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Biomedical subjects

C Kelly

Publications and source records attributed to C Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1998

Differences in cytotoxicity of native and engineered RIPs can be used to assess their ability to reach the cytoplasm.

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.

Amino Acid Sequence↗
PubMed1998

Developing 'FOCUS': a project to promote effective practice in child and adolescent mental health services in the UK.

UK health policy requires child and adolescent mental health service providers to demonstrate that their services are effective. The FOCUS project has been developed to improve the availability and accessibility of research evidence and innovation, to support purchasers in the effective commissioning of services and to help providers base service provision on evidence of effectiveness and develop methods of evaluation.

Adolescent↗
PubMed1998

Mechanism of action and the substrate-dependent pH maximum shift of the alpha-amylase of Bacillus coagulans.

The alpha-amylase of Bacillus coagulans is a saccharifying alpha-amylase which hydrolyses the disaccharide maltose [L. Keating, C. Kelly, and W. Fogarty, Biochem. Soc. Trans., 24 (1996) 44S]. The pH maximum for maltose hydrolysis is pH 5.0, differing from the pH maximum for starch hydrolysis which is pH 6.0. Studies using reducing end 14C-labeled maltooligosaccharides revealed a substrate-dependent pH maximum shift; hydrolysis of radiolabeled maltotriose (G3*) was maximal at pH 5.0 while the pH maximum for hydrolysis of radiolabeled maltopentaose (G5*) and maltohexaose (G6*) was pH 6.0. With maltotetraose (G4*) however, the pH maximum was pH 5.0-6.0. In addition, the bond cleavage pattern of G4* was dependent on pH. At pH 5.0, the pH maximum for maltose hydrolysis, the frequency of hydrolysis of the reducing end terminal bond of G4* was maximal. Determination of the pH maximum of the productive binding modes of the cleavage patterns of G3* to G6* illustrated the possible role of the occupation of subsite r + 2 in the pH control mechanism of B. coagulans alpha-amylase.

Bacillus↗
PubMed1998

Predischarge screening of very low birthweight infants by click evoked otoacoustic emissions.

OBJECTIVE: To evaluate the role of transient evoked otoacoustic emission (TEOAE) in screening very low birthweight (VLBW) neonatal intensive care unit (NICU) graduates for hearing loss in comparison with visual reinforcement orientation audiology (VROA) at 10 months. METHODOLOGY: The study population was all VLBW neonatal survivors discharged from a single regional NICU at John Hunter Childrens Hospital (JHCH), Newcastle, New South Wales, Australia, between April 1994 and March 1996. A TEOAE screen was performed prior to discharge and repeated if necessary until a pass was obtained in at least one ear. Infants were further screened by VROA at their local Australian Hearing Services (AHS) office at 10 months corrected age. Repeated TEOAE failures were referred directly for an ENT opinion. RESULTS: A total of 193 infants were eligible for enrolment during the study period. One hundred and forty-four (75%) received TEOAE testing. The median age of first screen was 36 weeks gestational age. Ninety-five (66%) of infants tested passed on a single screen. Of the remaining 49 infants, 26 passed on retesting (overall pass rate 84%). Twenty-three (16%) were deemed to have failed the TEOAE screen. Of the 121 infants who passed TEOAE, only 67 (55%) completed VROA. Two of these infants have a high frequency sensorineural loss and one of them has been aided. In the 23 who failed TEOAE, nine have subsequently had normal VROA, another, though not tested is clinically normal. three have hearing loss with middle ear disease and eight have confirmed sensorineural deafness, all aided. One infant has died and an infant with Down's syndrome has been adopted out of the area. It is of interest to note that the eight aided infants are all of less than 28 weeks gestation. If we restrict analysis to infants with completed VROA testing, the TEOAE has a 97% negative predictive value for sensorineural deafness and a 38% positive predictive value. CONCLUSIONS: This study has highlighted both the prevalence of hearing impairment in the very premature survivors and difficulties in compliance with a VROA based hearing screen. We see an advantage in directing resources towards an early screening test, such as TEOAE, that can be applied while the target population is still captive.

