Biomedical subjects

M Hackett

Publications and source records attributed to M Hackett.

At least 37 records · Page 2Linked to original sources

PubMed1999

Association of dialyzer reuse and hospitalization rates among hemodialysis patients in the US.

OBJECTIVES: To determine if reuse of hemodialyzers is associated with higher rates of hospitalization and their resulting costs among end-stage renal disease (ESRD) patients. METHODS: Noncurrent cohort study of hospitalization rates among 27,264 ESRD patients beginning hemodialysis in the United States in 1986 and 1987. RESULTS: Dialysis in free-standing facilities reprocessing dialyzers was associated with a greater rate of hospitalization than in facilities not reprocessing (relative rate (RR) = 1.08, 95% confidence interval (CI), 1.02-1.14). This higher rate of hospitalization was observed with dialyzer reuse using peracetic/acetic acids (RR = 1.11, CI 1. 04-1.18) and formaldehyde (RR = 1.07, CI 1.00-1.14), but not glutaraldehyde (p = 0.97). There was no difference among hospitalization rates in hospital-based facilities reprocessing dialyzers with any sterilant and those not reprocessing. Hospitalization for causes other than vascular access morbidity in free-standing facilities reusing dialyzers with formaldehyde was not different from hospitalization in facilities not reusing. However, reuse with peracetic/acetic acids was associated with higher rates of hospitalization than formaldehyde (RR = 1.08, CI 1.03-1.15). CONCLUSIONS: Dialysis in free-standing facilities reprocessing dialyzers with peracetic/acetic acids or formaldehyde was associated with greater hospitalization than dialysis without dialyzer reprocessing. This greater hospitalization accounts for a large increment in inpatient stays in the USA. These findings raise important concerns about potentially avoidable morbidity among hemodialysis patients.

Cohort Studies↗

PubMed1998

Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides.

The Salmonellae PhoP-PhoQ virulence regulators induce resistance to host cationic antimicrobial peptides (CAMP) after infection of vertebrate tissues, and Mg2+ or Ca2+ limitation. The PhoP-PhoQ activated gene, pagP, was identified as important to inducible CAMP resistance and increased acylation of lipid A, the major component of the outer leaflet of the outer membrane. pagP mutants demonstrated increased outer membrane permeability in response to CAMP, supporting the hypothesis that increased lipid A acylation is a CAMP resistance mechanism. Similarly, in response to Mg2+ limited growth, other enteric Gram-negative bacteria demonstrated increased lipid A acylation. Compounds that inhibit the ability to increase lipid A acylation may have utility as new antimicrobial agents.

Acylation↗

PubMed1998

PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance.

Antimicrobial peptides are distributed throughout the animal kingdom and are a key component of innate immunity. Salmonella typhimurium regulates mechanisms of resistance to cationic antimicrobial peptides through the two-component systems PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified that are necessary for resistance to polymyxin and for the addition of aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously identified as pagA (or ugd) that is predicted to encode a UDP-glucose dehydrogenase. The second locus, pmrF, is the second gene of a putative operon predicted to encode seven proteins, some with similarity to glycosyltransferases and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking this putative operon are also regulated by PmrA-PmrB and/or have been associated with S. typhimurium polymyxin resistance. This work represents the first identification of non-regulatory genes necessary for modification of lipid A and subsequent antimicrobial peptide resistance, and provides support for the hypothesis that lipid A aminoarabinose modification promotes resistance to cationic antimicrobial peptides.

Anti-Bacterial Agents↗

PubMed1998

Role of the consultant obstetrician in the delivery suite.

The role of consultant obstetricians is under considerable debate. This has particularly focused on the role of consultants in intrapartum care. The article explores the role of the consultant in delivery suite from the view point of a consultant, a clinical director, a training programme director and a chief executive. These viewpoints determine a range of common themes which mean the duties of consultants over their career lifecycle need to be addressed; the need to expand consultant posts; and the tensions which inevitably occur. The authors believe these need to be addressed because of the need to ensure consultant roles in delivery suite are developed as a key part of seeing quality improvement.

Attitude of Health Personnel↗

PubMed1998

Developing new professional partnerships with acute Trusts and general practitioners.

The development of locality commissioning models combined with demographic, therapeutic and service changes are driving new professional relationships between general practitioners and acute Trusts. To ensure a Trust releases its strategy in this environment, stakeholders must understand the benefits to be gained from these new levels of relationships. A review of the literature is undertaken and the conditions for successful partnerships between acute Trusts and general practitioners defined. The article determines that for acute Trusts it will mean an examination of core competences combined with a drive to "review" their organisations.

Cooperative Behavior↗

PubMed1998

Developing postgraduate medical education for trusts: a secret to long-term success.

