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Biomedical subjects

T McKay

Publications and source records attributed to T McKay.

At least 19 recordsLinked to original sources
PubMed2004

Detection of Campylobacter and Escherichia coli O157:H7 from filth flies by polymerase chain reaction.

Flies (Diptera: Muscidae) that breed in faeces and other organic refuse (filth flies) have been implicated as vectors of pathogenic bacteria including Escherichia coli O157:H7, which cause haemorrhagic colitis in humans, and Campylobacter, which is the principal causative agent of human enteritis. The potential role of filth flies in the epidemiology of these pathogens in the United States was investigated by examining the prevalence of Campylobacter spp. and E. coli O157:H7 from two Arkansas turkey facilities. Polymerase chain reaction was conducted on DNA extractions of individual Musca domestica Linnaeus, Stomoxys calcitrans (Linnaeus), Hydrotaea aenescens (Wiedemann), Adia cinerella Fallen and turkey faecal samples using primers specific for E. coli H7, O157 and Campylobacter spp. Culturing verified that the flies were carrying viable Campylobacter spp. and E. coli O157:H7. Results from this study indicated that M. domestica, S. calcitrans, H. aenescens and Anthomyids are capable of carrying Campylobacter in North American poultry facilities and that the E. coli O157:H7 is carried by house flies and black dump flies associated with poultry. This PCR method provided a rapid and effective method to identify Campylobacter spp. and E. coli O157:H7 directly from individual filth flies.

Animals↗
PubMed2003

Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway.

We have constructed Ad CMV-Smac, a recombinant adenovirus encoding Smac/DIABLO, the recently described second mitochondrial activator of caspases. Transfection of ovarian carcinoma cells with Ad CMV-Smac at multiplicities of infection of 3-60 pfu/cell leads to increasing apoptosis in a dose-dependent manner. Western blot analysis confirms that Smac-induced apoptosis proceeds via a pathway mediated primarily by caspase-9 that can be inhibited by zLEHD-fmk and overexpression of the X-linked inhibitor of apoptosis protein (XIAP). In contrast, there is no cleavage of either caspase-8 or caspase-12. Ad CMV-Smac appears to induce apoptosis independently of cytochrome c release from mitochondria and is not inhibited by overexpression of Bcl-2. Ad CMV-Smac can combine with other proapoptotic factors, such as cisplatin, paclitaxel, and procaspase-3, to produce greater levels of apoptosis in transfected cells.

Antineoplastic Agents↗
PubMed2003

High average power, all-solid-state external resonator Raman laser.

As much as 3 W of average power at 1064 nm from a diode-pumped Nd:YAG laser, Q switched at 4 kHz, was used to pump an external-resonator, crystalline Ba(NO3)2 Raman laser generating a maximum of 1.3-W output at the first Stokes wavelength of 1197 nm. The slope efficiency was 63% with respect to the fundamental power incident on the Ba(NO3)2 crystal. A reduction in the beam quality of the Stokes output from M2 approximately 1.4 at lower Stokes powers to M2 approximately 3.4 at higher powers is attributed to thermal loading of the Raman-active crystal.

Journal Article↗
PubMed2001

PDGF signal transduction inhibition ameliorates experimental mesangial proliferative glomerulonephritis.

BACKGROUND: Platelet-derived growth factor (PDGF) has been consistently implicated in the cell proliferation and extracellular matrix accumulation, which characterize progressive glomerular disease. In the present study, the effects of a potent and selective inhibitor of PDGF receptor tyrosine kinase, STI 571, were examined in vitro and in vivo. METHODS: Cultured mesangial cells were incubated with PDGF (50 ng/mL) and fibroblast growth factor-2 (FGF-2; 50 ng/mL) and treated with STI 571 (0.13 to 2.0 micromol/L). Experimental mesangial proliferative glomerulonephritis was induced in male Wistar rats with monoclonal OX-7, anti-rat Thy-1.1 antibody with rats randomized to receive either STI 571 (50 mg/kg intraperitoneally daily) or vehicle. Animals were examined six days later. RESULTS: In vitro, both PDGF and FGF-2 induced a threefold increase in mesangial cell 3H-thymidine incorporation. STI 571 reduced PDGF but not FGF-2-stimulated mesangial cell proliferation in a dose-dependent manner, with complete abolition at 0.4 micromol/L. In animals with Thy-1.1 glomerulonephritis, PDGF receptor tyrosine kinase blockade was associated with significant reductions in mesangial cell proliferation (P < 0.001), the number of activated (alpha-smooth muscle positive) mesangial cells, and glomerular type IV collagen deposition (P < 0.001). CONCLUSION: The amelioration of the pathological findings of experimental mesangial proliferative glomerulonephritis by blockade of PDGF receptor activity suggests the potential clinical utility of this approach as a therapeutic strategy in glomerular disease.

