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Biomedical subjects

J R Baker

Publications and source records attributed to J R Baker.

At least 55 records · Page 3Linked to original sources
PubMed2000

Estimating K(oc) for persistent organic pollutants: limitations of correlations with K(ow).

The n-octanol/water partition coefficient (K(ow)) is commonly used to predict the soil or aquatic particle water partition coefficient normalized to organic carbon (K(oc)). Many correlations are available covering several chemical classes and ranges of hydrophobicity. This work indicates the K(ow) may not be a strong predictor for persistent organic pollutants (POPs) which are defined here as chemicals with logK(ow) > 5.0. In addition, the correlation developed in this work for POPs will still result in a predicted value which is of by a factor of 15. Accordingly, care must be taken when applying K(oc) estimations using K(ow) for POPs until more suitable correlations are developed.

DDT↗
PubMed2000

Application of membrane-based dendrimer/DNA complexes for solid phase transfection in vitro and in vivo.

In this study a general description of the use of solid support membranes as the device for DNA delivery mediated by PAMAM dendrimers is presented. In contrast to the other DNA carriers, dendrimer/DNA complexes retain the ability to transfect after drying, which enabled coating or incorporation of complexes into poly(DL-lactide-co-glycolide) or collagen-based bioerodable membranes. These studies provide support for the use of this technology for in vitro and in vivo transfection of skin cells. Expression of luciferase or green fluorescent protein from pCF1-Luc and pEGFP1 plasmids indicated that dendrimer/DNA complexes can mediate transfection after dissociation from the solid support and/or when retained on the surface of the membranes. Modification of the membranes by incorporation of an anionic lipid, phosphatidyl glycerol (PG) at 1-5% concentrations, resulted in more efficient in situ transfection, particularly with dendrimer/DNA complexes formed at the low charge ratios (1-5). We also report data supporting the feasibility of membrane-based dendrimer/DNA complexes, particularly formed at lower than neutralizing conditions, for topical in vivo delivery of DNA to hairless mouse skin.

Administration, Topical↗
PubMed2000

Thyroid cell apoptosis. A new understanding of thyroid autoimmunity.

Apoptosis is a highly regulated mechanism of cell death involved in normal development, immune regulation, and homeostasis. Abnormal apoptotic activity has been implicated in a variety of diseases including cancer, autoimmunity, and degenerative disorders. In the thyroid, altered cell death may play a role in the pathogenesis of autoimmune disorders such as Hashimoto's thyroiditis and Graves' disease. Apoptosis-signaling pathways can be initiated through activation of death receptors or in response to cellular damage, such as in gamma irradiation. It has been demonstrated that Fas, tumor necrosis factor, and tumor necrosis factor-related apoptosis-inducing ligand pathways are present and functional in the thyroid, although the expression of these molecules and their roles in thyroid autoimmunity have been debated. Thyroid apoptosis is regulated at multiple levels, including receptor and ligand expression, and the expression of antiapoptotic proteins, such as FAP-1 and Bcl-2. These factors may provide potential mechanisms for modifying the pathogenesis of autoimmune thyroid disease.

Animals↗
PubMed2000

Antimicrobial mechanism of action of surfactant lipid preparations in enteric Gram-negative bacilli.

Two surfactant lipid preparations (SLPs) were investigated to determine their mechanism of antimicrobial action. 8N8, a water-in-oil emulsion, and W60C, a liposome, both have bactericidal activity against Gram-positive bacteria and non-enteric Gram-negative bacteria. Additionally, W60C is bactericidal for enteric Gram-negative bacilli when suspended in deionized water. Zeta potential measurements suggested that the resistance of Gram-negative bacilli to 8N8 might be caused by ionic repulsion. Addition of 50 micromol 1(-1) ethylene diamine tetra acetic acid in 100 mmol 1(-1) Tris buffer to either SLPs yielded efficient bactericidal activity against Gram-negative bacilli. This appeared to be due to disruption of the outer membrane and the chelation of divalent cations, as the addition of excess calcium inhibited the antimicrobial effect. Electron microscopy studies documented that 8N8 disrupts the bacterial cell wall, lysing the bacteria, while W60C fuses and internalizes within the cell, causing damage without immediate cell lysis. Understanding the mechanisms of action of these biocidal formulations will help to produce improved formulations with broader spectra of activity.

Anti-Bacterial Agents↗
PubMed2000

Prevention of murine influenza A virus pneumonitis by surfactant nano-emulsions.

