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Biomedical subjects

K A Green

Publications and source records attributed to K A Green.

At least 37 records · Page 2Linked to original sources
PubMed1994

Adoptive transfer of polyclonal and cloned cytolytic T lymphocytes (CTL) specific for mouse AIDS-associated tumors is effective in preserving CTL responses: a measure of protection against LP-BM5 retrovirus-induced immunodeficiency.

Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency.

Animals↗
PubMed1993

The properties of voltage-operated Ca(2+)-channels in bovine isolated trachealis cells.

Freshly-dispersed bovine trachealis cells were used for recording by the patch clamp technique of whole-cell and unitary currents through Ca(2+)-channels. Whole-cell Ca(2+)-current (ICa) activated at -40 mV and appeared to be carried by a single type of Ca(2+)-channel. Inactivation of ICa was increased by increasing the concentration of free Ca2+ within the recording pipette but reduced by using Ba2- as the charge carrier. Steady-state inactivation studies showed that the Ca(2+)-channels were half-maximally available following a conditioning depolarization to -35 mV. A two-pulse protocol showed that ICa induced by the step to a test potential was inversely related to ICa induced by the step to the conditioning potential. Unitary Ba(2+)-currents were activated at a threshold of -30 mV and had a reversal potential of +41 mV. The channel carrying the unitary Ba(2+)-currents had a slope conductance of 23 pS. Steady-state inactivation studies showed that the unitary Ba(2+)-currents were half-maximally available at a holding potential of -28 mV. ICa and unitary Ba(2+)-currents were inhibited by nifedipine (10 nM-1 microM) but augmented by Bay K 8644 (10 microM). It is concluded that the plasmalemma of bovine trachealis muscle contains a single population of voltage-dependent Ca(2+)-channels of the L-type. These channels may be subject to inactivation primarily by an increase in the concentration of free Ca2+ on the cytosolic side of the plasmalemma and secondarily by a voltage-dependent mechanism. Overlap of the inactivation and activation curves of ICa may allow the passage of 'window current' through the Ca(2+)-channels during sustained depolarization.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Potassium channel activators and bronchial asthma.

The cromakalim-like KCOs relax airways smooth muscle by an action that is associated with the opening of plasmalemmal K(+)-channels. The K(+)-channel involved may be analogous to the ATP-sensitive K(+)-channel identified in pancreatic beta-cells. It is unlikely to be open under normal circumstances and plays little role in determining the strong outward rectifying behaviour of the plasmalemma of the airways smooth muscle cell. K(+)-channel opening may cause relaxation of the airways smooth muscle cell by mechanisms additional to inhibition of Ca2+ influx through L-type VOCs. The cromakalim-like KCOs have bronchodilator activity in vivo and can depress NANC excitatory neuroeffector transmission in the lung at concentrations smaller than those required to relax airways smooth muscle. The mechanism of action of cromakalim in alleviating nocturnal asthma may not involve direct relaxation of airways smooth muscle. It is possible that cromakalim may instead act to inhibit the mechanisms underlying airway hyper-reactivity.

Animals↗
PubMed1992

Cytolytic T lymphocytes specific for tumors and infected cells from mice with a retrovirus-induced immunodeficiency syndrome.

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.

Animals↗
PubMed1991

Mechanical, biochemical and electrophysiological studies of RP 49356 and cromakalim in guinea-pig and bovine trachealis muscle.

Experiments have been performed using guinea-pig and bovine trachealis in order to determine whether cromakalim and RP 49356 share the same relaxant action and to analyse the mechanisms underlying this action. RP 49356 was approximately 3 times less potent than cromakalim in suppressing the spontaneous tone of guinea-pig trachea and, like cromakalim, was antagonised by glibenclamide and by phentolamine. Biochemical studies showed that relaxant concentrations of cromakalim and RP 49356 did not alter the cAMP or cGMP content of guinea-pig trachealis muscle and did not inhibit cAMP or cGMP hydrolysis by tracheal homogenates. Like cromakalim, RP 49356 caused marked hyperpolarisation of guinea-pig trachealis cells. Patch clamp recording using inside-out membrane patches from bovine trachealis showed that cromakalim, RP 49356, glibenclamide and phentolamine were each without effect on the open state probability (Popen) of large conductance, Ca(2+)-activated K(+)-channels. We conclude that cromakalim and RP 49356 share a similar action in opening K(+)-channels in the trachealis cell membrane. This action probably does not involve the intracellular accumulation of cyclic nucleotides and the channel involved is not the large conductance, Ca(2+)-dependent K(+)-channel.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

