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Biomedical subjects

D J Baker

Publications and source records attributed to D J Baker.

At least 73 records · Page 4Linked to original sources

Effect of opioid peptides and potassium on the release of vasoactive intestinal polypeptide and thyrotropin releasing hormone from perifused rat hypothalami.

Opioid peptides have been demonstrated to stimulate prolactin secretion, and it has been postulated that this is mediated, at least in part, by an effect on hypothalamic prolactin releasing and release-inhibiting factors and neurotransmitters. The aim of this study was to investigate the effect of opioid peptides and depolarizing concentrations of K+ on the release of both vasoactive intestinal polypeptide (VIP) and thyrotropin releasing hormone (TRH) from perifused rat hypothalami. Both met-enkephalin and beta-endorphin stimulated the release of VIP significantly whilst not affecting the release of TRH. In addition, leu-enkephalin was found to have no effect on the release of either VIP or TRH. In contrast, depolarizing concentrations of K+ (50 mM) were found to cause the immediate release of TRH, but not VIP, from the same perifusion. The results suggest a role for VIP, but not TRH, in opioid peptide stimulated release of prolactin. In addition, the data indicates that a substance may be released in response to K+ depolarization which is inhibitory to the release of VIP.

Animals↗

Normality of single fibre electromyographic jitter: a new approach.

The distribution of jitter values derived from single fibre electromyography (SFEMG) in normal extensor digitorum communis has been found to be skewed. A reciprocal transformation technique is presented which renders the distribution normal. The distribution enables SFEMG changes to be assessed using parametric statistics. The relationship of the new technique to existing methods of analysis of SFEMG is discussed.

Electromyography↗

Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogues.

By the use of molecular models of Escherichia coli dihydrofolate reductase (DHFR), analogues of trimethoprim (TMP) were designed which incorporated various 3'-carboxyalkoxy moieties in order to acquire ionic interactions with positively charged active-site residues. Certain of these compounds have shown exceptionally high affinity for this enzyme. For example, the 3'-(carboxypentyl)oxy analogue was found to be 55-fold more inhibitory than TMP toward E. coli DHFR (Ki = 0.024 nM vs. 1.32 nM for TMP). X-ray crystallographic studies of E. coli DHFR in binary complexes with TMP and two members of this acid-containing series of compounds defined the binding of these inhibitors and showed the carboxyl group of the latter two inhibitors to be ionically bound to Arg-57. These observations were in agreement with postulated binding modes that were based on receptor modeling.

Binding Sites↗

Presynaptic alpha-adrenoceptors: do exogenous and neuronally released noradrenaline act at different sites?

The effects of dopamine receptor and alpha-adrenoceptor agonists and antagonists on the stimulation-evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]-noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptake inhibitors, noradrenaline (0.1-1 X 10(-6)M) and dopamine (0.01-1 X 10(-6)M) both inhibited the stimulation-evoked overflow of radioactivity. Sulpiride (1 X 10(-6)M) was without effect and prazosin (1 X 10(-7)M) had little effect on stimulation-evoked overflow but yohimbine enhanced it approximately 2 fold; the effect of yohimbine was similar at concentrations of 1 X 10(-7) and 1 X 10(-6)M. Sulpiride abolished the inhibitory effect of dopamine on stimulation-evoked overflow, but was without effect against noradrenaline. When allowance was made for the effects of yohimbine, alone, on overflow, yohimbine (1 X 10(-7)M) had no effect against dopamine and minimal effects against noradrenaline. A similar result was obtained when the concentration of yohimbine was increased to 1 X 10(-6)M. Prazosin did not antagonize the effect of noradrenaline. In the absence of the uptake inhibitors, clonidine (0.01-1 X 10(-5)M) inhibited stimulation-evoked overflow of radioactivity. Yohimbine (1 X 10(-6)M) was without effect on its own and antagonized the effects of clonidine at a concentration of 0.1 X 10(-5)M, but not at 0.01 or 1.0 X 10(-5)M. These findings suggest that dopamine inhibits overflow by stimulating presynaptic dopamine receptors on the terminals of the noradrenergic nerves supplying the dog saphenous vein. The interaction between yohimbine and noradrenaline is discussed in terms of the current concepts of control of transmitter release mediated via presynaptic alpha 2-adrenoceptors.