Non-ionic surfactant nano-emulsions have extensive anti-microbial activity and are biocompatible with skin and mucous membranes at effective concentrations. Two nano-emulsion formulations (8N8 and 20N10) made from soybean oil, tributyl phosphate and Triton X-100, were tested for their ability to prevent murine influenza virus pneumonia in vivo. In the initial study, CD-1 mice were administered various dilutions of the nano-emulsions intranasally, and safe dosages and concentrations were determined. Non-toxic concentrations of the nano-emulsions were then mixed with influenza virus and applied to the nares of mice. Animals receiving mixtures of two different emulsions (8N8 or 20N10) and a LD50 of virus survived the challenge without evidence of viral infection. To determine if the nano-emulsions could prevent influenza virus infection in vivo when used as a prophylactic treatment, the nano-emulsions (8N8 at 1.0% and 20N10 at 1.0% or 0.2%) were applied to mouse nares 90 min before exposure to 5x10(5) p.f.u./ml virus by nebulized aerosol. Animals pretreated with the nano-emulsions had significantly decreased clinical signs of infection. Only 26.0% (8N8 at 1.0%), 31.25% (20N10 at 1.0%) and 37.0% (20N10 at 0.2%) of animals pretreated with nano-emulsion died from pneumonitis, whereas >80.0% of mock pretreated animals succumbed to infection (P<0.005). These findings suggest that non-ionic surfactant nano-emulsions have therapeutic potential for the prevention of influenza virus infection in vivo.

Animals↗
PubMed2000

Accidental over-anticoagulation: substitution error by a foreign pharmacy.

OBJECTIVE: To describe an episode of inadvertent and excessive anticoagulation caused by mistaken substitution of medication by a pharmacy outside the US. CASE SUMMARY: A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, "Romesa") instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, "Ramace"). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters. DISCUSSION: Medication errors contribute significantly to adverse events for patients. The frequency of different types of medication errors is reviewed, and problems specific to the use of warfarin are detailed. Circumstances that might lead to a patient seeking prescription medication outside of the US are also discussed. CONCLUSIONS: The acquisition of prescription medications from pharmacies outside of the US can have adverse consequences, especially if the foreign name of the medication is different from its American name, while sounding similar to other medications that also might be dispensed in foreign pharmacies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Comparison of greenhouse screening materials for excluding whitefly (Homoptera: Aleyrodidae) and thrips (Thysanoptera: Thripidae).

Twenty-eight greenhouse screening materials, with predetermined airflow resistance values, were evaluated for exclusion of the silverleaf whitefly Bemisia argentifolii Perring & Bellows and thrips from a mixed-species population. Screens differed in exclusion efficacy, expressed as a percentage of the fiberglass window screen control and at an approach velocity of 92 m/min, from -35 to 94% for silverleaf whitefly and from -13 to 95% for thrips. Seventeen screens excluded more silverleaf whitefly than did the window screen control, whereas only seven excluded more thrips. One material differentially excluded whitefly over thrips; many more differentially excluded thrips over whitefly. Airflow resistance, indicative of mesh hole size, did not necessarily correspond with degree of exclusion. Not all materials characterized as highly resistant to airflow provided significant exclusion. Exclusion of both types of pests was attained with several moderate- and one low-resistance screen. Another low-resistance screen excluded silverleaf whitefly only.

Animals↗
PubMed1999

Investigating potential associations between chronic exposure to polychlorinated biphenyls and infectious disease mortality in harbour porpoises from England and Wales.

Bioaccumulation of immunosuppressive organochlorines like polychlorinated biphenyls (PCBs) may pose a threat to the health and viability of cetacean populations. To investigate possible associations between chronic exposure to PCBs and infectious disease mortality in harbour porpoises Phocoena phocoena in UK waters, blubber concentrations of 25 individual chlorobiphenyl (CB) congeners in 34 healthy harbour porpoises that died due to physical trauma (mainly by-catch) were compared with CB concentrations in 33 animals that died due to infectious disease. The infectious disease group had significantly greater total 25 CBs (sigma 25CBs) concentrations than the physical trauma group (P < 0.001). The mean sigma 25CBs concentration in animals that died due to physical trauma was 13.6 mg kg-1 extractable lipid whereas the mean concentration in the infectious disease group was 31.1 mg kg-1 extractable lipid. The relationship between higher sigma 25CBs and the infectious disease group was not confounded by age, sex, nutritional status, season, location or year of stranding. In addition, adult females had significantly lower sigma 25CBs levels than adult males (P < 0.05) due to maternal transfer of CBs to offspring. These findings are consistent with the hypothesis that chronic PCB exposure predisposes harbour porpoises in UK waters to infectious disease mortality, although further research is required to test these associations more robustly.

