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Biomedical subjects

P J Dillon

Publications and source records attributed to P J Dillon.

At least 19 recordsLinked to original sources

Climate variability and forecasting surface water recovery from acidification: modelling drought-induced sulphate release from wetlands.

Climate-induced drought events have been shown to have a significant influence on sulphate (SO(4)(2-)) export from forested catchments in central Ontario, subsequently delaying recovery of surface waters from acidification. Field and modelling studies have demonstrated that water table drawdown during drought periods promotes oxidation of previously stored (reduced) sulphur (S) compounds in wetlands, with subsequent efflux of SO(4)(2-) upon re-wetting. Although climate-induced changes in processes are generally not integrated into soil-acidification models, MAGIC (Model of Acidification of Groundwater in Catchments) includes a wetland compartment that incorporates redox processes driven by drought events. The potential confounding influence of climate-induced drought events on acidification recovery at Plastic Lake, south-central Ontario (under proposed future S emission reductions) was investigated using MAGIC and two climate scenarios: monthly precipitation and runoff based on long-term means (average-climate scenario), and variable precipitation and runoff based on the past 20 years of observed monthly data (variable-climate scenario). The variable-climate scenario included several periods of summer drought owing to lower than average rainfall and higher then average temperature. Nonetheless, long-term regional trends in precipitation and temperature suggest that the variable-climate scenario may be a conservative estimate of future climate. The average-climate scenario indicated good recovery potential with acid neutralising capacity (ANC) reaching approximately 40 micromol(c)L(-1) by 2020 and 50 micromol(c)L(-1) by 2080. In contrast, the forecasted recovery potential under the variable-climate scenario was very much reduced. By 2080, ANC was forecasted to increase to 2.6 micromol(c)L(-1) from -10.0 micromol(c)L(-1) in 2000. Elevated SO(4)(2-) efflux following drought events (introduced under the variable-climate scenario) has a dramatic impact on simulated future surface water chemistry. The results clearly demonstrate that prediction of future water quality, using models such as MAGIC, should take into account changes or variability in climate as well as acid deposition.

Acid Rain↗

Mercury concentration in black flies Simulium spp. (Diptera, Simuliidae) from soft-water streams in Ontario, Canada.

Total Hg in Simulium spp. (Diptera, Simuliidae) was measured in 17 soft-water streams in the District of Muskoka and Haliburton County (Ontario, Canada) during 2003 and 2004. Black flies contained 0.07-0.64 microg/g total Hg (dry weight). The methylmercury concentration was measured in 6 samples of the 17, and ranged from 58% to 93% of total Hg. The concentration of total Hg is much higher than has been found in other filter feeding insects, and represents a significant potential source of Hg to fish. Mercury concentrations in Simulium spp. at different sites were strongly positively correlated with dissolved organic carbon, and the proportion of land within each catchment that was wetland. There was also a strong negative correlation with pH. By examining Hg concentration in filter feeding insects we have found a significant entry point for Hg and MeHg into the food web.

Animals↗

Climate-induced episodic acidification of streams in central ontario.

In this study we have analyzed the hydrochemical effect of drought conditions during 311 hydrological episodes in nine headwater streams in central Ontario over the past 20 years. Acid Neutralization Capacity (ANC) was logarithmically correlated (p<0.05) to antecedent discharge in eight of the nine streams, with the largest decline in ANC occurring after low antecedent flow. In eight of the nine streams SO4(2-) was the most important driving mechanism of ANC decline, but dilution as well as organic acidity was important in several streams. No decrease in the SO4(2-) driven ANC decline was observed over the 20 year study period despite a approximately 40% reduction in SO4(2-) deposition. The strong correlation between ANC decline and low antecedent discharge demonstrates that episodic acidification during rain events is strongly associated with preceding drought conditions, especially in wetland-dominated catchments. The results have important implications for recoveryfrom acidification, especially in northern ecosystems where climate scenarios forecast that warmer and drier conditions will be more common.

Acid Rain↗

Separation and characterization of NOM by high-performance liquid chromatography and on-line three-dimensional excitation emission matrix fluorescence detection.

By using high-performance size exclusion chromatography (HPSEC) and reversed-phase high-performance liquid chromatography with on-line three-dimensional excitation emission matrix fluorescence detection, we measured fluorescence properties of natural organic matter (NOM) as a function of molecular size (MS) and polarity. The work was carried out with Suwannee River Fulvic Acid, Aldrich Humic Acid, and a naturally occurring river NOM sample. Significant differences in fluorescence maximum pattern were found as NOM was separated chromatographically based on MS and polarity. There existed a strong relationship between MS, fluorescence pattern, and polarity. Humic-, fulvic-, and protein-like fluorescence fractions had distinct hydrophilic/hydrophobic nature. The results suggest that HPSEC may be better for characterizing major fulvic-like fluorescence and smaller MS fractions but not those having humic- and protein-like fluorescence and larger MS, which may be strongly adsorbed onto the HPSEC column because of their hydrophobic nature. This study has significant implications for further understanding the nature of NOM and its complexation with trace metals.

