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Nucleotide sequence of human prostatic acid phosphatase ACPP gene, including seven Alu repeats.

The protein-coding sequence of the human ACPP gene was shown to be interrupted by nine introns. The length of intron 1 was at least 5kb, while the sizes of introns 2 to 9 were estimated to be 3.4Kb, 0.5Kb, 5.5Kb, 5.0Kb, 2.0Kb, 5.0Kb, 2.5Kb and 3.5Kb, respectively. Therefore, the human ACPP gene has the size of more than 40kb. Thus far, the genomic sequence of 16,273 nucleotides, including the putative promoter region and seven Alu-repeats, have been determined. Three of these Alu-repeats are located immediately upstream to exon 1 and another is identified in intron 1. All of these Alu-sequences exhibit more than 85% identity to the consensus Alu-sequence.

Acid Phosphatase↗

One-shock versus three-shock defibrillation protocol significantly improves outcome in a porcine model of prolonged ventricular fibrillation cardiac arrest.

BACKGROUND: The success of resuscitation with a 1-shock versus the conventional 3-shock defibrillation protocol was investigated subject to the range of treatment variation imposed by automated external defibrillators (AEDs). METHODS AND RESULTS: Ventricular fibrillation was induced in 44 domestic pigs. After 7 minutes of untreated VF, animals were randomized among 4 groups representing all combinations of the 1- versus 3-shock protocol and 2 different AED regimens (AED1, AED2). Because few AEDs support a 1-shock protocol, manual defibrillators were used to replicate the AED treatment regimen: electrical waveform, dose sequence, and cardiopulmonary resuscitation (CPR) interruption intervals. Initial shock(s) were delivered, followed by 60 seconds of CPR, and the treatment was repeated until resuscitation was successful or for 15 minutes. The 1-shock protocol was associated with improved outcome, reducing CPR interruptions from 45% to 34% of total resuscitation time (P=0.019) and increasing survival from 64% to 100% (P=0.004). Survival was 91% for AED1 versus 36% for AED2 (P=0.024) with a 3-shock protocol but was increased to 100% for both by adoption of a 1-shock protocol. Improvements in postresuscitation left ventricular ejection fraction and stroke volume were observed with AED1 compared with AED2 (difference of means, 15% and 28% of baseline respectively, P<0.001) regardless of defibrillation protocol. CONCLUSIONS: Adoption of a 1-shock versus a 3-shock resuscitation protocol improved survival and minimized outcome differences imposed by variations in AED design and implementation. When a conventional 3-shock defibrillation protocol was used, however, the choice of AED had a significant impact on resuscitation outcome.

Animals↗

Complete nucleotide sequence of the rabbit beta-like globin gene cluster. Analysis of intergenic sequences and comparison with the human beta-like globin gene cluster.

The nucleotide sequence of the entire beta-like globin gene cluster of rabbits has been determined. This sequence of a continuous stretch of 44.5 x 10(3) base-pairs (bp) starts about 6 x 10(3) bp upstream from epsilon (the 5'-most gene) and ends about 12 x 10(3) bp downstream from beta (the 3'-most gene). Analysis of the sequence reveals that: (1) the sequence is relatively A + T rich (about 60%); (2) regions with high G + C content are associated with OcC repeats, a short interspersed repeated DNA in rabbits; (3) the distribution of polypurines, polypyrimidines and alternating purine/pyrimidine tracts is not random within the cluster; (4) most open reading frames are associated with known globin coding regions, OcC repeats or long interspersed repeats (L1 repeats); (5) the most prominent open reading frames are found in the L1 repeats; (6) different strand asymmetries in base composition are associated with embyronic and adult genes as well as the tandem L1 repeats at the 3' end of the cluster; and (7) essentially all the repeats appear to have been inserted by a transposon mechanism. A comparison of the sequence with itself by a dot-plot analysis has revealed nine new members of the OcC family of repeats in addition to the six previously reported. The OcC repeats tend to be clustered, particularly in the epsilon-gamma and gamma-psi delta intergenic regions. Dot-plot comparisons between the rabbit and the human clusters have revealed extensive sequence matches. Homology starts about 6 x 10(3) bp 5' to epsilon or as far upstream as the rabbit sequence is available. It continues throughout the entire cluster and stops about 0.7 x 10(3) bp 3' to beta, at which point several repeats have inserted in both rabbits and humans. Throughout the gene cluster, the homology is interrupted mainly by insertions or deletions in either the rabbit or the human genome. Almost all of the insertions are of known short or long repeated DNAs. The positions of the insertions are different in the two gene clusters, which indicates that both short and long repeats have been transposing throughout the genome for the time since the mammalian radiation. An alignment of rabbit and human sequences allows the calculation of the substitution rate around epsilon. Sequences far removed from the gene are evolving at a rate equivalent to the pseudogene rate, although some short regions show an apparently higher rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Charcoal enhancement of treatment for tricyclic-induced mania.