The delivery of effective postgraduate education for doctors in trusts is becoming vital to secure the individual services of trusts. Increasingly, training requirements are impacting on the location of clinical services that NHS trusts provide. Failure to understand the benefits and drawbacks of providing postgraduate education could affect the long-term strategic direction of trusts. The paper seeks to identify the case for investment, the need to address key deliverables to secure effective postgraduate education and the need for clinicians and managers to evaluate the effectiveness of such training for their organisations.

Education, Medical, Graduate↗

PubMed1998

Developing our leaders in the future.

The role of the chief executive in a transformed organisation is an extremely challenging one. The development of vision, building a commitment to it and communicating it constantly are key skills for a chief executive. However, the need to build and empower the stakeholders within and outside the organisation to support the changes required to deliver the vision requires leaders who can connect with a wide range of people and build alliances and partnerships to secure organisational success. A passion for understanding human intervention and behaviour is needed to encourage, cajole and drive teams and individuals to own and commit to change and a new direction. This requires leaders who have imagination and creativity--who seek connections and thread them together to create order out of incoherence. These skills are not taught in schools or textbooks, but are probably innate. They are what separate leaders from the rest. These skills need to be developed. A movement towards encouraging experimentation, career transfers and more individuality is needed if capable leaders of the future are to appear.

Administrative Personnel↗

PubMed1998

Developing consultant care on delivery suite.

The need to develop a consultant presence on the delivery suite has never been greater given the emerging quality agenda that is occurring within the speciality. This is identifying a clear impetus for changing consultant practice and also meeting the needs of women more effectively. The article describes these trends, the impetus for change and identifies practically how such a change was achieved within the largest women's hospital in the UK. It defines the basis for building a vision for an improved future and the practical use of management and transformational leadership skills to change consultant behaviour and attitudes with a clear set of outcomes that were achieved.

Delivery Rooms↗

PubMed1997

Stability enhancement for peptide analysis by electrospray using the triple quadrupole mass spectrometer.

Electrospray ionization sources, used with triple quadrupole mass spectrometers from PE/Sciex (API III+), Micromass (Quattro II), and Finnigan (TSQ 7000), were modified with a 35-gauge stainless steel needle. The dimensions of the needle were 63 microm i.d. by 145 microm o.d. with variable length, depending on the specific instrument. This modification led to enhanced signal stability, improved signal/noise ratios, and lowered sample consumption for a wide range of peptides. Stable baselines were observed with flow rates in the range of 50 nL/min to 5 microL/min. An alternative design, based on a metal wire housed within a fused silica capillary, led to the most stable signals of all during infusion, but caused excessive peak broadening with capillary chromatography. The Finnigan interface was further modified with an external postcolumn addition tee, used in conjunction with capillary liquid chromatography columns of 30 and 50 microm internal diameter. The best results with the modified Finnigan interface were acquired using the 50-microm column at a flow rate of 150 to 200 nL/min.

Factor VII↗

PubMed1997

Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ.

Bacterial pathogenesis requires proteins that sense host microenvironments and respond by regulating virulence gene transcription. For Salmonellae, one such regulatory system is PhoP-PhoQ, which regulates genes required for intracellular survival and resistance to cationic peptides. Analysis by mass spectrometry revealed that Salmonella typhimurium PhoP-PhoQ regulated structural modifications of lipid A, the host signaling portion of lipopolysaccharide (LPS), by the addition of aminoarabinose and 2-hydroxymyristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor-alpha expression by adherent monocytes. Thus, altered responses to environmentally induced lipid A structural modifications may represent a mechanism for bacteria to gain advantage within host tissues.

Acylation↗

PubMed1996

Leadership and vision in the NHS: how do we create the "vision thing"?

The development of NHS trusts has been a major part of the NHS reforms in the United Kingdom. The creation of trust boards has coincided with significant pressures from the combined forces for change and consolidation within publicly financed health care in the UK. The development of a long term strategic vision for trusts to ensure long-term survival is imperative. Considers evidence from international researchers and translates this into the context of NHS trusts. Discusses how they define and identify vision and ensure that vision building can be communicated and understood by key stakeholders within and outside the organization. Offers several practical suggestions on how their vision can be monitored and evaluated within the organization.

Evaluation Studies as Topic↗

PubMed1995

Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35.

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1 beta converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.

Amino Acid Sequence↗

PubMed1995

Hemolytic, but not cell-invasive activity, of adenylate cyclase toxin is selectively affected by differential fatty-acylation in Escherichia coli.

