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At least 1,315 records · Page 73Linked to original sources
PubMed2005

A critical review of congenital phantom limb cases and a developmental theory for the basis of body image.

Reports of phantom limbs amongst aplasics (i.e., subjects who congenitally lack one or several limbs) have often been presented as evidence that body image is 'hard-wired' in the brain and that neither sensory input nor proprioceptive feedback are essential to its formation. Although attempts have been made to account for these phantoms by other means, these have been on a case by case basis and no satisfactory alternative framework has been proposed. This paper collates the accounts of aplasic phantoms and presents them as compatible with a four-part hypothesis, in which body image is learnt from experience during both pre- and post-natal development, and in which cross-cortical connections and mirror neurons play prominent roles. This model unites several previously disparate theories to offer a viable solution to several longstanding phantom limb mysteries and serves to highlight avenues worthy of further inquiry.

Body Image↗
PubMed2005

Signal transduction activator of transcription 5 (STAT5) dysfunction in autoimmune monocytes and macrophages.

Autocrine granulocyte macrophage-colony stimulating factor (GM-CSF) sequentially activates intracellular components in monocyte/macrophage production of the pro-inflammatory and immunoregulatory prostanoid, prostaglandin E2 (PGE2). GM-CSF first induces STAT5 signaling protein phosphorylation, then prostaglandin synthase 2 (COX2/PGS2) gene expression, and finally IL-10 production, to downregulate the cascade. Without activation, monocytes of at-risk, type 1 diabetic (T1D), and autoimmune thyroid disease (AITD) humans, and macrophages of nonobese diabetic (NOD) mice have aberrantly high GM-CSF, PGS2, and PGE2 expression, but normal levels of IL-10. After GM-CSF stimulation, repressor STAT5A and B isoforms (80-77kDa) in autoimmune human and NOD monocytes and activator STAT5A (96-94kDa) and B (94-92kDa) isoforms in NOD macrophages stay persistently tyrosine phosphorylated. This STAT5 phosphorylation persisted despite treatment in vitro with IL-10, anti-GM-CSF antibody, or the JAK2/3 inhibitor, AG490. Phosphorylated STAT5 repressor isoforms in autoimmune monocytes had diminished DNA binding capacity on GAS sequences found in the PGS2 gene enhancer. In contrast, STAT5 activator isoforms in NOD macrophages retained their DNA binding capacity on these sites much longer than in healthy control strain macrophages. These findings suggest that STAT5 dysfunction may contribute to dysregulation of GM-CSF signaling and gene activation, including PGS2, in autoimmune monocytes and macrophages.

Adolescent↗
PubMed2005

Over expression of a tRNA(Leu) isoacceptor changes charging pattern of leucine tRNAs and reveals new codon reading.

During mRNA translation, synonymous codons for one amino acid are often read by different isoaccepting tRNAs. The theory of selective tRNA charging predicts greatly varying percentages of aminoacylation among isoacceptors in cells starved for their common amino acid. It also predicts major changes in tRNA charging patterns upon concentration changes of single isoacceptors, which suggests a novel type of translational control of gene expression. We therefore tested the theory by measuring with Northern blots the charging of Leu-tRNAs in Escherichia coli under Leu limitation in response to over expression of tRNA(GAG)(Leu). As predicted, the charged level of tRNA(GAG)(Leu) increased and the charged levels of four other Leu isoacceptors decreased or remained unchanged, but the charged level of tRNA(UAG)(Leu) increased unexpectedly. To remove this apparent inconsistency between theory and experiment we postulated a previously unknown common codon for tRNA(GAG)(Leu) and tRNA(UAG)(Leu). Subsequently, we demonstrated that the tRNA(GAG)(Leu) codon CUU is, in fact, read also by tRNA(UAG)(Leu), due to a uridine-5-oxyacetic acid modification.

Anticodon↗
PubMed1999

Efficacy and safety of simvastatin for high-risk hypercholesterolemia.