Adipose Tissue↗
PubMed1999

Enhancement of dendrimer-mediated transfection using synthetic lung surfactant exosurf neonatal in vitro.

Pulmonary surfactants enhance adenovirus-mediated gene transfer but inhibit cationic liposome-mediated transfection in lung epithelial cells in vitro. This study examines the effect of the synthetic lung surfactant Exosurf on dendrimer-mediated transfection in eukaryotic cells. Exosurf significantly enhanced dendrimer-luciferase plasmid transfection in a number of cell lines and was very effective in primary cells. Luciferase expression increased up to 40-fold in primary normal human bronchial/tracheal epithelial cells (NHBE). FACScan analysis demonstrated that the transfection rate of the human T cell leukemia Jurkat cell line has significantly improved from 10 to 90% of cells at 24 h after transfection. Analysis of the components of Exosurf revealed that the nonionic surfactant tyloxapol was responsible for the enhancement of dendrimer-mediated gene transfer. The tyloxapol effect was due to increased cell membrane porosity and DNA uptake. Our results demonstrate that Exosurf and its component, tyloxapol, constitute a powerful enhancer for dendrimer-mediated gene transfer in vitro.

Animals↗
PubMed1999

Inflammatory cytokine regulation of Fas-mediated apoptosis in thyroid follicular cells.

The occurrence of apoptosis in thyroid follicular cells induced by Fas activation has been a subject of much debate. This is due, in part, to the fact that no physiologically relevant treatment conditions have been reported to cause rapid and extensive Fas-mediated apoptosis in thyroid cells, whereas treatment with the protein synthesis inhibitor cycloheximide prior to Fas activation allows for massive cell death. This indicates that the Fas signaling pathway is present but that its function is blocked in the overwhelming majority of cultured thyroid cells. To reconcile the conflicting reports, we set out to identify physiologically relevant conditions in which rapid, massive thyroid cell apoptosis in response to Fas activation could be demonstrated. We determined that susceptibility to Fas-activated apoptosis could be influenced by certain combinations of inflammatory cytokines. Although no single cytokine was effective, pretreatment of thyroid cells with the combination of gamma-interferon and either tumor necrosis factor-alpha or interleukin 1beta allowed for massive Fas-mediated apoptosis. Susceptibility to Fas-induced death correlated with an increase in expression of a tunicamycin-inhibitable high molecular weight form of Fas but not with aggregate expression of Fas.

Apoptosis↗
PubMed1999

Radionuclides in seals and porpoises in the coastal waters around the UK.

It has been suggested that marine predators be assessed for biologically relevant contamination levels because of their trophic position. Accordingly, in studying radioactive contamination in the marine environment around the UK, tissues from seals and porpoises have been chosen. Liver and muscle tissue from dead seals and porpoises found stranded around the UK coast have been analysed for the following radionuclides: 134Cs, 137Cs, 238Pu, 239Pu + 240Pu. Multifactor analysis of variance indicated that, for radiocaesium, there was no significant difference for harbour seals, grey seals or porpoises in terms of species or gender; however, the tissue activity concentration increased with body weight and decreased with distance from Sellafield, the major nuclear reprocessing plant in the UK. The levels of radiocaesium in muscle were higher than those in liver, while there appeared to be a concentration factor of approximately 3-4 for muscle radiocaesium when compared to radiocaesium levels reported for fish, the main food source of the marine mammals under study. Approximate radiation dose calculations indicated that the average dose from radiocaesium was less than 10% of the dose from the naturally occurring radioisotope of potassium, 40K. The highest tissue activity concentration for plutonium of 0.037 Bq/kg (239Pu + 240Pu) was detected in a grey seal stranded at Rathlin Island in Northern Ireland. Calculation of approximate radiation doses from plutonium contamination showed that, as with radiocaesium, the average dose was small compared with that from 40K. In summary, the radiocaesium contamination in seals and porpoises decreased with distance from Sellafield indicating that the BNF plc processing plant was the major source of the contamination. The marine mammals concentrated radiocaesium from their environment by a factor of 300 relative to the concentration in seawater indicating the value of using marine mammal tissue to measure radiocaesium contamination in the marine environment. The maximum radiation dose to the marine mammals from radiocaesium was higher than doses previously assessed for critical groups of humans living near Sellafield, while the maximum dose from plutonium was comparable to the doses for humans.

