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At least 307 records · Page 17Linked to original sources

Genetic characterization of pcpS, encoding the multifunctional phosphopantetheinyl transferase of Pseudomonas aeruginosa.

Fatty acid synthases (primary metabolism), non-ribosomal peptide synthases and polyketide synthases (secondary metabolism) contain phosphopantetheinyl (Ppant)-dependent carrier proteins that must be made functionally active by transfer of the 4'-Ppant moiety from coenzyme A. These reactions are usually catalysed by dedicated Ppant transferases. Although rich in Ppant-dependent carrier proteins, it was previously shown that Pseudomonas aeruginosa possesses only one Ppant transferase, encoded by pcpS, which functions in both primary and secondary metabolism. Consistent with this notion are our findings that pcpS can genetically complement mutations in the Escherichia coli acpS and entD genes, encoding the apo-acyl carrier protein (ACP) synthase of fatty acid synthesis and a Ppant transferase of enterobactin synthesis, respectively. It also complements a Bacillus subtilis sfp mutation affecting a gene encoding a Ppant transferase essential for surfactin synthesis. A pcpS insertion mutant could only be constructed in a strain carrying the E. coli acpS gene on a chromosomally integrated element in trans, implying that the in vitro essentiality of pcpS is due to its requirement for activation of apo-ACP of fatty acid synthesis. The conditional pcpS mutant is non-fluorescent, does not produce pyoverdine and pyochelin, and does not grow in the presence of iron chelators. The data presented here for the first time confirm that PcpS plays an essential role in both fatty acid and siderophore metabolism.

Bacterial Proteins↗

Repression of ci-D in posterior compartments of Drosophila by engrailed.

A Drosophila strain was isolated that carries a lacZ-bearing recombinant P element integrated in the cubitus interruptus Dominant (ci-D) locus. This strain expresses beta-galactosidase in the anterior compartments of embryos and imaginal discs, suggesting that expression of ci-D is anterior-compartment specific. DNA from ci-D was cloned. In situ hybridization to imaginal discs confirmed that ci-D RNA is present only in anterior compartments. ci-D RNA is also limited to the anterior compartments at the germ-band extension stage of embryonic development, although not at earlier stages. In engrailed mutants, ci-D expression was derepressed in the posterior compartments of both embryos and imaginal discs. We postulate that engrailed, which is expressed in only the posterior compartments of embryos and imaginal discs, represses ci-D in these cells.

Animals↗

The managerial and clinical implications of patient-focused care.

Discusses five elements of patient-focused care (PFC). Clarifies issues surrounding the first element--aggregating patients--and debates the strengths and weaknesses of the second element--centralizing services in PFC units. Explores arguments for and against the third element--multiskilling and cross-training--including staff activity in conventional hospitals and PFC units, in depth. Discusses the structure of PFC teams and their management. Describes the main components of the fourth PFC element--integrated carepaths--and explores their role in clinical audit, computerization and seamless care. Examines the costs of PFC by comparing actual with expected costs. Makes managerial, clinical, educational and research implications throughout for staff working in or with PFC units.

Clinical Competence↗

A method for localizing EEG sources in realistic head models.

A computationally practical method for performing moving dipole calculations to localize EEG sources in realistic, boundary element (integral equation) type of head models is presented. This method makes use of a rapid method of solving the forward problem of calculating the EEG's produced by a dipole in a realistic head model. This rapid forward calculation method allows the use of standard Simplex search techniques to solve the inverse problem of localizing electrical sources in the brain from EEG's measured on the scalp.

Electroencephalography↗

A review of the impact and effectiveness of nurse-led care in dermatology.

