PubMed Health⌕ Search

Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 73 records · Page 4Linked to original sources
PubMed2000

Cloning, sequencing, and analysis of expression of a second IL-1beta gene in rainbow trout (Oncorhynchus mykiss).

The full-length sequence of a second IL-1beta gene (IL-1beta2) in rainbow trout (Oncorhynchus mykiss) has been obtained. As with the first IL-1beta gene, IL-1beta2 is organized into six exons/five introns. There are only small differences in their intron/exon sizes, with the exception of intron 3, which is 334 bp smaller in IL-1beta2. The transcript encoded by the IL-1beta2 gene contains a 5' untranslated region (UTR) of 121 bp, followed by a 762-bp open reading frame and a 518-bp 3'UTR. The 3'UTR contains seven instability attta motifs, typical of inflammatory genes, and a polyadenylation site 11 bp upstream of a 17-bp poly(A) tail. The predicted 254 amino acid sequence of the second IL-1beta gene has 82% similarity to the first gene, 45% similarity to carp IL-1beta, and 40% similarity to human IL-1beta. Comparison of the two trout genes reveals that the IL-1beta2 gene has a deletion of 9 bases in exon 3 and an altered splicing site at the 5' end of exon 4 giving rise to a further 9-bp deletion in the resulting cDNA. As with other nonmammalian IL-1beta genes, no interleukin-converting enzyme (ICE) cut site has been found but the alignment of the amino acid sequence with other species shows a possible cut site between Arg89 and Ala90 that would give arise to a 165-amino acid mature peptide. Expression studies performed by RT-PCR using primers specific for the IL-1beta2 transcript revealed a clear dose-dependent induction of this gene in cultured trout leukocytes by stimulation with lipopolysaccharide.

Amino Acid Sequence↗
PubMed2000

Molecular cloning of the gene for interleukin-1beta from Xenopus laevis and analysis of expression in vivo and in vitro.

The Xenopus cDNA for interleukin-1beta (IL-1B) was cloned and sequenced. The gene contains 1,462 nucleotides that translate in a single reading frame to give a predicted 283-amino acid IL-1beta molecule. The translated molecule contains a single potential glycosylation site, a readily identifiable IL-1 family signature, and has highest homology to chicken IL-1beta by phylogenetic tree analysis and sequence similarity. It lacks a signal peptide in common with other known IL-1B genes, and lacks a clear ICE (caspase) cut site in common with other nonmammalian IL-1B genes sequenced to date. RT-PCR was used to study sites of IL-1B transcript expression, 24 h following injection of lipopolysaccharide (LPS). Expression was detected in the brain, liver, kidney, and spleen, with expression weakest in the brain and strongest in the spleen. No transcript expression was detectable following injection of saline. Northern blot analysis was used to quantify the induction of IL-1B expression in splenocytes following in vivo or in vitro stimulation with LPS. The results are discussed in relation to the potential role of IL-1beta in amphibian immune responses.

Amino Acid Sequence↗
PubMed2000

Predictors of job stress and satisfaction among hospital workers during re-engineering: differences by extent of supervisory responsibilities.

After two years of rapid organizational change within a large teaching hospital, 83 percent of workers remained employed there. Among these "survivors," job satisfaction decreased and job stress increased regardless of whether they were employed in a supervisory position. This article examines the predictors of job satisfaction and job stress for managers, for people who indicated that they supervised others but were not managers, and for workers. There are areas of commonality in predictors across these groups, as well as some differences by level of supervisory responsibility. Examining and modifying job characteristics associated with high stress could result in healthier hospital work environments.

Hospital Administrators↗
PubMed2000

Digestive strategy of the south-east African lesser bushbaby, Galago moholi.

Galago moholi is a small nocturnal primate, which has a specialised diet of Acacia exudate and insects. Both exudate and insect exoskeletons contain beta-linked polysaccharides that can be used as an energy source by mammals via microbial fermentation. The morphology of the gastro-intestinal tract of G. moholi suggests that the complex, elongate caecum, proximal colon and ansa coli are most likely to be the fermentation compartment. The results of a digesta marker study showed that there was selective retention of the fluid phase of the digesta, a pattern commonly seen in small caecum-fermenting mammals. There was also retention of the particle marker in the gastro-intestinal tract. Comparison to these results with those from other mammals, including other bushbaby species, suggests that this was due to retention of particulate digesta in both the stomach and the ansa coli, a U-shaped loop in the proximal colon. The digestive strategy of the south-east African lesser bushbaby is best described as caeco-ansal fermentation, as the caecum, proximal colon and ansa coli function as distinct fermentation chambers. However, we contend that, because it is soluble polysaccharides in exudates travel with the fluid phase of the digesta, reach the hindgut sooner than particles of the insect exoskeleton, and are fermented faster than particulate digesta, that lesser bushbabies, in spite of their small size (approximately 200 g) are able to include an apparently low-quality food (exudate) in their diet.

