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Biomedical subjects

C Kennedy

Publications and source records attributed to C Kennedy.

At least 235 records · Page 13Linked to original sources
PubMed1988

AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens.

The authors studied 11 cases of Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS) for their reactivity with two monoclonal antibodies (B721 and E431) that recognize endothelial cell surface antigens. Reactivity of these antibodies with KS was compared with the reactivity of other known endothelial markers (F8rAg, Ia, HCL-1). Staining was done with avidin-biotin-alkaline phosphatase immunohistochemistry on acetone-fixed frozen sections. In all samples of tumor both the spindle cell component and the vascular lining cells stained with both B721 and E431. In general, the spindle cells stained less intensely than did the vascular lining cells. There was both intratumor and intertumor variability. B721 and E431 are proposed as two additional markers for KS, and it is suggested that their reactivity with the tumor supports the hypothesis that KS is derived from vascular endothelium. The possibility is also raised that the variability of staining for vascular markers could have diagnostic possibilities, and further studies for investigation of this hypothesis are suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effects of insulin on local cerebral glucose utilization in the rat.

The effects of hyperinsulinemia on local cerebral glucose utilization were studied by the quantitative autoradiographic 2-[14C]deoxyglucose method in normal conscious rats under steady-state normoglycemic conditions. Hyperinsulinemia and a steady state of normoglycemia were achieved and maintained during the experimental period by a continuous intravenous (i.v.) infusion of insulin given simultaneously with a programmed i.v. infusion of D-glucose. Hyperinsulinemia under normoglycemic conditions did not change the average rate of glucose utilization in the brain as a whole, but significant increases in local glucose utilization were found selectively in the ventromedial, dorsomedial, and anterior hypothalamic nuclei. The results suggest that a known anatomical pathway linking the dorsomedial and anterior nuclei with the ventromedial nucleus of the hypothalamus may be physiologically activated in response to hyperinsulinemia.

Animals↗
PubMed1987

[Met5]enkephalin acts via delta-opioid receptors to inhibit pelvic nerve-evoked contractions of cat distal colon.

1 The effects of opioids on the sacral parasympathetic outflow to cat distal colon were studied in vitro using muscle strips orientated in the axis of the longitudinal muscle layer, with pelvic nerves attached. Electrical stimulation of the pelvic nerves evoked contractions that were blocked by atropine (1 X 10(-6) M) and tetrodotoxin (3 X 10(-7) M). 2 [D-Pen2, D-Pen5]enkephalin and [Met5]- and [Leu5]enkephalin caused concentration-dependent, reversible inhibition of pelvic nerve-evoked contractions, with IC50 values of 8.3 X 10(-10) M, 2.2 X 10(-9) and 2.1 X 10(-9) M respectively. 3 Morphine (1 X 10(-7)-1 X 10(-5) M) and [D-Ala2, MePhe4, Gly-ol5]enkephalin (1 X 10(-8)-1 X 10(-6) M) and U-50,488H (1 X 10(-8)-10(-6) M) were much less potent as inhibitors than [Met5]- or [Leu5]enkephalin. 4 Naloxone (1 X 10(-7) M), an antagonist at each of the three opioid receptor types, antagonized the effects of both [Met5]enkephalin and morphine. However, ICI 174,864, a specific delta-opioid receptor antagonist, antagonised the effects of [Met5]enkephalin only. 5 The inhibitory actions of [Met5]enkephalin were inversely related to frequency of pelvic nerve stimulation. Also, [Met5]enkephalin at a concentration (3 X 10(-9) M) which produced a large inhibition of neurogenic contractions, had no effect on contractions to exogenous acetylcholine. These results suggest a prejunctional site for inhibitory opioid receptors. 6 In summary, prejunctional inhibitory delta-opioid receptors are present on the sacral parasympathetic outflow to cat distal colon; kappa- and/or mu-opioid receptors may also be present, but appear to be of lesser importance.

Animals↗
PubMed1987

Delta-opioid receptors mediate inhibition of fast excitatory postsynaptic potentials in cat parasympathetic colonic ganglia.

