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Biomedical subjects

I Kennedy

Publications and source records attributed to I Kennedy.

At least 19 recordsLinked to original sources

Do adenosine A3 receptors exist?

1. It has been suggested that adenosine A1 receptors may be sub-divided into A1 and A3 types, based on the relative potencies of 5'-N-ethylcarboxamidoadenosine (NECA) and selected N6-substituted adenosine analogues. At A1 receptors (rat adipocytes) N6-phenylisopropyladenosine (PIA) was reported to be approx. 100-fold more potent than NECA, whereas the compounds were equipotent at A3 receptors (those in cardiac and neuronal preparations). 2. The study reported here has systematically evaluated this proposal, the rank orders of potency of NECA, R- and S-PIA, N6-cyclopentyladenosine (CPA) and N6-cyclohexyladenosine (CHA) being determined in rat adipocytes, guinea-pig ileum and rat and guinea-pig atria. 3. R-PIA, CHA and CPA were found to have consistent potencies relative to NECA across all 6 tissues, including rat adipocytes. The rank order was CPA greater than or equal to CHA, R-PIA greater than or equal to NECA greater than S-PIA. 4. We conclude that the relative potencies of these agonists do not support the concept that adenosine A1 receptors in rat adipocytes differ from those in neuronal and cardiac tissues.

Adenosine

Somatosensory and auditory brain stem conduction after head injury: a comparison with clinical features in prediction of outcome.

Evoked potential conduction times in brain stem auditory (BCT) and central somatosensory pathways (CCT) were recorded from 23 normal subjects and 101 patients with severe head injury. Abnormalities in the CCT and the BCT findings correlated with the clinical indices of brain damage (coma score, motor response, pupil response, and spontaneous and reflex eye movements) in the head-injured patients and each correlated with outcome at 6 months from the injury. The CCT in the "best" hemisphere produced the strongest correlation with outcome (P less than 0.001). The correlation of the CCT with outcome was stronger in the 47 patients examined 2 to 3 days after the injury (P less than 0.001) compared to the 34 patients examined within 24 hours after the injury (P less than 0.02). No such difference was noted for the BCT. Serial studies within the first 2 weeks of injury did not show a consistent pattern and repetition of the investigation over this period did not provide any additional information. We used an INDEP-SELECT discriminant analysis program to determine whether information from the evoked potential data could improve prediction of outcome based on clinical data alone. With the addition of the CCT, the predictive accuracy (expressed as the correct classification probability) increased only slightly from 77 to 80%, and the difference was not significant. We conclude that central somatosensory and auditory brain stem conduction times provide useful prognostic information in paralyzed or sedated patients, but when neurological examination is feasible the benefits of evoked potential analysis do not justify the effort involved in data collection.

Acoustic Stimulation

The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea-pig trachea.

1. Isolated segments of guinea-pig trachea or perfused tracheal tubes were arranged for the recording of trachealis tension changes in Krebs solution containing indomethacin (2.8 microM). 2. In opened tracheal segments, epithelium removal caused modest (2-3 fold) potentiation of the effects of acetylcholine (ACh) and methacholine (MeCh) but failed to potentiate carbachol (CCh), bethanechol (BeCh), oxotremorine or KCl. 3. Pretreatment with ecothiopate potentiated effects of ACh and MeCh but not of CCh or BeCh. Removal of epithelium in ecothiopate-treated tissue potentiated effects of ACh and MeCh but not of CCh or BeCh. 4. Guinea-pig ileum challenged with ACh was used as a bioassay system for cholinesterase activity. Scrapings of tracheal epithelium did not hydrolyse ACh. 5. Histochemical staining revealed no fibres positive for acetylcholinesterase or pseudocholinesterase in the tracheal epithelium. However, the underlying tissues contained acetylcholinesterase-positive nerve fibres and the trachealis muscle itself stained positively for pseudocholinesterase activity. 6. Neither tetrodotoxin (3 microM) nor hexamethonium (500 microM) modified the ability of epithelium removal to potentiate ACh. 7. In perfused tracheal tubes where spasmogens were added to the luminal perfusate, epithelium removal potentiated effects of ACh (31 fold), CCh (10 fold), oxotremorine (2 fold) and KCl. 8. In perfused tracheal tubes where spasmogens were added to the Krebs solution superfusing the adventitial surface of the tissue, epithelium removal significantly reduced the potency of CCh, oxotremorine and KCl. 9. It is concluded that the selectivity and magnitude of the potentiation of cholinomimetics caused by epithelium removal depends on the route by which the cholinomimetic agent gains access to the trachealis muscle. The potentiation of acetic acid esters of choline seen in opened tracheal segments does not reflect the loss of epithelial cholinesterase activity and does not depend on the activity of nervous reflex arcs in the tracheal wall. The reduced potency of adventitially-applied cholinomimetics and KCl seen in epithelium-denuded tissue strongly suggests that the epithelium can moderate trachealis sensitivity to cholinomimetic agents not only by releasing epithelium-derived relaxing factor but also by acting as a barrier to drug diffusion.

Animals

Multiple Harvey-ras genes in the bovine genome.

