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K McFadden

Publications and source records attributed to K McFadden.

12 recordsLinked to original sources
PubMed1998

Peptides derived from the complementarity-determining regions of anti-Mac-1 antibodies block intercellular adhesion molecule-1 interaction with Mac-1.

Peptides or small molecules that can block the interaction of the integrin Mac-1 with its receptor, intercellular adhesion molecule-1 (ICAM-1), have not previously been developed. We studied this interaction by measuring the adherence of ICAM-1-expressing Chinese hamster ovary (CHO) cells to immobilized, purified Mac-1. Nucleotide sequence information was obtained for the complementarity determining regions (CDRs) of three antibodies (44aacb, MY904, and 118.1) shown to block Mac-1-mediated cell adherence. Peptides were synthesized based on the predicted amino acid sequences of the CDRs and tested for the ability to block cell adhesion to Mac-1. Peptides derived from CDR1 of 44aacb, CDR2 of 118.1, and CDRs 1 and 3 of MY904 heavy chains were found to possess blocking activity at 10-100 muM. This may indicate that one or two CDRs contribute disproportionately to the antibody binding affinity. The binding of ligands to Mac-1 has been shown to require a region of the alpha-chain known as the I- or A-domain. We have recombinantly produced Mac-1 I-domain, and show that it is also capable of supporting the adherence of ICAM-1-expressing CHO cells. The adherence of ICAM-1-CHO cells to the I-domain is inhibited by 44aacb and 118.1 and by the CDR peptides from 44aacb and 118.1. By using phage display of peptide libraries based on the 118.1 CDR peptide with five residues randomized, we were able to identify a novel peptide inhibitor of Mac-1 with substitutions at all five positions. These peptides provide lead structures for development of Mac-1 antagonists.

Amino Acid Sequence↗
PubMed1997

Nonclassical secretory dynamics of LH revealed by hypothalamo-hypophyseal portal sampling of sheep.

Continuous withdrawal of hypophyseal portal blood from unrestrained sheep has permitted detailed assessments of the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). To determine if this blood can also be used to characterize the sensory dynamics of pituitary hormones, patterns of luteinizing hormone (LH) in the hypophyseal portal blood of ovariectomized ewes was compared with previous patterns of GnRH and peripheral LH. Hypophyseal portal blood and jugular vein blood were collected every 5 min from six ovariectomized ewes over 6-12 h. Hypophyseal portal blood contained GnRH-associated, sharply defined LH pulses that were much larger than in the periphery. Pulses of secreted LH (hypophyseal portal LH less peripheral LH) showed much faster rates of rise and fall than peripheral and followed pulses of GnRH by an average of 1.26 min. In contrast to pulses in jugular blood, secreted LH pulses often reached a relatively unchanging interpulse nadir-plateau and thereby approached closely algorithm-estimated, extrapolated baselines. The interpulse baseline concentrations of secreted LH (99.6 ng/mL) in hypophyseal portal blood were 31-fold higher than those for jugular LH (3.23 ng/mL). These elevated concentrations also exceeded mean jugular peak concentrations (11.1 ng/mL) and, thus, primarily must represent newly secreted LH. The non-Gaussian profiles of this secreted LH were substantially more complex than the inputs predicted from jugular LH measurements by deconvolution. Furthermore, regardless of the analytical approach, estimations of the mass of secreted LH in each pulse did not correlate well with inputs predicted by deconvolution or Kushler-Brown pulsefit analysis of corresponding pulses in jugular blood (r2 ranging 0.40-0.48). Among alternative explanations is the possibility of heterogeneity in concentrations of GnRH in the portal vessels and variable distribution within the hypophysis. In summary, assay of hypophyseal portal blood obtained directly from the pituitary provides a method for direct assessment of secretory responses to hypothalamic peptides, and thereby serves as an unmatched method for studying the dynamics of LH secretion in vivo. With this approach, LH is revealed to be secreted as complex, non-Gaussian pulses that are far more sharply defined that those in the periphery, include non-GnRH-dependent, secretory components that cannot be predicted by deconvolution and are followed by periods of relatively constant, basal secretion.

Algorithms↗
PubMed1997

Neuroendocrine control of follicle-stimulating hormone (FSH) secretion. I. Direct evidence for separate episodic and basal components of FSH secretion.

