Biomedical subjects

J Elliott

Publications and source records attributed to J Elliott.

At least 91 records · Page 5Linked to original sources

PubMed1998

Regulation of cytoskeletal association by a basic amino acid motif in polyoma virus middle T antigen.

The subcellular localization of many oncogenic proteins is thought to be important for their function. In the case of the middle T antigen of the DNA tumour virus, polyoma, localization to membranes in a specific manner is essential for its cellular transforming activity. To investigate factors that influence this localization, heterologous membrane targetting sequences were substituted for the middle T antigen transmembrane domain and the properties of the resulting proteins studied. Whereas C-terminal lipid modification derived from the H-ras CaaX box restored oncogenic activity to non-transforming truncated middle T antigen species, N-terminal myristylation from pp60c-src did not. Furthermore, a region, rich in basic amino acids and adjacent to the middle T transmembrane domain, was found to mediate association with detergent-insoluble cytoskeleton. Co-operation between the basic motif and neighbouring membrane binding domains resulted in specific localization of proteins to particular membrane sites, characterized by the association with subcellular structures, likely to be cytoskeletal in nature. These results demonstrate that the cellular localization of MT is regulated by at least two determinants, a transmembrane sequence which confers membrane binding and a basic motif which specifies a particular site within the membrane.

Amino Acid Sequence↗

PubMed1998

Evidence for different 5-HT1B/1D receptors mediating vasoconstriction of equine digital arteries and veins.

5-hydroxytryptamine (5-HT) is a potent vasoconstrictor of equine digital arteries and veins which may play a role in the ischaemic disease, laminitis. The present investigation compared the properties of 5-HT1B/1D receptors in arteries with those in veins using isolated rings of equine digital blood vessels. The 5-HT1B/1D receptor-selective agonists, anpirtoline and sumatriptan were 17.9 and 10 times more potent and produced 4.1 and 5.6 times greater maximum contractions, respectively, in veins when compared to arteries. Other agonists tested were of equal potency and produced the same maximum responses in veins and arteries. Propranolol competitively inhibited 5-HT1B/1D receptor mediated responses in arteries, with a pKB of 6.7, but had no significant effects on responses in veins at 1 microM. Metergoline competitively inhibited 5-HT1B/1D receptor mediated responses in veins, with a pKB of 8.1, but had no significant effect in arteries at 0.1 microM. These data suggest that 5-HT1B/1D receptors mediating vasoconstriction in equine digital arteries are pharmacologically different to those found in digital veins.

Animals↗

PubMed1998

Community outbreak of psittacosis in a rural Australian town.

BACKGROUND: Health authorities in Victoria, Australia were notified of three men from a rural town with atypical pneumonia, admitted to hospital over 8 days. Initial serological testing suggested Chlamydia psittaci as the cause. We did a case-control study to find risk factors for psittacosis. METHODS: We searched for cases of pneumonia or severe flu-like illness through family physicians and the regional hospital. We selected three controls per case from the region's electoral roll. We collected blood for serological tests and administered questionnaires to all cases and controls. FINDINGS: We found 16 cases of psittacosis and one died. Most cases were clustered within a small geographical area, with a median age of 58 years (range 23-76), 15 (94%) of whom were male. Keeping, handling, or feeding domestic or wild birds was not associated with illness. Cases spent a median of 17.5 h per week in their garden, compared with a median of 5.2 h for controls (p=0.04) and were more likely to have mowed lawns during the 3 weeks before onset of illness than controls (odds ratio 4.81 [95% CI 1.08-33.37]). INTERPRETATION: We showed that psittacosis outbreaks are not limited to direct contact with birds and pose new challenges for disease control. Modifications may be needed to work outdoors to decrease the risk of psittacosis.

Adult↗

PubMed1998

Effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta.

The effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta were studied in vitro. Chylomicrons and chylomicron remnants were prepared in vivo. Aortic rings were incubated with the lipoproteins for 45 min before the vessels were constricted with phenylephrine and concentration relaxation response curves constructed to carbachol, ATP, A23187 and S-nitroso-N-acetylpenicillamine. Maximum % relaxations to carbachol were significantly reduced by both chylomicrons and chylomicron remnants but responses to ATP and S-nitroso-N-acetylpenicillamine were unaffected. In addition, chylomicrons significantly inhibited A23187-induced relaxation, causing an increase in the EC50 value. Chylomicron remnants cause selective inhibition of carbachol-induced relaxation suggesting an action at the receptor or G protein-coupled component of the receptor-mediated activation of the L-arginine-nitric oxide pathway. Chylomicrons appear to be less selective in their inhibition of the endothelium-dependent relaxation. This study demonstrates that lipoprotein particles of dietary origin may cause endothelial cell dysfunction.