Animals↗
PubMed2000

Weak Gravitational Lensing by the Nearby Cluster Abell 3667.

We present two weak lensing reconstructions of the nearby (zcl=0.055) merging cluster Abell 3667, based on observations taken approximately 1 yr apart under different seeing conditions. This is the lowest redshift cluster with a weak lensing mass reconstruction to date. The reproducibility of features in the two mass maps demonstrates that weak lensing studies of low-redshift clusters are feasible. These data constitute the first results from an X-ray luminosity-selected weak lensing survey of 19 low-redshift (z<0.1) southern clusters.

Journal Article↗
PubMed2000

Prompt Optical Observations of Gamma-Ray Bursts.

The Robotic Optical Transient Search Experiment (ROTSE) seeks to measure simultaneous and early afterglow optical emission from gamma-ray bursts (GRBs). A search for optical counterparts to six GRBs with localization errors of 1 deg2 or better produced no detections. The earliest limiting sensitivity is mROTSE>13.1 at 10.85 s (5 s exposure) after the gamma-ray rise, and the best limit is mROTSE>16.0 at 62 minutes (897 s exposure). These are the most stringent limits obtained for the GRB optical counterpart brightness in the first hour after the burst. Consideration of the gamma-ray fluence and peak flux for these bursts and for GRB 990123 indicates that there is not a strong positive correlation between optical flux and gamma-ray emission.

Journal Article↗
PubMed1999

Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the family of cytolethal distending toxins capable of causing a G2 arrest in human T cells.

We have previously shown that Actinobacillus actinomycetecomitans produces an immunosuppressive factor (ISF) capable of impairing human lymphocyte function by perturbing cell cycle progression. We now report that ISF is the product of the cdtB gene, one of three genes encoding the family of cytolethal distending toxins (Cdt). The ISF polypeptide exhibits >/=95% identity with Hemophilus ducreyi CdtB protein and </=60% homology with Escherichia coli or Campylobacter jejuni CdtB. Pretreatment of PHA-activated lymphocytes with 5-25 ng ISF results in G2 arrest of CD4+ and CD8+ T cells. Similarly, treatment of HeLa cells results in G2 arrest and cell elongation and distension. However, lymphocytes are at least 5 times more sensitive to ISF than HeLa cells and do not undergo the elongation and distension that characterizes interactions of Cdts with cell lines. ISF-treated lymphocytes express normal cyclin A and B1 levels, but contain reduced levels of cell cycle-dependent kinase-1 (Cdk1). Additionally, the majority of Cdk1 is in the hyperphosphorylated, inactive, form. In contrast, PHA-induced G2 cells contain elevated levels of the hypophosphorylated, active Cdk1. Failure of ISF-treated cells to dephosphorylate Cdk1 is not associated with decreased availability of Cdc25. These studies suggest that the CdtB protein alone is capable of inducing G2 arrest in lymphocytes and cell cycle arrest, elongation, and distension of HeLa cells. Our studies also suggest that lymphocytes may be primary targets for A. actinomycetemcomitans CdtB (ISF) and possibly for other Cdt family members as well. Thus, Cdts may function to impair host immunity and contribute to the pathogenesis of disease associated with Cdt-producing organisms.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions.

Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis were admitted to a tertiary urban hospital in The Gambia. Organisms were isolated from the cerebrospinal fluid in 64 per cent of cases. In the neonatal period Streptococcus pneumoniae was the single most common organism isolated. Amongst infants and children the two major pathogens were Haemophilus influenzae and S. pneumoniae. In the first year of life, children with S. pneumoniae meningitis were younger than those with H. influenzae infection (median age 3 months versus 6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent versus 17 per cent, p = 0.002). In view of the high case fatality rate, there is a need to review overall case management. This will include a review of more effective antibiotics, the possible role of dexamethasone, and the inclusion of efficacious vaccines against H. influenzae and S. pneumoniae disease.