Continuous sampling of hypophyseal portal blood from unrestrained sheep is providing an unprecedented means for measuring and defining the characteristics of the secretory profile of GnRH. With this method, GnRH has been shown to be released in discrete pulses lasting 5-8 min, with the amplitude of some pulses exceeding 50-fold. Although the relationship between these pulses and the accompanying pulses of LH measured in the jugular vein are unambiguous, the relationship of GnRH pulses to the release of FSH has not been well defined due to the longer clearance of FSH. In previous studies we have shown that hypophyseal portal blood, in addition to serving as a source material for hypothalamic secretions, provides a means to define secretory patterns of pituitary hormones. Because of this we hypothesized that the GnRH-FSH secretory relationship would be easier to define in hypophyseal portal than in jugular vein blood before the secretory products are subjected to dispersion and clearance in circulation. To test this possibility, we monitored hormonal patterns in blood collected at 5-min intervals for 6-12 h from the peripheral and hypophyseal portal circulation of six ovariectomized ewes from a previous study. In contrast to the nonpulsatile pattern of FSH in the peripheral blood, 93% of the GnRH pulses were associated with essentially coincident, discrete pulses of FSH in the portal plasma. Of potentially even greater interest, additional episodes of FSH release were clearly discernible between the GnRH-associated pulses of FSH. As concentrations of peripheral plasma FSH did not reach those in hypophyseal portal plasma, the inter-GnRH episodes of FSH secretion could not result from contaminating peripheral blood. In addition to the episodic mode of secretion, substantial amounts of FSH were found between FSH pulses. This basal component of FSH appeared to be the dominant mode of secretion rather than pulses. The results of this study not only confirm that GnRH pulses lead to pulsatile release of FSH, they also suggest that some other mechanism or factor may be controlling the non-GnRH-associated episodes as well as the basal components of FSH secretion.

Animals↗
PubMed1997

Cell migration in the developing chick diencephalon.

We previously reported that retrovirally marked clones in the mature chick diencephalon were widely dispersed in the mediolateral, dorsoventral and rostrocaudal planes. The current study was undertaken to define the migration routes that led to the dispersion. Embryos were infected between stages 10 and 14 with a retroviral stock encoding alkaline phosphatase and a library of molecular tags. Embryos were harvested 2.5-5.5 days later and the brains were fixed and serially sectioned. Sibling relationships were determined following PCR amplification and sequencing of the molecular tag. On embryonic day 4, all clones were organized in radial columns spanning the neuroepithelium, which was composed primarily of a ventricular zone at this age. No tangential migration was seen in the ventricular zone. On embryonic day 5, most clones remained radial with many cells located in the ventricular zone; however, a few clones had cells migrating perpendicular to the radial column, in either a rostrocaudal or dorsoventral direction. The tangential migration began just beyond the basal limit of the ventricular zone. On embryonic days 6 and 7, many clones had cells migrating perpendicular to the radial column, which spanned from the ventricular to the pial surface. The migrating cells appeared to be aligned along axes that were perpendicular to the radial column. Using a combination of DiI tracing, immunohistochemistry and electron microscopy, we have determined that axonal tracts are present and are aligned with the migrating cells, suggesting that they support the non-radial cell migration. These data indicate that migration along pathways independent of radial glia occur outside of the ventricular zone in more than 50% of the clones in the chick diencephalon.

Animals↗
PubMed1996

Prevalence of the eaeA gene in verotoxigenic Escherichia coli strains from dairy cattle in Southwest Ontario.

This study determined the prevalence of the eaeA gene and its relationship to serotype and type of verotoxin produced in a collection of 432 verotoxigenic Escherichia coli (VTEC) obtained from the faeces of healthy cows and calves in a systematic random survey involving 80 dairy farms in Southwest Ontario. A PCR amplification procedure involving primer pairs which target the conserved central region of the O157:H7 eaeA gene showed that 151 (35.2%) strains were positive for the eaeA gene. All isolates (9-21 for each O group) of O groups 5, 26, 69, 84, 103, 111, 145 and 157 were positive, whereas all isolates (7-34 for each O group) of O groups 113, 132, and 153 and serotype O156:NM (38 isolates) were negative for eaeA. Seventy-three percent of 130 isolates of eaeA-positive serotypes produced VT1 only compared with 20% of 253 isolates of eaeA-negative serotypes. We conclude that there is a strong association between certain O groups and the eaeA gene, that serotypes of eaeA-positive and eaeA-negative VTEC implicated in human and cattle disease are present at high frequency in the faeces of healthy cattle, that VT1 is more frequently associated with eaeA-positive than with eaeA-negative serogroups, and that the eaeA gene is more frequently found in VTEC from calves compared with VTEC from adult cattle.

