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D Burnett

Publications and source records attributed to D Burnett.

At least 37 records · Page 2Linked to original sources
PubMed1998

A direct correlation between nicotinamide N-methyltransferase activity and protein levels in human liver cytosol.

Phenotypic differences in nicotinamide N-methyltransferase (NNMT, E. C. 2.1.1.1) activity may be due to a genetic polymorphism. We report the characterisation of the hepatic NNMT activity in cytosol from normal human livers, enzyme protein levels determined by Western blotting and ELISA and mRNA levels determined by SDS-PAGE/Northern blotting. Subjects with high NNMT activity had high levels of NNMT protein and NNMT mRNA levels in hepatic cytosol and the converse was true for individuals with low NNMT activity. No differences in sequences were seen when cDNAs of individuals with high and low NNMT activity were compared. Thus phenotypic differences in the general population are due to differences in steady-state mRNA levels and not because of a polymorphism in the coding region of the NNMT gene.

Adolescent↗
PubMed1998

Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

Administration, Inhalation↗
PubMed1998

Cleavage of native type I collagen by human neutrophil elastase.

The ability of purified human neutrophil elastase (EC 3.4.21.37) to cleave native type I collagen has been investigated. Soluble human, bovine or rat type I collagen was incubated with neutrophil elastase for 16 h at 25 degrees C before catalysis was stopped with 3, 4-dichloroisocoumarin. Analysis by SDS/PAGE of the collagen digests revealed 3/4-length fragments similar in size to those produced by interstitial collagenase. The collagenolytic activity was dose dependent and was not due to a contaminating metalloproteinase or cysteine proteinase, as it was not inhibited by 1,10-phenanthroline, EDTA or L-trans-epoxysuccinyl-leucylamido-(4-guanidino)butane. The identity of the cleavage products was confirmed using a new antibody that recognizes the unwound alpha2(I)-chain. This detected the 3/4-length fragment of type I collagen following neutrophil elastase cleavage. In addition to cleaving soluble collagen, neutrophil elastase also cleaved reconstituted, radiolabelled type I collagen fibrils, at a rate of 16 microg/min per nmol. These results indicate that neutrophil elastase can cleave native type I collagen in the helix, an activity that might contribute to its roles in connective-tissue pathology.

Animals↗
PubMed1998

IgG subclasses in the serum and sputum from patients with bronchiectasis.

BACKGROUND: IgG subclass deficiency is often associated with recurrent pulmonary infections. The prevalence of deficiency in a large well characterised group of patients with bronchiectasis has not previously been established. METHODS: Serum IgG subclass concentrations in 89 patients with bronchiectasis were compared with those obtained from a group of 82 age and sex matched normal healthy controls. Sputum IgG subclass concentrations were also assessed in 44 of the patients. Albumin was measured as a marker of protein transudation from plasma to determine the degree of local IgG subclass production. RESULTS: The serum concentrations of IgG1, IgG2 and IgG3 were increased in the patients compared with the control group whereas IgG4 concentrations were not. There was an overall incidence of deficiency of 1% for subclasses 1-3 and 5% for subclass 4 in patients with bronchiectasis based on observed concentrations being below the lower limit of the control group range. The concentrations of IgG subclasses in sputum were partly dependent upon the degree of inflammation as assessed by the macroscopic appearance of purulence. A comparison of the ratio of sputum:serum subclass concentration and sputum:serum albumin, however, revealed that all of the subclasses were present at greater concentrations than could be accounted for by transudation alone. CONCLUSIONS: A new normal control range for serum IgG subclasses has been established and from this range it was found that IgG subclass deficiency in a group of unselected patients with bronchiectasis was comparatively rare. A significant degree of local IgG production was also suggested in the lungs of these patients.

Adult↗
PubMed1998

Additional Essential Criteria for Quality Systems of Medical Laboratories. European Community Confederation of Clinical Chemistry (EC4) Working Group on Harmonisation of Quality Systems and Accreditation.

