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Biomedical subjects

K McGuire

Publications and source records attributed to K McGuire.

At least 19 recordsLinked to original sources

Radiation hybrid mapping of all 10 characterized bovine Toll-like receptors.

Toll-like receptors (TLRs) are cell-surface signalling molecules that recognize a range of highly conserved pathogen molecules and instigate the appropriate immune response. Here, we report the mapping of all 10 characterized bovine TLR genes using a radiation hybrid panel. The genomic organization of the bovine TLRs is similar to that of humans and mice. TLR1, TLR6 and TLR10 map closely together on Bos taurus chromosome 6 (BTA6), while TLR7 and TLR8 map to the X chromosome. TLR2, TLR3, TLR4, TLR5 and TLR9 map to BTA17, BTA27, BTA8, BTA16 and BTA22 respectively. Our increased knowledge of the genomic organization of the bovine TLR genes may promote our understanding of their evolution and help in the identification of bovine genes underlying disease-resistance traits.

Animals↗

ZnO nanowires by pulsed laser vaporization: synthesis and properties.

We report a new pulsed-laser vaporization (PLV) technique to synthesize nanowires of single-crystal ZnO having a wurtzite structure by using colloidal gold nanoparticles as seeding catalysts. The average diameter of the nanowires is approximately 13 nm, with a very narrow range of 7 to 25 nm. The nanowires are straight for the most part, with the axes parallel to the [0001] growth direction. Raman and photoluminescence spectra from the nanowires and bulk ZnO are similar except for a approximately 510 nm band in the nanowires due to oxygen vacancies. The bulk-like vibrational and electronic properties of the nanowires is due to the diameter being larger than the threshold below which quantum confinement-induced effects are expected.

Crystallization↗

Effect of competitive training on T-cell mediated immune function in Master's female athletes.

Interest in the effects of intense exercise training on immune function has grown over the past decade. Currently, data on the immunocompetence of female endurance athletes are limited and do not present a clear picture. The objective of this study was to compare the T-cell mediated immune function of female Master's athletes (41 +/- 4.3 yr) during peak training with age-matched non-athletes (42 +/- 3.6 yr) using non-specific and antigen-specific stimulation. Samples of peripheral venous blood were taken at rest for determination of total circulating T-cell number, sub-population number and CD4 + helper T-cell function. No significant difference in total circulating T-cell number or in the number of cells in each of the tested lymphocyte subpopulations was detected between athletes (n = 19) and non-athletes (n = 20). In athletes, 7.9 % of cells responding to non-specific (PMA and ionomycin) stimulation produced IL-2 versus 3.9 % of responding cells in non-athletes (p < 0.05). No statistical difference was noted between athletes and non-athletes in the percentages of antigen-responding CD4 + helper T-cells producing IL-2 (2.4 % and 2.3 %, respectively). Results of this study suggest that T-cell mediated immune function may not be compromised in female Master's athletes during periods of competitive training.

Adult↗

Recombinant mannan-binding lectin (MBL) for therapy.

Mannan-binding lectin (MBL) is a plasma protein involved in the innate immune response. It binds to a number of micro-organisms and promotes killing of these through complement activation either directly or through opsonization. Clinical evidence indicates that in a variety of situations genetically determined low MBL levels are associated with increased susceptibility to infections. Infusions of plasma-derived MBL into MBL-deficient individuals was found to be safe in preliminary trials, but we considered that sufficient production and product safety could only be achieved through synthesis of recombinant MBL. A transfected human cell line produces MBL showing the same biological activity as plasma-derived MBL, and an essentially identical profile on MS. The production has been scaled up and clinical trials will start this year.

Animals↗

Overexpression of p65 and c-Jun substitutes for B7-1 costimulation by targeting the CD28RE within the IL-2 promoter.