Animals↗

Anaesthesia during the Falklands campaign. The experience of the Royal Navy.

The work of nine Naval anaesthetists deployed with the Task Force during the Falklands campaign is described. The anaesthetists worked in a field hospital (Ajax Bay), a hospital ship (SS Uganda), a troop ship (SS Camberra), aircraft carriers (HMS Hermes and HMS Invincible) and a Royal Fleet Auxiliary (Tidespring). The problems of staffing and providing the stores for various teams in different locations at short notice are discussed.

Anesthesia↗

An investigation into the possible physiological roles of vascular alpha 1- and alpha 2-adrenoreceptors.

1 We have investigated the influence of chemical sympathectomy or bilateral adrenal demedullation on vasopressor responses produced by the alpha 1-adrenoreceptor agonist, phenylephrine, and the alpha 2-adrenoreceptor agonist, M-7, in pithed rats to see whether either procedure induced selective supersensitivity to either of these compounds. 5-HT, a tryptaminergic vasopressor agent, was also used to discriminate between nonspecific change in vascular responsiveness and those mediated via alpha-adrenoreceptors. 2 Adrenal demedullation caused a slight reduction in the sensitivity to all agonists. Chemical sympathectomy significantly reduced the vasopressor responses to all doses of phenylephrine, but responses to 5-HT were unchanged. In contrast there was a tendency for responses to M-7 to be greater in sympathectomized rats than in untreated rats. 3 It is concluded that circulating adrenal medullary catecholamines do not physiologically modulate vascular alpha-adrenoreceptor function. The differential effect of chemical sympathectomy on the vasopressor responses to phenylephrine and M-7 might be explained in terms of a small increase in the ratio of vascular alpha 2 : alpha 1-adrenoreceptors, that receive a noradrenergic innervation.

Adrenal Medulla↗

Effects on superiority of ear of intonation of dichotically presented sentences.

A dichotic listening paradigm utilizing sentences of three monosyllabic words examined the effects of intonation on superiority of ear. Five types of intoned contours, i.e., declarative, interrogative, imperative, conditional, and monotone, were employed. Subjects consisted of 20 adults who had normal hearing bilaterally, were native English speakers, and were righthanded in 100% of their daily activities. The results indicated that, when three monosyllabic work sentences with four different intoned contours were dichotically presented, superiority of neither left nor right ear was evidenced. However, the declarative intoned contours, being linguistically less marked, were perceived with significantly less accuracy than the relatively more marked interrogative, imperative, and conditional intoned contours.

Adult↗

Susceptibility of a dwarf strain of chickens to rickets.

A sex-linked dwarf strain of chickens fed a practical chick starter had a high incidence of rickets while other strains, including the Cornell K strain reared under the same conditions, had no evidence of this disease. In studies of the calcium, phosphorus and vitamin D requirements of the dwarf and K strains, no strain differences in requirement for phosphorus or vitamin D for maximal bone mineralization were apparent. The vitamin D requirement for growth was less for dwarfs than for the K strain; the reverse was observed for phosphorus. A marginal level of calcium (0.6%) did not depress growth or bone ash in either strain. Dwarfs had significantly lower bone ash than chicks of the K strain when dietary levels of calcium, available phosphorus and vitamin D were adequate (1.0%, 0.73% and 400 I.U./kg., respectively). When the diet contained a low level of one nutrient (0.6% calcium, 0.33% of phosphorus or 100 I.U./kg. vitamin D), neither strain was affected. Low levels of two nutrients significantly decreased bone ash in dwarfs but not in the K strain. Low levels of all three nutrients depressed bone ash in both strains, but most markedly in the dwarfs. These studies indicate that chicks of the Cornell dwarf strain have a low bone mineral content and are unusually susceptible to rickets.

Animals↗