Animals↗
PubMed1996

Evidence for and impact of selective reporting of trauma triage mechanism criteria.

OBJECTIVE: To determine whether out-of-hospital care charts selectively report trauma triage criteria, and the impact of such documentation on triage guideline development. METHODS: A special structured data instrument that requested the presence or absence of the American College of Surgeons (ACS) trauma triage criteria was completed by emergency medical services (EMS) personnel transporting victims of motor vehicle crashes. The standard written EMS report forms for a subset of 199 patients with at least 1 ACS trauma triage mechanism criterion were reviewed by the investigators. Outcome data were obtained from medical record review. The structured data instrument and the standard EMS report were compared for concordance. The impact of method of data collection on the ability of the ACS criteria to predict patient outcome was determined. RESULTS: EMS reports and structured data instruments similarly noted the presence of anatomic, physiologic, and "other" trauma triage criteria (p > 0.07 for all individual comparisons). Most mechanism-of-injury criteria noted on the data instrument (pedestrian struck > 20 mph; crash speed > 20 mph; vehicle deformity; compartment intrusion; rollover; and ejection) were infrequently documented on the standard EMS report (median 28.5% noted, range 0-100%). Patients who had mechanism criteria noted on the EMS report were more likely to be admitted to the hospital (44% vs 13%; p = 0.006), to require major operative procedures (10% vs 0%; p = 0.005), and to have prolonged lengths of stay (26% vs 9%; p = 0.02) and injury severity scores > or = 16 (15% vs 3%; p = 0.03) than were patients who had mechanism criteria documented only on the structured data instrument. CONCLUSIONS: In the authors' EMS system, standard EMS report documentation underreports ACS trauma triage mechanism criteria. This underreporting appears to bias outcome analysis in the direction of a worse outcome and more resource utilization. Reporting of mechanism-of-injury criteria improves with use of a structured data instrument.

Accidents, Traffic↗
PubMed1993

Virulence of Salmonella enteritidis phagetypes 4, 8 and 13 and other Salmonella spp. for day-old chicks, hens and mice.

Virulence of three Canadian poultry strains of Salmonella enteritidis, namely phagetypes (PT) 4, 8 and 13, and one Salmonella heidelberg strain was assessed in orally and intraperitoneally inoculated one-day old chickens and compared to the virulence of a human S. enteritidis PT 4 strain from the United Kingdom (UK). The two PT 4 strains were also compared in orally inoculated adult laying hens. In addition, orally inoculated Balb/c mice were used to evaluate virulence of the above strains and two strains of Salmonella typhimurium containing different plasmids. In orally inoculated one-day old chickens, the UK S. enteritidis PT 4 strain was more virulent than the Canadian PT 4 strain. The UK PT 4 strain was also more virulent and invasive in adult laying hens than the Canadian PT 4 strain. The S. enteritidis PT 8 strain and one S. typhimurium strain isolated from a chicken hatchery were the most virulent for orally inoculated Balb/c mice. This strain of S. typhimurium contained the 60 megadalton plasmid associated with virulence for Balb/c mice which was not present in the S. typhimurium strain isolated from a pig with septicemic disease.

Animals↗
PubMedDate not supplied

Clinical supervision: the Cartmel NDU experience.

Much has been written about clinical supervision, but there is little published evidence to demonstrate its effectiveness. This article describes the introduction and development of clinical supervision in a mental health nursing development unit, charting the consequent change of culture to one in which nurses were able to pioneer innovative models of care.

Clinical Competence↗
PubMedDate not supplied

Redesigning patient education materials: one home care agency's approach.

Providing effective patient education material is a continuous challenge for all nurses. Developing patient education materials that address the myriad variations in intravenous therapy practice is particularly challenging. For patient education materials to be useful, especially on a national basis, they must be specific enough to be meaningful, yet generic. When designing patient education materials, a variety of issues including content, design, time, and budget must be considered. In this article, the author offers an overview of the design and materials testing process as experienced by one home care agency.

Fluid Therapy↗