1 The effects of opioids on synaptic transmission in cat sacral parasympathetic colonic ganglia were studied in vitro, using intracellular electrophysiological techniques. Electrical stimulation of the pelvic nerve evoked fast excitatory postsynaptic potentials (e.p.s.ps), which were blocked by hexamethonium and tetrodotoxin. 2 [D-Pen2, D-Pen5] enkephalin and [Met5]enkephalinamide, delta-opioid receptor agonists, caused concentration-dependent, reversible depression of fast e.p.s.ps, but had no effect on depolarizations evoked by pressure ejection of the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium. Cell transmembrane potential and membrane input resistance were also unaffected. 3 U-50,488H, a kappa-opioid receptor agonist, had a very small depressant action while [D-Ala2, MePhe4, Gly-ol5] enkephalin, a mu-opioid receptor agonist, had no effect on fast e.p.s.p. amplitude. Neither compound affected cell transmembrane potential or membrane input resistance. 4 The inhibitory actions of [D-Pen2, D-Pen5] enkephalin were antagonized by both naloxone, an antagonist at each of the three opioid receptor types, and by ICI 174,864, an antagonist selective for delta-opioid receptors. 5 Naloxone and ICI 174,864 both also potentiated fast e.p.s.p. amplitude per se in 50% of cells tested. 6 It is concluded that exogenous opioids act at presynaptic delta-opioid receptors to inhibit sacral parasympathetic synaptic transmission in cat colonic ganglia in vitro. Furthermore, the effects of opioid antagonists alone, suggest that endogenous opioids may also be released by preganglionic nerve stimulation and so regulate the release of acetylcholine in these ganglia.

Animals↗
PubMed1987

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia.

The effects of insulin on 3-O-[14C]methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [14C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [14C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [14C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [14C]methylglucose across the BBB, K1, and k2, respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. K1 and k2 were reduced by an average of 24 and 31%, respectively, in gray matter and 7 and 16% in white matter from values estimated similarly in normal insulinemic control rats. The equilibrium distribution ratio, K1/k2, for [14C]methylglucose in brain increased by approximately 10-11% in the hyperinsulinemic animals. Because 3-O-[14C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues.

3-O-Methylglucose↗
PubMed1986

Local cerebral glucose utilization in the adult cretinous rat.

Local rates of cerebral glucose utilization were determined in 5-month-old neonatally radiothyroidectomized and control (littermate) rats. Virtually all 48 brain regions examined in the thyroidectomized rats exhibited lower rates of glucose utilization than those of the controls with differences ranging from -24 to -58%. The decreases were particularly large in the cerebral cortex and throughout the auditory system. Altered patterns in the intrastructural distribution of rates of glucose utilization were seen in a number of regions and were particularly prominent in the hippocampus and inferior colliculus. Lesser changes were seen in hypothalamic regions involved in the synthesis of thyrotropin releasing hormone (TRH). The results indicate that the many structural, functional and biochemical abnormalities of cretinism are associated with widespread reductions in energy metabolism throughout the brain.

Animals↗
PubMed1986

The contributions of noradrenaline and ATP to the responses of the rabbit central ear artery to sympathetic nerve stimulation depend on the parameters of stimulation.

The possibility that ATP and noradrenaline act as cotransmitters from sympathetic perivascular nerves was studied in the isolated rabbit central ear artery. Electrical stimulation of the perivascular nerves for either 1 s, or continuously until a maximum response was reached, produced frequency-dependent contractions that were sensitive to tetrodotoxin and guanethidine. Contractions to continuous stimulation were significantly greater than those to a 1 s train of stimulation. Prazosin (10(-6) M) significantly reduced, but did not abolish, all neurogenic contractions such that contractions to both a 1 s train and to continuous stimulation were now of a similar magnitude. A higher concentration of prazosin (10(-5) M) had no additional inhibitory effect on neurogenic contractions even though it further significantly inhibited contractions to exogenous noradrenaline. The greatest resistance to alpha-adrenoceptor blockade was seen at low frequencies. Desensitisation of the postjunctional P2-purinoceptor by repeated administration of alpha, beta-methylene ATP inhibited the non-adrenergic neurogenic contractions and contractions to exogenous ATP, but had no effect on contractions to exogenous noradrenaline. It is concluded that ATP and noradrenaline are excitatory cotransmitters from sympathetic perivascular nerves innervating the rabbit central ear artery. The relative contribution of each compound to neurogenic contractions of the ear artery is highly dependent on the parameters of stimulation used. Short pulse bursts (1 s) at low frequency (2-5 Hz) favour the prazosin-resistant (purinergic) component of the response.

Adenosine Triphosphate↗
PubMed1986

Regulation of nitrogen metabolism in Azotobacter vinelandii: isolation of ntr and glnA genes and construction of ntr mutants.

