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Biomedical subjects

V O'Connor

Publications and source records attributed to V O'Connor.

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

Interactions of glycine and strychnine with their receptor recognition sites in mouse spinal cord.

Interactions between the inhibitory neurotransmitter glycine and its receptor antagonist strychnine have been studied in mouse spinal cord membranes and both agents employed to protect against residue selective protein modifying reagents in order to identify contact residues for ligand binding. Glycine was found to behave as a full competitive inhibitor of [3H]-strychnine binding, provided that precautions were taken to prevent radioligand binding to the glass-fibre filters used to terminate the assays. Hill coefficients for the glycine inhibition of [3H]-strychnine binding were not significantly different from one, indicating a lack of cooperative interactions. For the protection experiments, N-bromosuccinimide, tetranitromethane, diethylpyrocarbonate and 2,3-butanedione were used under conditions selective for tryptophan, tyrosine, histidine and arginine residues, respectively. Of these reagents, N-bromosuccinimide, tetranitromethane and diethylpyrocarbonate caused a decrease in total [3H]-strychnine binding without affecting the ability of unlabelled strychnine to compete. In contrast, the same reagents disrupted the ability of glycine to inhibit [3H]-strychnine binding. The presence of either excess glycine (10(-2) M) or strychnine (10(-4) M) during the above treatments was found to prevent the decrease in total and strychnine-specific [3H]-strychnine binding. However, only in the case of diethylpyrocarbonate treatment were both agonist and antagonist able to protect against the loss of glycine-specific [3H]-strychnine binding. The reagent 2,3-butanedione caused an increase in total and strychnine-specific [3H]-strychnine binding (which we have shown elsewhere to be at a site unrelated to the inhibitory glycine receptor). When the above protein modifying reagents were applied under the same conditions to specific strychnine binding antibodies, all four caused significant decreases in subsequent [3H]-strychnine binding. Strychnine was found to afford significant protection of the antibodies against N-bromosuccinimide, tetranitromethane and 2,3-butanedione, but not against diethylpyrocarbonate. Our results suggest that glycine and strychnine compete at overlapping but conformationally distinct sites on the receptor. Tyrosine, tryptophan, histidine and arginine residues are implicated as strychnine contact residues with a shared role for histidine in the recognition of glycine.

Animals↗
PubMed1996

The menopause and hormone replacement therapy: Australian general practitioners' self-reported opinions, attitudes and behaviour.

OBJECTIVES: We describe the attitude and views of general practitioners towards the menopause and hormone replacement therapy (HRT) in metropolitan Brisbane, Australia. METHODS: A total of 216 general practitioners were nominated by a random sample of urband-welling women aged 45-54 years who formed the Brisbane Women's health study. A 20-30 minute face-to-face questionnaire with the general practitioners was administered and analysed by demographic characteristics. RESULTS: There was a 93% response rate. Management of the menopause and HRT was routinely undertaken by general practitioners for their own patients. After deciding to initiate HRT, > 60% of general practitioners ordered five investigations or more. They may have confused the risk of thrombo-embolism from oestrogens used in the post-menopause with that for contraception. There were differences between male and female practitioners in some areas. Male general practitioners, in particular, reported more difficulty with tailoring and adjusting regimes. CONCLUSIONS: Specific areas for further education are explored to meet the educational needs of general practitioners.

Adult↗
PubMed1995

Clostridial neurotoxins compromise the stability of a low energy SNARE complex mediating NSF activation of synaptic vesicle fusion.

A 20S complex composed of the cytosolic fusion proteins NSF and SNAP and the synaptosomal SNAP receptors (SNAREs) synaptobrevin, syntaxin and SNAP-25 is essential for synaptic vesicle exocytosis. Formation of this complex is thought to be regulated by synaptotagmin, the putative calcium sensor of neurotransmitter release. Here we have examined how different inhibitors of neurotransmitter release, e.g. clostridial neurotoxins and a synaptotagmin peptide, affect the properties of the 20S complex. Cleavage of synaptobrevin and SNAP-25 by the neurotoxic clostridial proteases tetanus toxin and botulinum toxin A had no effect on assembly and disassembly of the 20S complex; however, the stability of its SDS-resistant SNARE core was compromised. This SDS-resistant low energy conformation of the SNAREs constitutes the physiological target of NSF, as indicated by its ATP-dependent disassembly in the presence of SNAP and NSF. Synaptotagmin peptides caused inhibition of in vitro binding of this protein to the SNAREs, a result that is inconsistent with synaptotagmin's proposed role as a regulator of SNAP binding. Our data can be reconciled by the idea that NSF and SNAP generate synaptotagmin-containing intermediates in synaptic vesicle fusion, which catalyse neurotransmitter release.

Adenosine Triphosphate↗
PubMed1995

SNAP-mediated protein-protein interactions essential for neurotransmitter release.

The constitutive fusion of transport vesicles with intracellular membranes requires soluble proteins called SNAPs. Certain presynaptic proteins implicated in synaptic vesicle exocytosis also bind SNAPs, suggesting that SNAPs participate in the calcium-regulated membrane fusion events mediating neurotransmitter release. Here we show that injection of recombinant SNAPs into the giant synapse of squid enhances transmitter release. Conversely, injection of peptides designed to mimic the sites at which SNAP interacts with its binding partners inhibits transmitter release downstream of synaptic vesicle docking. A SNAP-dependent protein complex must therefore mediate transmitter release, showing that transmitter release shares a common molecular mechanism with constitutive membrane fusion.