AIMS AND OBJECTIVES: To identify systematically, summarize and critically appraise the current evidence regarding the impact and effectiveness of nurse-led care in dermatology. BACKGROUND: A diverse range of nurse-led models of care exist in dermatology. Primary studies have been conducted evaluating these models, but review and synthesis of the findings from these studies have not been undertaken. METHOD: Systematic searches of CINAHL, MEDLINE, British Nursing Index (BNI) and the RCN Library Catalogue from 1990 until March 2005. The searches were supplemented by an extensive hand search of the literature through references identified from retrieved articles and by contact with experts in the field. RESULTS: Fourteen relevant publications were identified and included findings from both primary and secondary care. The evidence indicates that nurses are treating a number of dermatological conditions, primarily using treatment protocols, across a broad range of clinical settings. However, some nurses working in primary care, lack confidence to treat some of these conditions and the educational needs of these nurses are frequently unmet. A reduction in the severity of the condition and more effective use of topical therapies are benefits of nurse interventions on service delivery. Faster access to treatment, a reduction in referrals to the general practitioner or dermatologist and an increase in knowledge of their condition are benefits reported by patients. CONCLUSIONS: Findings of the review are generally positive. However, there are methodological weaknesses and under researched issues, e.g. cost effectiveness of nurse-led care and the prescription of medicines by nurses for patients with dermatological conditions that point to the need for further rigorous evaluation. RELEVANCE TO CLINICAL PRACTICE: Nurse-led care is an integral element of the dermatology service offered to patients. This review highlights the impact of this care and the issues that require consideration by those responsible for the development of nurse-led models of care in dermatology.

Dermatology↗

An analysis of clinical pharmacist interventions in an intensive care unit.

In a 6-month study period, 170 pharmacist interventions in an intensive care unit (ICU) were analysed. Of the interventions, 68.8% were solicited and 31.2% were initiated by the pharmacists. The majority of the interventions were initiated by specialists (69.4%) followed by the medical officers (15.9%) and nurses (9.4%). Most of the interventions occurred during the grand rounds (75.9%), followed by ward visits (12.9%) and communication through the satellite pharmacy (10.5%). The most frequent type of intervention made was for indication or therapeutic efficacy followed by general product information, drug regimen, laboratory assessment, disease state, pharmaceutical availability and adverse drug reaction or side effect. It was also found that 83.7% of pharmacists' suggestions were accepted, 6.4% were accepted with changes, and 9.9% were not accepted. The majority of the interventions were made by direct verbal communications followed by telephone and written communications. In conclusion the study indicates that pharmacist therapeutic recommendations form an important integral element of patient care in an ICU.

Attitude of Health Personnel↗

Transition-state regulators: sentinels of Bacillus subtilis post-exponential gene expression.

When Bacillus subtilis encounters a nutrient-depleted environment, it expresses a wide variety of genes that encode functions in alternative pathways of metabolism and energy production. Expression of these genes first occurs during the transition from active growth into stationary phase and is controlled by a class of proteins termed transition-state regulators. In several instances, a given gene is redundantly controlled by two or more of these regulators and many of these regulators control genes in numerous different pathways. The AbrB, Hpr and Sin proteins are the best-studied examples of these regulatory molecules. Their role is to prevent inappropriate and possibly detrimental functions from being expressed during exponential growth when they are not needed. They serve as elements integrating sporulation with ancillary stationary-phase phenomena and appear to participate in the timing of early sporulation events and in fine-tuning the magnitude of gene expression in response to specific environmental conditions.

Bacillus subtilis↗

Identification of the minimal replicon of plasmid pMEA300 of the methylotrophic actinomycete Amycolatopsis methanolica.

The actinomycete Amycolatopsis methanolica contains a 13.3 kb plasmid (pMEA300), capable of enhancing the spontaneous mutation frequency of its host. Depending on the growth medium pMEA300 is not only maintained as an integrated element but can additionally be present as a multicopy, autonomously replicating plasmid. The minimal replicon of pMEA300 was identified. Two unlinked DNA fragments of 2.6 kb and 0.8 kb were required for pMEA300 maintenance. Sequence analysis of the 2.6 kb fragment revealed at least two open reading frames, orfA and orfB, encoding putative proteins of 170 amino acids (18,373 Da) and 416 amino acids (45,260 Da), respectively. No clear similarities were found between the deduced amino acid sequences of the putative orfA and orfB products of pMEA300 and replication proteins identified for various Streptomyces plasmids. The pMEA300 proteins of A. methanolica thus may represent unfamiliar types. The 0.8 kb fragment contained a single complete open reading frame (korA), encoding a protein of 118 amino acids (12,917 Da). The putative KorA protein of pMEA300 shows sequence similarity with various other Streptomyces plasmid-encoded Kor proteins which may belong to the GntR family of transcriptional repressor proteins. The data provide preliminary evidence for the possible involvement of a kilkor system in autonomous replication of pMEA300.

Actinobacteria↗

In vitro analysis of sequence requirements for the excision reaction of the Bacteroides conjugative transposon, CTnDOT.