The ntrA, ntrB and ntrC products are responsible for regulating the transcription of many genes involved in the assimilation of poor nitrogen sources in enteric bacteria. The presence of a similar system in the non-enteric bacterium Azotobacter vinelandii is reported here. Genes analogous to ntrA and ntrC were isolated from an A. vinelandii gene library by complementation of Escherichia coli mutants. The gene encoding glutamine synthetase, glnA, was also isolated and found to be adjacent to ntrC but distant from ntrA, as it is in enteric organisms. The cloned Azotobacter genes also complemented Klebsiella pneumoniae mutants and hybridized to K. pneumoniae ntrA, ntrC and glnA gene probes. The role of ntrA and ntrC in A. vinelandii was established by using Tn5 insertions in the cloned genes to construct mutants by marker exchange. These mutants show that both ntrA and ntrC are required for the utilization of nitrate as a nitrogen source. However, ntrC is not required for nitrogen fixation by A. vinelandii, in contrast with K. pneumoniae where both ntrA and ntrC are essential.

Azotobacter↗
PubMed1986

ATP causes postjunctional potentiation of noradrenergic contractions in the portal vein of guinea-pig and rat.

Superfusion of the portal vein of rat and guinea-pig with Krebs' solution maintained at 25 degrees C greatly inhibits spontaneous contractions of the preparations and allows contractile responses to ATP and noradrenaline to be measured accurately. Under these conditions, continuous superfusion with ATP (10(-5) M), a concentration which had no effect on either basal tension or spontaneous activity, caused a significant shift to the left of the concentration-response curve to exogenous noradrenaline in both tissues. The mechanism of this potentiation induced by ATP may differ in the two tissues since in the rat portal vein potentiation appeared to be rapidly reversed by superfusing with ATP-free solution, whereas in the guinea-pig portal vein a further concentration-response curve to noradrenaline, in the absence of ATP, was still significantly shifted to the left compared with the control curve. However, potentiation in the rat portal vein may have had a longer duration than is suggested by the results since control concentration-response curves to noradrenaline in this tissue showed a progressive shift to the right which, although not significant, is likely to have affected the apparent time course of potentiation. It is concluded that ATP can potentiate contractions to exogenous noradrenaline in the portal vein of rat and guinea-pig via an, as yet, unidentified postjunctional mechanism.

Adenosine Triphosphate↗
PubMed1986

A dual function for adenosine 5'-triphosphate in the regulation of vascular tone. Excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent.

A dual function for adenosine 5'-triphosphate in the regulation of vascular tone is considered. Adenosine 5'-triphosphate can cause vasodilation, acting via P2-purinoceptors located on vascular endothelial cells to release an endothelium-derived relaxing factor which diffuses to the vascular smooth muscle and induces vasodilation. The main source of intraluminal adenosine 5'-triphosphate is likely to be endothelial cells, and its release can be measured during pathophysiological conditions such as ischemia and hypoxia, in amounts likely to be sufficient to activate endothelial P2-purinoceptors. Adenosine 5'-triphosphate can also be released during intravascular platelet aggregation and from intact and damaged vascular smooth muscle cells, and so may play a role in the complex physiological mechanisms controlling local vascular tone under normoxic conditions and during vessel injury. Evidence is also presented for adenosine 5'-triphosphate acting as an excitatory cotransmitter with noradrenaline from sympathetic perivascular nerves, to cause vasoconstriction via excitatory P2-purinoceptors located on vascular smooth muscle. The postjunctional mechanical and electrical responses of a number of blood vessels following perivascular nerve stimulation contain a component that is resistant to blockade of the alpha-adrenoceptor. This nonadrenergic response is mimicked by adenosine 5'-triphosphate and can be blocked by selective desensitization of the P2-purinoceptor by alpha,beta-methylene adenosine 5'-triphosphate. Vesicular storage of adenosine 5'-triphosphate and its release from sympathetic perivascular nerves has also been demonstrated. The functional significance of adenosine 5'-triphosphate acting intraluminally as a vasodilator and extraluminally as a vasoconstrictor neuronal agent in the control of vascular tone is discussed.

Adenosine Diphosphate↗
PubMed1985

Evidence for two types of P2-purinoceptor in longitudinal muscle of the rabbit portal vein.