Ten years' experience of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk patients is reported. All patients started with 20 mg simvastatin/day. The simvastatin dose was increased to 40 mg in 22 patients. Fourteen patients needed further addition of cholestyramine. Simvastatin reduced plasma cholesterol by 33% after 1 month and was further reduced after adjustment of the lipid-lowering treatment. The mean reduction in plasma cholesterol varied between 30% and 35% in 2 to 10 years. Low-density lipoprotein cholesterol demonstrated mean reductions of 34% to 42%. Mean plasma triglycerides were reduced by 26% after 1 month and by 1% to 19% the following years. High-density lipoprotein (HDL) cholesterol increased initially by 8% and remained elevated at 7% to 11% during the first 6 years, but then dropped slightly below baseline. HDL2 cholesterol increased by 9% to 25% the first 6 years and then decreased. HDL3 cholesterol showed a persistent elevation during simvastatin treatment. About half of the subjects had minor transient but clinical insignificant increases in creatine kinase. No cases of myopathy were seen. Mean serum aspartate aminotransferase and alanine aminotransferase increased significantly but within the normal ranges during the 10 years. The tolerability and compliance of simvastatin treatment was excellent as judged from patients' reports and from analyses of low-density lipoprotein cholesterol. This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long-term treatment of hypercholesterolemic patients at risk.

Alanine Transaminase↗
PubMed2003

Near-critical phenomena in intracellular metabolite pools.

The supply and consumption of metabolites in living cells are catalyzed by enzymes. Here we consider two of the simplest schemes where one substrate is eliminated through Michaelis-Menten kinetics, and where two types of substrates are joined together by an enzyme. It is demonstrated how steady-state substrate concentrations can change ultrasensitively in response to changes in their supply rates and how this is coupled to slow relaxation back to steady state after a perturbation. In the one-substrate system, such near-critical behavior occurs when the supply rate approaches the maximal elimination rate, and in the two-substrate system it occurs when the rates of substrate supply are almost balanced. As systems that operate near criticality tend to display large random fluctuations, we also carried out a stochastic analysis using analytical approximations of master equations and compared the results with molecular-level Monte Carlo simulations. It was found that the significance of random fluctuations was directly coupled to the steady-state sensitivity and that the two substrates can fluctuate greatly because they are anticorrelated in such a way that the product formation rate displays only small variation. Basic relations are highlighted and biological implications are discussed.

Biochemical Phenomena↗
PubMed2002

Yolk hormone levels in the eggs of snapping turtles and painted turtles.

Although yolk steroids appear to play important roles in the development, growth, and behavior of some birds, their effects in oviparous reptiles are largely unknown. These investigations were initiated to determine initial levels of steroid hormones in the yolks of eggs from two turtle species. Clutches of snapping turtle (Chelydra serpentina) and of painted turtle (Chrysemys picta) eggs were collected and individual egg yolks were analyzed for estradiol-17beta (E(2)) and testosterone (T) using specific RIAs. E(2) and T levels differed significantly between species, the mean E(2) value in snapping turtles was 2.78+/-0.095 (ng/g) compared to 0.89+/-0.064 (ng/g) for painted turtles, and the mean value for T in snapping turtle yolks was 2.56+/-0.098 (ng/g) compared to 0.68+/-0.045 (ng/g) for painted turtles. In addition, E(2) levels were greater than T levels in both species. Within each species, there were significant differences among clutches from different females. E(2) levels in the snapping turtle yolks varied from a clutch mean of 1.38 to 4.55 ng/g and in painted turtles, the clutch means for E(2) varied from 0.34 to 1.34 ng/g. T levels demonstrated similar phenomena within species, with levels in snapping turtles varying from a clutch mean of 0.68 to 4.71 ng/g. Painted turtle levels of T varied from a clutch mean of 0.22 to 0.72 ng/g. There were also significant differences in the E(2)/T ratio, however, E(2)/T ratios did not differ between species. Painted turtle follicles of different sizes showed significant differences in levels of both E(2) and T, and these differences may reflect differing deposition patterns of these steroids in the egg yolk of this turtle during vitellogenesis. The differences in E(2) and T concentration reported here could have important implications for development, growth, and behavior in oviparous reptilian species.

Animals↗
PubMed2002

Dynamics of yolk steroid hormones during development in a reptile with temperature-dependent sex determination.