Africa↗
PubMed2000

Can sodium valproate improve learning in children with epileptiform bursts but without clinical seizures?

This study aimed to determine whether sodium valproate (VPA) improves cognitive performance and behaviour in children with learning and behavioural problems associated with electrographic epileptiform discharges but without clinical seizures. A randomized, double-blind, single-crossover trial was carried out with VPA or placebo on eight participants with different learning and behaviour problems. Participants also underwent neuropsychological testing under video EEG and the parent and teacher Behaviour Check List (CBCL; Achenbach 1991a, b) during each treatment phase. Clinically none of the children improved on VPA. On formal testing children were more distractable, had increased delay in response time, and showed lower memory scores while on VPA. In addition, parents reported higher internalizing scores on the CBCL while children were on VPA. Our data do not support the use of VPA in similar patients.

Anticonvulsants↗
PubMed2000

Immunoprophylaxis in fish by injection of mouse antibody genes.

Antibodies are a crucial part of the body's specific defense against infectious diseases and have considerable potential as therapeutic and prophylactic agents in humans and animals. The development of recombinant single-chain antibodies allows a genetic application strategy for prevention of infectious diseases. To test this in a fish model, a gene construct encoding a neutralizing single-chain antibody to the fish-pathogenic rhabdovirus VHSV (viral hemorrhagic septicemia virus) was administered to rainbow trout by intramuscular injection of plasmid DNA. Circulating recombinant antibodies could later be detected in the fish, and protective immunity to the viral disease was established.

Animals↗
PubMed2000

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗
PubMed2000

Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies.

The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2alpha levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2alpha is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.

Adult↗
PubMed2000

Herpes simplex virus type 1 gene UL14: phenotype of a null mutant and identification of the encoded protein.

Herpes simplex virus type 1 (HSV-1) gene UL14 is located between divergently transcribed genes UL13 and UL15 and overlaps the promoters for both of these genes. UL14 also exhibits a substantial overlap of its coding region with that of UL13. It is one of the few HSV-1 genes for which a phenotype and protein product have not been described. Using mass spectrometric and immunological approaches, we demonstrated that the UL14 protein is a minor component of the virion tegument of 32 kDa which is expressed late in infection. In infected cells, the UL14 protein was detected in the nucleus at discrete sites within electron-dense nuclear bodies and in the cytoplasm initially in a diffuse distribution and then at discrete sites. Some of the UL14 protein was phosphorylated. A mutant with a 4-bp deletion in the central region of UL14 failed to produce the UL14 protein and generated small plaques. The mutant exhibited an extended growth cycle at low multiplicity of infection and appeared to be compromised in efficient transit of virus particles from the infected cell. In mice injected intracranially, the 50% lethal dose of the mutant was reduced more than 30,000-fold. Recovery of the mutant from the latently infected sacral ganglia of mice injected peripherally was significantly less than that of wild-type virus, suggesting a marked defect in the establishment of, or reactivation from, latent infection.

Amino Acid Sequence↗
PubMed2000

Clinical assessment of rehabilitation potential of the older patient: a pilot study.

Clinical assessment of 'rehabilitation potential' is an everyday occurrence in hospitals, where scarcity of dedicated rehabilitation facilities require clinicians to decide who is most likely to benefit from extended rehabilitation. We examined the reliability of this judgement by different interdisciplinary team members in 27 consecutive admissions to a geriatric rehabilitation ward. The reliability of a clinical judgement was in general quite poor (kappa = 0.21). A more reliable means of determining patient 'rehabilitation potential' is needed.

Aged↗
PubMed2000

Three-year prognosis of depression in the community-dwelling elderly.