Induction of mania by tricyclic antidepressants (TCAs) is controversial, with indirect evidence for and against it. Unusual direct evidence of it was observed in a 77-year-old female patient having ingested an amitriptyline overdose. Mania developed while the TCA blood levels were high, and responded to a combination of charcoal and valproate. However, mania reappeared when charcoal was discontinued, and disappeared again when it was restarted. This time course suggests a therapeutic advantage for adding charcoal to valproate in treating tricyclic-induced mania. Presumably, charcoal might have removed a mania-inducing metabolite of amitriptyline. Moreover, repeated doses of oral activated charcoal accelerated the elimination of TCA from the blood stream to several times its original rate, which is consistent with interruption of the enterohepatic circulation. This enhanced elimination and improved outcome illustrate the value of repeated charcoal doses after TCA overdose, and suggest its use when mania develops in a patient who takes an antidepressant, at least amitriptyline or nortriptyline.

Aged↗

Procainamide-induced changes in reentrant ventricular tachycardia with special reference to the tachycardia-interrupting critical paced cycle length during transient entrainment with rapid pacing.

With rapid ventricular pacing, sustained ventricular tachycardia (VT) is often entrained and interrupted at a critical paced cycle length. In this paper, the possible mechanism and determinant of the critical cycle length interrupting VT are addressed. Sixteen consecutive patients underwent rapid ventricular pacing in 18 morphologically distinct sustained VTs before and after procainamide. The VT morphology was identical before and after the drug. The VT origin was determined by endocardial mapping as the earliest site of activation of VT and an electrode catheter was located at the site. Rapid pacing was performed to entrain VT and repeated in 10 msec decrements of cycle length until VT was interrupted at a critical paced cycle length which was defined as the block cycle length. The effective refractory period was measured at the pacing site. The paced QRS duration and the local conduction time were measured and used as indices of conduction time in the normal myocardium. VT was entrained and interrupted in all patients. At the block cycle length, initial constant fusion was replaced abruptly by the fully paced QRS complex. At the same time, the local electrogram at the site of VT origin showed changes in the morphology and the timing of activation which were identical to those of the fully paced beat. This loss of fusion and the changes in the local electrogram were considered to be a result of orthodromic block and the block cycle length was assumed to represent the cycle length at which 1:1 conduction fails in the area of slow conduction. After procainamide, both the VT cycle length and the block cycle length were prolonged to a similar degree (p < 0.001) but the relative degree of change varied from patient to patient. The paced QRS duration and the conduction time were prolonged by procainamide but in smaller degrees than the cycle length of VT or the block cycle length (p < 0.02-01). The effective refractory period at the pacing site and the QT interval showed small changes after procainamide. The postrepolarization refractoriness rather than the duration of action potential can be responsible for the procainamide-induced prolongation of the block cycle length, and the block cycle length might be used as a new index to characterize the electrophysiologic property of the VT circuit and also the action of antiarrhythmic drugs.

Adolescent↗

Effects of single and repeated daily injections of morphine, clonidine, and l-nantradol on avoidance responding of rats.

Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.

Animals↗

When continuous surgical site infection surveillance is interrupted: the Royal Hobart Hospital experience.