Benzopyrans↗

Comparison of iron accumulation in lakes using sediment core and mass balance calculations.

The accumulation of iron (Fe) in several lakes in Ontario, Canada was determined by two independent approaches. First, Fe accumulation was calculated in cores collected from several sites in each lake by integrating Fe concentration profiles with sediment accumulation rates determined from Pb210 dating. These site-specific accumulation rates were corrected for sediment focussing so that whole-lake Fe accumulation values could be derived. Using this approach, recent whole-lake Fe accumulation in eight lakes ranged between approximately 750 and 4000 mg/m2 per year. Second, whole-lake Fe accumulation was estimated from lake mass budgets, which were measured over a maximum of 14 years. Accumulation measured using the mass balances ranged from 10 to 1330 mg/m2 per year. Comparison of the two approaches indicated that retentions calculated from the sediment cores were much greater than those estimated from the mass balances. The most likely explanation for this difference is that, in the two decades since the cores were collected, there has been a substantial decline in Fe retention (in mass units but not percent) in the study lakes, principally as a result of reduced inputs of Fe from the catchments.

Journal Article↗

Comparison of superior vena caval and femoroiliac venous pressure measurements during normal and inverse ratio ventilation.

OBJECTIVE: The aim of this study was to estimate the agreement between superior vena caval pressure (SVCP) and femoroiliac venous pressure (FIVP) measurements by using short (<20 cm) femoral catheters commonly used in an adult intensive care unit. In addition, the effects of two modes of ventilation on agreement were assessed. DESIGN: Measurements of central venous pressure were recorded from both sites by using the same pressure transducer connected to the catheters via a three-way stopcock. SVCP and FIVP were recorded at 5-min intervals for 40 mins with the patient in the supine position. Recordings were taken from ventilated patients during a randomized crossover sequence of normal and inverse ratio ventilation (IRV). Analyses included Pearson's correlation (r), intraclass correlation (ri), Bland-Altman plots, and repeated measures analysis of variance with crossover tests for period and period-treatment interactions. SETTING: Adult intensive care unit. PATIENTS: Adult intensive care patients. MEASUREMENTS: Central venous pressure. RESULTS: Twenty-two patients were enrolled in the study, giving 162 paired measurements; r was .97 (p < .0001), and ri was .96. The bias for SVCP-FIVP measurements was -0.75 mm Hg (95% confidence interval = -1.31 to -0.18), with 95% limits of agreement of -3.30 to 1.81 mm Hg. Seventeen patients were suitable for randomization to normal ratio ventilation and IRV. IRV significantly increased SVCP and FIVP (p < .002). Tests for the effect of mode of ventilation on agreement (p = .36), for period (p = .26), and for period-treatment interaction (p = .84) were not significant. CONCLUSION: The study showed excellent overall agreement with acceptable clinical agreement for SVCP and FIVP measurements that was not affected by changing the mode of ventilation. IRV significantly increased central venous pressure measurements from both catheter sites but had no effect on overall agreement.

Adult↗

Single nucleotide polymorphic discrimination by an electronic dot blot assay on semiconductor microchips.

We have developed a rapid assay for single nucleotide polymorphism (SNP) detection that utilizes electronic circuitry on silicon microchips. The method was validated by the accurate discrimination of blinded DNA samples for the complex quadra-allelic SNP of mannose binding protein. The microchip directed the transport, concentration, and attachment of amplified patient DNA to selected electrodes (test sites) creating an array of DNA samples. Through control of the electric field, the microchip enabled accurate genetic identification of these samples using fluorescently labeled DNA reporter probes. The accuracy of this approach was established by internal controls of dual labeled reporters and by using mismatched sequences in addition to the wild-type and variant reporter sequences to validate the SNP-genotype. The ability to customize this assay for multiple genes has advantages over other existing approaches.

Base Sequence↗

An unusual case of obstructive pulmonary oedema.

A four-year-old boy was admitted to intensive care via casualty having suffered an apnoeic episode due to compression of his chest by a heavy cattle bar. A petechial rash was noted on the upper chest and arms. A chest radiograph showed pulmonary oedema which resolved over a few hours following positive pressure ventilation and positive end expiratory pressure. We believe this to be an unusual presentation of obstructive pulmonary oedemia (Negative Pressure Pulmonary Oedema).

Accidents, Home↗

The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization.

