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Temporal characteristics of capsaicin sensitization and desensitization on the tongue.

Previous work has demonstrated that repeated applications of capsaicin can sensitize the tongue to subsequent exposures to capsaicin. However, if stimulation is interrupted for a period of minutes, the contrasting phenomenon of desensitization occurs. The purpose of the present study was to investigate the effect of interstimulus interval (ISI) on the development of both sensitization and desensitization to sequential capsaicin stimuli. It was determined in the first experiment that the rate of sensitization varied inversely with ISI for intervals briefer than 3.5 min; when ISI was lengthened to 5.5 min, sensitization was replaced by a trend toward desensitization. A second experiment established that increasing ISI from 9.5 min to 14.5 min tended to reduce rather than to enhance desensitization. It was therefore concluded that the sensitization process can be optimized by decreasing the time between successive stimuli (ISIs less than 3.5 min), whereas the trend toward desensitization appears to be optimal when stimuli are separated by at least 5.5 min but by less than 14.5 min.

Adult↗

Rats with dorsal hippocampal lesions do react to new stimuli but not to spatial changes of known stimuli.

The effect of visual distracting stimuli upon the straight alleyway performance of dorsal hippocampectomized Wistar rats was investigated. In comparison with control animals it was observed that dorsal hippocampectomized animals (1) ambulated more during the preexposure phase, (2) acquired at the same rate a running response for food (training phase), (3) reacted similarly to a new visual stimulus (black cards) presented in a sector of the alleyway, and (4) habituated to successive presentations of that stimulus in the same place. (5) However, dorsal hippocampectomized rats did not react, unlike the controls, to the presentation of the same stimulus in another place of the alleyway but (6) reacted to the visual pattern change of the stimulus (now black/white check cards) in the same place. These results indicate that under certain experimental conditions, hippocampus-lesioned animals are capable of interrupting a running response for food in order to explore a new conspicuously located stimulus, habituate to repeated presentations of that stimulus, and to react to a new pattern of visual stimulation. They suggest that hippocampectomized rats do not lose the capacity to react to a new stimulus; the disruption seems to be related to the spatial context of stimulus presentation, supporting a spatial mapping hypothesis of hippocampal function.

Animals↗

The measurement of airways resistance using the interrupter technique (Rint).

The interrupter technique (Rint) is a quick, easy and effort-independent way to obtain indirect measurements of airways resistance in the preschool child. Results may be obtained using a portable Rint machine or a whole-body plethysmograph. Normative data are available and recent studies have improved standardisation of the methodology. Despite this, between-occasion results can be variable, particularly in children with wheeze. This limits the usefulness of the test in the assessment of long-term interventions such as the administration of inhaled steroids. The most useful role for Rint, therefore, appears to be in the assessment of bronchodilator responsiveness where it is as sensitive as spirometry in separating children with reversible airways disease from healthy controls. This paper describes the physiology of the interrupter technique and the methodology needed to obtain reliable results. Normal ranges are provided. The clinical applicability, repeatability, strengths and limitations of the technique are also discussed.

Age Factors↗

Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage.

Soluble extracts of human cells repair gamma-ray-induced single-strand breaks in DNA. Accompanying NAD-dependent automodification of poly(ADP-ribose) polymerase is required for effective DNA rejoining. The kinetics of poly(ADP-ribose) synthesis by this polymerase, and subsequent polymer degradation by poly(ADP-ribose) glycohydrolase, have been compared with the rate of DNA repair. The results agree with previous in vivo data. In response to addition of gamma-irradiated plasmid DNA, rapid and heavy automodification of poly(ADP-ribose) polymerase occurred in NAD-containing human cell extracts. After 2 min at 30 degrees C, when very little DNA rejoining had yet occurred, synthesis of long polymers essentially ceased, although only a minor fraction of the NAD had been consumed. Poly(ADP-ribose) chains were then reduced to oligomer size by poly(ADP-ribose) glycohydrolase. These short chains were present for longer times and were sufficient to permit DNA repair. Thus, most but not all poly(ADP-ribose) synthesis could be suppressed without marked inhibition of DNA repair, and prolonged occurrence of long poly(ADP-ribose) chains in consequence to glycohydrolase inhibition did not improve DNA repair. The temporary presence of short poly(ADP-ribose) chains on poly(ADP-ribose) polymerase avoids inhibition of excision-repair by that protein, but the initial very transient formation of long and branched chains of poly(ADP-ribose) in response to DNA damage apparently serves an entirely different purpose. Local poly(ADP-ribose) synthesis in the vicinity of a DNA strand interruption causes negative charge repulsion, and this may function to prevent accidental homologous recombination events within tandem repeat DNA sequences.

