Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “repeat interruptions”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1979

Cytarabine and thioguanine for acute nonlymphocytic leukemia. Another look.

A modification of the protocol of cytarabine and thioguanine was used for remission induction in patients with acute nonlymphocytic leukemia. First, synchronization of the mitotically active leukemia cells was attempted by administering cytarabine alone in a dose of 5 mg/kg of body weight 24 hours prior to initiating daily therapy with both drugs. Second, in order to recover dormant leukemic cells into the proliferative pool, both drugs were continued without interruption and without regard to the suppression of the circulating leukocyte and platelet count until bone marrow aspirates, repeated daily if necessary, were free of leukemic blast cells. This usually resulted in severe but reversible bone marrow hypoplasia, and 16 of 21 patients (76%) so treated achieved complete hematologic remission.

Adolescent↗
PubMed1985

Effect of oral charcoal and urine pH on dextropropoxyphene pharmacokinetics.

The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of dextropropoxyphene were studied in six volunteers in a randomized, cross-over study. Serum and urine concentrations of dextropropoxyphene and norpropoxyphene were determined by GLC up to 72 h. Activated charcoal (50 g) given 5 min after dextropropoxyphene hydrochloride (130 mg), reduced its absorption by 97-99%. When given in repeated doses from 6 h on, 50 g followed by 12.5 g at 6 h intervals, charcoal significantly shortened the terminal serum half-life of dextropropoxyphene from 31.1 +/- 4.2 h to 21.2 +/- 3.1 h (p less than 0.05) and that of norpropoxyphene from 34.4 +/- 2.5 h to 19.8 +/- 3.4 h (p less than 0.001), and reduced their excretion into urine. The cumulative urinary excretion of unchanged dextropropoxyphene was increased 6-fold by acidification and reduced to 1/20 by alkalinization of urine, but the excretion of norpropoxyphene was much less dependent on urinary pH. However, the cumulative excretion of dextropropoxyphene and norpropoxyphene even into acidic urine accounted for less than 25% of the dose during 72 h. Because urinary pH has a great influence on the ratio of urinary versus serum dextropropoxyphene concentrations, pH should be taken into consideration, when the clinical significance of its concentration in urine is evaluated. Activated charcoal in high doses effectively prevents the absorption of that fraction of dextropropoxyphene which is in the stomach at the time of charcoal administration. Given in repeated oral doses, charcoal increases to some extent the rate of elimination of dextropropoxyphene and norpropoxyphene, probably by interrupting their enterohepatic or enteroenteric circulation.

Administration, Oral↗
PubMed1986

Pharmacokinetics of amitriptyline influenced by oral charcoal and urine pH.

The effects of orally given activated charcoal, sodium bicarbonate and ammonium chloride on the pharmacokinetics of amitriptyline were studied in 6 volunteers in a randomized, cross-over study. The serum and urine concentrations of amitriptyline and nortriptyline were determined by HPLC for up to 72 h. Activated charcoal (50 g), given within 5 min of the amitriptyline hydrochloride dose (75 mg), reduced its absorption by 99%. When given in repeated doses from 6 h on, 50 g followed by 12.5 g at 6-h intervals, charcoal shortened the serum half-life of amitriptyline by 20% and that of nortriptyline by 35% (p less than 0.05). The renal excretions of amitriptyline and nortriptyline increased 1000-fold by the acidification of urine pH to 4. However, the cumulative excretion of amitriptyline and nortriptyline even into acidic urine only accounted for up to 5% of the dose during 72 h. Since urinary pH has a great influence on the ratio of urinary versus serum amitriptyline and nortriptyline concentrations, pH should be taken into consideration, when the clinical significance of their concentrations in urine is evaluated. Activated charcoal in adequate doses very effectively prevents the absorption of that fraction of amitriptyline which is in the stomach at the time of charcoal administration. Furthermore, given in repeated oral doses, charcoal increases, to some extent, the rate of elimination of amitriptyline and nortriptyline, probably by interrupting their enterohepatic or enteroenteric circulation.

Administration, Oral↗
PubMed1985

Natural incidence of interruptions in the internal elastic lamina of caudal and renal arteries of the rat.

