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Biomedical subjects

S Barnes

Publications and source records attributed to S Barnes.

At least 181 records · Page 10Linked to original sources
PubMed1989

The role of marital intimacy in psychiatric help-seeking.

Epidemiological studies have shown that most people with diagnosable psychiatric illnesses do not seek professional help. Symptoms of non-psychotic emotional illness, interpersonal relationship quality and personality traits have demonstrable associations. The influence of these factors on help-seeking was examined by comparing 57 psychiatric outpatients with a community sample of 90 symptomatic individuals on self-report measures of marital intimacy, life events, and personality, while controlling for symptomatology. Compared to non-patients, outpatients reported less intimacy in their marriages across a variety of relationship dimensions on the Waring Intimacy Questionnaire, and scored higher on the Psychoticism scale of the Eysenck Personality Questionnaire. Marital Intimacy level proved to be the best single predictor of patient and non-patient status, suggesting that help-seeking behaviour may be partly motivated by unsatisfactory marriages. The detection of low marital intimacy in these help-seekers might be an indication for prescribing marital therapy.

Adult↗
PubMed1989

Bile acid sulfotransferase I from rat liver sulfates bile acids and 3-hydroxy steroids: purification, N-terminal amino acid sequence, and kinetic properties.

A bile acid:3'phosphoadenosine-5'phosphosulfate:sulfotransferase (BAST I) from adult female rat liver cytosol has been purified 157-fold by a two-step isolation procedure. The N-terminal amino acid sequence of the 30,000 subunit has been determined for the first 35 residues. The Vmax of purified BAST I is 18.7 nmol/min per mg protein with N-(3-hydroxy-5 beta-cholanoyl)glycine (glycolithocholic acid) as substrate, comparable to that of the corresponding purified human BAST (Chen, L-J., and I. H. Segel, 1985. Arch. Biochem. Biophys. 241: 371-379). BAST I activity has a broad pH optimum from 5.5-7.5. Although maximum activity occurs with 5 mM MgCl2, Mg2+ is not essential for BAST I activity. The greatest sulfotransferase activity and the highest substrate affinity is observed with bile acids or steroids that have a steroid nucleus containing a 3 beta-hydroxy group and a 5-6 double bond or a trans A-B ring junction. These substrates have normal hyperbolic initial velocity curves with substrate inhibition occurring above 5 microM. Of the saturated 5 beta-bile acids, those with a single 3-hydroxy group are the most active. The addition of a second hydroxy group at the 6- or 7-position eliminates more than 99% of the activity. In contrast, 3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oic acid (deoxycholic acid) is an excellent substrate. The initial velocity curves for glycolithocholic and deoxycholic acid conjugates are sigmoidal rather than hyperbolic, suggestive of an allosteric effect. Maximum activity is observed at 80 microM for glycolithocholic acid. All substrates, bile acids and steroids, are inhibited by the 5 beta-bile acid, 3-keto-5 beta-cholanoic acid. The data suggest that BAST I is the same protein as hydrosteroid sulfotransferase 2 (Marcus, C. J., et al. 1980. Anal. Biochem. 107: 296-304).

Amino Acid Sequence↗
PubMed1989

The group approach to living with stress: four years on.

In 1984, working as health visitors in the East Dorset Health Authority, we began to run courses to assist people with stress related conditions. The courses were based on counselling and group activity methods to encourage a positive health approach to solving the patients' problems. The initial results were very encouraging, and after completing three groups, we assessed our results which were reported in the Journal in January 1986 in a paper entitled 'the group approach to living with stress'. Requests for places in the stress groups have continued to be high, and courses are now a regular feature of the services offered at the health centre. This paper discusses the development of our stress management programmes, after a further three years experience, summarising our current methods, together with an assessment of the benefits achieved for patients. The study to determine the degree of improvement achieved, and whether this is maintained in the long term has been carried out with advice from Gerald Bennett, a clinical psychologist who also works for East Dorset Health Authority. Dr Bennett analysed the results of the study, and we are grateful to him for his considerable assistance in helping to present an objective view of our work, and in particular for the clear way in which he has written up the analysis, which has been embodied in this paper.

Counseling↗
PubMed1988

The effects of calcium channel agonists and antagonists on the release of endogenous glutamate from cerebellar slices.