Guinea-pig isolated trachealis: the effects of charybdotoxin on mechanical activity, membrane potential changes and the activity of plasmalemmal K(+)-channels.

1. A study has been made, in guinea-pig isolated trachealis, of the effects of charybdotoxin in modulating (a) the activity of large conductance K(+)-channels, (b) the spontaneous electrical activity of intact cells and (c) the mechanical effects of some bronchodilator drugs. 2. Single smooth muscle cells were isolated from guinea-pig trachealis by enzymic digestion and were studied by the patch clamp recording technique. Recordings were made from outside-out plasmalemmal patches when the medium bathing the external surface of the patches contained 1.2 mM Ca2+ and 6 mM K+ while that bathing the cytosolic surface contained 0.1 microM Ca2+ and 140 mM K+. Charybdotoxin (100 nM), applied to the external surface of patches held at 0 mV, abolished the unitary currents associated with the opening of large conductance K(+)-channels. 3. Opened segments of guinea-pig trachea were used for the simultaneous recording of membrane potential and tension changes. In these experiments charybdotoxin (100 nM) caused the conversion of spontaneous electrical slow waves into spike-like action potentials. This effect was accompanied by a very small reduction in resting membrane potential. 4. Tissue bath recording showed that charybdotoxin (100 nM) increased the spontaneous mechanical tone of the tissue, antagonized (2.8 fold in each case) the relaxant actions of isoprenaline and theophylline but did not antagonize the relaxant actions of cromakalim or RP 49356. 5. It is concluded that charybdotoxin is an effective inhibitor of large conductance K(+)-channels in guinea-pig trachealis cells. The ability of charybdotoxin to convert spontaneous slow waves into spike-like action potentials suggests that the large, charybdotoxin-sensitive, K+-channels play an important role in determining the strong outward rectifying behaviour of the cells. The ability of charybdotoxin to antagonize isoprenaline and theophylline, but not to antagonize cromakalim and RP 49356, suggests that opening of the large conductance, charybdotoxin-sensitive K+-channel is implicated in the action of the former but not the latter pair of bronchodilator drugs.

Adrenergic beta-Agonists↗
PubMed1991

A patch-clamp study of K(+)-channel activity in bovine isolated tracheal smooth muscle cells.

1. Single smooth muscle cells were isolated from bovine trachealis by enzymic digestion. The properties of large conductance plasmalemmal K(+)-channels in these cells were studied by the patch-clamp recording technique. 2. Recordings were made from inside-out plasmalemmal patches when [K+] was symmetrically high (140 mM) and when [Ca2+] on the cytosolic side of the patch was varied from nominally zero to 10 microM. Large unitary currents of both Ca(2+)-dependent and -independent types were observed. Measured between + 20 and + 40 mV, the slope conductances of the channels carrying these currents were 249 +/- 18 pS and 268 +/- 14 pS respectively. 3. Lowering [K+] on the cytosolic side of the patches from 140 to 6 mM, shifted the reversal potentials of the two types of unitary current from approximately zero to much greater than + 40 mV, suggesting that both currents were carried by K(+)-channels. 4. The Ca(2+)-dependent and -independent K(+)-channels detected in inside-out plasmalemmal patches could also be distinguished on the basis of their sensitivity to inhibitors (tetraethylammonium (TEA), 1-10 mM; Cs+, 10 mM; Ba2+, 1-10 mM; quinidine, 100 microM) applied to the cytosolic surface of the patches. 5. Recordings were made from outside-out plasmalemmal patches when [K+] was symmetrically high (140 mM) and when [Ca2+] on the cytosolic side of the patch was varied from nominally zero to 1 microM. Ca(2+)-dependent unitary currents were observed and the slope conductance of the channel carrying these currents was 229 +/- 5 pS. 6. Activity of the Ca2+-dependent K+-channel detected in outside-out patches could be inhibited by application of TEA (1 mM), Cs+ (10mM), Ba2(+210mM) or quinidine (100 microM) to the external surface of the patch. 4-Aminopyridine (4-AP; 1 mM) was ineffective as an inhibitor. 7. The activity of the Ca2+-dependent K+-channel recorded from outside-out patches was reversibly inhibited by charybdotoxin (100 nM). 8. When whole-cell recording was performed, the application of a depolarizing voltage ramp evoked outward current which was dependent on the [Ca2 +] in the recording pipette and which could be reversibly inhibited by charybdotoxin (50 nM-I microM) applied to the external surface of the cell.9. We conclude that bovine trachealis cells are richly endowed with charybdotoxin-sensitive, large conductance, Ca2 +-dependent K+-channels. These channels carry most of the outward current evoked by a depolarizing ramp and could play a major role in determining the outward rectifying properties of the trachealis cells. The role of the large Ca2 + -independent K+ -channels remains unclear.

