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Biomedical subjects

R S Harris

Publications and source records attributed to R S Harris.

At least 37 records · Page 2Linked to original sources
PubMed1996

Recombination-dependent mutation in non-dividing cells.

Over the past 6 years an unexpected way of making mutations in bacteria has challenged concepts of the genetic mechanisms behind evolution. Mechanistic studies of these so called 'adaptive' mutations are revealing a novel molecular mechanism involving DNA double-strand breaks, genetic recombination, probable DNA polymerase errors, and the possible suspension of mismatch repair during the reversion of a lac frameshift mutation in Escherichia coli. The molecular details of this process are altering our understanding of how mutations form in non-dividing cells.

Adaptation, Physiological↗
PubMed1996

Opposing roles of the holliday junction processing systems of Escherichia coli in recombination-dependent adaptive mutation.

Aspects of the molecular mechanism of "adaptive" mutation are emerging from one experimental system: reversion of an Escherichia coli lac frameshift mutation carried on a conjugative plasmid. Homologous recombination is required and the mutations resemble polymerase errors. Reports implicating a role for conjugal transfer proteins suggested that the mutation mechanism is ordinary replication error occurring during transfer synthesis, followed by conjugation-like recombination, to capture the replicated fragment into an intact replicon. Whereas conjugational recombination uses either of two systems of Holliday junction resolution, we find that the adaptive lac reversions are inhibited by one resolution system and promoted by the other. Moreover, temporary absence of both resolution systems promotes mutation. These results imply that recombination intermediates themselves promote the mutations.

Adaptation, Physiological↗
PubMed1995

Adaptive mutation sequences reproduced by mismatch repair deficiency.

Adaptive reversions of a lac frameshift mutation in Escherichia coli are -1 deletions in small mononucleotide repeats, whereas growth-dependent reversions are heterogeneous. The adaptive mutations resemble instability of simple repeats, which, in hereditary colon cancer, in yeast, and in E. coli occurs in the absence of mismatch repair. The postulate that mismatch repair is disabled transiently during adaptive mutation in E. coli is supported here by the demonstration that the growth-dependent mutation spectrum can be made indistinguishable from adaptive mutations by disallowing mismatch repair during growth. Physiologically induced mismatch repair deficiency could be an important mutagenic mechanism in cancers and in evolution.

Bacterial Proteins↗
PubMed1995

Molecular handles on adaptive mutation.

In one experimental system, several handles on the molecular mechanism of apparent adaptive mutation have emerged. The system is reversion of a lac frameshift mutation in Escherichia coli. The molecular handles include a requirement for homologous recombination; the implication of DNA double-strand breaks as a molecular intermediate; a unique sequence spectrum of -1 deletions in mononucleotide repeats which implies polymerase errors, and also implies a failure of postsynthesis mismatch repair on those errors; and the involvement of sexual functions at some stage of the process. These molecular handles are revealing an unexpected new mechanism of mutagenesis.

Conjugation, Genetic↗
PubMed1994

Adaptive mutation by deletions in small mononucleotide repeats.

Adaptive reversion of a +1 frameshift mutation in Escherichia coli, which requires homologous recombination functions, is shown here to occur by -1 deletions in regions of small mononucleotide repeats. This pattern makes improbable recombinational mechanisms for adaptive mutation in which blocks of sequences are transferred into the mutating gene, and it supports mechanisms that use DNA polymerase errors. The pattern appears similar to that of mutations found in yeast cells and in hereditary colon cancer cells that are deficient in mismatch repair. These results suggest a recombinational mechanism for adaptive mutation that functions through polymerase errors that persist as a result of a deficiency in post-synthesis mismatch repair.

Base Sequence↗
PubMed1994

Recombination in adaptive mutation.

The genetic requirements for adaptive mutation in Escherichia coli parallel those for homologous recombination in the RecBCD pathway. Recombination-deficient recA and recB null mutant strains are deficient in adaptive reversion. A hyper-recombinagenic recD strain is hypermutable, and its hypermutation depends on functional recA and recB genes. Genes of subsidiary recombination systems are not required. These results indicate that the molecular mechanism by which adaptive mutation occurs includes recombination. No such association is seen for spontaneous mutation in growing cells.

DNA Damage↗
PubMed1987

Continuous intercostal blockade after cardiac surgery.

The provision of analgesia using continuous bilateral intercostal blockade was compared with that provided by conventional i.v. narcotics for the first 48 h after cardiac surgery. The subjective quality of analgesia was significantly superior with the regional technique. However, pulmonary function tests, gas exchange, lung volume, and radiological and clinical evidence of pulmonary complications were not improved. The failure to reduce morbidity and the potential for complications such as pneumothorax, makes it difficult to recommend the regional analgesia technique in this situation.