The effects of compounds acting at the calcium channel on neurotransmitter release are equivocal. We report here the effects of the antagonists, verapamil, diltiazem and nifedipine; the agonists, bay K8644 and the calcium ionophore, A23187 on the release of endogenous glutamate from rat cerebellar slices. Of these compounds, only verapamil and diltiazem modified glutamate release and these were effective at relatively high concentrations (greater than 1 x 10(-5) M). It is suggested that the high-affinity binding sites found in neuronal tissue for the dihydropyridine-like compounds are not involved in neurotransmitter release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Formation of conjugates of 2-fluoro-beta-alanine and bile acids during the metabolism of 5-fluorouracil and 5-fluoro-2-deoxyuridine in the isolated perfused rat liver.

We have recently demonstrated that the major biliary metabolite of 5-fluorouracil (FUra) in cancer patients is a conjugate of the FUra catabolite 2-fluoro-beta-alanine (FBAL) and cholic acid (D.J. Sweeny, S. Barnes, G. Heggie, and R.B. Diasio. Proc. Natl. Acad. Sci. USA, 84:5439-5443, 1987). This finding prompted us to further examine the metabolism and biliary excretion of clinically relevant concentrations of the fluoropyrimidines FUra and 5-fluoro-2'-deoxyuridine (FdUrd) using the isolated perfused rat liver. During infusion of fluoropyrimidines, rates of appearance of metabolites in bile were similar with both 1 microM FUra and 1 microM FdUrd but were 9-fold higher with 25 microM FUra. Analysis by high performance liquid chromatography demonstrated that unmetabolized fluoropyrimidines and known catabolites (i.e., FBAL) accounted for less than 15% of the total metabolites in bile and that the majority of the biliary metabolites were eluted as three distinct nonpolar compounds. Fast atom bombardment-mass spectrometry demonstrated that these unique metabolites had molecular weights of 497 (peak 1), 497 (peak 2), and 481 (peak 3). These metabolites were hydrolyzed by cholylglycine hydrolase to FBAL and unconjugated bile acids that were identified by gas chromatography-mass spectrometry to be alpha-muricholic acid (peak 1), cholic acid (peak 2), and chenodeoxycholic acid (peak 3). Thus, the major biliary metabolites of FUra and FdUrd were identified as N-(bile acid)-FBAL conjugates. While the N-(bile acid)-FBAL conjugates were the major metabolites in bile, dihydroFUra was the major (greater than 70%) metabolite eliminated into perfusate. In summary, these results demonstrate that FUra and FdUrd undergo similar metabolism in the isolated perfused rat liver and, as was observed in humans, the major biliary fluoropyrimidine metabolites are conjugates of FBAL and bile acids.

Alanine↗
PubMed1988

A novel superfusion chamber for the measurement of endogenous glutamate release from cerebellar slices.

Methods are described for use in the study of potassium-stimulated release of endogenous glutamate and aspartate from perfused cerebellar slices using high performance liquid chromatography (HPLC) with fluorometric detection. Slices were cut at 250 micron in one direction only, and were thus similar to those used for electrophysiological techniques. Details of an easily constructed, simple superfusion system are given. HPLC isocratic separation was used to assay aspartate and glutamate release, glutamate alone showing calcium-dependent release. Repetitive pulses of high potassium-containing artificial cerebrospinal fluid induced release of glutamate (six pulses), demonstrating that the tissue was viable and capable of repeated release.

Animals↗
PubMed1988

Veratridine modifies open sodium channels.

The state dependence of Na channel modification by the alkaloid neurotoxin veratridine was investigated with single-channel and whole-cell voltage-clamp recording in neuroblastoma cells. Several tests of whole-cell Na current behavior in the presence of veratridine supported the hypothesis that Na channels must be open in order to undergo modification by the neurotoxin. Modification was use dependent and required depolarizing pulses, the voltage dependence of production of modified channels was similar to that of normal current activation, and prepulses that caused inactivation of normal current had a parallel effect on the generation of modified current. This hypothesis was then examined directly at the single-channel level. Modified channel openings were easily distinguished from normal openings by their smaller current amplitude and longer burst times. The modification event was often seen as a sudden, dramatic reduction of current through an open Na channel and produced a somewhat flickery channel event having a mean lifetime of 1.6 s at an estimated absolute membrane potential of -45 mV (23 degrees C). The modified channel had a slope conductance of 4 pS, which was 20-25% the size of the slope conductance of normal channels with the 300 mM NaCl pipette solution used. Most modified channel openings were initiated by depolarizing pulses, began within the first 10 ms of the depolarizing step, and were closely associated with the prior opening of single normal Na channels, which supports the hypothesis that modification occurs from the normal open state.

Animals↗
PubMed1988

Dysthymia: a randomized study of cognitive marital therapy and antidepressants.

