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Biomedical subjects

J M Barnes

Publications and source records attributed to J M Barnes.

At least 19 recordsLinked to original sources
PubMed2005

Application of stereolithographic custom models for studying the impact of biofilms and mineral precipitation on fluid flow.

Here we introduce the use of transparent experimental models fabricated by stereolithography for studying the impacts of biomass accumulation, minerals precipitation, and physical configuration of flow paths on liquid flow in fracture apertures. The internal configuration of the models ranged in complexity from simple geometric shapes to those that incorporate replicated surfaces of natural fractures and computationally derived fracture surfaces. High-resolution digital time-lapse imaging was employed to qualitatively observe the migration of colloidal and soluble dyes through the flow models. In this study, a Sphingomonas sp. and Sporosarcina (Bacillus) pasteurii influenced the fluid dynamics by physically altering flow paths. Microbial colonization and calcite deposition enhanced the stagnant regions adjacent to solid boundaries. Microbial growth and calcite precipitation occurred to a greater extent in areas behind the fabricated obstacles and less in high-velocity orifices.

Bacteriological Techniques↗
PubMed1999

Constraints facing the female medical practitioner in private family practice in the Western Cape.

OBJECTIVES: To assess the existence and extent of employment-related problems facing female family practitioners in the context of a rapidly growing number of female doctors in South Africa. SUBJECTS AND METHODS: A descriptive survey was conducted using bilingual questionnaires. These were posted to all 280 female family practitioners in private practice in the Western Cape. RESULTS: Of the 280 questionnaires posted 169 were returned, but 45 of these were missampled. A response rate of 53% was obtained. The largest age category was 30-39 years. Of those not in solo practice, 68 (75%) were able to negotiate the terms of their working hours, 13 (19%) negotiated sick leave on commencing work, and only half had paid leave. Vacation leave was negotiated by 34 (50%), while only 6 (9%) discussed maternity leave with employers or colleagues. Of the 124 practices included in the survey, 6 (5%) had formal arrangements to cope with maternity leave. One hundred and seven respondents (86%) felt there was a need for maternity leave guidelines in the private sector in South Africa. Regarding practice-related problems, 33 female family practitioners (27%) reported some incidents of sexual harassment by patients. Despite these constraints, 88 respondents (71%) planned to continue working in this field. CONCLUSION: Definite obstacles exist in private family practice with regard to working conditions, in particular the lack of national regulations regarding maternity leave and the absence of legislation on pregnancy discrimination. This has important implications for the inclusion of female doctors in group practices and managed health care organisations--private primary health care of the present and future!

Adult↗
PubMed1997

Distribution of S(-)-zacopride-insensitive [125I]R(+)-zacopride binding sites in the rat brain and peripheral tissues.

Increasing evidence indicates that the 5-HT3 receptor antagonist R(+)-zacopride labels an additional site in brain tissue that is not sensitive to 5-HT (non-5-HT R(+)-zacopride site, R(+)-site). Since the levels of R(+)-sites in the brain are relatively low, the present studies explored the use of [125I]R(+)-zacopride to label the R(+)-site; the incorporation of an [125I] atom considerably increasing the specific activity of the radioligand relative to [3H]R(+)-zacopride that has been utilised previously. Competition experiments with [125I]R(+)-zacopride (1.0 nM) binding to rat whole brain homogenates, in the presence of the 5-HT3 receptor antagonist granisetron (1.0 microM), identified that R(+)-zacopride and prazosin bound to two sites (pIC50: 7.59 and 5.28, respectively, for R(+)-zacopride; 6.75 and 4.42, respectively, for prazosin) whereas S(-)-zacopride and mianserin possessed relatively low affinity (pIC50: 4.37 and 3.80, respectively) while (-)sulpiride and 5-HT failed to compete for [125I]R(+)-zacopride binding at concentrations up to 10 microM. Autoradiographic radioligand binding studies using [125I]R(+)-zacopride (0.5 nM) identified a heterogeneous distribution of specific binding sites (defined by unlabelled R(+)-zacopride, 1.0 microM) throughout the rat brain. In the presence of a saturating concentration of granisetron (1.0 microM), highest levels of specific [125I]R(+)-zacopride, binding sites (defined by R(+)-zacopride, 1.0 microM; R(+)-site), were detected in the olfactory tubercle, thalamus, corpus callosum, colliculus, dorsal and median raphe nucleus, spinal cord and the pons (8.0-13.0 fmol/mg). Moderate densities of R(+)-sites were located in the striatum, nucleus accumbens, substantia nigra, ventral tegmental area, globus pallidus, septal nuclei, frontal cortex and cerebellum (2.0-7.9 fmol/mg). In the hippocampus, amygdala and cortical areas. R(+)-site levels were low but detectable (0.1-1.9 fmol/mg). [125I]R(+)-zacopride labelled R(+)-sites were also detected in some rat peripheral tissues, for instance kidney cortex, adrenal gland and liver (2.4-6.8 fmol/mg). The present results indicate that specific non-5-HT [125I]R(+)-zacopride sites are heterogeneously distributed throughout the rat brain and are expressed in various peripheral tissues.