The Ecm1 gene encodes an 85-kDa protein of unknown function that was originally identified as a secretory protein of the murine osteogenic stromal cell line MN7. This paper describes the isolation of a genomic clone containing the human ECM1 gene from a chromosome 1 cosmid library and the characterization of its exon-intron structure. The protein coding region comprises 10 exons. The ECM1 gene maps at chromosome 1q21 outside the epidermal differentiation complex region. The ECM1 gene appears to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils. The full-length human ECM1 transcript contains 1838 bp and has an overall homology of 79.6% with the mouse Ecm1 cDNA. This transcript codes for a protein of 540 amino acids that is 69.4% identical and 81.3% similar to the corresponding mouse protein. The alternatively spliced variant, 1450 bp long, encodes a protein of 415 amino acids.

Alternative Splicing↗

Effect of methohexitone and propofol with or without alfentanil on seizure duration and recovery in electroconvulsive therapy.

We have studied the effects of methohexitone and propofol with and without alfentanil on seizure duration and recovery in this observer-blinded, prospective, randomized, crossover study involving 24 patients undergoing electroconvulsive therapy (ECT). Each patient had four treatment sessions, and received the following four i.v. regimens in random order: methohexitone 0.75 mg kg-1, methohexitone 0.50 mg kg-1 and alfentanil 10 micrograms kg-1, propofol 0.75 mg kg-1, propofol 0.50 mg kg-1 and alfentanil 10 micrograms kg-1. Additional methohexitone or propofol was given as needed in 10-20-mg increments until loss of consciousness. Suxamethonium 1.0 mg kg-1 i.v. was given for muscular paralysis. Mean motor and EEG seizure durations were longer with methohexitone-alfentanil (44.7 (SD 15.0) and 70.5 (29.7) s) than with methohexitone (37.6 (12.6) and 52.6 (15.3) s) and similarly, seizures were longer with propofol-alfentanil (36.8 (15.2) and 54.5 (20.9) s) than with propofol alone (27.2 (11.9) and 39.2 (3.9) s). Seizures were longest with methohexitone-alfentanil and shortest with propofol. Recovery time was statistically shorter in patients receiving propofol compared with methohexitone-alfentanil and methohexitone alone. Alfentanil with a reduced dose of methohexitone or propofol provided unconsciousness and increased seizure duration in patients undergoing ECT. We conclude that the combination of methohexitone with alfentanil is a good regimen for ECT, especially for patients with short seizure duration.

Adult↗

Structural characterization of broadly neutralizing human monoclonal antibodies against the CD4 binding site of HIV-1 gp120.

The human monoclonal antibodies (mAbs) 15e and 21h are derived from HIV-1-infected individuals. They block CD4 binding, recognize conformation-dependent discontinuous epitopes on gp120 and neutralize a broad range of laboratory strains and primary isolates of HIV-1. To determine if a structural basis for neutralization could be identified, analysis of these CD4-binding site anti-gp120 human mAbs was performed, common features and differences were identified and a comparison was made with F105, a previously reported CD4-binding site anti-gp120 human mAb. The 15e and 21h mAb heavy chains are derived from different V region genes, i.e. V2-1 and VDP-35, which are members of the VHIV and VHIII families, respectively. Analysis of the genes encoding the heavy chain complementarity determining region (CDR) 3 revealed that both mAbs show a long DH segment of similar size that could arise from D-D fusions of the dxp1/dlr1 and daudi/d22-12 germline DH genes along with use of the JH6 and JH5 germline segments. Similarly, the 15e and 21h light chains are derived from different V region genes, i.e. Hum01/012 and Hum1v318, that are members of the V kappa I and V lambda IIIa gene families, respectively. These V genes are rearranged with J kappa 1 and J lambda 2 germline genes. For both mAbs, the pattern of replacement mutations in the V region genes of the heavy and light chains is consistent with a process of somatic mutation and antigen-driven clonal selection. By comparing the CDRs of 15e, 21h and F105, eight positions in the rearranged heavy chains and two positions in the rearranged light chains were found to have identical amino acids. These studies suggest that there is no absolute restriction in the use of V region germline genes and form the foundation for understanding the humoral immune response to the CD4-binding site of gp120.

Amino Acid Sequence↗

Response of the Plastic Lake catchment, Ontario, to reduced sulphur deposition.

As a consequence of decreases in the emission rate of sulphur in eastern North America in the late 1970s and early 1980s, sulphate deposition in central Ontario declined by about 40%, but has remained constant for about six years. Plastic Lake, a small, dilute lake on the Precambrian shield that the authors have studied since 1979, acidified between the start of the study and about 1986, but since then has not changed. The authors also monitored the chemistry of streamwater draining the Plastic Lake catchment. Water quality of runoff from an upland site improved rapidly (pH and alkalinity increased, SO4(2-) and Al decreased), but two factors offset these improvements. A small wetland area downstream reversed most of these changes, resulting in a constant output of strong acid from the catchment. In addition, in extremely dry years (1983, 1987, 1989) there were very high concentrations of SO4(2-) in the streamwater, suggesting substantial re-oxidation of reduced S in the catchment.

