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C Kennedy

Publications and source records attributed to C Kennedy.

At least 91 records · Page 5Linked to original sources
PubMed1998

The generation of human gammadelta T cell repertoires during fetal development.

The nature of how human gammadelta T cells are normally generated is not clear. We have used an RT-PCR assay and DNA sequencing to identify and compare delta-encoded TCRs (TCRDs) that are generated de novo in the fetal gut, liver, and thymus and to determine when, where, and how the TCRD repertoire is established during normal embryonic development. Rearranged TCRDV genes are first expressed outside of the thymus in the liver and primitive gut between 6 and 9 wk gestation. Although DV1Rs and/or DV2Rs predominated, differences in the pattern of TCRDV gene rearrangement and transcription in each tissue during ontogeny were identified. Specific, DV2-encoded TCRs are highly conserved throughout ontogeny in the tissues from the same and between genetically distinct donors. Although the thymic and intestinal gammadelta T cell repertoires partially overlap early in development, they diverge and become nonoverlapping during the second trimester, and the generation of the intestinal gammadelta T cell repertoire is characterized by differences in the processing of DV1Rs and DV2Rs. Whereas the structural diversity of DV1Rs progressively increases during gut development up to birth, DV2Rs have limited structural diversity throughout ontogeny. Together, our findings provide evidence for the ability of different fetal tissues to support the development of gammadelta T cells.

Animals↗
PubMed1998

Comparison of the actions of ATP and UTP and P(2X1) receptors in smooth muscle of the rat tail artery.

The actions of ATP and uridine 5'-triphosphate (UTP) were compared at P2X1 receptors in acutely dissociated smooth muscles cells of the rat tail artery. ATP (30 nM-100 microM) and UTP (1 microM-1 mM) elicited concentration-dependent inward currents. ATP was approximately 100-fold more potent than UTP. In both cases, currents were activated within 3 ms of agonist application and had similar time-courses of activation and inactivation. The decay of responses for both agonists was concentration-dependent and in most cells could be fitted by two exponentials. The P2X receptor antagonists suramin (100 microM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 5 microM) inhibited responses to both ATP and UTP. An action of UTP at P2X1 receptors has not previously been reported. However, since the responses to ATP and UTP had similar time-courses and as PPADS and suramin inhibited both agonists, it is concluded that ATP and UTP are acting at the same site in these cells, the P2X1 receptor.

Adenosine Triphosphate↗
PubMed1998

Tumour necrosis factor stimulates stress-activated protein kinases and the inhibition of DNA synthesis in cultures of bovine aortic endothelial cells.

In this study, we examined the ability of tumour necrosis factor-alpha (TNF) to stimulate the mitogen-activated protein (MAP) kinase homologues p42/44 MAP kinase, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase and its effect upon DNA synthesis in primary cultures of bovine aortic endothelial cells (BAECs). TNF strongly stimulated p38 MAP kinase and JNK activity in both a time- and concentration-dependent manner. By contrast, TNF was a very poor activator of p42/44 MAP kinase relative to the known activator of p42/44 MAP kinase in endothelial cells, adenosine triphosphate (ATP). TNF-stimulated activation of p38 MAP kinase, and MAPKAP kinase-2, a known downstream target of p38 MAP kinase, was strongly inhibited by pre-incubation with the p38 MAP kinase inhibitor SB203580, whereas the minor activation of p42/44 MAP kinase was abolished by pre-incubation of the cell with the novel MAP kinase kinase 1 inhibitor PD098059. Addition of TNF resulted in a 50-60% decrease in DNA synthesis in BAECs. Pre-incubation with PD098059 or co-incubation with ATP failed to modify the inhibitory effect of TNF upon DNA synthesis. SB203580 reduced basal DNA synthesis by approximately 50%; however, if failed to modify the inhibition mediated by TNF. These results indicate that TNF strongly activates both p38 MAP kinase, JNK and, to a minor extent, p42/p44 MAP kinase. It is likely that only one of these kinases, JNK, plays a role in the regulation of DNA synthesis in these cells.

Animals↗
PubMed1998

An audit of children referred with suspected epilepsy.

