PubMed Health⌕ Search

Biomedical subjects

C R Kennedy

Publications and source records attributed to C R Kennedy.

At least 19 recordsLinked to original sources
PubMed1995

Regulation of bradykinin-stimulated phospholipase C and arachidonic acid release by protein kinase A in MDCK-D1 cells.

Regulation of phospholipases C (PLC) and arachidonic acid (AA) release by cAMP-dependent protein kinase (PKA) was investigated in MDCK-D1 cells. Bradykinin (BDK) was used to stimulate PLC and AA release, while arginine vasopressin (AVP), forskolin (FSK), isobutylmethylxanthine (IBMX) were used to increase cAMP levels and stimulate PKA. When cells were preincubated for 20 min with 10 microM FSK + 0.5 mM IBMX, and subsequently treated with 1 microM BDK or control medium for 40 min, the basal and BDK-stimulated PLC activity, measured as accumulated labelled inositol phosphate (InsP) after 40 min and inositol trisphosphate (InsP3) after 10 s, were significantly inhibited. In a parallel manner, FSK + IBMX also significantly decreased both basal and BDK-stimulated diacylglycerol (DAG) production. The basal and BDK-enhanced AA release into the media was also significantly inhibited by pretreatment with FSK + IBMX. In parallel experiments, H-89, a specific inhibitor of PKA, was preincubated for 60 min prior to addition of BDK and this resulted in a reversal of FSK+IBMX-induced inhibition of basal and BDK-stimulated PLC activity and AA release. An inhibitor of inositide-hydrolysing PLC, U73122, (1 microM) was also found to blunt BDK-stimulated PLC activity and BDK-enhanced AA release which indicated that stimulation of AA release by the nonapeptide was second to PLC activation. The ionophore, A23187, (10 microM) greatly stimulated AA release and to a much lesser extent, PLC activity. Its effect on AA release however was not blocked by inhibiting protein kinase C (PKC) with staurosporine (SSP) and consequently did not notably involve the PLC-PKC cascade. Activation of PKA with FSK + IBMX was found to significantly inhibit the enhancement of AA release by ionophore. With 12-tetradecanoyl-phorbol-13-acetate (TPA) also present there was a synergistic increase in the A23187-stimulated AA release and activation of PKA under such conditions inhibited AA release to a similar extent though the synergistic effect remained. The results strongly suggest a role for PKA in the regulation of PLC activity and AA release in MDCK-D1 cells. Control of AA release by PKA, is mediated both by mechanisms which involve blunting of PLC activity and mechanisms which are downstream from the PLC-PKC cascade.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Protein C deficiency and stroke in early life.

Plasma concentrations of protein C, protein S and antithrombin III were measured in 33 unselected children with a history of cryptogenic stroke (group 1), four children with previously ascertained low plasma concentrations of protein C following stroke (group 2) and 42 healthy children undergoing minor surgery (group 3). Protein S and antithrombin III were normal in all patients. Low concentrations of protein C were found in two patients in group 1 and in six healthy children in group 3. Low protein C concentrations returned to normal over many months in three of the four patients in group 2. Prophylactic antithrombotic therapy and/or termination of pregnancy had been carried out unneccessarily in two families in whom inherited protein C deficiency was not confirmed. The suggestion that heterozygous protein C deficiency contributes to the risk of arterial stroke was not supported by this study.

Adolescent↗
PubMed1994

Small terminal deletions of the long arm of chromosome 2: two new cases.

We report on 2 girls with small de novo terminal deletions of the long arm of chromosome 2 and breakpoints within q37. Four cases with similar or more extensive deletions have been previously reported in full. Hypotonia and psychomotor retardation were the only manifestations common to all 6 cases. The phenotype associated with small terminal 2q deletions is variable and clearly not always as mild as indicated in previous reports. The abnormality may also be more common than has been assumed.

Child↗
PubMed1994

Host fragmentation and helminth parasites: hedging your bets against extinction.

We consider the probability of parasite extinction due to anthropogenic fragmentation of host populations and in the absence of host extinction. We conclude that extinction at infrapopulation and infracommunity levels is both common and trivial. Extinction may occur in communities at higher levels but only if metapopulations or suprapopulations become extinct. Suprapopulations are highly complex and unlikely to become extinct in the face of simple host fragmentation. We acknowledge parasite metapopulations as being the most likely to become extinct, but only locally. Our reasoning for this is that, in the absence of complete host extinction, populations of the parasite in other fragments are likely to serve as sources for reinvasion (e.g. a rescue effect). We identify a number of features that may act as hedges against extinction for many parasites and conclude by attempting to identify what form an extinction might take.

