever-present threat to crop yields, especially in countries where irrigation is an essential aid to agriculture. Although the tolerance of saline conditions by plants is variable, crop species are generally intolerant of one-third of the concentration of salts found in seawater. Attempts to improve the salt tolerance of crops through conventional breeding programmes have met with very limited success, due to the complexity of the trait: salt tolerance is complex genetically and physiologically. Tolerance often shows the characteristics of a multigenic trait, with quantitative trait loci (QTLs) associated with tolerance identified in barley, citrus, rice, and tomato and with ion transport under saline conditions in barley, citrus and rice. Physiologically salt tolerance is also complex, with halophytes and less tolerant plants showing a wide range of adaptations. Attempts to enhance tolerance have involved conventional breeding programmes, the use of in vitro selection, pooling physiological traits, interspecific hybridization, using halophytes as alternative crops, the use of marker-aided selection, and the use of transgenic plants. It is surprising that, in spite of the complexity of salt tolerance, there are commonly claims in the literature that the transfer of a single or a few genes can increase the tolerance of plants to saline conditions. Evaluation of such claims reveals that, of the 68 papers produced between 1993 and early 2003, only 19 report quantitative estimates of plant growth. Of these, four papers contain quantitative data on the response of transformants and wild-type of six species without and with salinity applied in an appropriate manner. About half of all the papers report data on experiments conducted under conditions where there is little or no transpiration: such experiments may provide insights into components of tolerance, but are not grounds for claims of enhanced tolerance at the whole plant level. Whether enhanced tolerance, where properly established, is due to the chance alteration of a factor that is limiting in a complex chain or an effect on signalling remains to be elucidated. After ten years of research using transgenic plants to alter salt tolerance, the value of this approach has yet to be established in the field.

Crops, Agricultural↗
PubMed1998

Gene amplification and transcriptional upregulation of the sarco/endoplasmic reticulum Ca2+ transport ATPase in thapsigargin-resistant hamster smooth muscle cells.

We have selected a series of cell lines from the parental Syrian hamster smooth muscle cell line DDT1-MF2that are resistant to thapsigargin (TG), a specific inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+transport ATPases (SERCAs). Cells were selected for resistance to TG in the presence or absence of cyclosporin (CSA), which is a competitive inhibitor of the multidrug transporter p-glycoprotein (pgp). Since TG is a known substrate for pgp, selection for TG resistance was carried out in the presence of CSA in an attempt to minimize the contribution of pgp, and to identify the potential range of adaptive responses of the SERCA pump itself, during the development of the TG-resistant phenotype. Irrespective of whether the selection is carried out in the presence or absence of CSA, pgp is overexpressed in the TG-resistant DDT1-MF2cells. SERCA protein is also overproduced in the TG-resistant cell lines, which occurs through one of several mechanisms. Included among these, is amplification of the SERCA gene and enhanced transcription of the gene. Enhanced transcription is observed only upon long-term selection and occurs through the SERCA gene proximal promoter elements. Although SERCA transcription in wild-type cells is dependent upon the -284 to -72 bp region of the SERCA promoter, the TG-resistant cells utilize both the -284 to -72 bp and the -72 to +80 bp promoter regions for enhanced SERCA transcription. That is, additional elements within the -72 to +80 bp region are recruited in the TG-resistant cells to allow for increased SERCA expression. A post-transcriptional step may also be recruited by the TG-resistant cells in their overall strategy to produce increased amounts of the SERCA protein. These studies demonstrate that the DDT1-MF2cells can utilize different mechanisms which lead to increased levels of SERCA protein as the cells adapt to inhibition of the ATPase by TG.

Animals↗
PubMed1999

Genetic variation for carbon isotope composition in honey mesquite (Prosopis glandulosa).