Members of the British Paediatric Neurology Association were invited to participate in a national audit of children presenting with a possible diagnosis of epilepsy. The audit was based on a 'standard' or set of pre-determined questions drawn up by an advisory audit group. The audit form comprised a total of 30 questions divided into four sections addressing history, examination, investigation, treatment and communication. Information for the audit was obtained retrospectively from the child's case notes. Each participating centre or consultant was asked to audit the case notes of 20 children. At the end of the 12-month recruitment period three centres responded, contributing audit forms on 50 children. The required information was provided for the majority of the questions in each of the four sections, thereby meeting the audit 'standard'. Within the history section, only 32 of the 50 (64%) case notes had recorded whether or not there was 'any obvious provoking factor or circumstance to the episodes'. Communication was the least satisfactorily completed section with between none and 48% of the case notes documenting that the child's family had been informed of the existence of a voluntary epilepsy organization. Despite the simplicity of the audit form, the response for this national audit was considerably lower than anticipated.

Adolescent↗
PubMed1998

Vitamin E up-regulates arachidonic acid release and phospholipase A2 in megakaryocytes.

The release of arachidonic acid is the rate limiting step in eicosanoid synthesis. In mammalian cells, the release of arachidonic acid is catalyzed by several enzymes. The 85 kDa cytosolic phospholipase A2 (cPLA2) is the key enzyme for the release reaction because of its specific acyl selectivity in phospholipid substrates. We have previously reported that vitamin E enrichment potentiates the arachidonic acid release as well as the spontaneous prostacyclin release in human endothelial cells. In contrast, similar enrichment of diets caused a dose-dependent suppression of platelet thromboxane synthesis. Therefore, the present study was undertaken to determine the effect of vitamin E on arachidonate release and phospholipaseA2 activity in a platelet precursor cell, the MEG-01 megakaryocyte cell line. When these cells were incubated with different concentrations of vitamin E, cellular incorporation was linear with the dosages of this vitamin. Determination of arachidonate release after labeling cells with [3H]-arachidonate showed that vitamin E enrichment caused a dose-dependent increase in ionophore A23187-induced [3H]-arachidonic acid release. Analysis of PLA2 activity showed that activity was detected in the cytosol and this activity was completely abolished by the addition of anti-cPLA2, antibody. Determination of cPLA2 activity demonstrated that vitamin E enrichment caused an increase in enzyme activity. Analysis of cPLA2 protein by Western blot revealed that vitamin E caused an increase in enzyme protein. These data showed that the potentiation of arachidonic acid release and cPLA2, activity by vitamin E was mediated by the enhanced expression of cPLA2 protein.

Arachidonic Acid↗
PubMed1998

Evidence that ATP acts at two sites to evoke contraction in the rat isolated tail artery.

1. The site(s) at which P2-receptor agonists act to evoke contractions of the rat isolated tail artery was studied by use of P2-receptor antagonists and the extracellular ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP (ARL 67156). 2. Suramin (1 microM(-1) mM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (0.3-300 microM) inhibited contractions evoked by equi-effective concentrations of alpha,beta-methyleneATP (alpha,beta-meATP) (5 microM), 2-methylthioATP (2-meSATP) (100 microM) and adenosine 5'-triphosphate (ATP) (1 mM) in a concentration-dependent manner. Responses to alpha,beta-meATP and 2-meSATP were abolished, but approximately one third of the peak response to ATP was resistant to suramin and PPADS. 3. Contractions evoked by uridine 5'-triphosphate (UTP) (1 mM) were slightly inhibited by suramin (100 and 300 microM) and potentiated by PPADS (300 microM). 4. Desensitization of the P2X1-receptor by alpha,beta-meATP abolished contractions evoked by 2-meSATP (100 microM) and reduced those to ATP (1 mM) and UTP (1 mM) to 15+/-3% and 68+/-4% of control. 5. Responses to alpha,beta-meATP (5 microM) and 2-meSATP (100 microM) were abolished when tissues were bathed in nominally calcium-free solution, while the peak contractions to ATP (1 mM) and UTP (1 mM) were reduced to 24+/-6% and 61+/-13%, respectively, of their control response. 6. ARL 67156 (3-100 microM) potentiated contractions elicited by UTP (1 mM), but inhibited responses to alpha,beta-meATP (5 microM), 2-meSATP (100 microM) and ATP (1 mM) in a concentration-dependent manner. 7. These results suggest that two populations of P2-receptors are present in the rat tail artery; ligand-gated P2X1-receptors and G-protein-coupled P2Y-receptors.