Cell Line↗

Structure of the pro alpha 2 (I) collagen gene.

Fifty-four kilobase pairs (kbp) of cloned chicken DNA containing the entire 38-kbp pro alpha 2 (I) collagen gene have been isolated and characterized. DNA sequence analysis of a select 4 kbp of the gene has precisely described 14 exons which comprise one-third of the sequences encoding the triple-helical domain of the collagen protein. These exons range in size from 45 to 108 base pairs (bp), are all multiples of the 9 bp that code for the repeating triplet, Gly-X-Y, and have an average size of 70 bp. About 50 introns interrupt this gene. Nevertheless, introns do not separate the coding sequences for the ends of the central triple-helical structural domain and the ends of the propeptide domains.

Amino Acid Sequence↗

The centromere1 (CEN1) region of Arabidopsis thaliana: architecture and functional impact of chromatin.

We have analysed the centromere 1 (CEN1) of Arabidopsis thaliana by integration of genetic, sequence and fluorescence in situ hybridisation (FISH) data. CEN1 is considered to include the centromeric core and the flanking left and right pericentromeric regions, which are distinct parts by structural and/or functional properties. CEN1 pericentromeres are composed of different dispersed repetitive elements, sometimes interrupted by functional genes. In contrast the CEN1 core is more uniformly structured harbouring only two different repeats. The presented analysis reveals aspects concerning distribution and effects of the uniformly shaped heterochromatin, which covers all CEN1 regions. A lethal mutation tightly linked to CEN1 enabled us to measure recombination frequencies within the heterochromatin in detail. In the left pericentromere, the change from eu- to heterochromatin is accompanied by a gradual change in sequence composition but by an extreme change in recombination frequency (from normal to 53-fold decrease) which takes place within a small region spanning 15 kb. Generally, heterochromatin is known to suppress recombination. However, the same analysis reveals that left and right pericentromere, though similar in sequence composition, differ markedly in suppression (53-fold versus 10-fold). The centromeric core exhibits at least 200-fold if not complete suppression. We discuss whether differences in (fine) composition reflect quantitative and qualitative differences in binding sites for heterochromatin proteins and in turn render different functional properties. Based on the presented data we estimate the sizes of Arabidopsis centromeres. These are typical for regional centromeres of higher eukaryotes and range from 4.4 Mb (CEN1) to 3.55 Mb (CEN4).

Arabidopsis↗

Inference-driven attention in symbolic and perceptual tasks: biases toward expected and unexpected inputs.

The aims of this paper are (a) to gather support for the hypothesis that some basic mechanisms of attentional deployment (i.e., its high efficiency in dealing with expected and unexpected inputs) meet the requirements of the inferential system and have possibly evolved to support its functioning, and (b) to show that these orienting mechanisms function in very similar ways in two perceptual tasks and in a symbolic task. The general hypothesis and its predictions are sketched in the Introduction, after a discussion of current findings concerning visual attention and the generalities of the inferential system. In the empirical section, three experiments are presented where participants tracked visual trajectories (Experiments 1 and 3) or arithmetic series (Experiments 2 and 3), responding to the onset of a target event (e.g., to a specific number) and to the repetition of an event (e.g., to a number appearing twice consecutively). Target events could be anticipated when they were embedded in regular series/trajectories; they could be anticipated, with the anticipation later disconfirmed, when a regular series/trajectory was abruptly interrupted before the target event occurred; and they could not be anticipated when the series/trajectory was random. Repeated events could not be anticipated. Results show a very similar pattern of allocation in tracking visual trajectories and arithmetic series: Attention is focused on anticipated events; it is defocused and redistributed when an anticipation is not confirmed by ensuing events; however, performance decreases when dealing with random series/trajectory--that is, in the absence of anticipations. In our view, this is due to the fact that confirmed and disconfirmed anticipations are crucial events for "knowledge revision"--that is, the fine tuning of the inferential system to the environment; attentional mechanisms have developed so as to enhance detection of these events, possibly at all levels of inferential processing.