Adenosine Triphosphate↗

PubMed1998

Statins and Pharmac.

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Fatty Acids, Monounsaturated↗

PubMed1998

Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor.

IL-18 inhibits osteoclast (OCL) formation in vitro independent of IFN-gamma production, and this was abolished by the addition of neutralizing antibodies to GM-CSF. We now establish that IL-18 was unable to inhibit OCL formation in cocultures using GM-CSF-deficient mice (GM-CSF -/-). Reciprocal cocultures using either wild-type osteoblasts with GM-CSF -/- spleen cells or GM-CSF -/- osteoblasts with wild-type spleen cells were examined. Wild-type spleen cells were required to elicit a response to IL-18 indicating that cells of splenic origin were the IL-18 target. As T cells comprise a large proportion of the spleen cell population, the role of T cells in osteoclastogenesis was examined. Total T cells were removed and repleted in various combinations. Addition of wild-type T cells to a GM-CSF -/- coculture restored IL-18 inhibition of osteoclastogenesis. Major subsets of T cells, CD4+ and CD8+, were also individually depleted. Addition of either CD4+ or CD8+ wild-type T cells restored IL-18 action in a GM-CSF -/- background, while IL-18 was ineffective when either CD4+ or CD8+ GM-CSF -/- T cells were added to a wild-type coculture. These results highlight the involvement of T cells in IL-18-induced OCL inhibition and provide evidence for a new OCL inhibitory pathway whereby IL-18 inhibits OCL formation due to action upon T cells promoting the release of GM-CSF, which in turn acts upon OCL precursors.

Animals↗

PubMed1998

Efficient presentation of endogenous superantigen by H-2Aq.

Endogenous superantigens encoded by mouse mammary tumor viruses associate with MHC class II and interact with T cells bearing particular V beta gene segments. H-2E is more efficient at presentation than H-2A, indeed Aq has not been shown to be capable of presenting endogenous superantigens. Atypically, the superantigen vSAG-3 encoded by Mtv-3 is presented efficiently in non-obese diabetic (H-2g7) mice by H-2A; we have examined the independent contributions of vSAG-3 and Ag7 to this process. Ag7 was not found to have a more general ability to efficiently present endogenous superantigens other than Mtv-3. Examination of Mtv-3-mediated thymic deletion of V beta 3+ thymocytes in the presence of H-2q additionally demonstrated the efficient presentation of vSAG-3 by Aq. Interaction of vSAG-3 with Aq and Ag7 is likely to reflect the unique sequence of Mtv-3 within the second polymorphic region previously implicated in MHC class II binding. The demonstration that mouse endogenous superantigens can be presented by a wider range of MHC haplotypes than previously thought is further evidence for their immunological impact on the mouse population.

Animals↗

PubMed1998

Consequences of hyper-aggressiveness in Siamese fighting fish: cheaters seldom prospered

Zahavi's handicap theory, formalized by Grafen, suggests that 'cheaters' must be at a disadvantage if a communication system such as ritualized aggression is to evolve (Grafen 1991, In: Behavioural Ecology: An Evolutionary Approach (Ed. by J. R. Krebs & N. B. Davies), pp. 5-31. Oxford: Blackwell Scientific). To determine whether cheating is disadvantageous in Betta splendens, we held a series of live interactions, after inducing hyper-aggression by socially isolating and then briefly 'priming' the fish. Primed isolates, which were no stronger than their rivals, 'cheated' by escalating rapidly to tailbeating and biting. These cheaters, however, usually lost fights to non-isolated opponents. Unprimed isolates, i.e. socially isolated fish that were not primed, were not initially hyper-aggressive and thus did not cheat. They lost fewer fights than the cheaters. Results suggested that cheaters lost because they exhausted themselves by their hyper-aggressiveness, allowing their non-hyper-aggressive opponents to win. This result is consistent with the Zahavi-Grafen model of how an 'honest' level of ritualized aggression can be stabilized in a population. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1998

Sympathetic and sensory axons invade the brains of nerve growth factor transgenic mice in the absence of p75NTR expression.