Essential Criteria for Quality Systems of Medical Laboratories have been published recently by the European Community Confederation of Clinical Chemistry (EC4) Working Group on Harmonisation of Quality Systems and Accreditation. The Essential Criteria address the majority of critical aspects of quality management in the medical laboratory. They have been accepted by the EC4 General Assembly and are endorsed by the Forum of European Societies for Clinical Chemistry (FESCC). However, a supplement to the Essential Criteria was necessary, addressing two aspects, which are only partly covered by the Essential Criteria: the management of resources and point of care testing. Thus, the EC4 Working Group on Harmonisation of Quality Systems and Accreditation has decided to formulate Additional Essential Criteria for Quality Systems of Medical Laboratories, directed at the issues of management of resources and point of care testing. Criteria on management of resources address financial aspects, information logistics and acceptance by clients. Criteria on point of care testing address responsibilities, education of non-laboratory staff and operational aspects. The Additional Criteria are supplementary to the previously published Essential Criteria and should be read as an integral part of these.

Accreditation↗
PubMed1997

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of hydrodesulfurized kerosine.

Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or = 93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.

Administration, Topical↗
PubMed1997

Severe pre-eclampsia and eclampsia: a broad overview with discussion of the nursing care required for the eclamptic patient.

Severe pre-eclampsia and eclampsia are conditions which are rarely seen in A & E departments today. Although the percentage of patients suffering from these conditions is extremely small, the author has been involved in the care and treatment of two patients with this severe complication of pregnancy. A lack of clear guidelines on this subject was the motivation which prompted further study. This paper covers definitions of pre-eclampsia, eclampsia, history, incidence, risks and pathophysiology. The main discussion is the nursing care and treatment of the eclamptic patient in the acute phase of the condition. The author hopes that by the end of this paper it is evident that all health care professionals should be aware of this dangerous condition and know the appropriate treatment to give to ensure the best quality of care possible.

Emergency Nursing↗
PubMed1997

Hospital's focus shifts to community services.

As one community hospital sought ways to reduce it costs, it discovered home care as a means to that end. The hospital used a consultant company to help it make the transition. It serves as a model for other hospitals and home care agencies to follow.

California↗
PubMed1997

Essential criteria for quality systems in medical laboratories.

The introduction of total quality systems in medical and clinical laboratories and accreditation of these laboratories is gaining more and more interest. In several countries laboratories have set up quality systems, and accrediation schemes are also operating. The standards of these schemes have much in common although several differences exist. There exists uncertainty in several countries on the choice of a system. Laboratory specialists are confronted with a new way of thinking concerning the management and daily practice of their laboratories. It is not clear, which standards should be used as a basis, and certainly not how to interpret such standards. Particulary in the European Union, harmonisation of criteria for quality systems is desirable. In the present paper, the document entitled "Essential Criteria for Quality Systems in Medical Laboratories" is presented. The document has been accepted in the general Assembly of the European Communities Confederation of Clinical Chemistry (EC4) and by the working group on Good Laboratory Services of the European Council on Laboratory Medicine (ECLM). The criteria in the document are focussed on the particular situation of medical laboratories, including pre- and post-analytical aspects. Reference is made, where applicable, to EN 45001, ISO 9001 and ISO guide 25 draft 3.

Chemistry, Clinical↗
PubMed1996

Doppa induces cell death but not differentiation of U937 cells: evidence for the involvement of PKC-beta 1 in the regulation of apoptosis.

Recent reports have claimed that activation of protein kinase C (PKC)-beta is sufficient for both differentiation and apoptosis in promyeloid HL60 cells. Phorbol esters which differentially activate PKC isoenzymes in vitro were used to induce differentiation and apoptosis in U937 cells; TPA and Dopp activate all U937 PKC isoenzymes, except PKC-zeta and Doppa activate only PKC-beta l. At concentrations of Doppa below 50 nM, only PKC-beta l was activated by 2 min and apoptosis was induced, but there was no differentiation of cells towards monocytes. TPA (1-25 nM) and Dopp (5-100 nM) activated PKC-alpha, -beta l and-gamma within 2 min and induced differentiation, but only increased apoptosis at the highest concentrations used. Thus, initial activation of PKC-beta l is insufficient for differentiation of U937 cells, but may lead to the induction of apoptosis.