CTnDOT, a Bacteroides conjugative transposon (CTn), initiates its transfer by excising to form a circular intermediate. This process has been shown to be complex, involving an unusual DNA intermediate with a short region of heterology and several CTn-encoded proteins. No information was available, however, about the sizes or sequence requirements of the att sites (attL and attR) at the ends of the integrated element where the processing occurs during excision. Using a newly developed in vitro competition excision assay, we have now localized attL to 153 bp and attR to 179 bp. Excision of CTnDOT involves staggered cuts that produce 5 bp chromosomal sequences at either end of the CTn. These 5 bp sequences (coupling sequences) form a region of heterology in the excised circular intermediate. Site-directed mutations that made the coupling sequences complementary and removed the region of heterology had no effect on excision. Thus, heterology is not essential. Mutagenesis of sequences adjacent to the coupling sequences revealed a 6 bp site in attR that was essential for excision. Mutating the analogous region in attL had little effect on excision. Regions within the attL site that appear to play a role in excision were found by introducing small insertions (phasing mutations) that could interfere with protein-protein or protein-DNA interactions. Similar insertion mutations in attR had no significant effect on excision. These results support the hypothesis that the CTnDOT excision reaction is asymmetrical with respect to likely protein binding sites and involves multiple protein-DNA interactions.

Bacterial Proteins↗

Horizontal transfer of Yersinia high-pathogenicity island by the conjugative RP4 attB target-presenting shuttle plasmid.

The high-pathogenicity island (HPI) encodes a highly efficient yersiniabactin system of iron acquisition responsible for mouse lethality in Yersinia. Although the HPI is widely disseminated among Enterobacteriaceae it lacks functions necessary for its replication and transmission. Therefore, the mechanism of its horizontal transfer and circulation is completely obscure. On the other hand, the HPI is a genetically active island in the bacterial cell. It encodes a functional recombinase and is able to transpose to new targets on the chromosome. Here we report on a possible mechanism of the HPI dissemination based on site-specific recombination of the excised HPI with the attB-presenting (asn tRNA gene) RP4 promiscuous conjugative shuttle plasmid. The resulting cointegrate can be transferred by conjugation to a new host, where it dissociates, and the released HPI integrates into any unoccupied asn tRNA gene target in the genome. This mechanism has been proven both with the 'mini' island carrying only the attP recognition site and genes coding for recombination enzymes and with the complete HPI labelled with an antibiotic resistance marker. After acquisition of the mobilized complete form of the HPI, the ability of the HPI-cured Yersinia enterocolitica WA-TH(-) strain to produce yersiniabactin has been restored. Such 'trapping' of pathogenicity islands and subsequent shuffling to new hosts by a conjugative replicon carrying a suitable attB site could be applied to other functional integrative elements and explain wide dissemination of PAIs.

Conjugation, Genetic↗

Prevention programmes of progressive renal disease in developing nations.

Development of strategies for the early detection and prevention of non-communicable diseases, including kidney disease, is the only realistic strategy to avert an imminent global health and economic crisis and enhance equity in health care worldwide. In this article, we briefly examine the burden of non-communicable diseases, including diabetes, hypertension, cardiovascular disease and how chronic kidney disease (CKD) represents a key integrated element in the setting, even in developing countries. A possible explanation of the increasing number of people who have or are at risk to develop CKD in poor countries is also given. A survey of major screening and intervention programmes performed or ongoing globally is then presented, highlighting differences and hurdles of projects planned in developed or developing nations as well as in unprivileged communities in developed countries. Finally, some recommendations on future steps to implement prevention programmes in emerging worlds are provided.

Developing Countries↗

The myth of informed consent.

Informed consent is an integral element of ethical medical practice. However, unlike gastrointestinal endoscopy, the consent process is not standardized. Moreover, informed consent is often viewed as a legal necessity rather than as an expression of patients' autonomy. Elevating informed consent to its rightful place can enhance doctor-patient relationship.

Endoscopy, Gastrointestinal↗

Mobilization of cutaneous immunity for systemic protection against infections.

This laboratory reported that a single subcutaneous (SC) injection of the natural steroid hormone dehydroepiandrosterone (DHEA) resulted in significant protection against a lethal herpes virus type 2 encephalitis or a systemic coxsackievirus B4 infection. Our previous results have shown that SC injection of DHEA resulted in upregulation of the specific host immune response resulting in protection against a lethal infection. This hormone did not have any direct antiviral effects in vitro. Furthermore, results indicate that, in vivo, DHEA is not the agent directly mediating the upregulation of the immune response. In the skin, DHEA is converted to androstenediol (AED) and it, in turn, is converted to androstenetriol; this is a metabolic process which appears unique to the skin. This report demonstrates that SC injection of AED results in markedly greater resistance against both viral and bacterial infection. Both DHEA and AED appear to function by facilitating and upregulating host immune responses via mobilization of cutaneous immunity to obtain systemic protection against infections. Because these steroids are native to the host and are regulated by the central nervous system, it is suggested that they may be an integral element of neuroimmunomodulation.