Animals↗
PubMed1990

The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) can activate a ligand-gated ion channel in Helix neurones.

This report presents evidence that the molluscan neuropeptide FMRFamide can directly activate a ligand-gated ion channel in Helix neurones. Using the patch-clamp technique we have observed unitary currents activated by the application of FMRFamide onto outside-out patches. As for the whole-cell response, Na+ ions are the main charge carriers. We conclude that FMRFamide may act as a fast depolarizing neurotransmitter in the Helix nervous system.

Animals↗
PubMed1988

Actions of baclofen on components of the Ca-current in rat and mouse DRG neurones in culture.

1. Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1 micron. The proportion of neurones responding to baclofen was low (less than 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones were responsive. 2. Three types of unitary Ca currents were observed in the rat DRG neurones, corresponding to the T-, N- and L-type currents of chick DRG neurones. 3. Baclofen produced two types of response on whole-cell currents of DRG neurones from both species. The first was on an early inactivating component of the Ca current. This early current was partially inactivated at a holding potential of -40 mV. It was also reduced during the second of a pair of depolarizing command pulses. The results suggest that this action of baclofen is due to an action on an N-type component of the current. The second response to baclofen persisted throughout the command step and was not reduced during the second of a pair of command pulses, indicating that this effect is due to an action on the L-type current. 4. Unitary or ensemble Ca currents recorded in cell-attached patches, on neurones previously shown to respond to baclofen in whole-cell clamp mode, were generally not inhibited by baclofen application external to the patch electrode. This indicates that a readily diffusible internal second messenger substance is probably not involved in coupling the GABAB receptor to the ion channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

The effect of jejunoileal bypass (JIB) in the obese Zucker rat on a sub-group of enteroendocrine cells.

The effect of jejunoileal bypass in lean and obese Zucker rats on a number of enteroendocrine cell types was investigated 5 weeks following surgery to remove 80 percent of the small bowel from continuity. The endocrine cells containing somatostatin, cholecystokinin, gastric inhibitory polypeptide, enteroglucagon and neurotensin were investigated. In control rats enteroglucagon cell number was decreased in obese compared to lean animals (5 +/- 1 vs 11 +/- 1 cells/mm). Following jejunoileal bypass the enteroglucagon cell population increased two-fold in both the functional and bypassed bowel in obese rats but was not elevated in lean animals. A significant increase in the number of cholecystokinin cells in the bypassed loop of the jejunum in both lean and obese bypassed rats was observed. The cholecystokinin cell population was also markedly elevated in the functional jejunum of obese but not lean bypassed rats. Only small changes were noted in cell numbers of gastric inhibitory polypeptide, somatostatin and neurotensin containing cells, suggesting that individual cell types have specific stimuli for proliferation. Epithelial height, a measure of intestinal adaptation, was similar in lean and obese rats in both the control and bypassed states, but weight loss in obese bypassed animals was significantly greater than that of lean bypassed rats. The hyperinsulinemia of obese rats was only partially normalized by jejunoileal bypass. These data indicate that jejunoileal bypass has effects on specific enteroendocrine cells which differ between lean and obese Zucker rats, and between individual cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Working ability and exercise tolerance during treatment of a mild hypertension. I. Comparison between a beta-adreno-receptor blocking drug and a calcium antagonist.