Preliminary data from a randomized study of the effectiveness of combined marital therapy and antidepressant medication in the treatment of dysthymic married women is presented. The study compares doxepin with placebo, and a marital therapy designed to enhance intimacy through facilitating self-disclosure between spouses with a more supportive and educational therapeutic approach. After ten weeks of combined treatment, the dysthymic women show statistically significant improvement on all the depression measures as well as on the intimacy scale. A trend is developing for greater reduction of depressive symptomatology in the group treated with self-disclosure. The evidence appears to suggest the possibility that the presence of a patient's husband as a supportive figure may of itself be a potent therapeutic manoeuvre in the treatment of dysthymic women.

Clinical Trials as Topic↗
PubMed1987

Structure of the dysprosium-glycocholate complex in submicellar aqueous solution: paramagnetic mapping by proton nuclear magnetic resonance spectroscopy. An approximation for the intrinsic "bound" relaxation rates in the case of nondilute paramagnetic systems.

A paramagnetic NMR study of the structure of the calcium-glycocholate complex in submicellar solution, utilizing dysprosium as an isomorphous lanthanide replacement of calcium, is presented. The dysprosium-induced relaxation rate (1/T1) enhancements of certain glycocholate protons have been used to estimate internuclear distances between these protons and the metal ion. An approximation to calculate the intrinsic relaxation rate (1/T1) enhancements for a nondilute paramagnetic solution is given in the Appendix. From these data, and analysis based on conformation averaging and minimum energy conformations, a molecular model of the dysprosium-glycocholate complex in submicellar aqueous solution has been constructed. In this model the metal ion has a unidentate, first-sphere interaction with the proximal oxygen atom of the glycine carboxyl. The metal ion has second-sphere interactions with the peptide bond carbonyl oxygen (3.6 A) and the distal carboxyl oxygen (4.4 A). The metal ion to hydroxyl oxygen distances (8.4-12.4 A) are not compatible with any metal ion to hydroxyl coordination. The side chain appears to exist in one predominant conformation. All six oxygen atoms of glycocholate, the peptide bond carbonyl, the carboxyl group, and the hydroxyl groups are on the alpha face of the bile salt molecule. On the basis of these features we conclude that in the submicellar state the solution structure of the dysprosium-glycocholate complex displays a metal ion enhanced segregation of polar versus nonpolar groups to the two separate faces of the molecule, which may result in a facilitated hydrophobic interaction of different complex units.

Computer Simulation↗
PubMed1987

Enantiomeric composition analysis of amphetamine and methamphetamine by chiral phase high-performance liquid chromatography-mass spectrometry.

N-(Trifluoroacetyl)-l-prolyl- (N-TFA-l-prolyl-) d- and l-amphetamine diastereoisomers were separated by high-performance liquid chromatography and confirmed by an interfaced mass spectrometer system, using the commercially available N-3,5-(dinitrobenzoyl)phenylglycine chiral column. A separation factor of 1.52 and resolution of 3.8 were observed. N-TFA-l-prolyl-d- and -l-methamphetamine diastereoisomers were only partially resolved. The chiral stationary phase-solute interactions were studied by varying the mobile phase (2-propanol in hexane). Results indicate the separation mechanism proceeds via dipolar and hydrogen-bond interactions between the chiral stationary phase and the solute. A modified "dipole-stacking" model takes into account these interactions and explains the difference in separability observed for N-TFA-l-prolyl-d- and -l-amphetamine and N-TFA-l-prolyl-d- and -l-methamphetamine.

Amphetamine↗
PubMed1987

Direct excitatory and lateral inhibitory synaptic inputs to amacrine cells in the tiger salamander retina.

Two distinct synaptic currents in amacrine cells were measured using whole cell patch clamp in retinal slices. Synaptic activity was elicited with transretinal current passed from photoreceptors to ganglion cells to depolarize bipolar cell terminals. Recordings made in line with the stimulating electrodes revealed inward synaptic currents that reversed near O mV, positive to spike threshold. Recording 400 micron lateral to the stimulating electrodes revealed synaptic currents that reversed near-60 mV, negative to spike threshold. The lateral signal was blocked by tetrodotoxin and strychnine. A current with reversal potential similar to the lateral input was elicited by direct application of glycine to the amacrine cells. The results suggest that bipolar, but not amacrine input can elicit spikes in neighboring amacrine cells, that amacrine cells are mutually inhibitory and the inhibitory lateral transmission is limited to the extent of processes of the excited, spiking cell.

Animals↗
PubMed1987

Metabolism of 5-fluorouracil to an N-cholyl-2-fluoro-beta-alanine conjugate: previously unrecognized role for bile acids in drug conjugation.