Many oviparous reptiles exhibit temperature-dependent sex determination (TSD); i.e., the temperature at which the egg is incubated determines the sex of the offspring. In TSD reptiles, yolk steroids not only may influence sex determination, but also may mediate hormonal effects on subsequent growth and behavior, as in some avian species. We investigated changes in the levels of estradiol (E(2)) and testosterone (T) during development in yolks of snapping turtle eggs, examined how incubation temperature affects hormone levels, and determined how hormones in turtle eggs are influenced by individual females (=clutch effects). Results indicate significant decreases in both hormones (>50% decline) by the end of the sex-determining period, when two-thirds of the development is complete. The declines in both E(2) and T were significantly affected by incubation temperature, but in different ways. Eggs incubated at female-producing temperatures maintained high levels, those incubated at male-producing temperatures had low E(2) values, and eggs incubated at pivotal temperatures had intermediate levels of E(2). At all three temperatures, T values underwent significant but approximately equal declines, except during the developmental stages just after the sex-determining period, when T levels decreased more at the male-producing temperature than at either of the other two temperatures. Initially, there were significant clutch effects in both hormones, but such differences, attributable to individual females, were maintained only for E(2) later in development. Here we report for the first time that incubation temperature significantly affects the hormonal environment of the developing embryo of a turtle with temperature-dependent sex determination. Based on this and related findings, we propose that yolk sex steroids influence sexual differentiation in these TSD species and play a role in sex determination at pivotal temperatures.

Animals↗
PubMed2003

Yolk steroid hormones and sex determination in reptiles with TSD.

In reptiles with temperature-dependent sex determination (TSD), the temperature at which the eggs are incubated determines the sex of the offspring. The molecular switch responsible for determining sex in these species has not yet been elucidated. We have examined the dynamics of yolk steroid hormones during embryonic development in the snapping turtle, Chelydra serpentina, and the alligator, Alligator mississippiensis, and have found that yolk estradiol (E(2)) responds differentially to incubation temperature in both of these reptiles. Based upon recently reported roles for E(2) in modulation of steroidogenic factor 1, a transcription factor known to be significant in the sex differentiation process, we hypothesize that yolk E(2) is a link between temperature and the gene expression pathway responsible for sex determination and differentiation in at least some of these species. Here we review the evidence that supports our hypothesis.

Animals↗
PubMed2003

The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site.

The Escherichia coli relBE operon encodes a toxin-antitoxin pair, RelE-RelB. RelB can reverse inhibition of protein synthesis by RelE in vivo. We have found that although RelE does not degrade free RNA, it cleaves mRNA in the ribosomal A site with high codon specificity. Among stop codons UAG is cleaved with fast, UAA intermediate and UGA slow rate, while UCG and CAG are cleaved most rapidly among sense codons. We suggest that inhibition of protein synthesis by RelE is reversed with the help of tmRNA, and that RelE plays a regulatory role in bacteria during adaptation to poor growth conditions.

Bacterial Toxins↗
PubMed2001

Microbiological quality and shelf-life of vacuum-packaged 'gravad' rainbow trout stored at 3 and 8 degrees C.

Microbiological and sensory changes of vacuum-packaged 'gravad' rainbow trout slices were studied during storage at 3 and 8 degrees C. At the time of spoilage, after 27 and 20 days of storage at 3 and 8 degrees C, respectively, both mesophilic viable counts (MVC) and psychrotrophic viable counts (PVC) reached 10(6)-10(7) cfu/g at 3 degrees C and 10(7)-10(5) cfu/g at 8 degrees C. H2S-producing bacteria constituted a high proportion of the PVCs and lactic acid bacteria (LAB) counts were lower than the other determined bacterial counts. Sensory scores decreased with increasing MVC and PVC. The judges considered samples unfit for human consumption at MVC and PVC levels exceeding 10(6) and 10(7) cfu/g for samples stored at 3 and 8 degrees C, respectively. At respective levels of 10(7) and 10(8) cfu/g, most of the samples were deemed unfit. The main reasons for sensory rejection at both storage temperatures were the lack of the typical product odour or an ammonia off-odour and colour change to dark violet. The shelf-lives of the rainbow trout slices based on microbiological and sensory analyses were 20 days and 18 days at 3 and 8 degrees C, respectively.