Three different Harvey-ras (Ha-ras) genes have been identified in the bovine genome by screening a lambda phage-bovine DNA library with the ras gene of the Harvey murine sarcoma virus. The genes have been characterized by hybridization and heteroduplex analysis with both the viral and human Ha-ras genes. Based on heteroduplex mapping, the putative direction of transcription and the approximate position of the coding regions of the bovine genes were established. Two genes, bovine Ha-ras 1 and 2, both show an arrangement of exons and introns typical of c-Ha-ras genes. However, they are distinct entities as they have different nucleotide sequences and physical maps, and heteroduplexes between them contain a region of non-homology upstream of exon 1. The third gene, c-Ha-ras 3, does not contain introns and is a pseudogene, analogous to human c-Ha-ras 2. The nucleotide sequence of both Ha-ras 1 and Ha-ras 2 has been determined and shows that Ha-ras 1 encodes a bona fide ras protein, whereas Ha-ras 2 has diverged considerably from a recognizably functional sequence.

Amino Acid Sequence

Spasmogen action in guinea-pig isolated trachealis: involvement of membrane K+-channels and the consequences of K+-channel blockade.

1. Acetylcholine (ACh), histamine, prostaglandin E2 and potassium chloride (KCl) each evoked concentration-dependent spasm of guinea-pig isolated trachealis treated with indomethacin (2.8 microM). 2. Neither tetraethylammonium (TEA; 0.1-10 mM) nor procaine (0.1-10 mM) potentiated these spasmogens. Indeed, procaine (10 mM) depressed the log concentration-effect curves of all the spasmogens while TEA (1-10 mM) caused some depression of the log concentration-effect curve of prostaglandin E2. 3. Intracellular electrophysiological recording was performed in trachealis bathed by normal Krebs solution or by Krebs solution containing 2.8 microM indomethacin. In either medium the majority of trachealis cells exhibited spontaneous electrical slow waves while some cells were electrically quiescent. In either medium the spasmogenic effects of ACh (1 mM) and histamine (0.2 mM) were accompanied by depolarization and abolition of slow wave discharge. In many cases the record of membrane potential subsequently exhibited noise which incorporated fast, hyperpolarizing transients. 4. In the absence and presence of indomethacin, TEA (10 mM) and procaine (5 mM) markedly reduced the membrane noise and hyperpolarizing transients evoked by ACh or histamine without augmenting the evoked tension. 5. It is concluded that slow wave discharge does not depend on prostaglandin synthesis. The membrane noise and hyperpolarizing transients evoked by ACh and histamine represent the opening of membrane K+-channels. While such K+-channel opening may offset spasmogen-induced depolarization it does not moderate the evoked tension.

Animals

Characterisation of the prostanoid receptors mediating contraction of guinea-pig isolated trachea.

The receptors mediating prostanoid-induced contraction of guinea-pig isolated trachea have been characterised in terms of a recently proposed general classification of prostanoid receptors. Results obtained on the trachea were compared with those obtained on guinea-pig fundus, which contains a sub-type of PGE2-sensitive (EP-) receptor termed the EP1-receptor, and guinea-pig lung strip, which contains a thromboxane-sensitive or TP-receptor. The following agonists were studied, PGE2, PGF2 alpha and the thromboxane-like agonists U-46619 and Wy17186. The antagonists studied were SC-19220 which selectively blocks EP1-receptors, and AH19437 which selectively blocks TP-receptors. On guinea-pig fundus the rank order of agonist potency was PGE2 greater than PGF2 alpha greater than Wy-17186 approximately equal to U-46619, and responses to all agonists were antagonised by SC-19220 but not by AH19437. On guinea-pig lung strip the rank order of potency was U-46619 greater than Wy17186 much greater than PGF2 alpha greater than PGE2 and responses to all agonists tested were blocked by AH19437 but not by SC-19220. On the trachea, the rank order was PGE2 = U-46619 greater than Wy17186 = PGF2 alpha. SC-19220 antagonised responses to PGE2 and PGF2 alpha, but not those to U-46619 or Wy17186. Conversely, AH19437 antagonised responses to U-46619 and Wy17186 but not those to PGE2 or PGF2 alpha. It is concluded that prostanoid-induced contractions of guinea-pig trachea can be mediated by both EP1- and TP-receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

A review of Leiske style semi-flexible intraocular lenses 1981-1984.

A consecutive series of 205 patients had 237 intracapsular cataract extractions performed with the insertion of a semi-flexible intraocular lens in the period 1981-1983. The average follow-up period was 17.8 months; 87.0% of cases obtained a visual acuity of 6/12 or better after operation, compared with 80.6% of cases whose preoperative visual acuity was 6/36 or worse. Twenty-six eyes (11%) had clinical cystoid macular oedema at some stage after operation, and seven eyes (3%) had persistent cystoid macular oedema at final follow-up. Only one eye had a postoperative retinal detachment. Thirty eyes (14.1%) required treatment for elevated intraocular pressure at some time after operation.

Aged

Antenatal records: do they help us? A new record for watching fetal growth.

An antenatal record is described which uses a questionnaire to detect mothers and babies at risk, and a graph for charting fetal growth indirectly, by maternal weight, height of fundus, and girth, to give a clear picture. By working out scores for fetal growth and cervical ripeness, guidance is given on when to take action to save babies likely to be born too soon or too late. Our slogan, "Be a Fetal Growth Watcher", serves as a mnemonic for: "Fundus, Girth, Weight".

Botswana