The role of Rel and activation protein-1 (AP-1) in IL-2 promoter activity in B7-1- and leukocyte function-associated Ag-3 (LFA. 3)-costimulated T cells has been evaluated. We demonstrate that overexpression of c-Jun but not c-Fos increases IL-2 promoter activity in both B7-1- and LFA-3-costimulated Jurkat T cells. Cotransfection of both c-Jun and c-Fos substitutes for B7-1 costimulation in driving an activation protein-1 response element but not for the IL-2 promoter. Overexpression of Rel proteins demonstrated that p65-expressing Jurkat cells transcribed equally well a nuclear factor kappabeta reporter construct when costimulated with B7-1 or LFA-3, but transcription of IL-2 promoter or CD28 response element (CD28RE)-driven reporters was superior in B7-1-costimulated cells. Combined expression of c-Jun and p65 induced vigorous transcription of IL-2 promoter- and CD28RE-driven reporter constructs in both LFA-3- and B7-1-costimulated Jurkat cells. Mutating the CD28RE but not the upstream nuclear factor kappabeta-binding site in the IL-2 promoter reduced B7-1-driven transcription >90%. The results implicates a major role of the CD28RE in the integration of p65/c-Jun-mediated transcription within the IL-2 promoter. We suggest that the transition from an autocrine LFA-3-driven immune response to a B7--induced paracrine immune response involves the activation of c-Jun and p65, which target the CD28RE region of the IL-2 promoter.

Adjuvants, Immunologic↗

Tracing the origins of louping ill virus by molecular phylogenetic analysis.

The nucleotide and deduced amino acid sequences of louping ill (LI) virus isolates, collected from representative regions of the British Isles and Norway, were determined for either the entire envelope gene (20 isolates) or for a portion of the envelope gene that spans a hypervariable region and includes an LI virus specific marker sequence (53 isolates). Phylogenetic analysis reveals the presence of three major geographical populations of LI virus in the British Isles, viz. Irish, Welsh and British LI viruses, which all cause encephalomyelitis in animals, predominantly sheep, and co-habit the same tick population. British LI virus occurs throughout Scotland, England, Ireland and Norway. Irish and Welsh LI viruses occur only in Ireland and Wales, respectively. Phylogenetic analysis also predicts that LI virus initially emerged in Ireland and that a descendant was introduced into Great Britain via Wales and was subsequently transported to the borders of Scotland, from where it was dispersed throughout Scotland, northern England and Norway. More recently, the British LI virus was reintroduced into Ireland and also into south-west England. Dates of lineage divergence, calculated from the synonymous substitution rate, indicate that LI virus emerged in the British Isles less than 800 years ago and most LI virus dispersal occurred during the last 300 years. By combining these data with historical records it appears that livestock movement can be implicated in the dispersal of LI virus.

Animals↗

Efficacy of acaricidal tags and pour-on as prophylaxis against ticks and louping-ill in red grouse.

This paper examines the efficacy of 10% lambdacyhalothrin-impregnated plastic tags and a deltamethrin pour-on preparation in protecting red grouse chicks from parasitism by ticks and subsequent infection with the louping-ill virus. In 1995, ten red grouse hens (Lagopus lagopus scoticus) in a free-living population in north-east Scotland were fitted with lambdacyhalothrin-impregnated plastic tags, glued to radio transmitters. Chicks of more than 10 days of age from a further ten untreated radio-collared hens were caught and fitted with individual tags to the ptagium. Both treatments significantly reduced tick burdens in the short term. The number of larvae and nymphs on chicks up to 45 days was less under both treatments than on control chicks and tagged chicks had fewer nymphs than chicks from treated hens. Nevertheless, treatments did not reduce viral infection rates nor increase survival to 10 weeks, possibly explained by incomplete treatment of tagged broods and/or direct or indirect mortality due to tags. In 1996 chicks in ten broods from hens with radio transmitters were individually treated at 14 days of age at a rate of 1 mg/kg of chick with a deltamethrin pour-on preparation. This preparation significantly reduced the number of larvae and nymphs on grouse chicks 7-10 days after application below the number on untreated controls. At 20 days from application, however, only larval numbers were lower on treated chicks. Nevertheless louping-ill virus infection prevalences were significantly reduced at 35 days of age and survival of chicks to 10 weeks increased.