Animals↗
PubMed2005

Ribosome bypassing at serine codons as a test of the model of selective transfer RNA charging.

Recently, a model of the flux of amino acids through transfer RNAs (tRNAs) and into protein has been developed. The model predicts that the charging level of different isoacceptors carrying the same amino acid respond very differently to variation in supply of the amino acid or of the rate of charging. It has also been shown that ribosome bypassing is specifically stimulated at 'hungry' codons calling for an aminoacyl-tRNA in short supply. We have constructed two reporters of bypassing, which differ only in the identity of the serine codon subjected to starvation. The stimulation of bypassing as a function of starvation differed greatly between the two serine codons, in good agreement with the quantitative predictions of the model.

Codon↗
PubMed2005

Selective charging of tRNA isoacceptors induced by amino-acid starvation.

Aminoacylated (charged) transfer RNA isoacceptors read different messenger RNA codons for the same amino acid. The concentration of an isoacceptor and its charged fraction are principal determinants of the translation rate of its codons. A recent theoretical model predicts that amino-acid starvation results in 'selective charging' where the charging levels of some tRNA isoacceptors will be low and those of others will remain high. Here, we developed a microarray for the analysis of charged fractions of tRNAs and measured charging for all Escherichia coli tRNAs before and during leucine, threonine or arginine starvation. Before starvation, most tRNAs were fully charged. During starvation, the isoacceptors in the leucine, threonine or arginine families showed selective charging when cells were starved for their cognate amino acid, directly confirming the theoretical prediction. Codons read by isoacceptors that retain high charging can be used for efficient translation of genes that are essential during amino-acid starvation. Selective charging can explain anomalous patterns of codon usage in the genes for different families of proteins.

Amino Acids↗
PubMed2004

Spontaneous separation of bi-stable biochemical systems into spatial domains of opposite phases.

Bi-stable chemical systems are the basic building blocks for intracellular memory and cell fate decision circuits. These circuits are built from molecules, which are present at low copy numbers and are slowly diffusing in complex intracellular geometries. The stochastic reaction-diffusion kinetics of a double-negative feedback system and a MAPK phosphorylation-dephosphorylation system is analysed with Monte-Carlo simulations of the reaction-diffusion master equation. The results show the geometry of intracellular reaction compartments to be important both for the duration and the locality of biochemical memory. Rules for when the systems lose global hysteresis by spontaneous separation into spatial domains in opposite phases are formulated in terms of geometrical constraints, diffusion rates and attractor escape times. The analysis is facilitated by a new efficient algorithm for exact sampling of the Markov process corresponding to the reaction-diffusion master equation.

Adaptation, Physiological↗
PubMed2005

Stochastic reaction-diffusion simulation with MesoRD.

UNLABELLED: MesoRD is a tool for stochastic simulation of chemical reactions and diffusion. In particular, it is an implementation of the next subvolume method, which is an exact method to simulate the Markov process corresponding to the reaction-diffusion master equation. AVAILABILITY: MesoRD is free software, written in C++ and licensed under the GNU general public license (GPL). MesoRD runs on Linux, Mac OS X, NetBSD, Solaris and Windows XP. It can be downloaded from http://mesord.sourceforge.net. CONTACT: johan.elf@icm.uu.se; johan.hattne@embl-hamburg.de SUPPLEMENTARY INFORMATION: 'MesoRD User's Guide' and other documents are available at http://mesord.sourceforge.net.

Algorithms↗
PubMed2001

Satisfaction with information and quality of life in patients undergoing chemotherapy for cancer. The role of individual differences in information preference.

Earlier studies have shown that patients are dissatisfied with the information they receive from doctors and nurses. The purpose of this study was to analyze satisfaction with information and quality of life in patients with cancer undergoing chemotherapy, considering the patient's information preference. Data were collected during interviews with 30 consecutive patients undergoing chemotherapy for cancer. The subject of the interviews was the satisfaction of patients with the information they received, and additional measures used were the Miller Behavioral Styles Scale and EORTC-QLQ-30. The results showed that 21 of 30 patients were satisfied with the information they received from health care. Married patients or cohabitants were satisfied more often than single patients. No significant differences in quality of life could be found between satisfied and dissatisfied patients. Regarding information preferences, the dissatisfied patients reported more information-avoiding behavior than those who were satisfied. The results must be interpreted cautiously because of the study's limitations, but one clinical implication can be stated: There is value in being aware of patients' information-seeking/avoiding behavior before starting to inform them.