Animals↗
PubMed1996

Regulation of glutamate release by presynaptic kainate receptors in the hippocampus.

Most reported actions of kainate are mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors. Here we report that, unlike AMPA which stimulates, kainate elicits a dose-dependent decrease in L-glutamate release from rat hippocampal synaptosomes and also depresses glutamatergic synaptic transmission. Brief exposure to kainate inhibited Ca(2+)-dependent [3H]L-glutamate release by up to 80%. Inhibition was reversed by kainate antagonists but not by the AMPA-selective non-competitive antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466). A corresponding reversible kainate-evoked depression of NMDA (N-methyl-D-aspartate) receptor-mediated excitatory postsynaptic currents (e.p.s.cs) was observed when AMPA receptors were blocked by GYKI 52466. The synaptic depression was preceded by a brief period of enhanced release and a small inward current was also observed. The effects of kainate were unaffected by metabotropic glutamate (mGlu), GABAA, GABAB, glycine and adenosine receptor antagonists. These results indicate that glutamate release can be modulated directly by kainate autoreceptors.

Animals↗
PubMed1996

Autoradiographic distribution of [3H]-(S)-zacopride-labelled 5-HT3 receptors in human brain.

Autoradiographic binding studies using the 5-HT3 (5-hydroxytryptamine3) receptor radioligand, [3H]-(S)-zacopride (0.5 nM), identified a heterogeneous distribution of specific binding sites (defined by granisetron, 1 microM) throughout the human brain. Highest radiolabelled 5-HT3 receptor densities were detected in discrete nuclei within the brainstem (nucleus tractus solitarius, area postrema, spinal trigeminal nerve nucleus; 50-200 fmol/mg tissue equivalent) with more modest levels of expression in the forebrain (e.g. hippocampus, nucleus accumbens, putamen, caudate; 4-17 fmol/mg tissue equivalent). Within the hippocampal formation, radiolabelled 5-HT3 receptors were differentially distributed with highest levels in the granule cell layer of the dentate gyrus. Saturation studies with [3H]-(S)-zacopride (0.05-16 nM; non-specific binding defined by granisetron, 10 microM) binding to homogenates of human putamen indicated that [3H]-(S)-zacopride (0.05-16 nM; non-specific binding defined by granisetron, 10 microM) binding to homogenates of human putamen indicated that [3H]-(S)-zacopride labelled an apparently homogenous population of binding sites (Bmax = 72 + 7 fmol mg-1 protein, pKd = 8.69 +/- 0.09, Hill coefficient = 0.99 +/- 0.06, mean +/- SEM, n = 4). The pharmacological profile of [3H]-(S)-zacopride binding to homogenates of putamen indicated the selective labelling of the human variant of the 5-HT3 receptor. The marked differences, however, in the pharmacology (e.g. low affinity for D-tubocurarine) and relative distribution (e.g. presence of 5-HT3 receptors in the human extrapyramidal system) of 5-HT3 receptors in the human forebrain when compared with other species further necessitates caution in predicting clinical responses based on data generated in animal models of disease.

