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Biomedical subjects

B J Davies

Publications and source records attributed to B J Davies.

15 recordsLinked to original sources

Nickel-responsive induction of urease expression in Helicobacter pylori is mediated at the transcriptional level.

The nickel-containing enzyme urease is an essential colonization factor of the gastric pathogen Helicobacter pylori, as it allows the bacterium to survive the acidic conditions in the gastric mucosa. Although urease can represents up to 10% of the total protein content of H. pylori, expression of urease genes is thought to be constitutive. Here it is demonstrated that H. pylori regulates the expression and activity of its urease enzyme as a function of the availability of the cofactor nickel. Supplementation of brucella growth medium with 1 or 100 microM NiCl(2) resulted in up to 3.5-fold-increased expression of the urease subunit proteins UreA and UreB and up to 12-fold-increased urease enzyme activity. The induction was specific for nickel, since the addition of cadmium, cobalt, copper, iron, manganese, or zinc did not affect the expression of urease. Both Northern hybridization studies and a transcriptional ureA::lacZ fusion demonstrated that the observed nickel-responsive regulation of urease is mediated at the transcriptional level. Mutation of the HP1027 gene, encoding the ferric uptake regulator (Fur), did not affect the expression of urease in unsupplemented medium but reduced the nickel induction of urease expression to only twofold. This indicates that Fur is involved in the modulation of urease expression in response to nickel. These data demonstrate nickel-responsive regulation of H. pylori urease, a phenomenon likely to be of importance during the colonization and persistence of H. pylori in the gastric mucosa.

Bacterial Proteins↗

The microbiology of infected and noninfected leg ulcers.

BACKGROUND: A clinical study was undertaken to investigate and compare specifically the aerobic and anaerobic microbiology of infected and noninfected leg ulcers. METHODS: Leg ulcers, defined as being infected on the basis of clinical signs, were swab sampled and investigated for aerobic and anaerobic microorganisms using stringent isolation and identification techniques. RESULTS: Two hundred and twenty isolates were cultured from 44 infected leg ulcers, in comparison with 110 isolates from 30 noninfected leg ulcers. Statistical analysis indicated a significantly greater mean number of anaerobic bacteria per infected ulcer (particularly Peptostreptococcus spp. and Prevotella spp.) in comparison with the noninfected ulcer group (2.5 vs. 1.3, respectively) (P < 0.05). Also, anaerobes represented 49% of the total microbial composition in infected leg ulcers compared with 36% in noninfected leg ulcers. The mean numbers of aerobes per wound in the two ulcer groups were not statistically different (P > 0.05). The study failed to demonstrate a clear correlation between commonly implicated facultative pathogens and wound infection. The isolation rate of Pseudomonas aeruginosa was generally low and, although Staphylococcus aureus was a frequent isolate in both wound types, it was more prevalent in noninfected leg ulcers. CONCLUSIONS: This study has demonstrated the complex aerobic-anaerobic microflora which exists in leg ulcers, the prevalence of anaerobes in infected wounds, and a poor correlation between the presence of specific aerobic pathogens and wound infection. In view of these findings, the role of microbial synergistic interactions in the pathogenesis of chronic wound infection may be of greater clinical importance than the isolated involvement of any specific potential pathogen.

Anti-Bacterial Agents↗

Infection control properties of some wound dressings.

The ability of some wound dressings to sequester and retain micro-organisms associated with wound fluid is perceived to provide beneficial properties regarding infection control. This study used an in vitro model to investigate and compare such properties in a range of fibrous absorbent dressings (alginate, hydrofibre and hydrophobic). Dressings were challenged with a simulated wound fluid containing common wound pathogens (Staphylococcus aureus or Pseudomonas aeruginosa). Bacterial sequestering and binding levels were monitored over time. A hydrofibre dressing and two calcium alginate dressings were shown to effectively sequester challenge organisms from a simulated wound fluid. However, the hydrophobic and hydrofibre dressings produced statistically significant results in their ability to adsorb and retain challenge organisms (p < 0.05). These investigations have demonstrated that a hydrofibre dressing effectively sequesters and retains micro-organisms upon exposure to simulated wound fluid, and may therefore provide a passive mechanism for reducing the microbial load in wounds and in the surrounding environment. Further in vivo studies are required to investigate these dressing properties.

Alginates↗

Microbial involvement in chronic wound malodour.

The role of specific micro-organisms in producing chronic wound malodour was investigated by directly comparing odour severity and microbiology in infected and non-infected leg ulcers. Malodour was most frequently associated with infected wounds involving mixed aerobic and anaerobic, Gram-positive and Gram-negative microbial populations. Infected ulcers that were not characterised by an offensive odour were rarely colonised with anaerobic bacteria. A reduced incidence of pigmented and non-pigmented Gram-negative anaerobes (Bacteriodes spp, Prevotella spp, Porphyromonas spp) was evident in non-infected, non-malodorous leg ulcers. These observations emphasise the significance of specific anaerobic bacteria in the generation of wound malodour, and it is probable that their effect is potentiated by coexistence with mixed facultative micro-organisms.