Collateral sprouting, a nerve growth factor (NGF)-mediated growth response of undamaged peripheral axons, can be divided into reparative and aberrant axonal growth. We have previously shown that aberrant growth occurs in transgenic mice overexpressing NGF centrally under the control of the glial fibrillary acidic protein promoter. Both sympathetic and sensory fibers, stained immunohistochemically for tyrosine hydroxylase and calcitonin gene-related peptide, respectively, invade the cerebellum of postnatal transgenic mice, whereas no such axons are seen in age-matched wild-type cerebellum. Recent examination of mice possessing a null mutation for p75NTR has suggested that axon growth may be influenced by the functional expression of this receptor. To address the potential role of p75NTR in axon growth, we have generated a new line of hybrid mice overexpressing NGF but lacking functional p75NTR expression. Postnatal (day 14) hybrid cerebellum possessed fewer aberrant sensory and sympathetic fibers compared to their age-matched transgenic counterparts. By adulthood, however, hybrid cerebellum displayed a robust plexus of axons stained immunohistochemically for calcitonin gene-related peptide and tyrosine hydroxylase. No neuronal or nonneuronal localization of p75NTR-immunoreactive elements was observed in postnatal and adult hybrid cerebellum. Interestingly, sympathetic axons within the hybrid cerebellum displayed a markedly reduced axon density and staining intensity for NGF, suggesting a possible alteration in axonal sequestration of NGF. These results show that p75NTR is not vital for new growth of NGF-sensitive sympathetic and sensory axons and that immunohistochemical detection of NGF at sympathetic axons requires the functional expression of p75NTR.

Animals↗

PubMed1998

MHC class II Ab diabetogenic residue 57 Asp/non-Asp dimorphism influences T-cell recognition and selection.

Human and mouse major histocompatibility complex class II beta chain alleles associated with predisposition to type I diabetes often encode a non-charged residue at position 57 rather than the negatively charged aspartate residue characteristic of non-susceptible haplotypes. The mechanism(s) whereby this polymorphism promotes eventual pancreatic beta cell destruction is unclear. The type I diabetes-susceptible mouse strain NOD (H2(g7)) encodes serine at Ab position 57 and is one of the few mouse class II molecules not encoding aspartate at this position. To gain insight into the structural impact of this amino acid substitution and any influence it may have on T-cell selection, we assessed whether T-cell repertoires selected by diabetogenic class II (Ag7) are tolerant of mutant Ab (residues 56 and 57) H2-Ag7. We find that NOD mice mount an allogeneic response to skin grafts expressing mutant position 57 (serine to aspartate) Abg7; but not to grafts expressing mutant position 56 (histidine to proline) Abg7. Graft rejection correlates with the presence of CD4(+) T cells specific for the mutant H2-Ag7 heterodimer. Genetic analyses are consistent with Ab position 57 aspartate/non-aspartate dimorphism influencing peptide selection and hence repertoire selection. Direct evidence for the serine to aspartate substitution at position 57 influencing T-cell selection is found by analysis of peripheral T-cell receptor (TCR) usage and the CD4/CD8 T-cell ratio.

Amino Acid Sequence↗

PubMed1998

The influence of chylomicron remnants on endothelial cell function in the isolated perfused rat aorta.

A system for the perfusion of the isolated rat aorta which allowed the study of both the uptake of chylomicron remnants by the artery wall and their effects on endothelial function was developed. Perfusion for 2 h with 125I-labelled native or oxidised (by treatment with copper sulphate) chylomicron remnants showed that small amounts became associated with the artery wall (0.111 +/- 0.034 and 0.216 +/- 0.082 ng protein/mg tissue, respectively). Tests on endothelial function were carried out in vessel rings prepared after perfusion of the aortas in the presence or absence of chylomicron remnants for 2 h. After perfusion of the vessels with oxidised chylomicron remnants, the maximum response to phenylephrine (PE) was significantly increased (from 0.34 +/- 0.06 to 0.51 +/- 0.04 g/mg tissue; P < 0.05), while the maximum % relaxation to carbachol (CCh) was significantly decreased (from 91.6 +/- 2.4 to 71.5 +/- 7.2; P < 0.05) and the response to S-nitroso-N-acetylpenicillimine (SNAP) was unaffected. Perfusion with native chylomicron remnants showed a tendency to induce similar effects, although the changes observed did not reach statistical significance. As the lipoproteins were not present in the solution bathing the vessel rings during these tests, these effects can be attributed to perfusion of the aortas with chylomicron remnants, despite only small quantities being associated with the artery wall. The results suggest that oxidised chylomicron remnants influence vascular endothelial function by interfering with the L-arginine-nitric oxide (NO) pathway. The observed potentiation of contraction to PE may be due to inhibition of the basal release of NO or to the release of contractile factors. These findings support a role for dietary lipoproteins in the modulation of endothelial cell function which occurs in the pathogenesis of atherosclerosis.