BACKGROUND: The prevalence of surgical site infections (SSI) is second only to urinary tract infections in hospitalized patients. They continue to threaten the health of hospitalized patients and impact negatively on the financial solvency of hospitals through prolonged hospitalization, increased rates of rehospitalization, and significantly increased health care costs. METHODS: We describe the effect of a 12-year surveillance program that included postdischarge follow-up and feedback to clinicians on the rate of SSI and the effect when surveillance is interrupted. Surgical procedures performed at the Royal Hobart Hospital (RHH), a university teaching hospital in Australia, between 1988 and 2001 were monitored for evidence of SSI in hospitals and for up to 30 days postoperatively. The surveillance program was inadvertently disrupted for 15 months from October 1990 to January 1992 and then recommenced. It has been ongoing since that time, apart from a 3-month interruption in 1998. Infection rates were determined on a regular basis, and these results were provided to surgeons, theatre staff, and surgical ward staff every 6 months. Patients included all adult surgical patients with an incisional wound, excluding burn patients and day-only surgical patients. RESULTS: Over the 12-year active surveillance period, 47,581 surgical procedures were followed for SSI. In-hospital SSI rates declined significantly over the study period from 4.7% (95% CI: 3.9%-5.6%) in 1988-1989 to 1.2% (95% CI: 0.8%-1.7%) in 2001 (P < .0001). Infection rates fell rapidly following the commencement of the program. This decline was halted during the period from October 1990 to January 1992 when the program was suspended. In-hospital SSI rates declined once again following the recommencement of the surveillance program, and these lower rates have been maintained. In contrast, postdischarge infection rates rose significantly from 1.2% (95% CI: 0.8%-1.7%) in 1988-1989 to 2.1% (95% CI: 1.6%-2.7%) in 2001 (P < .0001). CONCLUSION: The introduction of a program of continuous SSI surveillance at the RHH was associated with a reduction in the in-hospital and total SSI rate. This phenomenon was repeated following the recommencement of the program after a temporary interruption. Increasing numbers of SSIs are arising after hospital discharge. Many of these patients are readmitted to the hospital for further management of the SSI. Surveillance programs that do not perform postdischarge surveillance will have difficulty in capturing this data. Our experience supports the Study on the Efficacy of Nosocomial Infection Control (SENIC) findings, showing that health care facilities can achieve improved levels of infection management with active surveillance programs.

Adult↗

[Reversible dialytic encephalopathy after interruption of aluminium intake. 6 cases (author's transl)].

The cases presented with psychic troubles and repeated somnolence episodes accompanied by dysarthria in 5 cases, myoclonic jerks in 4 cases and epileptic seizures in 1 case. In all cases the EEG was disturbed. It showed symetrical, paroxystic, bilateral, monomorph slow activity with more or less frequent paroxysms. The average serum aluminium level was at 407 microgram/l in the acute phase, at 161 microgram/l in the remission phase and at 123 microgram/l three months later. After interruption of oral and dialytic aluminium intake the remission is maintained. However in 2 cases the transitory readministration of aluminium gel was followed by reversible recurrency. The role of both aluminium gel and dialysate aluminium as the origin of encephalopathy is discussed.

Aged↗

Distraction and action slips in an everyday task: evidence for a dynamic representation of task context.

We report here a novel and counterintuitive effect of distraction on routine sequential action. The effect, predicted by a recent computational model of sequential behavior, relates to the tendency for a momentary distraction, such as a brief interruption, to lead to subsequent slips of action. The specific prediction is that errors should be more likely following a distraction occurring toward the middle of a subtask sequence than following a distraction occurring at the end of a subtask. This was tested and confirmed in an experiment involving repeated performance of an everyday task (coffee making) under conditions involving frequent interruption. The observed effect provides differential support for existing models of sequential behavior and offers a highly constraining benchmark for future theories.

Adolescent↗

Repeated intravenous cocaine administration: locomotor activity and dopamine D2/D3 receptors.

The dopamine D3 receptor has been implicated as a possible mediator in the reinforcement or abuse of psychostimulants such as cocaine. The present studies examined the effects of repeated (14 day) intravenous cocaine administration (saline vehicle, 0.5, 1.0 and 3.0 mg/kg) on locomotor activity and dopamine D2 and D3 receptor density in the rat striatum and nucleus accumbens. Male Sprague-Dawley rats (n = 40) were implanted with an intravenous access port and allowed to recover for 2 days. An additional group of naive rats was included to control for surgical/injection stress (n = 10). Following 2 days of habituation trials, total, peripheral and central activity (photocell interruptions) data were collected during alternate daily 60-minute test sessions. Repeated cocaine treatment resulted in a significant dose-dependent increase in striatal D3 receptors which was predicted by daily 60-minute central locomotor activity. Conversely, D3 receptors in the nucleus accumbens exhibited a significant dose-dependent reduction which was predicted by the initial 5 minutes of central locomotor activity observed on peak sensitization days (days 6, 8 and 10). Sensitization to the locomotor stimulatory effects of cocaine was dose-dependent, with the time to peak sensitization day following the rank order of 0.5 > 1.0 > 3.0 mg/kg. The density of D2 receptors in the striatum and nucleus accumbens was unchanged by cocaine administration. These data suggest striatal and nucleus accumbens D3 receptor involvement in the expression of cocaine-induced behavioral sensitization. Thus, the D3 receptors in the striatum and nucleus accumbens may be differentially involved in the locomotor stimulation (striatal D3) and reinforcing aspects (nucleus accumbens D3) of repeated cocaine administration.