Animals↗
PubMed1994

Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological, biochemical, and genetic studies of a patient presenting with progressive myoclonic epilepsy.

An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.

Adolescent↗
PubMed1994

Regional versus local helminth parasite richness in British freshwater fish: saturated or unsaturated parasite communities?

The relationships between regional species richness and local species richness were examined in respect of helminth parasite communities in 32 species of freshwater fish in the British Isles. Fish were divided into 5 categories, for each of which the goodness of fit of the relationship to linear, exponential and power function models was tested. For all categories of fish combined, there was a significant, positive curvilinear relationship. Nested within this were two other patterns. For introduced fish, a linear model provided the best fit; for euryhaline and relict species it was impossible to determine the best model, but for the other categories the relationship was curvilinear and was best fitted by a power function model. The linear relationship found for introduced fish was interpreted as a temporary situation, reflecting the shortage of time for the communities to become saturated. It corresponded to the linear part of the curvilinear relationship of the other categories, which is believed to represent the fundamental form of the relationship for parasite communities. The communities reached a saturation level of richness, corresponding to the asymptote of the curve, which fell well below regional species richness. Explanations for local saturation are discussed, but neither community structure nor supply-side ecology can yet be preferred. It is concluded that local patterns in helminth community richness, in contrast to those in fish assemblages, are not significantly influenced by patterns on a larger, regional spatial scale and so regional species richness is not a key determinant of local species richness, nor does a knowledge of regional patterns improve predictability of local patterns.

Animals↗
PubMed1994

The relationship between pattern and scale in parasite communities: a stranger in a strange land.

Problems of pattern and scale are considered in relation to helminth communities of freshwater fish by examining them at different hierarchical taxonomic and spatial scales, with a view to seeking generalizations of heuristic value, assessing the importance of phylogenetic and ecological determinants of community structure and improving understanding of unpredictable communities. Initially, communities were analysed at the level of salmonid genera, focusing on Oncorhynchus, in its heartland in Canada: then in O. mykiss throughout its global range and finally in individual localities to which it has been introduced in Britain. In the heartland, communities are dominated by salmonid specialist helminths, forming a phylogenetic element: the minority ecological element comprises broad generalists and non-salmonid specialists. Most species except generic specialists are shared between host genera. As the distance to which O. mykiss was translocated from its heartland increases, so generic specialists disappear first and then salmonid specialists decline. The community is thus increasingly composed of generalists and it also becomes increasingly poor. Helminths may be acquired from native salmonids and/or unrelated hosts, depending on availability. This same pattern is paralleled in individual localities in a restricted region: the phylogenetic element reflects the native salmonid species present and the ecological element the presence of other genera of fish; i.e., a supply-side situation. The change of scale in analysis has thus enabled the recognition of generalizations and patterns of heuristic value and improved the understanding of unpredictable communities by interpreting local variation as ecological 'noise' that often obscures fundamental patterns. In this and other taxa of fish, phylogenetic elements dominate helminth communities in the heartlands, but ecological elements dominate as the host increasingly becomes a stranger in a strange land.

Animals↗
PubMed1994

X-linked adrenoleukodystrophy with non-diagnostic plasma very long chain fatty acids.

Measurement of plasma very long chain fatty acids is widely recognised as a sensitive screening test for X-linked adrenoleukodystrophy (X-ALD). This test has particular importance because of the highly variable clinical expression of X-ALD. In this affected family the progressive childhood form of X-ALD was accompanied by "non-diagnostic" concentrations of plasma very long chain fatty acids. The implications for diagnosis of X-ALD are discussed.

Adrenoleukodystrophy↗
PubMed1994

Feasibility of otoacoustic emission detection followed by ABR as a universal neonatal screening test for hearing impairment.

The feasibility of attempting a two-stage universal screening test for auditory impairment was assessed at a large district maternity hospital. The first stage was measurement of otoacoustic emissions using the Programmable Otoacoustic Emission Measurement System. Those failing the first stage proceeded to automated analysis of auditory brainsteam responses. A single tester working for 6 h on 6 days per week attempted to test all babies born between the hours of midday and midnight for 2 weeks and then all babies born between midnight and midday for a further 2 weeks. Of 217 babies born during the study periods, one infant died and three were still receiving intensive care at the end of the study. Of the remaining 213 infants, auditory testing was undertaken in 201 infants (94%). Eight infants (4%) who failed the first stage of the screening test did not undergo the second stage. Of those 193 infants completing the screen, one (0.5%) failed the screen unilaterally. There were no bilateral failures. Three testers, working two and a half whole-time equivalents, should be adequate to achieve a coverage of 90% and a specificity of 99% for this screen in this clinical setting.