Adult↗
PubMed1996

Barriers to compliance with OBRA'90 regulations in community pharmacies.

OBJECTIVE: To identify which barriers have been most significant to community pharmacists in their ability to comply with the Omnibus Budget Reconciliation Act of 1990 (OBRA'90) regulations during its first year of implementation. METHODS: Mailing of a two-page survey in April 1994. SETTING: Four hundred randomly selected community pharmacies in the Commonwealth of Massachusetts. PARTICIPANTS: Of 400 pharmacies surveyed, 156 surveys were completed and returned for analysis. RESULTS: Barriers that were considered most significant to pharmacies surveyed in their ability to implement OBRA'90 regulations were excessive workload, lack of financial compensation, and patients' attitudes. Of least significance were inadequate knowledge about drugs, inadequate references, and store layout. Almost half the responding pharmacists indicated that OBRA'90 regulations had not affected or changed their practice, one-quarter of the pharmacists believed their practice was less rewarding after OBRA'90, and about one-fifth believed it was more rewarding. CONCLUSIONS: Community pharmacists in Massachusetts are making an attempt to comply with OBRA'90, but there are specific barriers that are affecting their ability to do so. The OBRA'90 regulations appear to have had little impact on the practice of most community pharmacies. Community pharmacy management needs to examine (1) expanded roles of supportive personnel to give pharmacists more time to spend counseling patients, (2) reimbursement mechanisms for cognitive service, and (3) approaches to educating patients about these changes in the pharmacy profession.

Costs and Cost Analysis↗
PubMed1994

Quantitative analysis of the distributions of glutamatergic ligand binding sites in goldfish brain.

Goldfish brain is a widely used model system for the study of the mechanisms involved in neuronal regeneration and synaptic plasticity. Because of the proposed role of glutamate receptors in these processes we have investigated the anatomical localisations of [3H]AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate), [3H]kainate, [3H]CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and [3H]L-glutamate binding sites in horizontal and sagittal sections. Binding sites for [3H]L-glutamate were the most widespread and both NMDA (N-methyl-D-aspartate) and non-NMDA sensitive components were detected. The density of [3H]kainate binding was very high in the cerebellum compared to other regions and in comparison with the other radioligands used. Conversely, relatively low amounts of [3H]AMPA binding were present with the telencephalon being the most densely labelled structure. [3H]CNQX binding was most densely localised in the tectum with the cerebellum also possessing high binding. In addition, there was a small population of [3H]CNQX binding sites located in the telencephalon and lobus vagi that appeared insensitive to AMPA and kainate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Cyclothiazide unmasks AMPA-evoked stimulation of [3H]-L-glutamate release from rat hippocampal synaptosomes.

The effect of alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) on Ca(2+)-sensitive, tetrodotoxin (TTX)-insensitive K(+)-stimulated [3H]-L-glutamate release from rat hippocampal synaptosomes was determined. AMPA in the presence, but not in the absence of cyclothiazide, a drug which blocks AMPA receptor desensitization, elicited a dose-dependent increase in K(+)-stimulated [3H]-L-glutamate release but had no effect on basal release. The AMPA/cyclothiazide stimulation was blocked by CNQX and by GYKI 52466, an antagonist at the cyclothiazide site. These results indicate that AMPA receptors are present on presynaptic terminals and suggest that they may play a role in the regulation of neurotransmitter release.

Animals↗
PubMed1993

Autoradiographic distribution of glutamatergic ligand binding sites in Xenopus brain: evidence for intracellular [3H]AMPA binding sites.

The binding of a series of [3H]glutamatergic ligands was determined by receptor autoradiography of membrane homogenate pellets and horizontal sections of Xenopus brain. Consistent with previous reports that a 'unitary' glutamate receptor is present in Xenopus CNS, the radioligands showed similar densities of binding sites in the membrane homogenate pellets. Furthermore, [3H]kainate binding was completely displaced by AMPA or CNQX, [3H]AMPA binding was completely displaced by kainate or CNQX and [3H]CNQX binding was completely displaced by AMPA or kainate. However, in whole brain sections there were apparently 2- to 5-fold more [3H]AMPA and [3H]CNQX than [3H]kainate sites. The absence of these extra sites in broken-washed membrane preparations suggests that the additional [3H]AMPA and [3H]CNQX binding may be due to cytosolic sites. The observation that all [3H]AMPA and [3H]CNQX binding in the brain sections is displaced by kainate indicates that the putative cytosolic sites are sensitive to relatively high concentrations of kainate but that they differ from the previously characterised Xenopus CNS unitary receptors.