Acute Disease↗
PubMed1998

An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery.

We have synthesized a linear, bifunctional peptide that comprises an integrin-targeting domain containing an arginine-glycine-aspartic acid tripeptide motif and a DNA-binding moiety consisting of a short stretch of 16 lysine residues. This peptide can form distinctive, condensed complexes with DNA and is capable of mediating its delivery and expression in a variety of mammalian cells in culture. Internalization is mediated by cell surface integrin receptors via a mechanism that is known to be phagocytic. We have analyzed the relationship between DNA and peptide and have investigated the conditions suitable for optimal gene delivery. The formation of condensed peptide DNA complexes leads to resistance to nuclease degradation. The level of reporter gene expression obtained is dependent on the peptide-to-DNA ratio and is enhanced in the presence of the endosomal buffer chloroquine, polyethyleneimine, and deactivated adenovirus during gene delivery. Under optimal conditions the levels of reporter gene expression obtained approach or even exceed those obtained with DNA delivered with the commercial liposome Lipofectamine. The ability to produce an efficient gene delivery system using small, easily modified, and well-defined constructs that have no constraint of particle size demonstrates the advantages of integrin-targeting peptides for gene transfer.

3T3 Cells↗
PubMed1998

Rapid detection of anticardiolipin antibodies.

A rapid screening method for the detection of antiphospholipid antibodies is described. Dense, red dyed polystyrene beads coated with cardiolipin were incubated with test sera for a short period of time, then added to a microtube containing anti-human IgG in a gel provided within a pre-cast card (DiaMed ID Microtyping System). The card was centrifuged at 150g for 5 min and then examined for movement of the beads through the gel. Beads without bound antibody travelled through the gel and formed a pellet on the bottom of the tube. Anti-human IgG within the gel matrix impeded cardiolipin-coated beads when antiphospholipid antibodies bound to the beads. Positivity was indicated by the formation of a layer of beads on the top of the gel matrix. Prospective analysis of 103 samples for the presence of antiphospholipid antibodies by flow cytometry and the gel-card technique showed good correlation between the two methods. All samples found to be positive by flow cytometry (23 of 103) were identified as positive by the gel-card technique. Two samples were identified as positive by the gel-card method but negative by flow cytometry. The technique is simple to perform and should prove useful as a rapid screening method for the detection of antiphospholipid antibodies.

Antibodies, Anticardiolipin↗
PubMed1997

Counselling dilemmas associated with the molecular characterisation of two Angelman syndrome families.

We report the molecular characterisation of two families with Angelman syndrome referred for prenatal diagnosis, in which atypical molecular findings resulted in counselling dilemmas. The first is a familial case of Angelman syndrome in which the two affected children have mutations which affect the imprinting mechanism, as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN and biparental inheritance of 15q11-q13 markers. DNA prepared from a 21 week fetal blood sample detected a fetus with normal maternal and paternal DNA methylation patterns at D15S63, but inheritance of the same maternal chromosome 15q11-q13 as the two affected sibs. This is probably a result of germline mosaicism in the mother. The second is a case of Angelman syndrome with an atypical deletion of 15q11-q13, which involves both unusual proximal and distal breakpoints. The deletion was characterised in order to assess the risk of Angelman syndrome in a second pregnancy in the mother of this child.

Angelman Syndrome↗
PubMed1993

Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes.

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjögren-Vogt, or Batten, disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci.

Alleles↗
PubMed1989

Nicardipine after spinal cord compression in the lamb.

To study the effects of the calcium channel blocker nicardipine on spinal cord blood flow and spinal evoked potentials, the following study was undertaken. After cord compression, which was productive of paraparesis, nicardipine was administered intravenously in 10 anesthetized lambs. Ten control animals were subjected to compression but received saline instead. Nicardipine produced a significant decrease in mean arterial pressure when compared to the control group. Thirty minutes after compression, spinal cord blood flow also was lower in the nicardipine group compared with controls. Spinal evoked potentials did not recover after compression in either group.

Animals↗