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Biomedical subjects

D A Conn

Publications and source records attributed to D A Conn.

13 recordsLinked to original sources
PubMed2001

A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stability.

DNA polymerase beta (pol beta) offers a simple system to examine the role of polymerase structure in the fidelity of DNA synthesis. In this study, the M282L variant of pol beta (M282Lbeta) was identified using an in vivo genetic screen. Met282, which does not contact the DNA template or the incoming deoxynucleoside triphosphate (dNTP) substrate, is located on alpha-helix N of pol beta. This mutant enzyme demonstrates increased mutagenesis in both in vivo and in vitro assays. M282Lbeta has a 7.5-fold higher mutation frequency than wild-type pol beta; M282Lbeta commits a variety of base substitution and frameshift errors. Transient-state kinetic methods were used to investigate the mechanism of intrinsic mutator activity of M282Lbeta. Results show an 11-fold decrease in dNTP substrate discrimination at the level of ground-state binding. However, during the protein conformational change and/or phosphodiester bond formation, the nucleotide discrimination is improved. X-ray crystallography was utilized to gain insights into the structural basis of the decreased DNA synthesis fidelity. Most of the structural changes are localized to site 282 and the surrounding region in the C-terminal part of the 31-kDa domain. Repositioning of mostly hydrophobic amino acid residues in the core of the C-terminal portion generates a protein with enhanced stability. The combination of structural and equilibrium unfolding data suggests that the mechanism of nucleotide discrimination is possibly affected by the compacting of the hydrophobic core around residue Leu282. Subsequent movement of an adjacent surface residue, Arg283, produces a slight increase in volume of the pocket that may accommodate the incoming correct base pair. The structural changes of M282Lbeta ultimately lead to an overall reduction in polymerase fidelity.

Amino Acid Substitution↗
PubMed2001

Spiritual healing as a therapy for chronic pain: a randomized, clinical trial.

Spiritual healing is a popular complementary and alternative therapy; in the UK almost 13000 members are registered in nine separate healing organisations. The present randomized clinical trial was designed to investigate the efficacy of healing in the treatment of chronic pain. One hundred and twenty patients suffering from chronic pain, predominantly of neuropathic and nociceptive origin resistant to conventional treatments, were recruited from a Pain Management Clinic. The trial had two parts: face-to-face healing or simulated face-to-face healing for 30 min per week for 8 weeks (part I); and distant healing or no healing for 30 min per week for 8 weeks (part II). The McGill Pain Questionnaire was pre-defined as the primary outcome measure, and sample size was calculated to detect a difference of 8 units on the total pain rating index of this instrument after 8 weeks of healing. VASs for pain, SF36, HAD scale, MYMOP and patient subjective experiences at week 8 were employed as secondary outcome measures. Data from all patients who reached the pre-defined mid-point of 4 weeks (50 subjects in part I and 55 subjects in part II) were included in the analysis. Two baseline measurements of outcome measures were made, 3 weeks apart, and no significant differences were observed between them. After eight sessions there were significant decreases from baseline in McGill Pain Questionnaire total pain rating index score for both groups in part I and for the control group in part II. However, there were no statistically significant differences between healing and control groups in either part. In part I the primary outcome measure decreased from 32.8 (95% CI 28.5-37.0) to 23.3 (16.8-29.7) in the healing group and from 33.1 (27.2-38.9) to 26.1 (19.3-32.9) in the simulated healing group. In part II it changed from 29.6 (24.8-34.4) to 24.0 (18.7-29.4) in the distant healing group and from 31.0 (25.8-36.2) to 21.0 (15.7-26.2) in the no healing group. Subjects in healing groups in both parts I and II reported significantly more 'unusual experiences' during the sessions, but the clinical relevance of this is unclear. It was concluded that a specific effect of face-to-face or distant healing on chronic pain could not be demonstrated over eight treatment sessions in these patients.

Aged↗
PubMed1997

Protein dynamics derived from clusters of crystal structures.