Carbon isotope composition (delta(13)C) is a useful surrogate for integrated, plant water-use efficiency (WUE) when measured on plants grown in a common environment. In a variety of species, genetic variation in delta(13)C has been linked to the distribution of genotypes across gradients in atmospheric and soil water. We examined genetic variation for delta(13)C in seedlings of honey mesquite (Prosopis glandulosa Torr.), an invasive grassland shrub that thrives in the southwestern USA. Fifteen maternal families, representing progeny of 15 adult trees, were studied in three common garden experiments in a greenhouse. The 990-km east-west transect along which the adult trees were located encompasses a wide precipitation gradient, and includes mesic grassland, semiarid grassland, and Chihuahuan desert ecosystems. Genetic variation for delta(13)C in mesquite was substantial, with the rank order of half-sib families based on delta(13)C relatively stable across experiments, which were conducted under different environmental conditions. Conversely, rankings of families by mean seedling height (an index of growth rate) varied markedly among experiments. Seedlings derived from Chihuahuan desert adults emerged more quickly and had more negative delta(13)C (indicative of lower WUE) than seedlings derived from the other regions. Although delta(13)C and seedling height were not correlated, these results suggest that mesquite genotypes at the drier, western extreme of the species' range are adapted for quicker emergence and possibly faster growth than genotypes from mesic areas. Together, these traits may facilitate exploitation of infrequent precipitation events.

Journal Article↗
PubMed1994

Sources of stress and psychological well-being in high-dependency nursing.

The present study examined occupational stress in four areas of high-dependency nursing: theatres, liver/renal, haematology/oncology and elective surgery. A total of 60 nurses from one large NHS hospital completed questionnaires on sources and levels of stress, psychological well-being and ways of coping; interviews with a small sub-sample were carried out. The results indicated that the amount of stress experienced was similar across all four departments, but its sources varied. Theatre nurses experienced less stress through patients' death and dying. Other factors which influenced both the level and sources of stress included post-qualification training, number of children and partnership-status. Nurses with post-qualification training perceived higher levels of stress. Social support was found to influence psychological well-being. Nurses who were living with a partner or were married experienced fewer stress symptoms than those with no partner, and nurses with two children experienced significantly less stress through dealing with patients and relatives. Reactions to stress elicited a range of adaptive and maladaptive coping styles. Nurses sampled indicated universal support for the introduction of 'nurse-for-a-day' and management 'swap-overs' as practised in Boston, USA. This study recommends sending nurses on management and administration courses and stress-management programmes.

Activities of Daily Living↗
PubMed2006

Loss of At4 function impacts phosphate distribution between the roots and the shoots during phosphate starvation.

Plants display a range of adaptive responses to phosphate (Pi) starvation including an increase in the proportion of Pi allocated to the roots, which enhances lateral root development and consequently Pi acquisition. The mechanisms by which plants sense Pi and signal Pi reallocation are largely unknown. Previously, we cloned At4, a gene predicted to contain multiple short open-reading frames (ORFs), whose expression is strongly induced by Pi starvation. At4 is a member of a small gene family whose members, AtIPS1 and two additional genes reported here, At4.1 and At4.2, share little conservation among the predicted ORFs but high conservation of a 22-nt sequence located in the 3' half of the transcript. Here, we show that under Pi-starvation conditions, At4 is expressed in the vascular tissue and transcript levels are regulated by both cytokinin and ABA. at4, an At4 loss-of-function mutant fails to redistribute Pi to the roots correctly in response to Pi deprivation and At4 shoots continue to accumulate a greater proportion of Pi relative to wild type. Consistent with this, the primary root growth rate in at4 is faster than wild type in low-Pi conditions. The conserved sequence found in all members of the At4 gene family hybridizes to a small RNA present in Pi-starved roots. These data support a role for At4 in the internal allocation of Pi and suggest that the At4 gene is not only subject to Pi-starvation-inducible expression, but that transcript levels may be adjusted at a post-transcriptional level by the activity of an miRNA.

Abscisic Acid↗
PubMed2006

Patient age is a strong independent predictor of 13C-aminopyrine breath test results: a comparative study with histology, duplex-Doppler and a laboratory index in patients with chronic hepatitis C virus infection.

1. Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath test (ABT) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis. We aimed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis. 2. Eighty-three patients (median age 49 years (28-78 years)) with chronic HCV infection underwent the ABT after an oral load of 75 mg N,N-dimethyl-13C-aminopyrine. Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate aminotransferase to platelet ratio index or APRI) was calculated. Parameters were compared with liver histology. 3. The cumulative 13C-recovery differed significantly between patients without relevant fibrosis (fibrosis score 0-2) and cirrhosis (5-6), beginning after 30 min of sampling (P < 0.05). The ABT did not discriminate patients with fibrosis scores 3-4 from the remaining two patient groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4-82.8% and 63.2-68.4%, depending on the sampling time. Compared with the fibrosis score (P = 0.04), patient age was a highly significant independent predictor for the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and 63.2%vs. 68.4% specificity. 4. Our data suggest an age-dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation. This is also consistent with former pharmacodynamic trials. Age-adapted reference ranges could improve ABT results.

Adult↗
PubMed1995

Differences in the temporal properties of human longwave- and middlewave-sensitive cones.

In recent years a number of electrophysiological and psychophysical observations have suggested that the temporal properties of the human longwave- and middlewave-sensitive cones might be different. However, until now the issue has remained unresolved, despite its obvious importance. We have succeeded in probing, electrophysiologically, the temporal properties of the two classes, under a range of adapting conditions, in a normal human observer. Here we present evidence that the temporal properties of these cone types are indeed different and that this difference is constant irrespective of the state of light adaptation, suggesting that light adaptation has little effect on the kinetics of transduction in human cones.

Adaptation, Physiological↗
PubMed2001

Central angiotensin and baroreceptor control of circulation.

Angiotensin (Ang) receptors are located in many important central nuclei involved in the regulation of the cardiovascular system. While most interest has focused on forebrain circumventricular actions, areas of the brainstem such as the nucleus of the solitary tract and the ventrolateral medulla contain high concentrations of AT1 receptors. The present review encompasses the physiological role of Ang II in the hindbrain, particularly in relation to its influence on baroreflex control mechanisms. In rabbits there are sympatho-excitatory AT1 receptors in the rostral ventrolateral medulla (RVLM), accessible to Ang II from the cerebrospinal fluid. Activation of these receptors acutely increases renal sympathetic nerve activity (RSNA) and RSNA baroreflex responses. However, blockade of endogenous Ang receptors in the brainstem also shows sympathoexcitation, suggesting there is greater endogenous activity of a sympathoinhibitory Ang II action. Microinjections of angiotensin antagonists into the RVLM showed relatively little tonic activity of endogenous Ang II influencing sympathetic activity in conscious rabbits. However, Ang II receptors in the RVLM mediate sympathetic responses to airjet stress in conscious rabbits. Similarly with respect to heart rate baroreflexes, there appears to be little tonic effect of angiotensin in the brainstem in normal conscious animals. Chronic infusion of Ang II for two weeks into the fourth ventricle of conscious rabbits inhibits the cardiac baroreflex while infusion of losartan increases the gain of the reflex. These actions suggest that Ang II in the brainstem modulates sympathetic responses depending on specific afferent and synaptic inputs in both the short term but importantly also in the long term, thus forming an important mechanism for increasing the range of adaptive response patterns.

Angiotensins↗
PubMed2001

Computerized image analysis: estimation of breast density on mammograms.

An automated image analysis tool is being developed for the estimation of mammographic breast density. This tool may be useful for risk estimation or for monitoring breast density change in prevention or intervention programs. In this preliminary study, a data set of 4-view mammograms from 65 patients was used to evaluate our approach. Breast density analysis was performed on the digitized mammograms in three stages. First, the breast region was segmented from the surrounding background by an automated breast boundary-tracking algorithm. Second, an adaptive dynamic range compression technique was applied to the breast image to reduce the range of the gray level distribution in the low frequency background and to enhance the differences in the characteristic features of the gray level histogram for breasts of different densities. Third, rule-based classification was used to classify the breast images into four classes according to the characteristic features of their gray level histogram. For each image, a gray level threshold was automatically determined to segment the dense tissue from the breast region. The area of segmented dense tissue as a percentage of the breast area was then estimated. To evaluate the performance of the algorithm, the computer segmentation results were compared to manual segmentation with interactive thresholding by five radiologists. A "true" percent dense area for each mammogram was obtained by averaging the manually segmented areas of the radiologists. We found that the histograms of 6% (8 CC and 8 MLO views) of the breast regions were misclassified by the computer, resulting in poor segmentation of the dense region. For the images with correct classification, the correlation between the computer-estimated percent dense area and the "truth" was 0.94 and 0.91, respectively, for CC and MLO views, with a mean bias of less than 2%. The mean biases of the five radiologists' visual estimates for the same images ranged from 0.1% to 11%. The results demonstrate the feasibility of estimating mammographic breast density using computer vision techniques and its potential to improve the accuracy and reproducibility of breast density estimation in comparison with the subjective visual assessment by radiologists.