Journal Article↗

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

The sequence reported in our 22 March 1991 report "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NFkappaB" [Science 251, 1490 (1991)], contained some errors. Resequencing under strong denaturing conditions revealed three insertions at nucleotide positions 1194, 1212, and 1220, which changed the AA sequence from RSAR-PRLGP to QISQASALAP (residues 372 to 380), thus accounting for some of the divergence in this region. A corrected sequence has been sent to GenBank.

Amino Acid Sequence↗

Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B.

A DNA probe that spanned a domain conserved among the proto-oncogene c-rel, the Drosophila morphogen dorsal, and the p50 DNA binding subunit of NF-kappa B was generated from Jurkat T cell complementary DNA with the polymerase chain reaction (PCR) and degenerate oligonucleotides. This probe was used to identify a rel-related complementary DNA that hybridized to a 2.6-kilobase messenger RNA present in human T and B lymphocytes. In vitro transcription and translation of the complementary DNA resulted in the synthesis of a protein with an apparent molecular size of 65 kilodaltons (kD). The translated protein showed weak DNA binding with a specificity for the kappa B binding motif. This protein-DNA complex comigrated with the complex obtained with the purified human p65 NF-kappa B subunit and binding was inhibited by I kappa B-alpha and -beta proteins. In addition, the 65-kD protein associated with the p50 subunit of NF-kappa B and the kappa B probe to form a complex with the same electrophoretic mobility as the NF-kappa B-DNA complex. Therefore the rel-related 65-kD protein may represent the p65 subunit of the active NF-kappa B transcription factor complex.

Amino Acid Sequence↗

Structural and functional analysis of the human immunodeficiency virus type 2 Rev protein.

The Rev proteins of the human immunodeficiency virus (HIV) are necessary for expression of viral structural gene products. Site-directed mutations were made within the HIV-2 rev gene to identify functional domains. We observed that similar to HIV-1 Rev, the HIV-2 Rev protein was phosphorylated, albeit to a much lesser extent than was HIV-1 Rev. We also found that like HIV-1 Rev, HIV-2 Rev localized to the nucleus, with a marked accumulation in the nucleolus. Mutations within a stretch of basic residues prevented both nuclear and nucleolar localization. Furthermore, mutant Rev proteins able to localize in the nucleus but unable to localize in the nucleolus were nonfunctional.

Amino Acid Sequence↗

Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression.

Examination of the life cycle of the human immunodeficiency virus (HIV) has shown that multiple levels of regulation exist, including some which require the virus-encoded Rev protein. In the absence of Rev, mRNAs encoding the structural proteins remain untranslated, a phenomenon which appears, in part, to be caused by nuclear entrapment of these RNA species. To examine the basis for repression of structural gene mRNA expression, a heterologous assay system was utilized to determine whether regions present within gag and pol contain elements capable of suppressing gene expression when present in cis. Both genes were found to contain cis-acting repressor sequences (CRS) that block gene expression when present within the 3' untranslated portion of a heterologous gene transcript. The element within pol was found to have the strongest repressive effect. While Rev alone was unable to reverse the repression observed with the pol sequence, addition of the env Rev-responsive element (RRE) in cis and Rev in trans did cause reversal of inhibition. Deletion mutagenesis defined a 260-bp element within the 3' portion of pol that contains a potent CRS which functions when present in the sense orientation. The corresponding region in HIV-2 pol was found to contain a functionally similar CRS element. To examine the mechanism of repression, the effects of the CRS elements on both the abundance and subcellular distribution of the mRNAs were examined. Neither was dramatically altered when examined in the context of a heterologous reporter (chloramphenicol acetyltransferase) mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Construction of a replication-competent murine retrovirus vector expressing the human immunodeficiency virus type 1 tat transactivator protein.

A replication-competent Akv murine leukemia virus-based vector encoding the human immunodeficiency virus tat cDNA under control of the simian virus 40 early promoter sequences was constructed. The simian virus 40 tat sequences were placed within the U3 region of the 3' long terminal repeat. The resulting virus, derived by transfection, replicated efficiently in mouse NIH 3T3 cells and maintained the tat cDNA insert. It has been suggested that Tat function requires the presence of a human-specific cofactor, which is absent in murine cells. However, infection of murine cells with the Akv virus encoding tat resulted in significant transactivation of a human immunodeficiency virus long terminal repeat-driven reporter gene, indicating that human cofactors are not always required for Tat function. The vector system described may be useful for introduction of foreign genes in vivo and in whole animals when virus spread is required for efficient infection and levels of gene expression.

Animals↗