Adult↗

Tetanus-induced changes in apparent recovery after bolus doses of atracurium or vecuronium.

The current study evaluated the duration and magnitude of post-tetanic effects in 56 patients recovering from a bolus dose of nondepolarizing relaxant to assess the impact of tetanus on monitoring in a common clinical setting. After induction of general anesthesia (thiopental, fentanyl, oxygen, nitrous oxide, and isoflurane), a baseline response to train-of-four (TOF) stimulation was recorded using an adductor pollicis force transducer, and the ratio of the fourth response (T4) to the first (T1) was calculated. Patients then received a bolus dose of either atracurium 0.50 mg.kg-1 (n = 28) or vecuronium 0.10 mg.kg-1 (n = 28). TOF was recorded at 12-s intervals between 25% and 75% recovery of T1 (time25-75%, first data set); then, block was reestablished with the same agent (atracurium 0.10 or vecuronium 0.02 mg.kg-1), and monitoring of time25-75% was repeated (second data set). Subjects were randomized such that none, one, or both sets had TOF monitoring interrupted by a 5-s, 50-Hz tetanic stimulus at 50% recovery (TET). For each drug, 7 patients were assigned to each of the four possible sequences: no tetanus (NOTET) set followed by NOTET set; NOTET-TET; TET-NOTET; and TET-TET. After either drug, the TET data sets demonstrated significant acceleration of recovery of T1 from 50% to 75% (time50-75%) of its baseline height (P less than 0.05 by paired t test). After atracurium, time50-75% was shortened by the tetanic stimulation from a control of 6.3 +/- 1.1 to 5.0 +/- 1.3 min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

restless, an active Ac-like transposon from the fungus Tolypocladium inflatum: structure, expression, and alternative RNA splicing.

Elements of the hAT transposon family, such as the maize activator (Ac), have been discovered in a large number of eukaryotic species. This type of class II transposon, present in both plants and animals, has not been previously detected in any fungal organism. However, using a differential screening method to detect repetitive DNA, we have identified a hAT transposon in the hyphomycete Tolypocladium inflatum. The transposon, which we named restless, is 4,097 bp long, carries 20-bp inverted repeats and an 8-bp target site duplication, and encodes a long open reading frame which is interrupted by a single intronic sequence. The derived mRNA exhibits alternative splicing, resulting in the formation of two transcripts that may be translated into polypeptides of 157 or 803 amino acids. The predicted amino acid sequence of the larger polypeptide demonstrates significant homology with transposases from the hAT transposon family. A chromosomal analysis using pulsed-field gel electrophoresis showed that all seven chromosomal bands carry copies of the 4.1-kb transposon. This was confirmed in hybridization experiments with rare-cutting restriction endonucleases which indicate that about 15 copies are present in T. inflatum. The genomic distribution of restless and its transcriptional expression, alternative mRNA splicing, and genomic mobility all imply a potential role for this element in developing a transposon tagging system for use in filamentous fungi.

Alternative Splicing↗

Orthodromic capture of the atrial electrogram during transient entrainment of atrioventricular nodal reentrant tachycardia.