Animals↗

PubMed1998

Periodic limb movement in sleep in children with Williams syndrome.

OBJECTIVE: Williams syndrome (WS) is associated with neurobehavioral abnormalities that include irritability and attention-deficit/hyperactivity disorder. Parents often report children having difficulties initiating and maintaining sleep because of restlessness and arousals. Therefore we evaluated a group of children with WS for the presence of a movement arousal sleep disorder. METHODS: Twenty-eight families of children with WS participated in a telephone survey aimed to screen for a movement arousal disorder. Of the 16 children identified as having such a disorder, 7 (mean age, 3.9 +/- 2.2 years) underwent polysomnography. Their studies were compared with those of 10 matched control subjects (mean age, 5.3 +/- 2.0 years). RESULTS: The 7 subjects with WS who were screened by the survey had sleep latency, total sleep time, arousals, and awakenings that were similar to those of control subjects. However, they presented with a disorder of periodic limb movement in sleep (PLMS). The PLMS index in the subjects with WS was 14.9 +/- 6.2 versus 2.8 +/- 1.9 in control subjects (P < .0001). In addition, arousal and awakening in subjects with WS were strongly associated with PLMS. Moreover, children with WS spend more time awake during sleep periods than control subjects (10.0% +/- 7.0% vs 4.4% +/- 4.7%; P < .05). Five children were treated with clonazepam, and in 4 a significant clinical response was noted. CONCLUSION: We report an association between WS and PLMS. Clonazepam may reduce the clinical symptoms of PLMS in some of these children.

Anticonvulsants↗

PubMed1998

The morphological and spectral phenotype of apoptosis in HeLa cells varies following exposure to UV-C and the addition of inhibitors of ICE and CPP32.

Numerous extra- and intracellular factors, including UV radiation, can initiate a programme of cell death by apoptosis. While apoptosis is commonly defined morphologically, the relationships between morphology and molecular events are not well established. To investigate these relationships in HeLa cells, eight morphometric criteria for cell proliferation and damage and 10 criteria for apoptotic phenotype were examined using light microscopy, and corroborated by ultrastructure and spectral imaging. They were identified (1) during a time course after irradiation with 0, 10 or 30 J/m2 UV-C; (2) after separation of apoptotic from normal cells on a Percoll gradient; and (3) after irradiation with UV-C plus perturbation of the apoptotic pathway by treatment with inhibitors of two caspases, ICE and CPP32. The number of cells in apoptosis increased in a dose-dependent manner after UV-C treatment. Centrifugation of irradiated cells on a Percoll gradient increased the collection of apoptotic cells tenfold. The stereotypical apoptotic phenotype, in which cells have deep cytoplasmic blebbing and highly condensed DNA, comprised only a few percent of all apoptosis, and was rarely seen in groups receiving caspase inhibitors. The most common apoptotic phenotype was a rounded cell with large spherical nucleolus and associated DNA. After treatment with UV-C plus inhibitors the apoptotic index was decreased by about 30% compared to UV-C radiation alone. These apoptotic cells had dark spherical cytoplasm with small blebs, greatly increased numbers of cytoplasmic ribosomes, abundant nucleolar material with a large separate granular component, and chromatin condensed at the nuclear membrane. Using the technique of spectral imaging, it was found that the spectrum obtained from the granular component of the nucleolus, which was elevated in apoptotic cells treated with UV-C plus inhibitors, was similar to the dense accumulation of ribosomes in the apoptotic cytoplasm. The data indicate that spectral imaging may be a useful tool for identifying and characterizing variations in the apoptotic process, and that the caspase inhibitors used here do not completely abolish UV-C induced apoptosis, but rather alter its incidence and progression.

Amino Acid Chloromethyl Ketones↗

PubMed1998

Characterization of vasodilatory adenosine receptors in equine digital veins.