Cardiac Surgical Procedures↗
PubMed1985

The importance of proximal and distal air bronchograms in the management of atelectasis.

Correlation of chest radiographic appearances with concurrent fibreoptic bronchoscopy in patients observed while in intensive care, and with lobar or multilobar atelectasis due to retained secretions, suggests that three levels of air bronchogram can be identified: Proximal: air is visible only to the level of the main bronchus, bronchus intermedius or lobar bronchi. Intermediate: air is visible down to the segmental bronchi. Distal: air is visible down to the subsegmental bronchi or beyond. Proximal or intermediate air bronchograms signify accumulation of secretions in central bronchi and indicate the need for fibreoptic bronchoscopy to aspirate secretions: a distal air bronchogram signifies peripheral bronchial obstruction thus precluding effective fibreoptic bronchoscopy; chest physiotherapy is then a more appropriate treatment. The proximal air bronchogram may change in extent or definition-sometimes rapidly; a receding or an increasingly poorly defined proximal air bronchogram are danger signals of centrally accumulating secretions which may lead to respiratory arrest.

Adolescent↗
PubMed1984

Changing caesarean section rates. Experience at a Sydney obstetric teaching hospital.

The Caesarean section rate has been rising in Australia in recent years. This study compares Caesarean section rates and indications for Caesarean section in 2 separate 2-year periods, 1970-71 and 1980-81, in a Sydney teaching hospital. The Caesarean section rate increased from 6.4% to 16.2% in this decade. Dystocia is now the most frequent indication for Caesarean section and accounted for 33.2% of the increase in rate while fetal distress contributed 23.8% of that increase. Repeat Caesarean section and breech presentation contributed 16.9% and 13.3% of the increase respectively. Caesarean section rates for all birthweights increased, but particularly in the very small infant and those above 3,500 g. Caesarean sections for public patients rose from 3.4% to 9.3% while for private patients the rate increased from 12.0% to 20.7%. While there has been some convergence of rates for public and private patients during the decade, private patients were still twice as likely to have a Caesarean section in 1980-81. The contribution of dystocia, as an indication for Caesarean section, to the increase in the rate over this period is consistent with recent international experience and indicates a strong trend towards procedural intervention.

Australia↗
PubMed1983

Seasonal distribution of births in Australia.

Seasonal variations of births in Australia from 1911 to 1940 and 1962 to 1979 are analysed using stepwise periodic regression analysis. It is shown that the seasonality pattern has changed significantly from a September peak in the early 1960s to a February-March peak in the late 1970s. There also appears to be a significant geographical trend in seasonality of births with a February-March peak in the more northern States of Australia giving way to a September-October peak in the southernmost States. The seasonality of Australian births in 1976 to 1979 is shown to be independent of legitimacy and birth order but dependent on maternal age. The evidence suggests that environmental factors play a more important role than sociocultural factors in the causation of seasonal variations in births.

Adolescent↗
PubMed1983

Normal ventilatory movement of the right hemidiaphragm studied by ultrasonography and pneumotachography.

The ventilatory movement of the right dome of the diaphragm was studied over the range of the inspiratory capacity in 50 healthy adults in the supine position using simultaneous ultrasonography and pneumotachography. Regional differences were found in movement of the hemidiaphragm; there was greater movement of the middle and posterior thirds of the diaphragm than of the anterior third. A significant positive correlation was found between body weight and amount of diaphragm movement. An apparently greater degree of movement of the diaphragm was found in males than females; this may be related to weight. About 64% of diaphragm movement has occurred by the time midinspiratory capacity is reached. These data may help to define normal movement and also to differentiate abnormal from normal diaphragm movement.

Adult↗
PubMed1980

The pre-operative chest film in relation to post-operative management--some effects of different projection, posture and lung inflation.

An essential feature in the assessment of chest films is the comparability of successive examinations. This is particularly important in post-operative care and there are several factors which make the conventional departmental chest film an inappropriate standard for assessment of post-operative chest films. Pre-operative chest films in patients undergoing cardiac surgery have, therefore, been taken in both upright and supine positions at full inspiration (total lung capacity) (TLC) and at resting expiration (functional residual capacity) (FRC) and then compared with those taken post-operatively. Significant differences in transverse cardiac diameter, cardio thoracic ratio, mediastinal width and vertical lung height were found in films taken with the patient supine, AP at inspiration or resting expiration, circumstances in which many chest films are taken in both post-operative and in intensive care patients. The taking of pre-operative films at lung volumes and in postures comparable with those occurring post-operatively is advocated.

Cardiac Surgical Procedures↗