Animals↗
PubMed1999

TRAIL death pathway expression and induction in thyroid follicular cells.

To determine whether programmed cell death in thyroid follicular cells can be related to activation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, we examined the expression and function of this pathway in primary thyroid follicular cells and a papillary thyroid carcinoma cell line in vitro. Despite the expression of TRAIL receptors death receptor 4 and death receptor 5, purified TRAIL could not induce programmed cell death (PCD) in any of the thyroid follicular cells examined. However, pre-incubation with cycloheximide before TRAIL facilitated the induction of rapid and massive PCD. This suggested that despite the presence of a labile inhibitor of the TRAIL pathway, TRAIL could mediate PCD under appropriate conditions. To determine whether there were sources of TRAIL in the thyroid that could interact with thyroid follicular cell TRAIL receptors, RNase protection assays were used to determine TRAIL mRNA expression. TRAIL message was expressed in intrathyroidal lymphocytes isolated from a patient with thyroiditis, and unexpectedly, thyroid follicular cells themselves could be induced to express abundant TRAIL message in the presence of the inflammatory cytokines interferon gamma, tumor necrosis factor alpha, and interleukin 1beta. Furthermore, the papillary thyroid carcinoma cell line could be induced to kill the TRAIL-sensitive lymphoma cell line BJAB through a TRAIL-dependent mechanism.

Apoptosis↗
PubMed1999

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Aspartic Acid↗
PubMed1999

Optimization of in situ cellular ELISA performed on influenza A virus-infected monolayers for screening of antiviral agents.

Viral susceptibility testing has been traditionally performed by the plaque reduction assay (PRA) which is laborious, time consuming, relatively expensive, and requires subjective input by the reader. An in situ cellular enzyme-linked immunosorbent assay (ELISA) has been developed with the potential to overcome many of the limitations of PRA and has been applied to a variety of viruses. This study establishes the specific conditions necessary for susceptibility testing of influenza A virus to antiviral agents such as amount of inoculum size, duration of incubation, fixative type, and cell number; factors which are critical to the performance of the in situ cellular ELISA. In situ cellular ELISA was found to correlate strongly with the plaque assay (PA) (R2 = 0.997, P < 0.002). Both assays were applied to test the susceptibility of influenza A virus to a new antiviral emulsion agent and yielded comparable data. The optimized in situ cellular ELISA can serve as a reliable assay for the rapid screening of large numbers of antiviral agents.

Adsorption↗
PubMed1999

A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species.

Two nontoxic, antimicrobial nanoemulsions, BCTP and BCTP 401, have been developed. These emulsions are composed of detergents and oils in 80% water. BCTP diluted up to 1:1000 inactivated>90% of Bacillus anthracis spores in 4 h and was also sporicidal against three other Bacillus species. This sporicidal activity is due to disruption of the spore coat after initiation of germination without complete outgrowth. BCTP 401 diluted 1:1000 had greater activity than BCTP against Bacillus spores and had an onset of action of <30 min. Mixing BCTP or BCTP 401 with Bacillus cereus prior to subcutaneous injection in mice reduced the resulting skin lesion by 99%. Wound irrigation with BCTP 1 h after spore inoculation yielded a 98% reduction in skin lesion size, and mortality was reduced 3-fold. These nanoemulsion formulas are stable, easily dispersed, nonirritant, and nontoxic compared with other available sporicidal agents.

Animals↗
PubMed1999

Analytical error of home glucose monitors: a comparison of 18 systems.

In a quality review of 18 home blood glucose monitors, we measured the imprecision and incidence of significant error of 12 colorimetric and six amperometric systems by using capillary blood specimens from patients attending diabetes clinics. Imprecision at the mean glucose concentration found in the respective blood specimens (about 9 mmol/L) gave coefficients of variation (CV) ranging from 5.2 to 22.8%. Eight monitors including five of amperometric design had a CV of less than 10%. The incidence of significant error (defined as the proportion of specimens differing in value by more than 15% from a reference hexokinase assay of glucose in capillary blood) varied from 6 to 76%. Among the eight monitors identified as being most precise, the majority produced results that differed markedly from the reference assay, underlining the need for a common approach to calibration of home glucose monitors.

Blood Glucose Self-Monitoring↗