Adenosine Triphosphatases↗
PubMed1998

Pharmacological properties of P2X3-receptors present in neurones of the rat dorsal root ganglia.

1. The electrophysiological actions of several agonists which may differentiate between P2X1- and P2X3-receptors were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-4 day old rat dorsal root ganglia. 2. Beta,gamma-Methylene-D-ATP (beta,gamma-me-D-ATP) (1-300 microM), diadenosine 5',5'''-P1,P5-pentaphosphate (AP5A) (100 nM - 300 microM), diadenosine 5',5'''-P1,P4-tetraphosphate (AP4A) (300 nM - 300 microM) and uridine 5'-triphosphate (UTP) (1 microM - 1 mM) all activated concentration-dependent inward currents with a latency to onset of a few ms. 3. The concentration-response curves for beta,gamma-me-D-ATP and AP5A and ATP had similar maximum values, while that for AP4A had a lower maximum. The concentration-response curve to UTP was shallow and did not reach a maximum. Beta,gamma-Methylene-L-ATP was virtually inactive. The rank order of agonist potency was ATP > AP5A approximately AP4A > beta,gamma-me-D-ATP > UTP > > beta,gamma-methylene-L-ATP. 4. The inward currents were inhibited by the P2-receptor antagonists suramin (100 microM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10 microM). PPADS also inhibited responses to ATP (800 nM) and alpha,beta-methylene ATP (2 microM) in a concentration-dependent manner. 5. This study shows that beta,gamma-me-D-ATP, AP5A, AP4A and UTP all act via a suramin- and PPADS-sensitive P2X-receptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The very low activity of beta,gamma-methylene-L-ATP suggests that the agonists were acting at the P2X3-subtype to produce these effects.

Adenosine↗
PubMed1998

Characterization of the glnK-amtB operon of Azotobacter vinelandii.

To determine whether in Azotobacter vinelandii the PII protein influences the regulation of nif gene expression in response to fluxes in the ammonium supply, the gene encoding PII was isolated and characterized. Its deduced translation product was highly similar to PII proteins from other organisms, with the greatest degree of relatedness being exhibited to the Escherichia coli glnK gene product. A gene designated amtB was found downstream of and was contranscribed with glnK as in E. coli. The AmtB protein is similar to functionally characterized ammonium transport proteins from a few other eukaryotes and one other prokaryote. glnK and amtB comprise an operon. Attempts to isolate a stable glnK mutant strain were unsuccessful, suggesting that glnK, like glnA, is an essential gene in A. vinelandii. amtB mutants were isolated, and although growth on limiting amounts of ammonium was similar in the mutant and wild-type strains, the mutants were unable to transport [14C]methylammonium.

Azotobacter vinelandii↗
PubMed1998

The Internet in managed health care.

Blue Shield of California recognized it could realize business gains by implementing solutions that would streamline health care administration. It began looking for opportunities to apply the Internet to the core business and defining which of those services would benefit quickly from implementation. It selected Internet technology from Healtheon Corp., a Silicon Valley startup in Palo Alto, California.

Blue Cross Blue Shield Insurance Plans↗
PubMed1997

The ecto-ATPase inhibitor ARL 67156 enhances parasympathetic neurotransmission in the guinea-pig urinary bladder.

The influence of enzymatic degradation on the neurotransmitter actions of ATP was studied using the ecto-ATPase inhibitor 6-N,N-diethyl-D-beta,gamma-dibromomethyleneATP (ARL 67156). Field stimulation of the parasympathetic nerves innervating guinea-pig urinary bladder muscle strips (1-8 Hz for 20 s) produced characteristic biphasic contractions, the peak magnitudes of which were significantly increased by 29-32% by ARL 67156 (100 microM). A similar degree of enhancement was seen in the presence of atropine (1 microM), consistent with ARL 67156 acting to enhance the action of neuronally released ATP. The effects of ARL 67156 reversed rapidly on washout of the drug. Contractions evoked by exogenous ATP (100 microM) were also potentiated by ARL 67156 (100 microM), but those to the stable analogue alpha,beta-methyleneATP (5 microM) were unaffected. ARL 67156 (100 microM) also enhanced contractions to exogenous acetylcholine (1 microM) and histamine (3 microM), but this potentiation was abolished by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (100 mciroM). It is concluded that when ATP acts as a neurotransmitter its postjunctional actions are attenuated by enzymatic degradation. ARL 67156 inhibits this breakdown.