Audiometry, Evoked Response↗
PubMed1998

Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product.

The PML gene product is associated with a defined nuclear structure (10-20 per cell) known variously as PML-bodies, ND10, PODs or Kr bodies. Certain conditions are known to compromise the integrity of PML-bodies; these include environmental stress (e.g. heat shock), a chromosomal translocation-associated acute promyelocytic leukaemia, and infection with certain viruses [including human cytomegalovirus (HCMV), herpes simplex virus type 1 and adenovirus]. Expression of the HCMV major immediate early (IE) protein (IE1(491aa)) is by itself sufficient to cause disruption of PML-bodies, resulting in the dispersal of the PML antigen uniformly throughout the nucleus. In uninfected cells undergoing mitosis PML is excluded from chromatin. However, both IE1(491aa) and PML were observed to associate with mitotic chromosomes in cells infected with HCMV or transfected with the IE1 gene. A series of in-frame IE1 deletion mutants was used in DNA transfection experiments to identify two large sequence elements (aa 132-274 and the C-terminal aa 347-491) not required for dispersal of the PML antigen. However, a putative leucine-zipper domain (aa 105-139), a putative zinc-finger domain (aa 267-286) and exon 2 and 3 coding sequences (aa 6-85) were required. The association of the IE1 gene product with chromatin required an acidic domain near the C terminus (aa 421-486). The interaction of IE1(491aa) with chromatin was therefore not required for the disruption of PML-bodies. Exon 2 (aa 1-24) was shown to encode a nuclear localization signal.

Animals↗
PubMed1998

A review of contributions to disasters: 1977-1996.

Since the first issue in 1977. Disasters has been one of the pre-eminent refereed journals on the study and reporting of disasters. This article reviews 703 articles and reports in the journal through 1996 to provide a snapshot of the nature of the journal throughout 20 years of publication. The results indicate the most common contributions: first, were research articles by authors from the North Atlantic; second, most often dealt with natural disaster relief or impact; and third, most frequently focused on Africa. These generalisations, however, do not reflect attention paid to food-related and political disasters and greatly understate the broad diversity of material presented in the journal. To improve the topical and geographic coverage of Disasters probably requires a proactive effort to close gaps in the journal's coverage of disasters.

Authorship↗
PubMed1998

Nithsdale schizophrenia surveys. 17. Fifteen year review.

BACKGROUND: In recent years there has been a shift to 'community care' and the introduction of several 'atypical' antipsychotic drugs. We report the impact of these changes. METHOD: In Nithsdale, Dumfries and Galloway, Scotland, the population of patients with schizophrenia was identified in 1996. This census replicated a study carried out in 1981. The population with schizophrenia were compared on clinical and social variables. The whereabouts in 1996 of the 1981 population was determined. RESULTS: In comparison with the 1981 population, more patients in 1996 had positive, negative and non-schizophrenic symptoms. More showed tardive dyskinesia. Social adjustment had not changed. They had spent less time in hospital; fewer (13%) were living with their parents; and fewer (8%) were employed. By 1996, 35% of the 1981 cohort had died (standardised mortality rate male-154; female-162). CONCLUSIONS: The mental health of a community of people with schizophrenia living in a rural area in 1996 was poorer than in 1981.

Adult↗
PubMed1998

The effects of depression awareness seminars on general practitioners knowledge of depressive illness.

The Royal Colleges of Psychiatry and General Practice wish to increase knowledge of depressive illness among patients and professionals. This study reports the results of a series of depression education seminars in a Health Board in Northern Ireland. Seminars lasted 2 1/2 hours and included didactic teaching and interactive case management vignettes. 88 general practitioners took part (39% of those eligible). Seminars increased knowledge as measured by questionnaire immediately, but this did not appear to be sustained at one year, when compared to a group of general practitioners with no access to such seminars. Educational programmes as described do not appear to have a sustained effect on general practitioners' knowledge of depressive illness.