Androstenediols↗

Stimulation of adenosine A3 receptors in cerebral ischemia. Neuronal death, recovery, or both?

The role of the adenosine A3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A3 receptors and, based on the available evidence, discusses the possibility of adenosine A3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.

Adenosine↗

Dentist-patient relationship and quality care 1. Introduction.

Although quality is a genuine concern for dentistry, nowadays more emphasis is placed on quality issues. As dentist-patient interaction is involved in many aspects of care and it is more crucial for dentistry when compared to many other professions, a good dentist-patient relationship is an integral element of quality care. This series of 'practice articles' examines various important dimensions of this interaction. The first and second papers examine the value of trust and communication, the third paper focuses on informed consent and the fourth paper evaluates the relatively broadened role of dentists in behavioural modification.

Dental Care↗

Dentist-patient relationship and quality care 4. Professional information and informed consent.

As patients become relatively more knowledgeable on health issues and more aware of their rights, they become more concerned about receiving professional information and making informed choices. A healthy decision-making process can only be achieved through clear information and fair discussions. Thus, rather than signing a form, quality information for patients and the process of informed consent need to be considered as integral elements of a treatment alliance, a fair dialogue, quality oral care and a sign of respect for patients' rights for self-determination.

Dentist-Patient Relations↗

Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo.

Nitric oxide (NO) is an important regulator of blood flow, but its role in permeability is still challenged. We tested in vivo the hypotheses that: (a) endothelial nitric oxide synthase (eNOS) is not essential for regulation of baseline permeability; (b) eNOS is essential for hyperpermeability responses in inflammation; and (c) molecular inhibition of eNOS with caveolin-1 scaffolding domain (AP-Cav) reduces eNOS-regulated hyperpermeability. We used eNOS-deficient (eNOS-/-) mice and their wild-type control as experimental animals, platelet-activating factor (PAF) at 10(-7) m as the test pro-inflammatory agent, and integrated optical intensity (IOI) as an index of microvascular permeability. PAF increased permeability in wild-type cremaster muscle from a baseline of 2.4 +/- 2.2 to a peak net value of 84.4 +/- 2.7 units, while the corresponding values in cremaster muscle of eNOS-/- mice were 1.0 +/- 0.3 and 15.6 +/- 7.7 units (P < 0.05). Similarly, PAF increased IOI in the mesentery of wild-type mice but much less in the mesentery of eNOS-/- mice. PAF increased IOI to comparable values in the mesenteries of wild-type mice and those lacking the gene for inducible NOS (iNOS). Administration of AP-Cav blocked the microvascular hyperpermeability responses to 10(-7) m PAF. We conclude that: (1) baseline permeability does not depend on eNOS; (2) eNOS and NO are integral elements of the signalling pathway for the hyperpermeability response to PAF; (3) iNOS does not affect either baseline permeability or hyperpermeability responses to PAF; and (4) caveolin-1 inhibits eNOS regulation of microvascular permeability in vivo. Our results establish eNOS as an important regulator of microvascular permeability in inflammation.

Animals↗

Genome sequence of the PCE-dechlorinating bacterium Dehalococcoides ethenogenes.

Dehalococcoides ethenogenes is the only bacterium known to reductively dechlorinate the groundwater pollutants, tetrachloroethene (PCE) and trichloroethene, to ethene. Its 1,469,720-base pair chromosome contains large dynamic duplicated regions and integrated elements. Genes encoding 17 putative reductive dehalogenases, nearly all of which were adjacent to genes for transcription regulators, and five hydrogenase complexes were identified. These findings, plus a limited repertoire of other metabolic modes, indicate that D. ethenogenes is highly evolved to utilize halogenated organic compounds and H2. Diversification of reductive dehalogenase functions appears to have been mediated by recent genetic exchange and amplification. Genome analysis provides insights into the organism's complex nutrient requirements and suggests that an ancestor was a nitrogen-fixing autotroph.

Amino Acids↗