A method is presented to mathematically extract concerted structural transitions in proteins from collections of crystal structures. The "essential dynamics" procedure is used to filter out small-amplitude fluctuations from such a set of structures; the remaining large conformational changes describe motions such as those important for the uptake/release of substrate/ligand and in catalytic reactions. The method is applied to sets of x-ray structures for a number of proteins, and the results are compared with the results from essential dynamics as applied to molecular dynamics simulations of those proteins. A significant degree of similarity is found, thereby providing a direct experimental basis for the application of such simulations to the description of large concerted motions in proteins.

Animals↗
PubMed1995

Experimental infection of zebra mussels Dreissena polymorpha (Mollusca:Bivalvia) by metacercariae of Echinoparyphium sp. (Platyhelminthes:Trematoda).

The zebra mussel Dreissena polymorpha a species recently introduced to North America from Europe, was studied to determine whether it could potentially serve as host for echinostomatid metacercariae. Forty adult mussels were collected from the St. Lawrence River and exposed to cercariae of Echinoparyphium sp. that was emerging from naturally infected Physa sp. collected from a native population in northern New York state. When necropsied 24-30 hr postexposure, 2 (5%) of the 40 harbored a metacercaria of Echinoparyphium sp. in the gonad. None of 200 control mussels collected from the same site was infected. This is the first report of any species or stage of echinostomatid from this host species worldwide. This is also the first report of an echinostomatid metacercaria from the gonad of any host species.

Animals↗
PubMed1995

Spontaneous respiration versus controlled ventilation anaesthesia with halothane for intra-ocular surgery.

One hundred and thirty-seven patients were randomly allocated to receive halothane anaesthesia for intra-ocular surgery either by IPPV (n = 71) or breathing spontaneously (n = 66). Both techniques provided satisfactory operating conditions in 87% and 80% of procedures, respectively. Intra-ocular pressure was reduced in a similar majority of patients, rose in a similar percentage (spontaneous = 11%, controlled = 21%) and remained unchanged in a few. Surgeons' reports of good operative conditions correlated very well with intra-ocular pressure changes whether they rose or fell intra-operatively. The duration of anaesthesia and the time taken to achieve full recovery following the two techniques were similar. Post-operative vomiting, headache, sore throat and confusion occurred with similar frequency, and analgesic and antiemetic requirements were not influenced by the technique. Resumption of ambulation, oral intake and micturation occurred similarly. In both groups, patients with a low normal pre-operative intra-ocular pressure tended to show a rise in intra-ocular pressure during anaesthesia, and those with a high normal pre-operative intra-ocular pressure tended to show a fall.

Anesthesia, Inhalation↗
PubMed1994

Importance of components of the curriculum vitae in determining appointment to senior registrar posts.

To evaluate the opinions of regional education advisers, academics and other consultants about features of the curriculum vitae, we undertook a small attitude survey. The response rate was 73%, which provided data from a total of 78 influential anaesthetists. The respondents' attitude to each feature of the curriculum vitae was reported using a linear visual analogue scale. The three groups had similar attitude scores to most features, but not to research time, training time, higher degrees and abstracts of papers presented to the Anaesthetic Research Society. Publications in the main anaesthesia journals, time in other major medical specialties, research and the possession of a higher degree were scored highly by all respondents. Papers in non-peer-reviewed journals, letters, unsubmitted papers, and time in training for general practice attracted lower scores. The free text comments of many respondents indicated a considerable disillusionment about the whole appointments process.

Anesthesiology↗
PubMed1993

Changes in pulmonary function tests during spinal anaesthesia for caesarean section.

We report the changes in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate during caesarean section under spinal anaesthesia, as indirect indices of the ability to cough effectively. There were progressive falls in forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) from the onset of anaesthesia till the abdomen was open, with these results failing to return to pre-incision levels by the time the patient reached the recovery room. Although none of our patients complained of dyspnoea or difficulty in coughing such falls in PEFR and FEV(1) may lead to an inability to cough effectively or clear inhaled vomit especially in patients with previously impaired respiratory function.

Journal Article↗