Acetylcholine↗
PubMed1997

Neuronal release of soluble nucleotidases and their role in neurotransmitter inactivation.

Efficient control of synaptic transmission requires a rapid mechanism for terminating the actions of neurotransmitters. For amino acids and monoamines, this is achieved by their uptake into the cell by specific high-affinity transporters; acetylcholine is first broken down in the extracellular space and then choline is taken up by the cell. Because ATP is hydrolysed to adenosine by membrane-bound enzymes (ectonucleotidases) that are present in most tissues, it has been assumed that these enzymes terminate the neurotransmitter actions of ATP in the brain and in the periphery. We show here, however, that stimulation of sympathetic nerves innervating the guinea-pig vas deferens releases not only neuronal ATP, but also soluble nucleotidases that break down this ATP to adenosine, indicating that inactivation of ATP is increased by nerve activity. This release of specific nucleotidases together with ATP represents a new mechanism for terminating the actions of a neurotransmitter.

Adenosine Triphosphate↗
PubMed1997

Telemedicine; here to stay.

Telemedicine is a technology of the future, available today. Here, we describe successful telemedicine systems used across Australia and review barriers to further implementation. Greater academic and multidisciplinary involvement, as well as adequate funding, is needed for the further development and evaluation of these systems.

Australia↗
PubMed1997

Collaboration between local public health and community mental health agencies.

Public health agencies (PHA) and community mental health agencies (CMHA) generally are organizationally and functionally autonomous. Collaboration between PHA and CMHA was explored in a statewide survey of nursing directors of PHA (n = 135) and executive directors of CMHA (n = 214). Findings indicated staff did not know each other well; clients, funds, and information were infrequently exchanged; public health nurses rarely were included in planning for the care of those with mental illness; and satisfaction with relationships was minimal. Path analysis was used to test an interagency collaboration model. Awareness of staff from other agencies increased satisfaction with interagency processes and interagency relationships.

Administrative Personnel↗
PubMed1997

Laparoscopic colposuspension. Is it cost-effective?

BACKGROUND: The laparoscopic approach must be shown to be cost-effective as well as safe and technically effective before being widely adopted. A review of 54 consecutive patients who underwent open and laparoscopic colposuspension is presented and a cost-analysis is performed comparing the two approaches. METHODS: This study was a retrospective controlled review of patient records and accounts of in-hospital costs incurred at a private hospital. RESULTS: Theater costs were significantly greater in the laparoscopic group but this was balanced by a shorter length of stay and subsequent reduced accommodation cost. There was no difference in the overall in-hospital costs between the two groups. CONCLUSION: The laparoscopic surgical approach is safe and effective and by no means more expensive than the open approach. In the future, the laparoscopic approach can only become more cost efficient; techniques will improve and there will be earlier returns to work and, subsequently, greater productivity.

Adult↗
PubMed1997

Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT scanning and reasons for nonresponse.

In patients with cholesterol-rich gallbladder stones and a patent cystic duct, complete stone clearance rates of 65-90% have been reported with oral bile acids (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy; ESWL). The aims of the present study were to analyze pretreatment gallstone characteristics that predict the speed and completeness of dissolution with OBAs +/- ESWL, and to assess, in patients with incomplete dissolution, the reasons for the poor response. We compared pretreatment gallstone characteristics in 43 patients who became stone-free after a median of 9 months OBAs +/- ESWL with those in 43 age- and sex-matched patients whose stones failed to dissolve after two years of treatment. In those with incomplete gallstone dissolution, we repeated the oral cholecystogram and computed tomogram (CT) and, in selected patients, obtained gallbladder bile by percutaneous fine-needle puncture. In patients who became stone-free, those with stones that were isodense with bile and/or had CT scores of < 75 Hounsfield units had the fastest dissolution rates. In the 43 nonresponders, the main causes for treatment failure were impaired gallbladder contractility and acquired stone calcification. CT-lucent, noncholesterol stones, or failure of desaturation of bile with the prescribed bile acids, occurred in a minority. We conclude that the pretreatment CT attenuation score predicts both the speed and completeness of gallstone dissolution. In patients with incomplete stone dissolution, the combination of oral cholecystography, CT, and analysis of gallbladder bile will determine the underlying reasons for treatment failure in most, but not all, cases.

Administration, Oral↗