Interruptions in the internal elastic lamina (IEL) have been quantified by light microscopy in the caudal arteries of different strains of rats and in caudal and renal arteries of (i) male and female virgin rats up until 2 years of age, (ii) repeatedly bred rats and (ii) hypertensive rats. Results showed that gaps in the IEL exist in caudal arteries of adult males in all strains studied, but to a lesser extent in the hairless mutant. In the virgin Wistar rat these interruptions in the IEL form with age in both caudal and renal arteries, and are more numerous (i) in the male than in the female in both arteries, and (ii) in the caudal than in the renal artery in both sexes. Repeated breeding in the Wistar rat abolishes the sex difference in incidence of IEL gaps in both renal and caudal arteries. The Sprague-Dawley breeder rat is more susceptible than the Wistar breeder to their formation in the renal artery. Hypertension in the male consistently increases the formation of IEL gaps in the renal but not in the caudal artery. The importance of local factors, e.g. hemodynamics, in the formation of these defects in the IEL, and their possible relationship with the development of arteriosclerosis is discussed.

Age Factors↗
PubMed1996

[Molecular and genetic features of fragile X syndrome].

The fragile-X syndrome is the most frequent cause of sexlinked mental retardation. In the majority of the cases the mutation responsible for the Martin Bell syndrome is produced when an expansion of the (CGG)n repetition is present in the region 5' of the exón 1 of the gene for X-fragile mental retardation 1 (FMR1), together with a hipermethylation in the CpG promoter region of the gene. The result of this situation is the absence of FMRP protein coded by the gene. The correlation between length of the (CGG)n sequences and of the X-fragile phenotype has permitted a more precise diagnosis of affected and carrier individuals by means of direct DNA analysis. Nevertheless the molecular genetic basis of the instability and expansion of the (CGG)n sequence represents a problem not yet resolved. Two polymorphic microsatellite (AC)n repetitions, FRAXAC1 and FRAXAC2 that flank the FMR-1 gene have been recently described. It has been suggested that some haplotypes of FRAXAC1 and FRAXAC2 could be associated to long (CGG)n repetitions and that these haplotypes would confer more instability to the repeated fragment thus increasing the probability of expansion. It has also been described that the (CGG)n repetition of the FMR-1 gene is interrupted by AGG trinucleotides and that the loss of one AGG would be an important mutational event in the generation of predisposing unstable alleles of of the X-fragile syndrome.

Chromosome Mapping↗
PubMed1996

Electrocorticographic activity during repeated vs continuous hypoxia in piglets.

To assess the effects on brain activity of repeated vs continuous hypoxia, 16, 10- to 22-day-old piglets were instrumented chronically for electrocortical and arterial pH and gas tension measurements. They inhaled 10% or 6% O2 in N2 for 21 min, either continuously, or during seven, 3 min exposures interrupted by 3 min recovery periods in air, all while behaving naturally within a sealed, temperature controlled, plexiglass box. An isoelectric electrocorticogram (ECoG) and/or seizures, related to the onset of hypoxia, occurred repeatedly in 6 of the 10 exposures to 6% repetitive hypoxia, only twice in 8 exposures to 6% continuous hypoxia, and never in 10% hypoxia. A frequency analysis of the ECoG, excluding all sections exhibiting isoelectric and seizure activity, revealed no changes with 10% hypoxia, but a shift towards the lower bands during both repetitive and continuous 6% hypoxia. The extent of these shifts was greater in records that also displayed isoelectric ECoG and/or seizures. The ECoG spectrum recovered at the end of the hypoxic exposure, but not when isoelectric ECoG and/or seizures coexisted. We conclude that repeated, frequent episodes of hypoxia are more detrimental than a prolonged single event, and may contribute to the occurrence of Sudden Infant Death.

Animals↗
PubMed1999

Pharmacist's attitudes towards dispensing errors: their causes and prevention.

OBJECTIVE: To assess the attitudes of pharmacists towards the issue of dispensing errors. METHOD: A postal survey was undertaken among all Tasmanian-registered pharmacists residing in Australia. The anonymous questionnaire sought opinions on whether the risk of dispensing errors and the actual numbers of errors are increasing, the major factors contributing to the occurrence of dispensing errors, factors that can best minimize the risk of dispensing errors, the number of prescription items that one pharmacist can safely dispense in a day and whether Australia should have a regulatory maximum dispensing load, and an estimation of the number of recent errors at the pharmacist's workplace. RESULTS: Completed questionnaires were received from 209 pharmacists (50% response rate). Most pharmacists (82%) believed that the risk of dispensing errors is increasing. The principal contributing factors nominated were: high prescription volumes, pharmacist fatigue, pharmacist overwork, interruptions to dispensing, and similar or confusing drug names. The main factors identified as being important in reducing the risk of dispensing errors were: having mechanisms for checking dispensing procedures, having a systematic dispensing workflow, checking the original prescription (duplicate) when dispensing repeats, improving the packaging and labelling of drug products, having drug names that are distinctive, counselling patients at the time of supply, keeping one's knowledge of drugs up-to-date, avoiding interruptions, reducing workloads on pharmacists, improving doctors' handwriting, and privacy when counselling patients. Most pharmacists (72%) stated that they were aware of dispensing errors that had left the pharmacy undetected, in their place of practice during the past 6 months. The median number of such dispensing errors that they were aware of was three. A median of 150 was nominated as the maximum number of prescription items that can be safely dispensed per 9-h day (i.e. 17 items per hour) by or in the presence of one pharmacist. Most pharmacists (58%) stated that there should be a regulatory guideline for the safe dispensing load in Australia. CONCLUSION: Dispensing errors are occurring in numbers well above reports to regulatory authorities or professional indemnity insurance companies, and seem to be accepted as part of practice. High prescription volumes, pharmacist fatigue and overwork appear to be important factors. The profession needs to be proactive and standards must be set appropriately high (i.e. zero error tolerance).