Chronic Disease↗

Canada's health system.

AIM: To examine the Canadian health system, in particular as it relates to health care, and to assess the functions of the provincial and federal governments in relation to health care, spending, funding, and reform. METHODS: Description and analysis of the Canadian health care system, including the overall structure, funding and spending, history, necessary reforms, and future of the system. RESULTS: Canada's health care system, through funding from both the federal and provincial/territorial governments, provides insured hospital and medical care services to all eligible Canadian residents. In order for the provinces to receive funding from the federal government, five criteria as stated in the Canada Health Act, must be met, namely: public administration, comprehensiveness, universality, accessibility, and portability. Funding is provided primarily through taxation, with some provinces also utilizing ancillary funding methods, such as health care premiums. In the latest review of Canada's health care system, the National Forum on Health reported in 1997 that the system must become more efficient, effective, and reflective of contemporary practices in health care delivery. CONCLUSIONS: The benefits of our system can be seen in the favorable health status of Canadians. Canada has been successful in its efforts to contain health expenditures and begin the process of reallocating resources. Health care is recognized as only one element of a larger health system, encompassing a broader range of services, providers, and delivery sites.

Canada↗

Cost containment mechanisms in Canada.

AIM: Describe the mechanisms currently being used by federal and provincial/territorial governments, medical associations, and private insurers to control the cost of health care in our country. METHODS: Descriptive method used. Statistics on percentage GDP spent on health, and health status of the population, were compared with other OECD countries. Questions discussed: importance of cost control, why difficult to control, and what is needed to control costs. RESULTS: System-wide mechanisms used to control health care costs include: single payer financing, universal coverage for hospital/physician services, global budgets, preventive health services, evidence-based information systems, and regionalization. Sector specific mechanisms used to control costs of physicians, hospitals, drugs, and technology. Cost control within the health care sector allows spending on other sectors (e.g., employment) that have a proven impact on one's health. Future health care cost containment policies must focus on restraining private sector costs and encouraging movement towards the determinants of health approach. CONCLUSIONS: Canada's relative success in containing costs is the result of public financing of the health insurance system. Our single payer, publicly financed health care system, allows for cost containment and universal access based on need for services rather than ability to pay. The shift of costs from the public to private sector must be curtailed. The determinants of health approach is instrumental in containing and channeling future spending on health.

Canada↗

Serine proteases in rodent hippocampus.

Brain serine proteases are implicated in developmental processes, synaptic plasticity, and in disorders including Alzheimer's disease. The spectrum of the major enzymes expressed in brain has not been established previously. We now present a systematic study of the serine proteases expressed in adult rat and mouse hippocampus. Using a combination of techniques including polymerase chain reaction amplification and Northern blotting we show that tissue-type plasminogen activator (t-PA) is the major species represented. Unexpectedly, the next most abundant species were RNK-Met-1, a lymphocyte protease not reported previously in brain, and two new family members, BSP1 (brain serine protease 1) and BSP2. We report full-length sequences of the two new proteases; homologies indicate that these are of tryptic specificity. Although BSP2 is expressed in several brain regions, BSP1 expression is strikingly restricted to hippocampus. Other enzymes represented, but at lower levels, included elastase IV, proteinase 3, complement C2, chymotrypsin B, chymotrypsin-like protein, and Hageman factor. Although thrombin and urokinase-type plasminogen activator were not detected in the primary screen, low level expression was confirmed using specific polymerase chain reaction primers. In contrast, and despite robust expression of t-PA, the usual t-PA substrate plasminogen was not expressed at detectable levels.

Amino Acid Sequence↗

Effects of verapamil on thromboxane synthesis and pulmonary hypertension in sheep.

Infusion of plasma containing zymosan-activated complement into sheep produces leukopenia, pulmonary leukostasis, pulmonary hypertension, hypoxia and increased plasma levels of thromboxane. We investigated the effects of the calcium channel blocking agent verapamil in this system using conscious sheep. Verapamil in 5 mg and 10 mg doses was administered by intravenous infusion prior to an infusion of autologous plasma containing zymosan-activated complement. Pretreatment with verapamil inhibited thromboxane synthesis, the rise in pulmonary artery pressure and the hypoxia without affecting the transient leukopenia. These effects are similar to those previously demonstrated with nonsteroidal antinflammatory drugs, suggesting that verapamil is acting at one or more early steps of the arachidonic acid cascade in addition to its influence on the calcium-sensitive protein interactions involved in smooth muscle function.

6-Ketoprostaglandin F1 alpha↗