Aged↗
PubMed2002

Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care.

OBJECTIVE: To evaluate today's refined neurosurgical intensive care of patients with traumatic brain injury after implementation of an organized secondary insult program focused on the importance of avoiding secondary brain damage together with a standardized treatment protocol system. DESIGN: Clinical observational patient study. PATIENTS: A total of 154 patients 16-79 yrs of age with acute head trauma and pathologic computed tomographic findings treated between 1996 and 1997. SETTING: Neurointensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Good recovery was obtained in 44% of the patients, moderate disability in 35%, severe disability in 16%, and no patient remained in a vegetative state. Six percent of the patients died, but only two of these patients (1.3%) died as direct result of their head injury. When the results for patients with Glasgow Coma Scale motor scores of >or=4 were compared with the periods 1980-1981 (preneurosurgical intensive care) and 1987-1988 (basic neurosurgical intensive care), mortality had decreased from 40% in the first period to 27% in the second period and to 2.8% in the present series. Favorable outcome in the same group of patients had increased steadily from 40% in the first period, to 68% in the second period, and finally, to 84% in the present series. CONCLUSIONS: The main observation in this hospital series of traumatic brain injury patients was a low rate of death directly caused by head injury and a high rate of favorable outcome. The comparison of patients with Glasgow Coma Scale motor scores of >or=4 with the previously reported results from the same unit indicate that substantial improvement in outcome has been achieved.

Adolescent↗
PubMed1998

Comparative analysis of Pseudomonas aeruginosa penicillin-binding protein 7 in the context of its membership in the family of low-molecular-mass PBPs.

The Pseudomonas aeruginosa pbpG gene encoding penicillin-binding protein 7, a homologue of the Escherichia coli gene encoding a DD-endopeptidase, was cloned and sequenced, pbpG was located immediately downstream of the phenylalanine hydroxylase (phh) operon. DNA sequencing revealed an open reading frame of 936 bp (starting with a GTG codon) which encodes a protein of 34,115 Da. N-terminal amino acid sequencing confirmed the presence of a cleavable N-terminal signal peptide of 23 amino acids. Verification that the protein is a penicillin-binding protein was directly demonstrated by labelling with 125I-labelled penicillin X. Inactivation of P. aeruginosa pbpG by interposon mutagenesis resulted in no obvious phenotypic changes, but when P. aeruginosa PbpG was overexpressed in E. coli using a T7 expression system, cell lysis resulted. P. aeruginosa PbpG resembled E. coli PbpG in being associated with the membrane fraction. Two additional members of the PbpG subfamily were identified in the database. P. aeruginosa PbpG shows 63% identity with E. coli penicillin-binding protein 7 (PbpG) and 60% identity with Vibrio cholerae PbpG, but only 23% identity with Haemophilus influenzae PbpG. The PbpG subfamily and three other subfamilies constituting the low-molecular-mass PBP protein family were analysed by multiple alignment of 26 sequences. PbpG exhibited the consensus motifs of other penicillin-binding proteins. Ten anchor residues were identified that are conserved at the family level within the superfamily of serine-active-site penicillin-interacting proteins.

Amino Acid Sequence↗
PubMed2003

Fast evaluation of fluctuations in biochemical networks with the linear noise approximation.

Biochemical networks in single cells can display large fluctuations in molecule numbers, making mesoscopic approaches necessary for correct system descriptions. We present a general method that allows rapid characterization of the stochastic properties of intracellular networks. The starting point is a macroscopic description that identifies the system's elementary reactions in terms of rate laws and stoichiometries. From this formulation follows directly the stationary solution of the linear noise approximation (LNA) of the Master equation for all the components in the network. The method complements bifurcation studies of the system's parameter dependence by providing estimates of sizes, correlations, and time scales of stochastic fluctuations. We describe how the LNA can give precise system descriptions also near macroscopic instabilities by suitable variable changes and elimination of fast variables.

Artifacts↗