BACKGROUND: Depression is the most common mental disorder in the community-dwelling elderly. AIMS: To determine the three-year prognosis of depression in a cohort of 127 community-dwelling elderly subjects and identify factors relevant to outcome. METHOD: The subjects, diagnosed depressed at year 0 using the GMS-AGECAT package, were followed up three years later. A number of factors were investigated for an association with recovery from, or persistence of, depression. RESULTS: At follow-up, 30.2% of the depressed subjects had died, 34.9% had persistent or relapsed case-level depression, 24.5% had other case- or sub-case-level mental illness and 10.4% had recovered completely. Physical ill-health, bereavement and positive family history of depression were associated with poor outcome, whereas treatment with antidepressant medication significantly improved prognosis. CONCLUSIONS: Late-life depression in community-dwelling subjects is a chronic condition. However, the positive response to antidepressant medication suggests that it should be vigorously treated.

Aged↗
PubMed2000

A question sheet to encourage written consultation questions.

PROBLEM: Interviews with parents and children attending a hospital paediatric neurology clinic indicated they had difficulties in asking questions during consultations. AIM: To set up a process to enable parents and children to get the information they wanted. BACKGROUND AND SETTING: Two paediatric neurology clinics in separate hospitals in Greater Manchester, UK with a similar client group run by one consultant. DESIGN: Various styles of question sheets were evaluated. The one that was chosen asked patients to write down questions and hand these to the doctor at the beginning of the consultation. Question sheets were given to all patients attending one clinic over a 13 week period. STRATEGIES FOR CHANGE: Use of sheets: number of patients taking or refusing a sheet, with reasons for refusal, were recorded. Doctors noted those who handed questions sheets to them Satisfaction with sheets: patients completed a short feedback form after the consultation Effect on consultations: evaluated through interviews with the doctors. EFFECTS OF CHANGE: In total, 66 (41%) of the 162 patients offered the sheet declined: 14 had already prepared questions; eight being seen for the first time felt they did not know what to ask. Seventeen had used the sheet on a previous visit and did not need it again; 19 gave no reason; the rest said they had no questions. Seventy six (47%) patients produced a sheet in the consultation. Of those using the sheet, 64 (84%) liked it and 61 (80%) found it useful. Fifty two (68%) wished to use it at future consultations. The doctors reported that through questions articulated on the sheets many issues, fears, and misunderstandings emerged which otherwise would not have been identified. Concerns about increasing consultation time and clinical disruption did not materialize. In contrast, doctors reported patients to be taking more initiative and control, particularly on subsequent visits. None of these changes was noted in the comparison clinic. LESSONS LEARNT: An attractive, clear question sheet proved a simple but effective intervention in the consultation. Parents felt empowered to take control. The approach may have wider applicability, but implementation requires staff training and support to ensure its continuing use; this ensures medical staff adjust to a new consultation format, and that clinic nurses see the value of the sheets and continue to provide them.

Child↗
PubMed2000

A framework for addressing Māori knowledge in research, science and technology.

This paper seeks to identify and discuss some of the issues for Māori research and in doing so presents a framework for considering the range of research activities which attempt to provide or develop Māori knowledge. The paper goes on to discuss kaupapa Māori research in depth as the particular approach of the Research, Science and Technology sector that is most likely to consistently develop Māori knowledge. According to Treaty of Waitangi analysis, the special relationship between tangata whenua and the Crown acknowledges the right of a distinct position based on the Māori view of knowledge as a taonga. Secondly, there is the clear acknowledgment of the undermining of the Māori knowledge base since the signing of the Treaty and that supporting kaupapa Māori research can in part offer redress in terms of re-establishing lost knowledge. The framework provided here may be used to reorient the balance of the research purchase. First, the framework allows the identification of the location of specific projects and enables an 'audit-map' of research purchase/investment over time. Secondly, research purchasers need to operate systems of assessment and performance monitoring which can respond to the range of 'Māori' research. Third, the development of methods and methodologies for Māori-centred and kaupapa Māori approaches is an area of active investment and complements the effort to develop a skilled Māori research workforce.

Attitude to Health↗
PubMed1999

TGF-beta3 exists in bony fish.

A partial nucleotide sequence of transforming growth factor-beta3 (TGF-beta3) has been isolated from the Siberian sturgeon (Acipenser baeri), rainbow trout (Oncorhynchus mykiss) and European eel (Anguilla anguilla), confirming a ubiquitous presence in the ray-finned (Actinopterygian) bony fish. The bony fish TGF-beta3 is highly conserved, with some 83-84% nucleotide identity (coding region) and 90-95% predicted amino acid identity to known homeotherm TGF-beta3's. Far lower homologies are apparent with other known TGF-beta isoforms in fish (e.g. 64-66% and 81-82% amino acid identity to trout TGF-beta 1/5 and carp TGF-beta2 respectively). Phylogenetic tree analysis showed that the fish TGF-beta3's clustered with the known homeotherm TGF-beta3's. The relatively tight clustering of TGF-beta1, TGF-beta2 and TGF-beta3 was in contrast to the TGF-beta5's, which are clearly a more heterogenous group.