Adult↗
PubMed1987

Completion of the amino acid sequence of the alpha 1 chain of human basement membrane collagen (type IV) reveals 21 non-triplet interruptions located within the collagenous domain.

The cDNA and protein sequences of the N-terminal half of human basement membrane collagen (type IV) have been determined. Overlapping cDNA clones were constructed by repeated primer extension with synthetic oligonucleotides. They cover 2953 bp, beginning at the 5' end of the corresponding mRNA. At the protein level, the sequence of the cyanogen bromide peptide CB6 adjacent to the 7S domain has been additionally elucidated. The data presented here complete the protein sequence and nearly the entire cDNA sequence of the human alpha 1(IV) chain. The amino-terminal half of the alpha 1(IV) chain contains 8 cysteine residues involved in intramolecular and intermolecular cross-links. The entire triple-helical domain of alpha 1(IV) is interrupted by 21 non-triplet regions.

Amino Acid Sequence↗
PubMed2000

Intraerythrocytic polyubiquitin expression in Plasmodium falciparum is subjected to developmental and heat-shock control.

The polyubiquitin gene of the human protozoan parasite Plasmodium falciparum (PfpUB) was cloned and shown to be comprised of five tandem repeats of the ubiquitin open reading frame, present as a single copy on chromosome 12. The 1672 bp of PfpUB is interrupted at the 5' end by a single intron of 526 bp. PfpUB expression is developmentally regulated in intraerythrocytic stages with a marked increase in both steady-state transcript and polyubiquitin protein levels in late trophozoite stages. On response to heat shock, late stage parasites (late trophozoites and schizonts) have a slightly elevated PfpUB transcript level as well as readily observable increases in the amount of polyubiquitin and ubiquitin-conjugated proteins.

Amino Acid Sequence↗
PubMed1999

Interrupted expression of NAC-1 augments the behavioral responses to cocaine.

NAC-1 is an mRNA that is increased selectively in the nucleus accumbens after acute and repeated cocaine administration. Antisense or control oligonucleotides were microinjected into the nucleus accumbens of rats to define the role of NAC-1 in the behavioral responses to acute systemic cocaine. Antisense oligonucleotides decreased NAC-1 mRNA levels by 26% and markedly enhanced the motor stimulant response to an acute cocaine injection compared to sense oligonucleotide microinjections. The augmentation in cocaine motor behavior produced by NAC-1 antisense pretreatment in the nucleus accumbens was not associated with increased dopamine release as estimated by microdialysis. In contrast, the behavioral response to dopamine microinjection into the nucleus accumbens was increased after antisense oligonucleotide treatment, while the motor response to mu-opioid receptor stimulation was unaltered. These data suggest that the induction of NAC-1 by cocaine may be a compensatory mechanism that minimizes the behavioral impact of cocaine administration by regulating postsynaptic dopamine transmission within the nucleus accumbens.

Animals↗
PubMed1988

Amygdaloid kindling with bicuculline methiodide in rats.