Recently we demonstrated clinically significant levels of a previously unrecognized metabolite of the anticancer drug 5-fluorouracil (FUra) in bile of cancer patients. In the present study, reanalysis of bile from these patients demonstrated the presence of not one but two previously unrecognized metabolites. The major unrecognized metabolite was purified by reversed-phase HPLC, after which its molecular weight was determined by fast-atom-bombardment mass spectrometry to be 497. The similarity in HPLC retention times and molecular weights of this FUra derivative and the bile acids N-cholylglycine (Mr 465) and N-cholyltaurine (Mr 515), along with the structural similarity of the FUra catabolite 2-fluoro-beta-alanine and the amino acids glycine and taurine, led to the hypothesis that this metabolite could be a conjugate of 2-fluoro-beta-alanine and cholic acid. This hypothesis was tested and confirmed by hydrolyzing the purified metabolite by cholylglycine hydrolase after which: 2-fluoro-beta-alanine was demonstrated by using a sensitive HPLC technique capable of resolving all of the known putative FUra metabolites, and unconjugated cholic acid was identified by both GC and GC-MS. Additionally, chemically synthesized N-cholyl-2-fluoro-beta-alanine was shown to cochromatograph on HPLC and TLC with the purified biliary metabolite. In summary, this study demonstrates a unique, so far as we know, pathway of drug metabolism in man in which an amino acid drug metabolite is conjugated with cholic acid and eliminated into the bile. Furthermore, the finding that 2-fluoro-beta-alanine is conjugated to bile acids may provide some insight into the mechanism of cholestasis that is frequently observed after administration of fluoropyrimidine by hepatic arterial infusion.

Alanine↗
PubMed1987

The interaction of ionic currents mediating single spike activity in retinal amacrine cells of the tiger salamander.

We investigated the ionic interactions responsible for the characteristic nonrepetitive spike activity of amacrine cells. First we measured 4 pharmacologically separable ionic components: a voltage-gated, transient inward sodium current, a voltage-gated, sustained inward calcium current, a calcium-gated, sustained outward potassium current, and a voltage-gated, transient outward potassium current. The measurements provided the time course and magnitudes of the underlying conductances as functions of voltage. Each current was simulated following conventional Hodgkin-Huxley theory. A composite of the simulated currents was analytically reassembled to generate an approximation of the voltage response to a current step. By artificially varying the magnitude and kinetics of the different conductances in the simulation, we determined the range of values that supported the nonrepetitive spike-like response. Amacrine cells tend to remain refractory following an initial spike because (1) the entire activation range for potassium is located at positive potentials with respect to sodium inactivation, so sodium inactivation is never fully extinguished, and (2) the fully activated sodium conductance is of insufficient magnitude to subsequently reach threshold, given this residual inactivation. Shifting the sodium inactivation range by 10 mV, or increasing sodium conductance by 5 times, leads to a more repetitive form of activity. Changes in the magnitude, time course, or activation range of the potassium conductance cannot alter these conditions.

Animals↗
PubMed1986

Gated currents generate single spike activity in amacrine cells of the tiger salamander retina.

Amacrine cells form the neural networks mediating the second level of lateral interactions in the vertebrate retina. Members of a prominent class of amacrine cells, found in most vertebrates, respond at both the onset and termination of steps of illumination with a single, large transient depolarization. We show here how specific relationships between membrane currents control this single spike activity. Using whole-cell patch clamp on living retinal slices, we studied the membrane currents in amacrine cells. The currents elicited by depolarizing voltage steps could be separated into three main ionic components: a transient inward voltage-gated sodium current, a relatively small sustained inward voltage-gated calcium current, and a calcium-dependent outward current. A specific relationship between the sodium and potassium current alone appears to preclude repetitive spike activity. Potassium current is activated at potentials positive to -20 mV, but the sodium inactivation, between -60 and -20 mV, does not intersect potassium activation. Therefore, a steady depolarizing current step elicits an initial spike but then the membrane cannot be sufficiently hyperpolarized by potassium current to remove sodium inactivation and the cell remains refractory.

Action Potentials↗
PubMed1986

Biologic properties of cell lines derived from canine mammary carcinomas.

Six canine mammary tumor cell lines (5 epithelial, 1 myoepithelial) were established from dogs with spontaneous mammary carcinomas. The cells were characterized for features of morphology and growth patterns on plastic, ultrastructure, cloning efficiency in soft agar, tumorigenicity in athymic nude mice, and hormonal receptor status. Biologic properties of the cell lines were distinct and preserved during long-term culture in vitro. All cell lines were clonogenic, 5 of 6 were tumorigenic, and 3 of 5 were receptor positive for estrogen and/or progesterone.

Animals↗