Isolated equine digital veins (EDVs) which had been denuded of their endothelium were used to study adenosine receptors causing vasodilation. When the blood vessel wall tension was raised with the thromboxanemimetic, U44069 (30 nM), the order of vasodilator potency of adenosine receptor agonists was: 5'-N-ethylcarboxamidoadenosine (NECA) > 2-p-(2-carboxyethyl)phenyl amino-5'-N-ethylcarboxamido-adenosine (CGS 21680) > 5'-N-methylcarboxamido-adenosine (MECA) > N6-cyclohexyladenosine (CHA) > N6-cyclopentyladenosine (CPA) > N6-2-(4-Aminophenyl)ethyladenosine (APNEA) > adenosine. Removal of the endothelium had no significant effect on the responses to NECA. The adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A1-selective) and xanthine amine cogener (XAC; non-selective antagonist) inhibited responses to NECA and CHA in a competitive manner and XAC proved to be 8-25 times more potent than DPCPX against both agonists. These data support the presence of A2 adenosine receptors in EDVs, located on the vascular smooth muscle cells, which are most likely to be of the A2A-adenosine receptor subtype. A direct comparison between the potency and efficacy of NECA and adenosine as vasodilators of EDV and equine digital arteries was made and both agonists proved to be significantly more potent and efficacious as vasodilators of EDVs. These data suggest that adenosine may be an important local mediator regulating blood flow through the digital circulation and that its generation under hypoxic conditions would lead to selective venodilation.

Adenosine↗

PubMed1998

Clinical issues surrounding the use of terbutaline sulfate for preterm labor.

beta-mimetics have been prescribed by physicians to arrest or prevent premature labor for more than 20 years. Although not approved by the Food and Drug Administration (FDA) for tocolytic use, terbutaline sulfate has been the most widely prescribed beta-mimetic in the United States. Recently, the role of terbutaline in the treatment and prevention of preterm labor has been questioned by the FDA. Because the off-label use of drugs is a formally accepted practice in medicine when scientific studies support such use, we reviewed the currently available clinical literature on terbutaline use in various routes of delivery: intravenous, oral, and subcutaneous via infusion pump. This review describes the clinical evidence that supports the safe and effective use of terbutaline as a tocolytic agent in certain patient populations. Practicing physicians should continue to have unrestricted use of terbutaline for tocolysis as one of the few remaining therapeutic options remaining in the fight against preterm birth.

Administration, Oral↗

PubMed1998

Increased perception of airway narrowing in patients with mild asthma.

To compare the perception of airway narrowing of nonasthmatic subjects with those having wheeze or mild asthma (doctor-diagnosed), the relationship between FEV1 and breathlessness was examined in 123 subjects from a general population sample. Scores for breathlessness, using the Borg scale, were recorded before and after inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in the previous 12 months, and doctor-diagnosed asthma was obtained by questionnaire. At any given level of FEV1 there was wide variation in Borg scores between subjects, however median Borg scores and the mean slope of Borg score on FEVI was greater in the asthmatic subjects or those with wheeze compared with nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic subjects, those with airway hyperresponsiveness had increased maximum symptom scores and maximum changes in FEVI, but similar Borg scores relative to change in FEVI, compared with those without hyperresponsiveness. We conclude that the perception of mild and moderate degrees of airway narrowing varies widely between individuals but is increased in subjects with a history of mild asthma or wheeze in the last 12 months, independently of airway responsiveness.

Adult↗

PubMed1998

Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995.

Clinical and laboratory findings at the time of first diagnosis in 80 cats with chronic renal failure (CRF) were examined in a prospective study to determine the survival time of these animals and identify possible factors contributing to the progression of feline CRF. On the basis of clinical presentation, animals were assigned to one of three groups; compensated (n = 15), uraemic (n = 39) and end-stage (n = 26) CRF. Loss of renal concentrating ability was a common finding, even before clinical signs of renal disease were evident. The plasma creatinine concentration at initial presentation was a poor predictor of survival time and the presence of significant anaemia was indicative of a poor prognosis. The study demonstrated the highly variable degree of renal impairment present at the time of diagnosis and the potentially long survival time of many compensated and uraemic cases.

Animals↗

PubMed1998

Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992 and 1995.

Eighty cats with chronic renal failure (CRF) were evaluated in a prospective study to investigate the prevalence and aetiopathogenesis of renal secondary hyperparathyroidism (RHPTH), using routine plasma biochemistry and assays of parathyroid hormone (PTH), blood ionised calcium and 1,25 dihydroxycholecalciferol (1,25[OH]2D3). Hyperparathyroidism was a frequent sequela of CRF, affecting 84 per cent of cats with CRF, the severity and prevalence of RHPTH increasing with the degree of renal dysfunction. Compared with an age-matched control population, plasma concentrations of phosphate and PTH were significantly higher and 1,25(OH)2D3 concentrations were significantly lower in the two groups of cats presenting with clinical signs of CRF. Significant ionised hypocalcaemia was present only in cats with end-stage renal failure. However, a number of cats were hyperparathyroid in the absence of abnormalities in the parameters of calcium homeostasis measured in this study. There was a significant correlation between plasma phosphate and PTH concentrations.

Animals↗