BACKGROUND: The reentry circuit of atrioventricular nodal reentrant tachycardia (AVNRT) has not been fully demonstrated. We hypothesized that if an upper common pathway was present, the atrial electrogram could not be captured orthodromically during transient entrainment of AVNRT by rapid atrial pacing. Based on this hypothesis, the presence of an upper common pathway was investigated. METHODS AND RESULTS: The atrial electrogram at the recording site of the His bundle potential was identified during induced AVNRT in 9 patients. To entrain AVNRT transiently, rapid pacing from the high right atrium and coronary sinus was applied at a cycle length 10 milliseconds shorter than that of AVNRT and repeated after a decrement of the paced cycle length in steps of 5 milliseconds until AVNRT was interrupted. In 5 of 7 patients, orthodromic capture of the atrial electrogram at the recording site of the His bundle potential was observed during transient entrainment of AVNRT by coronary sinus pacing, ie, the first postpacing interval of the atrial electrogram at the recording site of the His bundle potential was the same as the paced cycle length. In these 5 patients, the mean minimum paced cycle length capable of orthodromic atrial capture was 349 milliseconds, and the mean difference from the cycle length of AVNRT was only 16 milliseconds. During transient entrainment of AVNRT by high right atrial pacing, the atrial electrogram could not be captured orthodromically. CONCLUSIONS: Observation of orthodromic capture of the atrial electrogram at the recording site of the His bundle potential by coronary sinus pacing ruled out the presence of an upper common pathway in AVNRT, and the concept that perinodal atrial tissue is involved in the reentry circuit of AVNRT was supported.

Atrial Function↗

A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery.

OBJECTIVE: To assess clinical efficacy of IV paracetamol 1 g and IV metamizol 1 IV metamizol 1 g on a 24-h dosing schedule in this randomized, double-blinded, placebo-controlled study of 38 ASA physical status I-III patients undergoing retinal surgery. RESEARCH DESIGN AND METHODS: General anaesthesia using remifentanil, propofol, and desflurane was performed for surgery. The patients were randomly allocated to three groups, receiving infusions of paracetamol 1 g/100 mL (Para Group), of metamizol 1 g/100 mL (Meta Group), or of 100 mL of saline solution as placebo control (Plac Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to intravenous opioid rescue medication. MAIN OUTCOME MEASURES: The primary efficacy variables were pain scores at rest over 30 h postoperatively analysed by using repeated ANOVA measurement. Secondary efficacy variables were pain scores on coughing, also analysed by repeated ANOVA measurement. RESULTS: Five patients in the Plac Group and one patient in the Meta Group interrupted the study protocol. Regarding pain scores at rest, Mauchly-test of sphericity was significant (p = 0.03). For the p time effects a significant result was detected (p < 0.001). The main effect between the three treatment groups was significantly different (p = 0.01). The Bonferroni adjusted pair wise comparisons between p the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.024; mean difference 14.8; p 95% CI 1.6-28.0), between the Plac Group and the Meta Group in favour of IV metamizol (p = 0.025; mean difference 14.4; 95% CI p 1.5-27.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; mean difference 0.4; 95% CI-12.8 to 13.6). Pain scores on coughing showed a significant different main effect between the three treatment groups (p = 0.022). The Bonferroni adjusted pair wise comparisons between the Plac Group and the Para Group showed a significant difference in favour of IV paracetamol (p = 0.032; mean difference 17.9; 95% CI 1.3-34.6), a p difference, though not reaching statistical significance, in favour of IV metamizol between the Plac Group and the Meta Group (p = 0.081; p mean difference 15.0; 95% CI -1.4 to 31.4), and no significant difference between the Para Group and the Meta Group (p = 1.0; p mean difference 2.9; 95% CI -13.8 6 to 19.6). None of the patients experienced itching; one patient in the Meta Group developed a mild erythema. There was no statistical difference in the incidence of nausea (Plac vs. Para Group: p = 0.94, Plac vs. Meta Group: p = 0.98, Para vs Meta Group: p = 0.95) or vomiting (Plac vs. Para Group: p = 0.73, Plac vs. Meta Group: p = 0.85, Para vs Meta Group: p = 0.86) between the groups. Patients in the Plac Group experienced significantly more often sedation than patients in the Meta Group (p = 0.049). There was a trend of higher sedation in the Plac Group than in the Para Group, which did not reach statistical significance (p = 0.07). There was no difference in sedation between the Meta and the Para Groups (p = 0.84). CONCLUSION: IV paracetamol 1 g has a similar analgesic potency as IV metamizol 1 g for postoperative analgesia after retinal surgery.

Acetaminophen↗

Single-channel properties of synaptic and extrasynaptic GABAA receptors suggest differential targeting of receptor subtypes.