Depressive Disorder↗
PubMed1998

Investing or discounting self: are moral decisions shaped by conditions in the workplace?

Modern socioeconomic trends contribute to the complexity and diversity of ethical issues encountered in clinical nursing practice. Despite growing interest in ethical decision making among nurses, little is known about the contextual influences. The article describes an exploratory study of how nurses make ethical decisions and what factors hindered or helped them to act on their moral choices. Two central constructs were identified: investing and discounting self. The article explains essential subprocesses of these constructs within the context of clinical nursing practice.

Adult↗
PubMed1997

Carbonic anhydrase II and carbonic anhydrase-related protein in the cerebellar cortex of normal and lurcher mice.

The developmental profiles of carbonic anhydrase II (CA-II) and a carbonic anhydrase related protein (CARP) were studied in rat and mouse cerebella. Enzyme histochemistry, immunohistochemistry, in situ hybridisation and Western blotting were used to study the synthesis and expression of these enzymes in cerebellar sections from age matched control, CA-II deficient and lurcher mice, the latter being characterised by Purkinje cell degeneration. Both CA-II and CARP were first found to be expressed in the Purkinje cells in the 9 day old mouse, and the immunoreactivity of both peptides increased with time. Immunohistochemistry showed more intense staining of CARP than of CA-II in Purkinje cells throughout the developmental profile of the mouse, and this was mirrored by the mRNA levels determined by in situ hybridisation. Immunohistochemistry of CA-II and CARP also demonstrated the progressive dendritic growth of the mouse and rat Purkinje cells. CA-II and CARP immunoreactivity ceased by the end of cerebellar maturation. The onset of Purkinje cell degeneration was detected at day 10 in the lurcher mouse, with concomitant marked decrease in CA-II level: however CARP expression was found to be unchanged. By postnatal day 16 neither CA-II mRNA, protein, nor activity was detectable in contrast to CARP which remained at a decreased level unit the Purkinje cells population had completely degenerated. Our findings suggest a role of CA-II in the degenerative processes of the lurcher Purkinje cells, with CARP playing an important role in the development and maturation of the cerebellar cortex.

Animals↗
PubMed1997

Induction of heat shock protein 72kDa expression is associated with attenuation of ischaemia-reperfusion induced microvascular injury.

Leukocyte-endothelial interaction is a pivotal step in the pathogenesis of ischemia-reperfusion (I/R) injury. Exposure of cells to a subcritical heat stress may protect cells from subsequent I/R injury, through induction of a 72-kDa heat shock protein (HSP72). The aim of this study was to investigate the effect of thermotolerance on leukocyte adherence and migration during an I/R period in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control (sham I/R), I/R, and thermotolerance+I/R groups. Thermotolerance was induced 18 hr prior to I/R, which was in turn established by occlusion of the superior mesenteric vascular pedicle for 10 mins, followed by 60 mins of reperfusion. The blood flow, leukocyte rolling velocity, and the number of adherent and migrated leukocytes in postcapillary venules were measured by intravital microscopy. I/R significantly decreased the rolling velocity of leukocytes; increased the number of adherent leukocytes at 10, 30, and 60 mins after reperfusion; and also increased the number of migrated leukocytes at 60 mins after reperfusion. Thermotolerance induction expression of HSP72 in pulmonary, intestinal, and mesenteric tissues was determined by Western immunoblotting. Thermotolerance significantly prevented the I/R-induced decrease in rolling velocity of leukocytes, the increase in the number of adherent leukocytes at 30 and 60 mins, and the increase in the number of migrated leukocytes at 60 mins. This results suggest that thermotolerance attenuates I/R injury by modulating leukocyte-endothelial interaction in vivo, possibly by increasing tissue expression of HSP72.

Animals↗
PubMed1997

High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats.

Arachidonic acid (AA), an n-6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n-6 class of eicosanoids and is the most abundant n-6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO compared with the vehicle control animals. Being highly enriched in AA, ARASCO offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies.

Animals↗