Biophysical Phenomena↗
PubMed1997

Anticipatory breeding for resistance to rust diseases in wheat.

Anticipatory resistance breeding is the process of predicting future pathotypes and producing resistant germplasm to avert future losses. It is made possible by a national pathotype surveillance program and knowledge that new pathotypes arise predominantly from mutation in existing pathotypes. This is supported by genetic analyses to catalogue the identity and distribution of resistance genes in current cultivars. A national germplasm enhancement program ensuring that both currently effective and potentially new sources of resistance are available in a wide range of adapted genotypes enables rapid cultivar replacement before or soon after the occurrence of new pathotypes. The policy of recommending only rust-resistant cultivars in the more rust-prone areas has resulted in significant reductions in pathogen population size and variability. With increased and more rapid international human travel and transport, there is an increased threat of exotic pathotypes, the effects of which are more difficult to predict. As the frequency and magnitude of epidemics decline, public awareness programs will be required to achieve and maintain the use of rust resistance by the entire wheat industry.

Journal Article↗
PubMed2004

Impact of rearing conditions and short-term light exposure on signaling performance in Drosophila photoreceptors.

The amount of visual information an animal can extract from its environment is ultimately limited by the signaling performance of its photoreceptors. To maximize their performance, photoreceptors must be able to accommodate large changes in input caused by the dynamic properties of the visual environment and the animal's own behavior. This is likely to require a range of adaptation mechanisms operating over multiple time scales. Using intracellular recordings, we investigated the effects of developmental light rearing conditions and the effects of 2 h light or dark exposure prior the experiment on the signaling performance of adult Drosophila melanogaster photoreceptors. We show that light-rearing amplifies photoreceptors' voltage responses to light contrast changes by >or =20% and accelerates them by 3 ms. We argue that these differences mostly reflect changes in the timing of the early phototransduction reactions, some of which are persistent. However, being born and nurtured in certain lighting conditions does not set an ultimate limit for the signaling performance of Drosophila photoreceptors. Two-hour light exposure prior to the experiment can improve the information capacity of dark-reared photoreceptors close to the values of light-reared photoreceptors by reducing voltage noise. This effect may originate from plastic changes in the utilization of phototransduction proteins and ion channels.

Animals↗
PubMed2006

Reduced relationship to cortical white matter volume revealed by tractography-based segmentation of the corpus callosum in young children with developmental delay.

OBJECTIVE: The corpus callosum is the primary anatomical substrate for interhemispheric communication, which is important for a range of adaptive and cognitive behaviors in early development. Previous studies that have measured the corpus callosum in developmental populations have been limited by the use of rather arbitrary methods of subdividing the corpus callosum. The purpose of this study was to measure the corpus callosum in a clinical group of developmentally delayed children using a subdivision that more accurately reflected the anatomical properties of the corpus callosum. METHOD: The authors applied tractography to subdivide the corpus callosum into regions corresponding to the cortical regions to and from which its fibers travel in a clinical group of very young children with developmental delay, a precursor to general mental retardation, in comparison with typically developing children. RESULTS: The data demonstrate that the midsagittal area of the entire corpus callosum is reduced in children presenting with developmental delay, reflected in the smaller area of each of the fiber-based callosal subdivisions. In addition, while the area of each subdivision was strongly and significantly correlated with the corresponding cortical white matter volume in comparison subjects, this correlation was prominently absent in the developmentally delayed group. CONCLUSIONS: A fiber-based subdivision successfully separates lobar regions of the corpus callosum, and the areas of these regions distinguish a developmentally delayed clinical group from the comparison group. This distinction was evident both in the area measurements themselves and in their correlation to the white matter volumes of the corresponding cortical lobes.