Animals↗
PubMed1993

Molecular size of the kainate binding protein in goldfish brain determined by radiation inactivation.

Radiation inactivation analysis was used to estimate the target size of a putative glutamate receptor subtype in goldfish brain. A simple, linear inactivation curve was obtained. The calculated molecular size of the [3H]kainate binding site was 33.8 kDa. The results presented here are comparable to the molecular masses determined for putative glutamate receptors in other lower vertebrates but are markedly different from the sizes of the corresponding glutamate receptor subtypes in mammalian central nervous system.

Animals↗
PubMed1993

Differential binding characteristics of agonists at 5-HT3 receptor recognition sites in NG108-15 neuroblastoma-glioma cells labelled by [3H]-(S)-zacopride and [3H]granisetron.

The pharmacological characteristics of 5-HT3 receptor (5-hydroxytryptamine3 receptor) recognition sites labelled with [3H]-(S)-zacopride and [3H]granisetron in membranes prepared from NG108-15 neuroblastoma-glioma cells were directly compared to investigate further differences in the binding characteristics of these two radioligands. Competition curves generated with increasing concentrations of 5-HT3 receptor ligands emphasized the pharmacological similarity of the two recognition sites labelled by [3H]-(S)-zacopride and [3H]granisetron. However, analysis of the nature of the competition curves indicated that 5-HT3 receptor agonists (5-hydroxytryptamine, 2-methyl-5-hydroxytryptamine, phenylbiguanide) and quipazine generated Hill coefficients greater than unity when the 5-HT3 receptor recognition sites were labelled with [3H]granisetron whilst these competing compounds displayed Hill coefficients of around unity when the sites were labelled with [3H]-(S)-zacopride. Competition for either [3H]-(S)-zacopride or [3H]granisetron binding by the 5-HT3 receptor antagonists granisetron and ondansetron generated Hill coefficients around unity. Furthermore, addition of unlabelled (S)-zacopride (1.0 nM) failed to alter the nature by which quipazine competed for the [3H]granisetron-labelled 5-HT3 receptor recognition site. Consistent with 5-HT3 receptors radiolabelled in rat cortical membranes, the present studies indicate that [3H]-(S)-zacopride may label a different site on the 5-HT3-receptor complex compared to [3H]granisetron.

Animals↗
PubMed1993

Identification and characterisation of angiotensin II receptor subtypes in human brain.

Autoradiographic and homogenate binding studies using the radioligand, [125I]angiotensin II, identified a heterogeneous distribution of specific binding sites (defined by angiotensin II, 1.0 microM) throughout the human forebrain. Highest AT receptor densities were detected in the paraventricular nucleus, median eminence, substantia nigra, putamen and caudate nucleus (2.4, 1.2, 1.0, 0.30 and 0.24 fmol/mg tissue equivalent, respectively). The AT1 receptor antagonist, losartan (1.0 microM) competed for the majority of the specific binding. [125I]Angiotensin II-specific binding (although not consistently above non-specific binding levels) was also detected in various other brain regions (e.g. amygdala, entorhinal cortex, frontal cortex, hippocampus, inferior colliculus, nucleus accumbens, parietal cortex, periaquaductal grey, superior colliculus, striate cortex, temporal cortex, thalamus). In the presence of losartan (1.0 microM), angiotensin II, saralasin, losartan and PD123177 competed for [125I]angiotensin II binding to membranes prepared from the cerebellum or substantia nigra with a rank order of affinity; angiotensin II = saralasin > PD123177 > losartan. In the presence of PD123177 (1.0 microM), the rank order of affinity of losartan and PD123177 was reversed. These studies indicate the presence of both AT1 and AT2 receptor subtypes within various regions of the human forebrain.

Aged↗