Many neurons express a multiplicity of GABAA receptor subunit isoforms. Despite having only a single source of inhibitory input, the cerebellar granule cell displays, at various stages of development, more than 10 different GABAA subunit types. This subunit diversity would be expected to result in significant receptor heterogeneity, yet the functional consequences of such heterogeneity remain poorly understood. Here we have used single-channel properties to characterize GABAA receptor types in the synaptic and extrasynaptic membrane of granule cells. In the presence of high concentrations of GABA, which induced receptor desensitization, extrasynaptic receptors in outside-out patches from the soma entered long-lived closed states interrupted by infrequent clusters of openings. Each cluster of openings, which is assumed to result from the repeated activation of a single channel, was to one of three main conductance states (28, 17, or 12 pS), the relative frequency of which differed between patches. Such behavior indicates the presence of at least three different receptor types. This heterogeneity was not replicated by individual recombinant receptors (alpha1beta2gamma2S or alpha1beta3gamma2S), which gave rise to clusters of a single type only. By contrast, the conductance of synaptic receptors, determined by fluctuation analysis of the synaptic current or direct resolution of channel events, was remarkably uniform and similar to the highest conductance value seen in extrasynaptic patches. These results suggest that granule cells express multiple GABAA receptor types, but only those with a high conductance, most likely containing a gamma subunit, are activated at the synapse.

Animals↗

Measurement of proteins with the Behring Nephelometer. A multicentre evaluation.

The selective multi-protein analyser Behring Nephelometer was examined according to the ECCLS guidelines in a multicentre evaluation involving five laboratories. IgG, IgA, IgM, C-reactive protein, C3c, C4, apolipoprotein A-I and B were measured in serum, and albumin and IgG were measured in cerebrospinal fluid. All values obtained were included in the evaluation without correcting for outliers. The trial, which lasted three months and involved over 20,000 analyses, basically yielded the following results: 1. The precision was generally better than that of comparative procedures. For the majority of methods, the between-day coefficients of variation were below 4.5%. The highest coefficient of variation was 7.2% (for C-reactive protein) and the lowest 1.35% (for C3c). 2. The fraction of assigned values of control materials varied between 0.95 and 1.08. 3. Good agreement was found with results from the comparison procedures: Beckman ICS, Behring Laser Nephelometer, Hyland Laser Nephelometer. 4. No carry-over effects were observed. 5. No interferences were observed for IgG, IgA and IgM determinations using hyperbilirubinaemic or haemolytic samples. In contrast lipaemic samples and some with monoclonal immunoglobulin M showed an influence on the immunoephelometric reaction. 6. Because of the large measuring range, it is necessary to repeat analyses only in extremely rare cases. 7. During the entire evaluation period no instrument malfunctions or interruptions occurred. As a result of its reliability, the Behring Nephelometer is well suited for routine operation and emergency analyses in medium and large-sized laboratories.

Albumins↗

[Digitalis therapy in the aged].

Cardiac glycosides still belong to the most frequently prescribed drugs, although the usefulness of digitalization in patients with sinus rhythm has been repeatedly challenged. In elderly patients, especially, the objective hemodynamic improvement remains minimal and treatment can often be interrupted without subsequent deterioration. On the other hand, signs of digitalis toxicity, such as nausea, vomiting, AV-block, ventricular extrasystoles or CNS-symptoms, occur in 15-30% of patients. Adverse effects are mainly due to toxic accumulation of digoxin in cases with age related reduction of kidney function. In view of its non-renal elimination digitoxin would seem to have a certain advantage in geriatric patients, however, its long t 1/2 (6-7 days) makes dose adjustments more difficult, as peak effects will only be attained after 4-5 weeks. For these reasons digitalis treatment in elderly patients should not be given without clinically manifest congestive heart failure and/or atrial fibrillation. Even in such cases a periodic reassessment of the therapeutic indication is recommended. Suspected "latent" cardiac failure or cerebrovascular insufficiency are no reasons for utilizing such potentially toxic drugs.

Aged↗

Nucleotide sequence analysis of a proline-rich protein cDNA and peptide homologies of rat and human proline-rich proteins.