Atrophy↗
PubMed1988

The computer enhancement of digital grey-scale fluorography images.

In this article we describe the results of a preliminary investigation of computerized processing of digital grey-scale fluorography (DGF) images. Image processing techniques used include dynamic range equalization, adaptive contour enhancement and non-linear transformation of grey-scale data. Original and processed images derived from non-subtractive digital angiography and digital spot-film investigations are used to illustrate our findings. The quality of the processed images confirms the promise of digital image processing in DGF.

Algorithms↗
PubMed2002

Does writing about suicidal thoughts and feelings reduce them?

To assess whether writing with cognitive change or exposure instructions reduces depression or suicidality, 121 undergraduates screened for suicidality wrote for 20 minutes on 4 days over 2 weeks. They were randomly assigned to reinterpret or to write and rewrite traumatic events/emotions, or to write about innocuous topics. The three groups (N = 98) who completed pre-, post-, and 6-week follow-up were not different on suicidality or depression. All subjects reported fewer automatic negative thoughts over the 2 weeks; they also reported higher self-regard but more health center visits at follow-up. Suicidal thoughts may be more resistant than physical health to writing interventions.

Adaptation, Psychological↗
PubMed2003

Does writing reduce posttraumatic stress disorder symptoms?

To see if writing about their trauma lessened PTSD and related symptoms, 57 undergraduates, previously screened for traumatic experiences, wrote for 15 minutes on 4 days across 2 weeks about either their trauma or a trivial topic. They reported PTSD, impact, suicide ideas, dissociation, and depression pre-, post-, and at 6-week follow-up testing. Trauma and trivial writers were not different. Surprisingly, at follow-up everyone reported less severe PTSD symptoms, impact, and dissociation, and fewer health visits, but about the same suicidal ideation and depression. On PTSD symptoms and impact, the pattern of improvement was different: Those writing about trauma got worse at posttesting, but improved to better than their initial state by follow-up. Those writing about a trivial topic got better by posttesting, and held that position at follow-up. In this project, writing seemed to reduce PTSD symptoms regardless of whether it concerned the trauma or what they ate for lunch.

Adaptation, Psychological↗
PubMed2003

High-speed video analysis of the escape responses of the copepod Acartia tonsa to shadows.

The copepod Acartia tonsa exhibits a vigorous escape jump in response to rapid decreases in light intensity, such as those produced by the shadow of an object passing above it. In the laboratory, decreases in light intensity were produced using a fiber optic lamp and an electronic shutter to abruptly either nearly eliminate visible light or reduce light intensity to a constant proportion of its original intensity. The escape responses of A. tonsa to these rapid decreases in visible light were recorded on high-speed video using infrared illumination. The speed, acceleration, and direction of movement of the escape response were quantified from videotape by using automated motion analysis techniques. A. tonsa typically responds to decreases in light intensity with an escape jump comprising an initial reorientation followed by multiple power strokes of the swimming legs. These escape jumps can result in maximum speeds of over 800 mm s(-1) and maximum accelerations of over 200 m s(-2). In A. tonsa, photically stimulated escape responses differ from hydrodynamically stimulated responses mainly in the longer latencies of photically stimulated responses and in the increased number of power strokes, even when the stimulus is near threshold; these factors result in longer escape jumps covering greater distances. The latency of responses of A. tonsa to this photic stimulus ranged from a minimum of about 30 ms to a maximum of more than 150 ms, compared to about 4 ms for hydrodynamically stimulated escape jumps. Average response latency decreased with increasing light intensity or increasing proportion of light eliminated. Little change was observed in the vigor of the escape response to rapid decreases in visible light over a wide range of adaptation intensities.

Animals↗