A randomized cross-over trial was undertaken on 21 occupationally active persons who had a stable mild or moderate hypertension with the purpose of comparing the effect of a beta-adreno-receptor blocking agent (atenolol) with that of a calcium channel inhibitor (nifedipine). The doses recommended by the manufactures were used. Atenolol (100 mg) given once a day resulted in a marked hypotensive effect at rest as well as during exercise, the compliance was satisfactory, and the hemodynamic changes were not reflected in unfavourable side effects during muscular exercise or in the subjects own personal assessment of fatigue during the exercise tests which ranged in energy expenditure from about three to six times the resting level. However, unfavourable, modest side effects occurred in two subjects during atenolol medication to the extent that they wanted to terminate the study. Nifedipine therapy with doses of 10 mg, three times a day, resulted in a modest, but statistically insignificant reduction in arterial blood pressure, which contrasts with previous published results. It is suggested that the modest effect is caused or related to the poor compliance and a daily dose that was quantitatively too small. No unfavourable side effects were seen during muscular efforts when the subjects were on nifedipine medication.

Adrenergic beta-Antagonists↗
PubMed1985

Working ability and exercise tolerance during treatment of mild hypertension. II. A comparison between atenolol and prazosin medication.

The treatments of mild hypertension with atenolol and prazosin in occupationally active men and women were compared in a double blind cross-over with placebo. The hypotensive effect of the beta-adreno-receptor blocking drug, atenolol, were striking and in accordance with current knowledge, using one daily dose of 100 mg. In contrast, the hypotensive effect of taking 2 mg prazosin twice a day was modest, averaging about 3% when compared with placebo, somewhat less but still detectable during the performance of muscular exercises. Atenolol medication significantly reduced heart rate and blood pressure responses to muscular exercises, covering a range of work loads experienced during ordinary working days. No increased feeling of muscular fatigue or other discomfort during muscular work compared to that on prazosin and placebo medication could be detected. It was therefore concluded that atenolol medication was a useful treatment of mild hypertension and did not reduce the normal working ability and exercise tolerance. Prazosin medication did not significantly change working ability and exercise tolerance.

Adult↗
PubMed1985

Some neurobiological applications of the BBC Model B microcomputer and Unilab 8-bit interface.

Four computer programs written for the BBC Model B microcomputer (coupled to a Unilab 8-bit interface) are discussed. These programs enable the system to be used as (1) a transient recorder, (2) a rapid signal averager, (3) a spike-train analyser and (4) an instrument for measuring the amplitude of single channel currents. Flow-charts illustrating the operation of each program are given along with a detailed discussion of how the programs may be used in the laboratory. The discussion is illustrated using recordings taken from experiments conducted on a range of neurobiological preparations.

Animals↗
PubMed1985

The effect of total parenteral nutrition in the rat on a sub-group of enteroendocrine cells.

The effect of total parenteral nutrition (TPN) in rats on a number of enteroendocrine cells was investigated. The rats were given a continuous intravenous infusion of basal TPN solution for 7 days. Samples from duodenum, jejunum and ileum were collected, immunostained and the immunoreactive cells quantified using a computerised morphometrics system. The endocrine cells containing somatostatin, cholecystokinin (CCK), gastric inhibitory polypeptide (GIP), neurotensin and enteroglucagon were investigated. The results demonstrated a significant reduction in the number of CCK cells in the duodenum and jejunum. In the ileum the neurotensin-immunoreactive cells were significantly increased in number (P less than 0.02). No change was seen in the number of cells immunostained for somatostatin, GIP or enteroglucagon. These data indicate that short term TPN has a definite effect on the enteroendocrine cell population which may be linked to the side effects of TPN seen in man.

Animals↗