The actions of ATP, 2-methylthioATP, alpha, beta-methyleneATP, beta, gamma-methyleneATP, adenosine and non-adrenergic, non-cholinergic inhibitory nerve stimulation were compared on the ergotamine-contracted longitudinal muscle of the isolated rabbit portal vein with the vessel endothelium either intact or removed by mechanical rubbing. Non-adrenergic, non-cholinergic inhibitory nerve stimulation produced frequency-dependent relaxations. The purines (except alpha, beta-methyleneATP) also caused relaxation with the following potency order: 2-methylthioATP greater than ATP greater than beta, gamma-methyleneATP = adenosine. 8-Phenyltheophylline, a potent P1-purinoceptor antagonist, antagonised relaxations to adenosine but not those to ATP indicating that ATP and its analogues act directly via a P2-purinoceptor and not via a P1-purinoceptor after breakdown to adenosine. alpha, beta-MethyleneATP produced contractions which were not maintained and was tachyphylactic. The contractions were unaffected by tetrodotoxin and therefore unlikely to be due to release of a contractile substance from a neuronal source following initiation of an action potential. Removal of the endothelium did not affect the actions of non-adrenergic, non-cholinergic inhibitory nerve stimulation, ATP, alpha, beta-methyleneATP, beta, gamma-methyleneATP or adenosine. Thus purine action does not have an endothelium-dependent component in the rabbit portal vein longitudinal muscle. The results indicate the possibility that there may be more than one type of P2-purinoceptor in this tissue.

Adenosine Triphosphate↗
PubMed1985

P2-purinoceptors mediate both vasodilation (via the endothelium) and vasoconstriction of the isolated rat femoral artery.

The distribution of P1- and P2-purinoceptors in isolated rat femoral artery was studied by comparing responses to ATP, alpha, beta-methylene ATP and adenosine, both when endothelial cells were intact and when they had been removed by mechanical rubbing (as confirmed by histochemical staining and abolition of relaxations to acetylcholine). alpha, beta-Methylene ATP and ATP (but not adenosine or acetylcholine) contracted preparations at resting tone. alpha, beta-Methylene ATP was significantly more potent than ATP. The potency of both alpha, beta-methylene ATP and ATP was significantly increased in the absence of the endothelium. These contractions were unaffected by tetrodotoxin, phentolamine and methysergide in concentrations sufficient to abolish contractions to perivascular nerve stimulation, noradrenaline or 5-hydroxytryptamine. Acetylcholine, ATP and adenosine relaxed arteries whose tone had been raised by 10(-6) M noradrenaline. Removal of the endothelium abolished relaxations to ATP (contractions were seen instead) and acetylcholine, but not to adenosine. alpha, beta-Methylene ATP further contracted the high tone preparation and was again more potent when the endothelium was absent. ATP and alpha, beta-methylene ATP were more potent as contractile agents when noradrenaline was present. These results confirm that endothelial cells can mediate vasodilation. They also show that ATP can act at P2-purinoceptors at two locations in the isolated rat femoral artery; one on the endothelium leading to vasodilation, and the other on the smooth muscle leading to vasoconstriction. P1-Purinoceptors, however, appear to be located on the smooth muscle only and mediate vasodilation. At the smooth muscle P2-purinoceptor, alpha, beta-methylene ATP is more potent than ATP, whereas at the endothelial P2-purinoceptor, the reverse is true.

Adenosine↗
PubMed1985

Is there a basis for distinguishing two types of P2-purinoceptor?

It is suggested that the P2-purinoceptor may be separated into two subtypes largely on the basis of the rank order of agonist potency of structural analogues of ATP and also on the activity of antagonists at the P2-purinoceptor: Subtype 1 (designated P2X), potency order: alpha, beta-methyleneATP, beta, gamma-methyleneATP greater than ATP = 2 methylthioATP; antagonism by ANAPP3 and selectively desensitisation following administration of alpha, beta-methyleneATP; present in the vas deferens and urinary bladder of guinea-pig and rat, frog and rat ventricle, and also in the smooth muscle of the rat femoral artery and rabbit central ear artery, where they mediate excitation. Subtype 2 (designated P2Y), potency order: 2-methylthioATP much greater than ATP greater than alpha, beta-methyleneATP, beta, gamma-methyleneATP; weak antagonism by ANAPP3 and desensitisation following administration of alpha, beta-methyleneATP; present in the guinea-pig taenia coli and the longitudinal muscle layer of the rabbit portal vein, where they mediate relaxation and also on the vascular endothelial cells of the rat femoral artery and pig aorta (where occupation leads to the production of endothelium-derived relaxing factor). Differences in the structure of the P2-purinoceptor in various tissues may be useful in the development of drugs for the treatment of vascular, gastrointestinal and urinoglenital disorders.

Adenosine Triphosphate↗