Apoptosis↗
PubMed1996

Evidence based practice: clinicians' use and attitudes to near patient testing in hospitals.

AIM: To survey the use made of laboratory services for urgent tests and clinicians' attitudes to near patient testing. METHODS: A questionnaire was sent to clinicians working in acute hospitals within Trent and North West Thames Regions. RESULTS: 197 replies were received. Most demand came from intensive care units. Overall, clinicians requested a median of six urgent tests a day. Blood glucose and dip stick urine testing were the most commonly performed bedside tests, but 41% of clinicians did not use ward testing. The most frequently cited indication for bedside testing was the need for speed. 85% of clinicians trusted results obtained in their central hospital laboratory, but there was an almost equal division between those who did (34%) and those who did not (38%) trust the results from near patient testing. A slightly larger proportion indicated they would accept responsibility (44%) for results obtained on the ward than would not (35%). Most staff indicated that better transport to the laboratory would remove the need for near patient testing. CONCLUSIONS: Clinicians have demonstrated an apparent need for rapid response testing but there is a strong preference for rapid transport systems and central laboratory analysis rather than bedside testing as a solution to this problem. There is a need to investigate the clinical and cost-effectiveness of near patient testing as a solution to rapid response testing.

Attitude of Health Personnel↗
PubMed1996

Exercise and exhaustion effects on glycogen synthesis pathways.

Female Sprague-Dawley rats were infused with [1-13C]glucose to measure the effect of endurance training and the effect of various metabolic conditions on pathways of hepatic glycogen synthesis. Four metabolic states [sedentary (S), trained (T), sedentary exhausted (SE), and trained exhausted (TE)] were studied. T and TE rats were trained on a motor-driven treadmill (30 m/min, 15% grade, 1.0 h/day, 5 days/wk) for 8-10 wk. After a 24-h fast, SE and TE rats were run to exhaustion (sedentary average = 78 min, trained average = 155 min) at a training pace and immediately infused with labeled glucose for 2 h. S and T rats were infused after a 24-h fast. After infusion, tissues were removed and glycogen was isolated and hydrolyzed to glucose. The glucose was measured for distribution of 13C by using nuclear magnetic resonance. Glycogen was synthesized predominantly by the indirect pathway for all metabolic states, indicating that infused glucose was first metabolized primarily in the peripheral tissue. The direct-pathway utilization was greater in rested S than in rested T animals (30 vs. 14%); however, for exhausted animals, the trained use of the direct pathway was greater (22 vs. 9%). Both TE and rested T animals utilize the indirect pathway a comparable amount. Sedentary animals, on the other hand, dramatically decreased utilization of the direct pathway, with exhaustive exercise changing from 30 to 9%. The results indicate that endurance training modifies glucose utilization during glycogen synthesis after fasting and exhaustive exercise.

Animals↗
PubMed1995

Synthesis and secretion of procathepsin B and cystatin C by human bronchial epithelial cells in vitro: modulation of cathepsin B activity by neutrophil elastase.

Procathepsin B and cystatin C are found in human lung secretions. We investigated the capacity of human bronchial epithelial cells to synthesize and secrete these proteins. Immunoprecipitation of [35S]methionine-labeled proteins from cultured bronchial epithelial cell lysates, followed by denaturing gel electrophoresis and autoradiography, showed the presence of newly synthesized procathepsin B of M(r) 42,000; no mature form was detected. Cathepsin B in conditioned medium from epithelial cells was tagged with benzyloxycarbonyl-125I-tyrosyl-alanine-diazomethane before and after treatment of the medium with neutrophil elastase. Control medium again showed a predominant form of cathepsin B with a M(r) of 42,000, but upon treatment with neutrophil elastase this protein was converted to a M(r) of 38,000, similar to the active form previously found in lung secretions, and cathepsin B activity was generated. The medium also contained the cathepsin B inhibitor, cystatin C, but cystatins A, B, S, SN, SA, and kininogen were not detected. After removal of cystatin C from the medium, elastase was still required to activate procathepsin B. These results suggest that bronchial epithelial cells are a source of procathepsin B and cystatin C in lung secretions. Cleavage both of cystatin C and procathepsin B by neutrophil elastase is essential for the generation of cathepsin B activity in the medium.