Amino Acid Sequence↗
PubMed1999

Fish macrophages express a cyclo-oxygenase-2 homologue after activation.

In mammals, the increased generation of prostaglandins (PG) during the onset of inflammatory responses and activation of immune cell types has been attributed to the induction of a novel cyclo-oxygenase (COX) isoform, termed COX-2, which is distinct from the well-characterized constitutive activity (COX-1). Goldfish (Carassius auratus) macrophages exposed to bacterial lipopolysaccharide and leucocyte-derived macrophage-activating factor(s) showed a significant increase in the generation of the major COX product, PGE2, within the first 6 h of stimulation. The selective COX-2 inhibitor, NS398, inhibited this elevated generation of PGE, whereas the basal level of this product synthesized by unstimulated macrophages was unaffected by such exposure. PGE generation by goldfish macrophages was similarly inhibited by the glucocorticoid, dexamethasone, and an inhibitor of protein synthesis, cycloheximide, suggesting that this stimulation may be due to an inducible enzyme equivalent to mammalian COX-2. The complete coding sequence of rainbow trout (Oncorhynchus mykiss) COX-2 was obtained by PCR. The gene contains a 61 bp 5'-untranslated region (UTR), a 1821 bp open reading frame and a 771 bp 3'UTR containing multiple copies of an mRNA instability motif (ATTTA). The predicted translation product had high homology to known mammalian and chicken COX-2 (83-84%) and COX-1 (77%) sequences. Reverse-transcriptase PCR with cDNA from control and bacterially challenged fish revealed that trout COX-2 expression was not constitutive but could be induced. Overall, these studies show for the first time that the inducible isoform of COX has a long evolutionary history, probably dating back to the evolution of fish over 500 million years ago.

Aeromonas↗
PubMed1999

Cloning of two chemokine receptor homologs (CXC-R4 and CC-R7) in rainbow trout Oncorhynchus mykiss.

Two rainbow trout chemokine receptors have been sequenced, with homology to CXC-R4 and CC-R7 molecules. The CXC-R4 sequence consisted of 1681 nucleotides, which translated into a mature protein of 357 amino acids, with 80.7% similarity to human CXC-R4. The CC-R7 sequence consisted of 2287 nucleotides, which translated into a 368-amino acid mature protein with 64.5% similarity to human CC-R7. Both sequences contained seven hydrophobic regions, representing the seven transmembrane domains (TM) typical of G-protein-coupled receptors. Extracellular cysteines, transmembrane prolines, and the DRY motif immediately following TM3 were conserved. Phylogenetic tree analysis revealed a tight clustering of trout CXC-R4 with CXC-R3-5 genes. Trout CC-R7 clustered with CC-R6-7 and CXC-R1-2. Reverse transcriptase-polymerase chain reaction analysis demonstrated a wide tissue distribution of CXC-R4 and CC-R7 message in trout, being present in head-kidney leukocytes, blood, gill, brain, spleen, and liver.

Amino Acid Sequence↗
PubMed1999

Molecular cloning of interleukin 1beta from rainbow trout Oncorhynchus mykiss reveals no evidence of an ice cut site.

The complete coding sequence of rainbow trout IL-1beta has been obtained. The gene contains a short 5' UTR (97 bp), a 780 bp open reading frame and a 466 bp 3' UTR, which includes a polyadenylation signal, 7 ATTTA motifs and an 18 bp poly A tail. The predicted amino acid sequence (260 amino acids) contains 3 potential glycosylation sites, with a predicted molecular weight of 29 kDa, and shows between 49 and 56% amino acid similarity to mammalian IL-1betas and 57% similarity to carp IL-1beta. Greatest homology was apparent within the secondary structure of the gene, with few of the amino acids known to bind to the IL-1 receptor being conserved. No ICE cut site was apparent but multiple alignment with mammalian sequences allowed a putative mature peptide of 166 amino acids to be identified, in which Ala(95)would be the amino terminus. Northern blot analysis showed that whilst no IL-1beta expression was detectable in head kidney leukocytes immediately after isolation, expression could be induced by stimulation with LPS for 4 h in culture. Similarly, with isolated head kidney macrophages expression was significantly increased following stimulation with LPS.

3' Untranslated Regions↗