Animals↗

Tenascin-Y: a protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue.

Tenascin-Y was identified in chicken as a novel member of the tenascin (TN) family of ECM proteins. Like TN-C, TN-R, and TN-X, TN-Y is a multidomain protein consisting of heptad repeats, epidermal growth factor-like repeats, fibronectin type III-like (FNIII) domains and a domain homologous to fibrinogen. In contrast to all other known TNs, the series of FNIII domains is interrupted by a novel domain, rich in serines (S) and prolines (P) that occur as repeated S-P-X-motifs, where X stands for any amino acid. Interestingly, the TN-Y-type FNIII domains are 70-100% identical with respect to their DNA sequence. Different TN-Y variants are created by alternative splicing of FNIII domains. Although, based on sequence comparisons TN-Y is most similar to mammalian TN-X, these molecules are not species homologues. TN-Y is predominantly expressed in embryonic and adult chicken heart and skeletal muscle and, to a lower extent, also in several non-muscular tissues. Two major transcripts of approximately 6.5 and 9.5 kb are differentially expressed during heart and skeletal muscle development and are also present in the adult. Anti-TN-Y antibodies recognize a approximately 400-kD double band and a approximately 300-kD form of TN-Y on immunoblots of chicken heart extracts. In situ hybridization and immunofluorescence analysis of aortic smooth muscle, heart, and skeletal muscle revealed that TN-Y is mainly expressed and secreted by cells within muscle-associated connective tissue. Cultured primary muscle fibroblasts released a approximately 220-kD doublet and a approximately 170-kD single TN-Y variant only when cultured in 10% horse serum but not in medium containing 10% fetal calf serum. All TN-Y variants isolated bind to heparin under physiologically relevant conditions that may indicate an important function retained in all tenascins.

Age Factors↗

Phenotypic effects of expanded ataxin-1 polyglutamines with interruptions in vitro.

Spinocerebellar ataxia type 1 is a neurodegenerative disease caused by expansion of an uninterrupted glutamine repeat in ataxin-1 protein. Protein aggregation and immunoreactivity to 1C2 monoclonal antibody are two distinct pathognomonic features of expanded ataxin-1, as well as of other polyglutamine disorders. Rare cases of non-affected elderly subjects carrying expanded ataxin-1 alleles were found in random population. However, in these alleles the glutamine stretch was interrupted by histidines. Due to lack of phenotype, these alleles should be considered "normal". Most importantly, occurrence of these unusual alleles provides a unique opportunity to investigate which molecular properties of expanded ataxin-1 are not coupled to polyglutamine pathogenesis. Towards this goal, we compared in vitro the immunoreactivity to 1C2 antibody and the ability to form aggregates of interrupted and uninterrupted alleles. Immunoblotting showed that expanded-interrupted ataxin-1 had an affinity to 1C2 resembling that of normal ataxin-1. On the contrary, filter assay showed that aggregation rate of expanded-interrupted ataxin-1 resembles that of expanded-uninterrupted ataxin-1. These observations indicate that affinity for 1C2 does not directly correlate with self-aggregation of ataxin-1. Moreover, self-aggregation is not directly affected by histidine interruptions. In conclusion, these results support the hypothesis that mechanisms underlying neuronal degeneration are triggered by protein misfolding rather than by protein aggregation.

Amyloidosis↗

Gel and free solution electrophoresis of variably charged polymers.

To assess the role of charge density on polyelectrolyte mobility, both gel and free solution electrophoresis experiments are performed on poly(acrylic acid) and acrylic acid/acrylamide copolymers. Control of charge density for poly-(acrylic acid) is achieved through solution pH, while control for acrylic acid/ acrylamide copolymers is obtained through chain composition. In either approach, the effective fraction of charged repeat units can be varied from 0 to 100% without a major interruption of solvent quality. Polyelectrolyte mobility in the presence of a monovalent counterion is observed to rise linearly with charge density when this density is low. A transition to charge density independence then occurs over a surprisingly narrow window of charge density. For vinyl polymers of the sort examined here, the transition occurs when 35-40% of the repeat units are charged. These observations are qualitatively consistent with the free solution electrophoresis model proposed by Manning and several previous data sets. An unexpected overlap of normalized gel and free solution data reveals that the charge density exerts a comparable influence in either environment. Results from the present study help define the experimental conditions in which electrophoresis can provide polymer separation by charge density and those in which the method can provide polymer separation by molecular weight.

Acrylates↗

Precursor arrays for triplet repeat expansion at the fragile X locus.