Animals↗

Constitutively activated JNK is associated with HTLV-1 mediated tumorigenesis.

Human T cell leukemia virus type I (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy, also called tropical spastic paraparesis (HAM/TSP). Both clinical and in vitro evidence have demonstrated that the virus or its transactivator Tax, are transforming. However, transformation appears to require additional, as yet poorly characterized, genetic changes in infected cells. JNK is a recently characterized member of the MAP kinase family. Its signaling cascade is distinct from other members and has been demonstrated to play an important role in T-cell activation, at least partially through its downstream targets, c-jun and ATF-2. Here we demonstrate constitutive activation of the JNK cascade in human lymphocytes transformed in vitro by HTLV-1 and also in Tax transformed murine fibroblasts. Such activation is not induced by Tax expression alone, and occurs only when infected lymphocytes become IL-2 independent or immortalized. Constitutive JNK activation was also found in leukocytes isolated from ATL patients. The acquisition of constitutive JNK activation may represent an important later event in HTLV-1 tumorigenesis.

Animals↗

Menarche age, fatness, and fat distribution in Hawaiian adolescents.

Menarche age was assessed in 93 adolescent females in a sample of public schools in East Hawaii. Native Hawaiian girls had significantly lower reported age at menarche than non-Hawaiian classmates. Age at menarche was significantly correlated with total fatness as measured by the sum of six skinfolds in girls who had reached menarche at least 2 years previous to measurement. When fatness was controlled in comparisons, the ethnic differences were not significant. Fat distribution, independent of fatness, was also significantly related to age at menarche. Socioeconomic, cultural, and admixture variables were not significantly related to age at menarche. Adiposity appears to be both a cause and a consequence of early age at menarche, with the relationship dependent on the elapsed time between menarche and measurement. This suggests that studies relating body composition to age at menarche must carefully control for the time interval between measurement and the date of menarche.

Adolescent↗

Telephone follow-up after discharge from the hospital: does it make a difference?

Two systems of telephone follow-up of discharged patients were compared in this 3-month study. All medical and surgical patients on five nursing units of one acute care institution were included, yielding a sample of over 1,400 patients. One group of patients was called 2 to 3 days after discharge; another group received a brochure describing a nurse-run telephone service they could call. A third group of patients received no intervention. More than 90% of patients who were called had questions about self-care and recovery at home. Only nine patients initiated calls to the nurse telephone service. The three groups did not differ in patient satisfaction with health education or readmission rates within 30 days of discharge. This study suggests that patients have continued health education needs after discharge but are unlikely to actively seek needed information from a hospital-based telephone service.

Follow-Up Studies↗

Integument and sensillum auriforme of the opisthosoma of Rhipicephalus appendiculatus (Acari:Ixodidae).

The opisthosomal integument and sensilla auriformia of Rhipicephalus appendiculatus Neumann larvae, nymphs, females and males, both unfed, fed, and during molt, were examined by light and electron microscopy in relation to semiochemical production. The integument consists of epidermis, endocuticle, exocuticle, epicuticle, a superficial wax layer and a variable additional deposit. The integument of immature instars and females grows greatly during feeding. The integument is traversed by pore canals from the epidermis to the outer wax canals. The epidermis can secrete material to the exterior by way of the pore canals and wax canals. The sensillum auriforme is a common disk-shaped organ, with a complex internal chamber open to the exterior by way of a pore. It has no apparent secretory capacity and is of presumed sensory function. It is located in the integument of scutum and alloscutum of all instars.

Animals↗

Integumental glands of the tick Rhipicephalus appendiculatus (Acari:Ixodidae) as potential producers of semiochemicals.