Adenylate cyclase toxin from Bordetella pertussis requires posttranslational acylation of lysine 983 for the ability to deliver its catalytic domain to the target cell interior and produce cyclic adenosine monophosphate (cell-invasive activity) and to form transmembrane channels (hemolytic activity). When the toxin is expressed in Escherichia coli, it has reduced hemolytic activity, but comparable cell-invasive activity to that of adenylate cyclase toxin from B. pertussis. In contrast to the native protein from B. pertussis, which is exclusively palmitoylated, recombinant toxin from E. coli is acylated at lysine 983 with about 87% palmitoylated and the remainder myristoylated. Furthermore, the recombinant toxin contains an additional palmitoylation on approximately two-thirds of the lysines at position 860. These observations suggest that the site and nature of posttranslational fatty-acylation can be dictated by the bacterial host used for expression and can have a significant, but selective, effect on protein function.

Acylation↗

PubMed1995

Multiplicity of N-terminal structures of medium-chain alcohol dehydrogenases. Mass-spectrometric analysis of plant, lower vertebrate and higher vertebrate class I, II, and III forms of the enzyme.

Ten different alcohol dehydrogenases, representing several classes of the enzyme and a wide spread of organisms, were analyzed for patterns of N-terminal structures utilizing a combination of conventional and mass spectrometric peptide analysis. Results show all forms to be N-terminally acetylated and allow comparisons of now 40 such alcohol dehydrogenases covering a large span of forms and origins. Patterns illustrate roles of acetylation in proteins in general, define special importance of the class I N-terminal acetylation, and distinguish separate acetylated structures for all classes, as well as a common alcohol dehydrogenase motif.

Acetylation↗

PubMed1995

Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases.

Interleukin-1 beta converting enzyme (ICE) is a cytoplasmic cysteine protease required for generating the bioactive form of the interleukin-1 beta cytokine from its inactive precursor. We report the identification of ICH-2, a novel human gene encoding a member of the ICE cysteine protease family, and characterization of its protein product. ICH-2 mRNA is widely expressed in human tissues in a pattern similar to, but distinct from, that of ICE. Overexpression of ICH-2 in insect cells induces apoptosis. Purified ICH-2 is functional as a protease in vitro. A comparison of the inhibitor profiles and substrate cleavage by ICH-2 and ICE shows that the enzymes share catalytic properties but may differ in substrate specificities, suggesting that the two enzymes have different functions in vivo.

Amino Acid Sequence↗

PubMed1994

Internal lysine palmitoylation in adenylate cyclase toxin from Bordetella pertussis.

A number of bacterial protein toxins, including adenylate cyclase (AC) toxin from Bordetella pertussis, require the product of an accessory gene in order to express their biological activities. In this study, mass spectrometry was used to demonstrate that activated, wild-type AC toxin was modified by amide-linked palmitoylation on the epsilon-amino group of lysine 983. This modification was absent from a mutant in which the accessory gene had been disrupted. A synthetic palmitoylated peptide corresponding to the tryptic fragment (glutamine 972 to arginine 984) that contained the acylation blocked AC toxin-induced accumulation of adenosine 3',5'-monophosphate, whereas the non-acylated peptide had no effect.

Acylation↗

PubMed1993

Isolation and identification of a cardioactive peptide from Tenebrio molitor and Spodoptera eridania.

We isolated several cardioactive peptides from extracts of whole heads of the mealworm, Tenebrio molitor, and the southern armyworm, Spodoptera eridania, using a semi-isolated heart of Manduca sexta for bioassay. We have now isolated from each species the peptide with the strongest effect on rate of contraction of the heart. The peptides were identified using micro Edman sequencing and mass spectrometric methods. This cardioactive peptide has the same primary structure from both species: Pro-Phe-Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH2, a cyclic nonapeptide which is identical to crustacean cardioactive peptide (CCAP) originally isolated from the shore crab, Carcinus maenas, and subsequently isolated from Locusta migratoria and Manduca sexta. This is additional evidence that CCAP has widespread occurrence in arthropoda.

Amino Acid Sequence↗

PubMed1992

Dioxin intoxication from chronic exposure of horses to pentachlorophenol-contaminated wood shavings.

Investigations into the cause of health problems on a horse-breeding farm led to the discovery of high concentrations (630 to 9,810 mg/kg of bedding) of pentachlorophenol in wood shavings used as bedding for horses over a period of 2 to 4 years. Toxicologic signs in the horses were characteristic of toxic effects associated with exposure of polychlorinated dibenzo-p-dioxins and dibenzofurans. Tissue residue analysis confirmed presence of toxic polychlorinated dibenzo-p-dioxin and dibenzofuran isomers known to be in pentachlorophenol, substantiating the bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans in the wood shavings. The findings provide evidence that residue concentrations in the range of 2 ng/g of toxic polychlorinated dibenzo-p-dioxin isomers in liver or fat correlate with toxicologic effects in horses.

Animals↗