Cross-Sectional Studies↗
PubMed1994

A comparison of neonatal evoked otoacoustic emissions obtained using two types of apparatus.

The transient evoked otoacoustic emission (TEOAE), generated by a click and recorded in the ear canal is influenced by many factors. Of these, the form of the stimulus, the characteristics of the microphone, amplifiers and filter are probably the major ones. In addition, the acoustical loading of the ear canal by the probe may interact with the TEOAE measurement. Data presented here were obtained from 64 babies tested on each of 3 days post partum. The differences in the TEOAEs produced by the ILO88 and POEMS instruments can be quite marked. The ILO88 TEOAEs consistently have larger high frequency components than do the emissions from the POEMS system. The ILO88 system also gives higher correlations between repeat recordings. Such differences point out the need for explicit standards in probe design.

Equipment Design↗
PubMed1992

Species richness in helminth communities: the importance of multiple congeners.

Using data sets derived from published literature, the contribution of congeneric species to helminth component community richness is evaluated. Consideration of the frequency distribution of congeners in relation to host and parasite groups reveals that the distributions are unimodal, that singletons are the commonest class and that the frequency of occurrence of congeners decreases with increasing number of species per genus. Congeners may be found in any group of hosts or parasites, but are more common amongst cestodes of aquatic birds. Two patterns of occurrence of congeneric species are recognized: one in which from a few to multiple congeners are found within a single helminth genus, exemplified by dactylogyrid monogeneans and cloacinid nematodes, and the other in which there is a simultaneous occurrence of congenerics and confamilials such that there are several genera involved, but each represented by fewer species, exemplified by strongyles in horses. The question of whether these patterns can be considered examples of species flocks is discussed. We conclude that multiple congeners and species flocks are interesting phenomena but, except in isolated cases, they make insignificant contributions to community richness.

Animals↗
PubMed1991

Potential interactions between Acanthocephalus anguillae and Pomphorhynchus laevis in their natural hosts chub, Leuciscus cephalus and the European eel, Anguilla anguilla.

Chub and eels were experimentally infected via intermediate hosts harbouring cystacanths, with Pomphorhynchus laevis alone, or Acanthocephalus anguillae alone, or simultaneously with mixtures of both species in varying proportions, and sampled at 7, 56 or 112 days post-infection. Examination of chub revealed that both species showed low establishment and growth rates, differing markedly from British field data, where chub is apparently one of the most important hosts, and preventing further meaningful experiments. Both species showed higher establishment rates in eels, but A. anguillae both grew faster and matured to a greater extent than P. laevis, reflecting field data. No evidence of any interactions, competitive or otherwise, was found in the mixed infections in eels at low or high infection levels. The results were interpreted with regard to British field data and current theories of the role of interspecific competition in structuring fish helminth communities.

Acanthocephala↗
PubMed1991

Site availability and density-dependent constraints on the acanthocephalan Pomphorhynchus laevis in rainbow trout, Oncorhynchus mykiss (Walbaum).

Threshold density levels were investigated experimentally in rainbow trout, Oncorhynchus mykiss, for the acanthocephalan Pomphorhynchus laevis. Fifty small fish 120-150 mm long were infected with 50 cystacanths each every 4 weeks for 16 weeks, and samples of up to 10 fish examined at 1, 5, 9, 13 and 17 weeks after the original infection. The mean intestinal length was found to have increased significantly over this period, from a mean of 125 to 173 mm and the mean number of parasites recovered increased after each interval of 4 weeks, and significantly from 19.30 to 86.40 per fish over the 17 weeks. The distribution of the parasites in the alimentary tract of O. mykiss was unaltered, indicating that the favourable region for establishment had remained unchanged. The failure to detect any manifestations of competition is discussed, and the relevance of conventional approaches to experimental investigations of both intra- and interspecific competition in fish was queried, and contrasted to the situation in birds and mammals.

Acanthocephala↗
PubMed1991

Herpes simplex encephalitis with relapse.

Three children are described in whom herpes simplex encephalitis (HSE) followed a clearly biphasic course. The secondary deterioration may be due to a resurgence of the viral infection and calls into question the adequacy of current treatment regimens for HSE. Alternatively, a postinfectious neuroallergic process may be active in which case immunomodulatory treatment might be more appropriate than further antiviral treatment.

Acyclovir↗