The effect of repeated intraamygdaloid injection of bicuculline methiodide (BM) was studied in rats. Chemitrodes for both microinjection and electrographic recording were implanted into the left basolateral amygdala. Two weeks after the surgery, a subconvulsive dose of BM (0.2 or 0.4 nmol) was administered through the chemitrodes every fourth day. Repeated injections caused a progressive seizure development which was comparable to that seen with electrical kindling. The kindling effect persisted after a 6-month interruption of the stimulation. When a mixture of BM and GABA agonist (GABA 20 nmol, muscimol 2 nmol, or baclofen 5 nmol) was injected into the amygdala of kindled rats, seizure activity was markedly suppressed to stage 0 or 1. On the other hand, an intraamygdaloid injection of picrotoxin (0.8 nmol) brought about the same seizure as induced by BM, whereas no seizure was observed with strychnine (4 nmol). No histological change specific to this kindling was detected. The present results indicate that chemical kindling can be induced by repeated local injection of BM into the amygdala, and that the mechanism underlying this kindling is closely associated with local postsynaptic GABA receptors in the amygdala. This GABAergic system may also be important in other types of kindling.

Amygdala↗
PubMed1997

Two distinct models account for short and long deletions within sequence repeats in Escherichia coli.

In Escherichia coli, (GpC)n sequences cloned into plasmid DNA molecules are deletion-prone with the occurrence of both short (<2 bp) and long (>2 bp) deletion events. These repetitive tracts can be stabilized by interrupting the strict monotony of the repetition with a variant dinucleotide sequence. The stabilization of short deletion events that is mediated by the variant sequence is completely lost in E. coli mismatch repair-deficient strains. In contrast, this repair pathway has no influence on the frequency of occurrence of long deletion events, even in sequences containing the variant repeat. These results lead us to propose two distinct models to account for short and long deletions within repetitive sequences in E. coli. Furthermore, this study reveals that the deletions occur preferentially at the end of the repeat sequence that is distal with respect to the origin of replication.

DNA Repair↗
PubMed1996

The structure of the prostaglandin EP4 receptor gene and related pseudogenes.

The EP4 prostaglandin receptor (EP4R) is a member of the seven transmembrane receptor superfamily. We have obtained the human EP4 receptor gene sequence and determined its structure relative to EP4R cDNA synthesized from peripheral blood lymphocytes. The EP4R gene spans approximately 22 kb and consists of three exons separated by two introns. The first exon (530 bp) is noncoding. After an intron of 472 bp, the second exon contains a short (43 bp) 5' sequence before a 289-amino-acid open reading frame (ORF). An 11.5-kb intron is found at the end of transmembrane 6, and the rest of the ORF is in exon 3. The gene structure is analogous to those of the thromboxane, PGI, and PGD receptors. The deduced initiation site does not contain a conventional TATA box but is 70% GC-rich and contains CCAAT boxes, SP1 and AP2 motifs, and motifs consistent with activation by proinflammatory cytokines. Southern blot analysis of human genomic DNA shows two genes with homology to the EP4R gene. Both appear to be pseudogenes with 70% amino acid identity to the EP4R up to the "ERY" sequence at the end of transmembrane 3, where an Alu-like repetitive sequence element was found. The ORF sequence is also interrupted by a stop codon. The pseudogenes differ in that one contains a second "repetitive element" (a line 1 repeat) in the 5' end of the ORF. Northern blot analysis of human mRNA using a pseudogene probe showed hybridization only to the EP4 receptor transcript. PCR also failed to detect expression of either pseudogene. This study defines the gene structure of EP4R and suggests the existence of two related pseudogenes.

Amino Acid Sequence↗
PubMed1992

An anatomically guided approach to atrioventricular node slow pathway ablation.

Radiofrequency ablation of the "slow" pathway of the atrioventricular (AV) node reentrant circuit may be guided by electrophysiologic ("slow pathway potential") or anatomic landmarks. Experience with a systematic, anatomically guided approach in 25 patients (20 women and 5 men, aged 38 +/- 15 years) with typical AV node reentry is described. The slow pathway is assumed to be the posterior input to the AV node, approaching the nodal region in the corridor between the tricuspid annulus and the orifice of the coronary sinus. A series of radiofrequency lesions are given to interrupt this corridor at its entrance to Koch's triangle. If this is unsuccessful, the series of lesions are repeated progressively at higher levels approaching the AV node. The major end point for success is elimination of the slow pathway as determined by extrastimulus testing. A mean of 1.2 +/- 0.2 ablative sessions (20 +/- 12 applications of energy) achieved clinical success in 24 of 25 patients (96%) at a follow-up of 8.6 +/- 2.2 months. Anterograde Wenckebach cycle length increased from 361 +/- 67 ms to 398 +/- 70 ms (p = 0.01), yet the atrio-Hisian interval in sinus rhythm did not change (69 +/- 17 ms before vs 65 +/- 15 ms after ablation), p = 0.22. Retrograde Wenckebach cycle length was not affected (348 +/- 78 ms before vs 366 +/- 82 ms after ablation). During ablation, transient third-degree AV block occurred in 6 patients with no permanent sequelae. This approach provides a systematic, expedient technique to eliminate slow pathway conduction based on anatomic landmarks.