Bronchi↗
PubMed1995

Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by central nervous system inflammation and demyelination. Retinoids regulate cell differentiation and growth by binding to and activating retinoic acid receptors, which seem to be nuclear transcription factors. The effect of retinoids on chronic relapsing EAE produced by the transfer of myelin basic protein (MBP)-specific lymph node cells (LNC) was studied. All-trans-retinoic acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro. However, the capacity of these cells to transfer EAE was markedly reduced by concentrations of tRA that only mildly inhibited T cell proliferation. The presence of tRA during in vitro MBP-specific LNC activation resulted in a considerable increase in IL-4 mRNA, whereas mRNA for IL-2, TNF-alpha, and IFN-gamma was decreased. Increased IL-4 also was detected in culture supernatants. However, the presence of a neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did not reverse the inhibition of encephalitogenicity caused by tRA. The administration of retinoids in vivo resulted in an improved clinical course, even when given after disease onset. These findings suggest that T cell activation in the presence of tRA results in the development of T cells of the Th2 phenotype, which, in turn, might be responsible for the decrease in the encephalitogenicity of MBP-specific T cells. The modulation by retinoids of an immune response dominated by Th1-like T cells to one in which the protective cytokines of Th2-like cells predominate may have potential relevance for human demyelinating diseases such as multiple sclerosis.

Animals↗
PubMed1995

Changes in protein kinase C isoenzyme expression associated with apoptosis in U937 myelomonocytic cells.

Spontaneously apoptotic U937 cells from exponentially growing cell cultures were enriched on discontinuous Percoll density gradients. Increased PKC-beta and reduced PKC-zeta expression were detected in apoptotic cells by Western blotting. Using confocal microscopy, changes in the level of PKC isoenzymes were confirmed and in addition alterations in the subcellular location of PKC isoenzymes were detected in apoptotic cells compared with nonapoptotic cells. The data indicate that the expression of specific PKC isoenzymes is modulated during apoptosis and that PKC-beta and PKC-zeta may play specific roles in the regulation of the apoptotic program.

Apoptosis↗
PubMed1995

Neutrophil elastase and cathepsin G protein and messenger RNA expression in bone marrow from a patient with Chediak-Higashi syndrome.

Aims-To determine whether neutrophil elastase and cathepsin G are expressed, at transcriptional or translational levels, in the bone marrow from a patient with Chediak-Higashi syndrome.Methods-Blood neutrophils were isolated from three patients with Chediak-Higashi disease and bone marrow was collected from one. Cell lysates were analysed for neutrophil elastase and cathepsin G activity by enzyme linked immunosorbent assay and western immunoblotting. Northern blotting was used to detect messenger RNA (mRNA) for cathepsin G, elastase and beta-actin in bone marrow extracts, and immunohistochemistry was used to localise the enzymes in marrow myeloid cells.Results-Elastase and cathepsin G were not detected in blood neutrophils from the patients with Chediak-Higashi disease, but were present in bone marrow cells, although immunohistochemistry showed they were not within cytoplasmic granules. The concentrations of elastase and cathepsin G in Chediak-Higashi bone marrow were about 25 and 15%, respectively, of those in normal marrow. Quantitative scanning of northern blots showed that elastase and cathepsin G mRNA, corrected for beta-actin mRNA, were expressed equally in normal marrow.Conclusions-Transcription of elastase and cathepsin G mRNA in promyelocytes of patients with Chediak-Higashi disease is normal, but the protein products are deficient in these cells and absent in mature neutrophils. This suggests that the translated proteins are not packaged into azurophil granules but are degaded or secreted from the cells.

Journal Article↗