To determine factors governing triplet repeat expansion at FMR1, we need to understand the basis of normal variation. We have sequenced the FMR1 repeat from 102 normal X chromosomes and show that most are interrupted with a regularly spaced AGG trinucleotide giving an ordered structure to the array. Five types of arrays were identified consisting of varying numbers of a core unit with consensus [AGG(CGG)9]. Additional variation in the length of the (CGG)n portion within each unit generates the continuum of lengths seen on normal chromosomes. Ten per cent contain long, uninterrupted tracts of (CGG)n, and their lengths suggest they have arisen by the loss of AGG triplets from longer interrupted arrays. Haplotype analysis of arrays carrying long, uninterrupted (CGG)n tracts suggests that they occur more frequently on genetic backgrounds which are more highly represented on fragile X chromosomes. These arrays may well be precursors from which the larger fragile X associated arrays have arisen by further expansion.

Base Sequence↗

Double-strand breaks increase the incidence of genetic deletion associated with intermolecular recombination in bacteriophage T7.

An in vitro DNA replication system based on extracts prepared from Escherichia coli cells infected with bacteriophage T7 was used to study deletion associated with the repair of double-strand breaks. The gene for T7 ligase was interrupted by a DNA insert which included 17-bp direct repeats. Deletion between the repeats restored the reading frame of the gene, and these DNA molecules could be detected by their ability to give rise to ligase-positive phage after in vitro packaging. T7 genomes that had a pre-existing double-strand break located between the direct repeats were incubated together with intact genomes which had the same direct repeats. Genetic markers placed on either side of the insert in the ligase gene allowed identification of the source of DNA molecules that underwent deletion between the direct repeats. This allowed an assessment of the participation of the molecules with strand breaks in the deletion process, under conditions where any mechanism could contribute to deletion. Approximately three-quarters of the T7 molecules that had lost the region between the direct repeats contained one or both of the partial genomes originally introduced into the reactions. About 50% of the genomes which had undergone deletion had recombined markers between the partial and intact genomes. The data demonstrate that double-strand breaks substantially enhance the contribution of intermolecular recombination to deletion.

Bacteriophage T7↗

[Obstructive sleep apnea and hypopnea syndrome: cephalometric analysis].

Obstructive sleep apnea and hypopnea syndrome (OSAHS) are characterized by repeated pauses in breathing during sleep, usually associated with sleep interruption and decreased oxyhemoglobin saturation. Cephalometric analysis has become an important method in diagnosis, reporting specific craniofacial characteristics such as posterior air pharyngeal space, tongue length and hyoid position, which may predispose some people to develop SAHOS. The purpose of this revision is to present several anatomic aspects by cephalometric analysis that may have a predisposition to the development of upper airway occlusion.

Cephalometry↗

Homologous genes encode two distinct histidine-rich proteins in a cloned isolate of Plasmodium falciparum.

Two genes encoding distinct histidine-rich proteins in a Plasmodium falciparum clone exhibit high levels of homology, suggesting they have originated by duplication and divergence from a common ancestral sequence. Both genes have a similar interrupted structure and an exon that encodes closely related tandem repeats of very high histidine and alanine content. The most common repeat encoded by one gene, the hexapeptide Ala-His-His-Ala-Ala-Asp, differs in the sixth position from the most common repeat encoded by the other gene, the hexapeptide Ala-His-His-Ala-Ala-Asn. The divergence of the repeat domains is greater than that of the flanking regions, which exhibit 85-90% homology, including untranslated sequences. This suggests the tandem repeats are relatively labile elements within the genome that may provide the parasite with a means of rapid evolutionary change.

Amino Acid Sequence↗

Gastrointestinal decontamination for acute poisoning.

Acute poisoning remains a common cause of morbidity and even mortality in children and adults. The goal of gastrointestinal decontamination is to eliminate or to reduce the potentially life-threatening effects of the ingested poison. Methods of gastrointestinal detoxication in case of acute poisoning, such as induced emesis, gastric lavage, administration of activated charcoal and intestinal cleansing are discussed. As far as induced emesis is still concerned, only the administration of Ipecac-syrup can be retained. The controversy between emesis and gastric lavage still remains. For those toxins well adsorbed by activated charcoal, the administration of activated charcoal, followed or not by gastric lavage, is the treatment of choice. Single doses of activated charcoal can be insufficient. In certain kinds of poisoning, repeated doses of activated charcoal are advisable because of the interruption of the entero-hepatic and entero-enteric circulation. The benefit and the indications for intestinal cleansing in case of acute poisoning seem to be very limited.

Cathartics↗