Plasmids containing cDNAs for proline-rich proteins have been isolated from a cDNA library prepared from parotid glands of isoproterenol-treated rats. The nucleotide sequence of one of these cDNAs (pRP33) has been determined, and it encodes an acidic proline-rich protein. The N-terminal 13 amino acids are highly hydrophobic and may be part of a signal peptide. The next 66 amino acids constitute an acidic domain which is interrupted by a short (8 residue) basic region. The sequence beginning at proline 80 contains six tandemly repeated regions of 18 to 19 amino acids in length with the prototype sequence PPPQGGPQXPPQPGXPQG. Two pairs of these repeats (amino acid residues 116 to 152 and 153 to 189) are 93% homologous in nucleotide sequence. The high homology in both nucleotide and amino acid sequences in the repeat region suggests that this protein may have evolved by duplication of internal portions of a progenitor gene.

Amino Acid Sequence↗

[Endothelin-1-induced vasoconstriction in retinal blood vessels in the rabbit].

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide which is synthesized in retinal vessels. In order to investigate its effect on retinal blood vessels, we injected ET-1 intravitreally (10(-12), 3 x 10(-12), 10(-11), 3 x 10(-11), 10(-10) mole) and examined the change in diameters of retinal arteries in rabbits by fundus photography. After injection of a high dose (10(-10) mole) of ET-1, fluorescein angiography was used to investigate whether complete occlusions of retinal blood vessels occurred or not. 3 x 10(-12) mole ET-1 induced contraction of retinal arteries and the contraction of those induced by 10(-10) mole ET-1 showed complete occlusion. A medium dose (10(-11) mole) of ET-1 caused repeated vasospasms and segmental vasoconstrictions of retinal blood vessels. Fluorescein angiograms revealed that retinal blood flow was interrupted transiently by injection of a high dose (10(-10) mole) of ET-1. These findings suggested that intravitreal injection of ET-1 could provide a new model of experimental transient occlusion of retinal vessels in rabbits.

Animals↗

Generation of new DNA binding specificity by truncation of the type IC EcoDXXI hsdS gene.

The hsdS subunit of a type IC restriction-modification enzyme is responsible for the enzyme's DNA binding specificity. Type I recognition sites are characterized by two defined half-sites separated by a non-specific spacer of defined length. The hsdS subunit contains two independent DNA binding domains, each targeted towards one DNA half-site. We have shown previously that the 5' half of hsdS can code for a functional substitute of the full-length hsdS. Here we demonstrate that the 3' half of the gene, when fused to the appropriate transcriptional and translational start signals, also codes for a peptide which imparts DNA binding specificity to the enzyme. About half the natural hsdS size, the mutant peptide contains a single DNA recognition domain flanked by one copy of each internal repeat found in the full-length hsdS. Deletion of either repeat sequence results in loss of activity. Like the 5' hsdS mutant, the 3' mutant recognizes an interrupted palindrome, GAAYN(5)RTTC, suggesting that two truncated subunits participate in DNA recognition. Co-expression of the 5' hsdS mutant and the 3' hsdS mutant along with hsdM regenerates the wild-type methylation specificity. Thus, there is a free assortment of subunits in the cell.

Adenine↗

Microsatellite mutation models: insights from a comparison of humans and chimpanzees.

Using genomic data from homologous microsatellite loci of pure AC repeats in humans and chimpanzees, several models of microsatellite evolution are tested and compared using likelihood-ratio tests and the Akaike information criterion. A proportional-rate, linear-biased, one-phase model emerges as the best model. A focal length toward which the mutational and/or substitutional process is linearly biased is a crucial feature of microsatellite evolution. We find that two-phase models do not lead to a significantly better fit than their one-phase counterparts. The performance of models based on the fit of their stationary distributions to the empirical distribution of microsatellite lengths in the human genome is consistent with that based on the human-chimp comparison. Microsatellites interrupted by even a single point mutation exhibit a twofold decrease in their mutation rate when compared to pure AC repeats. In general, models that allow chimps to have a larger per-repeat unit slippage rate and/or a shorter focal length compared to humans give a better fit to the human-chimp data as well as the human genomic data.

Animals↗