The opisthosomal integument and associated secretory organs of Rhipicephalus appendiculatus Neumann larvae, nymphs, females and males, both unfed and fed were examined by light and electron microscopy. Type 1 dermal glands were found on the alloscutum and scutum of all ticks. They were undeveloped in unfed ticks and reached full development in engorging ticks. They produced secretory granules from 2 glandular cells but without accumulation of a reservoir of secreted material. Type 2 dermal glands were found in all ticks, with pores on the alloscutum, edge of scutum, and on anal plates. These glands produced secretion during feeding and accumulated large reservoirs of secreted material that were present in engorging, recently detached and questing ticks. Spiracular glands were found in all ticks below the spiracle plate. They produced small amounts of secretion and had pores to the exterior by way of spiracle goblets. No obvious cycle of secretory activity was recorded. Foveal glands were present and produced secretions in nymphs, females, and males. They were largest in females with an accumulation of secretory vesicles in feeding ticks. The potential function of these glands is discussed in the context of the chemical ecology of this tick.

Animals↗

Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease.

Although visuoconstructive impairment has been reported in both Alzheimer's (DAT) and Huntington's (HD) disease, there is little knowledge concerning how this cognitive deficit differs quantitatively and qualitatively in these two progressive dementias. To address this issue, the present study compared performances on the Clock Drawing Test (CDT: command and copy) of 25 DAT patients, 25 equally demented HD patients, and 25 elderly normal controls (NC). In the command condition, both patients groups were significantly impaired compared to the NC group. Although there was no significant difference between DAT and HD patients' total quantitative scores, a qualitative error analysis revealed a number of dissociations between the two patient groups. Graphic difficulties, very common in HD patients, were virtually absent in DAT patients; in contrast, conceptual errors were almost exclusively seen in DAT patients and were related to the severity of their dementia. Perseveration and "stimulus-bound" responses were also more frequent in DAT patients, and both groups made visuospatial errors. In the copy condition, the DAT, but not the HD, patients evidenced a marked improvement in performance. These results indicate that while both DAT and HD patients have significant visuoconstructive difficulties even in the early stages of their disorders, the specific cognitive processes underlying their quantitative impairments are quite different. It is possible that the DAT patients' conceptual errors are yet another indicator of the deterioration of their semantic knowledge.

Aged↗

Dietary enrichment with omega-3 fatty acids partially protects against lipopolysaccharide-induced atrial depression in rats.

We tested the hypothesis that pretreatment with a diet enriched with omega-3 fatty acids can prevent lipopolysaccharide (LPS)-induced atrial dysfunction. Sprague-Dawley rats were fed a diet containing 20% safflower oil (control diet; CD) or 19.5% menhaden/0.5% safflower oil (experimental diet; ED). After 28 days, the animals were injected I.V. with LPS (20 mg/kg) or normal saline (S). Two hours later, the atria were harvested, connected to a force displacement transducer-amplifier-recorder system and maintained in vitro in oxygenated 37.5 degrees C Krebs-Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) and maximal rate of rise of contraction (dF/dt, g/sec) and relaxation (-dF/dt, g/sec) were similar in the CD-S (n = 6) and ED-S (n = 6) groups. FOCI, dF/dt, and -dF/dt were lower (P less than 0.05) in rats injected with LPS compared with rats injected with S irrespective of diet, but were significantly higher (P less than 0.05) in LPS-ED rats (n = 11) compared with LPS-CD rats (n = 11). Chronotropic and inotropic responses to graded doses (0.1, 0.5, 1.0, and 5.0 microM) of isoproterenol were not significantly different among groups. LPS-induced production of thromboxane B2 but not 6-keto-prostaglandin F1 alpha, was inhibited in ED fed rats. The ED did not enhance survival when rats were challenged with a 20 mg/kg I.V. dose of LPS. These results indicate that dietary enrichment with omega-3 fatty acids in rats partially protects against LPS-induced alterations in atrial function but does not change mortality after an LD100 dose of LPS.

6-Ketoprostaglandin F1 alpha↗