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Biomedical subjects

A J Newson

Publications and source records attributed to A J Newson.

12 recordsLinked to original sources

Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice.

Centromere protein A (Cenpa for mouse, CENP-A for other species) is a histone H3-like protein that is thought to be involved in the nucleosomal packaging of centromeric DNA. Using gene targeting, we have disrupted the mouse Cenpa gene and demonstrated that the gene is essential. Heterozygous mice are healthy and fertile whereas null mutants fail to survive beyond 6.5 days postconception. Affected embryos show severe mitotic problems, including micronuclei and macronuclei formation, nuclear bridging and blebbing, and chromatin fragmentation and hypercondensation. Immunofluorescence analysis of interphase cells at day 5.5 reveals complete Cenpa depletion, diffuse Cenpb foci, absence of discrete Cenpc signal on centromeres, and dispersion of Cenpb and Cenpc throughout the nucleus. These results suggest that Cenpa is essential for kinetochore targeting of Cenpc and plays an early role in organizing centromeric chromatin at interphase. The evidence is consistent with the proposal of a critical epigenetic function for CENP-A in marking a chromosomal region for centromere formation.

Animals↗

All here are agog with the chloroform.

Two letters written by James Y. Simpson are included among a bound collection of 25 of his pamphlets held in the Gordon Craig Collection of the Library of the Royal Australasian College of Surgeons. Both letters are written in pamphlets relating to Simpson's championing of chloroform. The first letter is written in a proof copy of a pamphlet titled Notice of a new anaesthetic agent as a substitute for Sulphuric ether in Surgery and Midwifery. This very rare pamphlet was posted to Dr Fleetwood Churchill, a Dublin obstetrician, on 13 November 1847, 9 days after the 'dining room experiment' in Simpson' s home, when the anaesthetic properties of chloroform were dramatically demonstrated. The second letter is written 10 months later and is also addressed to Dr Fleetwood Churchill. The content of both letters is discussed, as is also the rarity of the proof copies of the first printed document describing the use of chloroform.

Anesthesia, Inhalation↗

Investigations using logistic regression models on the effect of the LMA on morphine induced vomiting after tonsillectomy.

The effect of intraoperative airway management on postoperative vomiting after tonsillectomy is unknown. Logistic regression was used in a retrospective study to investigate the effect of the laryngeal mask airway (LMA) on a morphine dose-vomiting response curve. Charts were reviewed in 351 children in whom the airway was managed with either a LMA (n=177) or a tracheal tube (n=174). A mean perioperative morphine dose of 0.10 mg.kg(-1) (SD 0.09) was used in 248 children and a further 103 children were given no opioid. One hundred and eighteen of these 248 children vomited (47.6%) compared to 14 of 103 children given no morphine (13.6%). The probability of vomiting was related to morphine dose using logistic regression with both a linear and an E(max) model. Both the calibration (Hosmer-Lemishow goodness of fit chi-squared test lambda(2), P=0.81) and discrimination (area under the receiver operating characteristic plot, AUC ROC=0.67) of the E(max) model were better than the linear model (lambda(2), P=0.49; AUC ROC=0.64). Pharmacodynamic parameter estimates for the Emax model were P(0) (the baseline probability of vomiting) 0.139, P(max) (the maximal probability of vomiting due to morphine) 0.96, ED(50) (morphine dose that induces an effect equivalent to 50% of the logit P(max)) 0.09 mg.kg-1. The probability of vomiting was 50% after morphine 0.125 mg.kg-1. The use of the LMA had no effect on this dose-response curve. A covariate analysis investigating propofol for induction or isoflurane for the intraoperative maintenance of anaesthesia, however, showed that both drugs shifted the curve to the right. The probability of vomiting was 50% after morphine 0.17 mg.kg(-1) and 0.21 mg.kg(-1) for the isoflurane and propofol use curves, respectively. The concomitant use of propofol and isoflurane, but not the use of the LMA, decreases the probability of vomiting due to morphine.

Adolescent↗

Gene structure and sequence analysis of mouse centromere proteins A and C.

We have determined the genomic structure and organization of the mouse Cenpa and Cenpc genes. CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres. The Cenpa cDNA encodes a 134-amino-acid product that is 70% identical and 84% similar to its human homolog. The mouse Cenpa gene is approximately 8 kb in length and contains five exons. Sequence analysis of the 5' DNA sequence of the gene revealed two consensus CAAT boxes, a putative TFIID-binding site, an Sp1-binding domain, and two cell cycle regulatory motifs, but no consensus TATA element. The mouse Cenpc gene spans 60 kb and contains 19 exons that range in size from 44 to 602 bp. Sequence analysis of the C+G-rich promoter region showed the presence of known promoter elements, including a CpG island, a CAAT box, and several GC boxes, but the absence of a consensus TATA element.

Amino Acid Sequence↗

Chromosomal localization of mouse Cenpa gene.

Using a previously isolated mouse centromere protein A (Cenpa) probe, we have localized the gene to the proximal region of mouse Chromosome 5, between the known Il6 and Yes1 loci near [Adra2C-D5H4S43-Hdh]. Comparison of this localization with that of human CENPA, which maps to chromosome 2, is consistent with the presence of a new region of conserved synteny between the two species.

Animals↗

Comparison of midazolam with thiopentone for outpatient anaesthesia.

The water soluble benzodiazepine, midazolam, was compared with thiopentone as an intravenous induction agent in unpremedicated patients undergoing cystoscopy as out-patients. Induction time was longer with midazolam, though subsequent transition to halothane inhalation anaesthesia was smooth and uneventful. Both drugs had similar effects on the cardiovascular and respiratory systems and were without local irritation following intravenous injection. Recovery was more prolonged with midazolam, tests of memory and unaided mobility showing greater impairment one hour after anaesthesia. Notwithstanding a slower and less predictable onset of unconsciousness and somewhat slower recovery phase, midazolam provides a safe alternative to thiopentone as an induction agent suited to minor surgical procedures.

Adolescent↗

The effectiveness and duration of preoperative antacid therapy.

The administration of 10 ml of magnesium trisilicate mixture to premedicated patients, maintains the pH of gastric contents below pH 2-5 during subsequent general anaesthesia. This effect was sustained for over seven hours--the longest anaesthetic time studied. No antacid supplementation is required to offer protection from acid aspiration during emergence and initial recovery from general anaesthesia.

Adolescent↗

Pre-operative neutralization of gastric acidity.

The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent.

Administration, Oral↗

New Zealand's first general anaesthetic.

The administration of New Zealand's first general anaesthetic took place at the Colonial Gaol, Wellington, on the morning of Monday, September 27th, 1847. The agent used was sulphuric ether which was administered by Mr. Marriot, the manufacturer of the Herapath-type inhaler used on this occasion. The operation, a dental extraction, was performed by the Colonial Surgeon, Dr. J. P. Fitzgerald.

Anesthesia, Inhalation↗