Adult↗
PubMed1992

The flax ribosomal RNA-encoding genes are arranged in tandem at a single locus interspersed by 'non-rDNA' sequences.

The ribosomal RNA (rRNA)-encoding genes (rDNA) in flax, estimated to be present in about 2400 copies per diploid nucleus, have been reported as a single homogeneous repeat unit of 8.6 kb. In situ hybridization analysis indicated that these genes were located at a single site on one pair of chromosomes. However, an analysis of a flax variety, CI 1303, has revealed heterogeneity in the intergenic spacer of the rDNA repeat unit. A genetic analysis of rDNA inheritance in two flax lines, Stormont Cirrus and CI 1303, has again supported the observation that there is a single rDNA locus in this plant species. Screening of four different genomic libraries made in methylation-sensitive and -insensitive systems, and the analysis of 40 phage clones, demonstrate a much higher number than that expected of junctions between rDNA and non-rDNA. Direct evidence of rRNA-encoding genes being present in tandem comes from a few phage clones that contain more than two rDNA repeats. The evidence presented here indicates that rDNA, although present at a single locus in tandem arrays, may be interrupted frequently by other non-rDNA sequences, thus giving rise to questions about their organization into long tandem arrays.

Blotting, Southern↗
PubMed1996

Variability in the upstream promoter and intron sequences of the human, mouse and chick type X collagen genes.

The type X collagen gene is specifically expressed in hypertrophic chondrocytes during endochondral ossification. Transcription of the type X collagen gene by these differentiated cells is turned on at the same time as transcription of several other cartilage specific genes is switched off and before mineralization of the matrix begins. Analysis of type X collagen promoters for regulatory regions in different cell culture systems and in transgenic mice has given contradictory results suggesting major differences among species. To approach this problem, we have determined the nucleotide sequences of the two introns and upstream promoter sequences of the human and mouse type X collagen genes and compared them with those of bovine and chick. Within the promoter regions, we found three boxes of homology which are nearly continuous in the human gene but have interruptions in the murine gene. One of these interruptions was identified as a complex 1.9 kb repetitive element with homology to LINE, B1, B2 and long terminal repeat sequences. Regulatory elements of the human type X collagen gene are located upstream of the region where the repetitive element is inserted in the mouse gene, making it likely that the repetitive element is inserted between the coding region and regulatory sequences of the murine gene without interfering with its expression pattern. We also compared the sequences of the introns of both genes and found strong conservation. Comparisons of the mammalian sequences with promoter and first intron sequences of the chicken type X collagen gene revealed that only the proximal 120 nucleotides of the promoter were conserved, whereas all other sequences displayed no obvious homology to the murine and human sequences.

Animals↗
PubMed1978

Ovalbumin gene: evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries.

Selected regions of cloned EcoRI fragments of the chicken ovalbumin gene have been sequenced. The positions where the sequences coding for ovalbumin mRNA (ov-mRNA) are interrupted in the genome have been determined, and a previously unreported interruption in the DNA sequences coding for the 5' nontranslated region of the messenger has been discovered. Because directly repeated sequences are found at exon-intron boundaries, the nucleotide sequence alone cannot define unique excision-ligation points for the processing of a possible ov-mRNA precursor. However, the sequences in these boundary regions share common features; this leads to the proposal that there are, in fact, unique excision-ligation points common to all boundaries.

Animals↗
PubMed1988

Structure of a fish (rainbow trout) growth hormone gene and its evolutionary implications.

We have isolated and sequenced a clone from a rainbow trout (Salmo gairdneri) genomic library that carries a gene encoding a fish growth hormone (GH). This gene spans a region of approximately equal to 4 kilobases, nearly twice that of mammalian GH genes. The trout GH gene is comprised of six exons, in contrast with five exons in mammals. The additional intron in the fish gene interrupts translated regions that are analogous to the last exon of its mammalian counterpart. In addition, the alleged internally repeating sequence in mammalian GH, prolactin (Prl), or placental lactogen (PL) is not observed in the predicted polypeptide sequence of fish GH. Direct repeats that flank exons I, III, and V of the mammalian GH, Prl, and PL genes are absent in the fish GH gene. These findings indicate that the rainbow trout GH gene structure does not support the current hypothesis that internally repeated regions in GH, Prl, and PL arose from a small primordial gene.

Animals↗