Amino Acid Sequence↗
PubMed1995

Women's perceptions and experience of menopause: a focus group study.

Focus groups were used to investigate women's perception and experience of menopause, hormone replacement therapy, osteoporosis and doctor-patient relationships. Forty women aged between 45 and 55 years participated in seven focus groups. Most women thought that these topics were not widely or freely discussed in the community. Nevertheless they were able to share their experiences on this occasion. Lack of reliable, accessible and current information on menopause and related topics was identified as a problem. This was compounded by the contradictory nature of the information which was available. Hysterectomy and osteoporosis were identified as specific areas in which information was inadequate and not readily accessible. Solutions suggested by the women included distributing information pamphlets with contact numbers for further information to non-health-related settings such as hairdressing salons. The need to foster open discussion between women and their doctors was highlighted, with contributions required from both parties to develop a more equal partnership. A review of doctors' and women's surveillance practices with regard to hormone replacement therapy may also be warranted. We found focus groups a useful method for accessing women's experiences and perceptions. There was particular benefit in researchers being involved as moderators and scribes, and in an early post-focus group meeting to amplify and clarify records of the discussions. Small group size and an emphasis on confidentiality were, we believe, helpful strategies in encouraging discussion of intimate topics.

Attitude to Health↗
PubMed1994

Fusion complex formation protects synaptobrevin against proteolysis by tetanus toxin light chain.

The clostridial neurotoxin, tetanus toxin, is a Zn(2+)-dependent protease which inhibits neurotransmitter exocytosis by selective cleavage of the synaptic vesicle protein, synaptobrevin. Synaptobrevin is thought to serve as a receptor for two neuronal plasma membrane proteins, syntaxin and SNAP-25, which in the presence of non-hydrolyzable ATP analogs form a 20 S fusion complex with the soluble fusion proteins NSF and alpha-SNAP. Here we show that synaptobrevin, when in this 20 S complex, or its 7 S precursor, is protected against proteolysis by the enzymatically active tetanus toxin light chain. Our data define distinct pools of synaptobrevin, which provide markers of different steps of vesicle/plasma membrane interaction.

Animals↗
PubMed1994

The N-ethylmaleimide-sensitive fusion protein (NSF) is preferentially expressed in the nervous system.

NSF and SNAPs (soluble NSF attachment proteins), originally identified as cytosolic components of intracellular vesicular transport mechanisms, have recently been implicated in Ca(2+)-triggered neurotransmitter release from synaptic terminals. Here, we have investigated the temporal and spatial expression pattern of the rodent NSF and SNAP genes. A single transcript of 4.5 kb is highly expressed in rat brain, whereas only minor amounts of NSF mRNA are found in liver, kidney, heart, lung and skeletal muscle. In situ hybridisation revealed NSF transcripts as early as embryonic day 10 preferentially in the nervous system of mouse embryos. In the adult brain NSF is widely expressed with particularly high levels in the hippocampus. An identical expression profile was observed for alpha/beta-SNAP. Our data are consistent with a central function of NSF and SNAPs in neurotransmission.

Animals↗
PubMed1994

General practitioners in public obstetrics--an underutilized resource.

We questioned 229 general practitioners (GPs), 288 women who had recently delivered babies in public hospitals, 26 public hospital doctors, and 33 midwives in South Brisbane. Shared antenatal care was undertaken by 84% of mothers, and recently provided by 88% GPs. Mothers valued having sufficient time with their antenatal clinician, continuity of care, and short waiting and travel times. They preferred a GP to provide antenatal care, and a hospital midwife to deliver them. GPs were interested in providing even more obstetric care--one third in providing intrapartum care--and in gaining continuing education in obstetrics. Hospital doctors and midwives were supportive of women choosing the personnel to deliver them, and of an increased GP and midwife role in public hospital obstetrics, but unenthusiastic about home deliveries. There is widespread support for an increased role for GPs in public obstetrics.

Attitude of Health Personnel↗
PubMed1987

Consumer obstetrics.

OBJECTIVE: To investigate the perceptions of patients about delivery of their babies. METHOD: One hundred and forty four out of 200 surveyed women answered consumer orientated questions before and after delivery. RESULTS: They were on the whole satisfied with antenatal classes (there seemed to be a need for more information in the form of an on-the-ward postnatal class), disliked the practice of perineal shaves (but did not object to enemas or rupture of membranes) and felt they had adequate analgesia (although not for after-pains or the discomfort of haemorrhoids in the puerperium). Women who intend to deliver in the more (western) conventional positions are less likely to be disappointed. Women expressed the desire to be more actively involved in some aspects of delivery such as cutting the cord, putting the baby to the breast and being alone with partner and baby immediately after delivery. Cardiotocography (CTG) is more reassuring than frightening. A "Birthing Room" is seen as a satisfactory alternative to home delivery.

Anesthesia, Obstetrical↗