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Biomedical subjects

C Buckley

Publications and source records attributed to C Buckley.

At least 19 recordsLinked to original sources
PubMed1999

Localized bowel vasculitis: postoperative cyclophosphamide or not?

We describe 2 patients with necrotizing vasculitis localized to the bowel, who were treated by excision of the involved tissue. Postoperatively, there was no evidence of active vasculitis, and both patients remain in remission on followup, without the use of immunosuppressive treatment. Evidence that an abnormal local microenvironment is necessary to sustain chronic inflammation may explain why surgical excision can be an important tool in the treatment of vasculitis.

Adult↗
PubMed1998

The diagnosis of lameness associated with distal limb pathology in a horse: a comparison of radiography, computed tomography and magnetic resonance imaging.

A cadaver limb from an eight-year-old horse with right forelimb lameness that was relieved with an intra-articular distal interphalangeal joint block was imaged with radiographs, spiral computed tomography (CT) and magnetic resonance imaging (MRI). Spiral CT demonstrated several lucencies within the deep digital flexor tendon immediately proximal to the navicular bone. On MRI these areas had increased signal and there was enlargement of the tendon at this site. Effusion in the proximal interphalangeal joint and navicular bursa and thinning of the fibrocartilage of the navicular bone were also observed on MRI images. These changes were not detected on radiographs. Histopathology confirmed that there were focal areas of collagen necrosis within the deep digital flexor tendon with thinning and degenerative changes in the fibrocartilage of the navicular bone.

Animals↗
PubMed1998

A missense mutation in the zinc-finger domain of the human hairless gene underlies congenital atrichia in a family of Irish travellers.

Congenital atrichia is a rare, recessively inherited form of hair loss affecting both males and females and is characterized by a complete absence of hair follicles. Recently, a mutation in the human hairless gene was implicated in the pathogenesis of congenital atrichia. The human hairless gene encodes a putative single zinc-finger transcription-factor protein with restricted expression in brain and skin, which is believed to regulate catagen remodeling in the hair cycle. In this study, we report the identification of a missense mutation in the zinc-finger domain of the hairless gene in a large inbred family of Irish Travellers with congenital atrichia. The mutated arginine residue is conserved among human, mouse, and rat, suggesting that it is of significant importance to the function of the zinc-finger domain.

Alopecia↗
PubMed1998

Neutrophils rolling on immobilised platelets migrate into homotypic aggregates after activation.

Interactions between platelets and leucocytes are implicated in the pathology of thrombotic vascular disease. Using a flow-based adhesion assay we have investigated a novel route for the formation of neutrophil aggregates on the surface of immobilised activated platelets. Neutrophils perfused over a platelet monolayer formed numerous rolling attachments but rapidly stopped and spread after the superfusion of N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor (both at 10(-7) M). Subsequent integrin-mediated migration across the platelet monolayer enabled formation of homotypic neutrophil aggregates, which was significant within 2.5 min of receipt of either stimulus. Aggregates increased in size with time and had an average projected area of approximately 500 microm2 after 10 min. Increasing size was correlated with an increasing tendency for movement downstream and large aggregates sometimes tumbled in that direction. The formation and stability of homotypic aggregates was dependent on several adhesive mechanisms. Antibody blockade demonstrated that interactions involving CD11a/CD18 and ICAM-3, between alpha(v)beta3-integrin and CD31 and between L-selectin and an unidentified counter-ligand were all required for the complete aggregatory response. Furthermore, blockade of L-selectin allowed initial aggregation which then reversed, suggesting that this receptor might regulate the interactions between other adhesion molecules that directly supported cell-cell adhesion. We propose that this novel route for leucocyte aggregation could promote vascular occlusion in thrombotic vessels or at distal sites in the event of embolisation.

Antibodies, Monoclonal↗
PubMed1997

Cross-talk between cell adhesion molecules regulates the migration velocity of neutrophils.

BACKGROUND: Although the adhesive mechanisms underlying the capture and immobilization of circulating neutrophils in inflamed blood vessels have been well described, factors controlling the subsequent migration of neutrophils over and through the blood vessel endothelium are poorly understood. Directional rearrangement of the actin cytoskeleton within the neutrophil, along with modulation of integrin-mediated adhesion, are necessary for neutrophil migration. Signals from chemotactic agents and from the adhesive substrate may regulate these processes, but little is known about their relative importance or their mode of integration. RESULTS: We examined the kinetics of neutrophil migration after formyl tripeptide or platelet-activating factor was perfused over neutrophils that were already rolling on the adhesion molecule P-selectin, which was presented either on the surface of immobilized platelets or in purified form coated on glass capillaries. Upon activation, neutrophils stopped rolling, spread and began to migrate; each of these processes was dependent on beta2 integrin (CD11b/CD18). The rate of migration increased over a period of about 8 minutes and was modulated directly by both the P-selectin and the CD31 surface receptors. Antibody blockade of either CD31 or P-selectin on platelets resulted in a reduction in the velocity of migration, and simultaneous blockade of both receptors reduced velocity further. Purified CD31 and P-selectin (but not a control adhesion molecule, ICAM-1) increased migration velocity in a concentration-dependent and additive manner that reconstituted the migratory behaviour observed on platelets. CONCLUSIONS: These studies show that binding of ligands to CD31 and/or P-selectin modifies the rate of integrin-supported neutrophil migration. This novel example of 'cross-talk' between surface receptors suggests that cell adhesion molecules might generally transduce accessory signals between adjacent cells to modify their migratory responses to chemotactic signals.

Animals↗
PubMed1997

Mobile atheroma of the aortic arch is an underestimated source of embolization.

BACKGROUND: Mobile atheroma are associated with increased perioperative strokes in patients undergoing coronary artery bypass surgery. Peripheral embolization is an additional risk. Transesophageal echocardiography (TEE) accurately identifies mobile atheroma. Recent reports have discussed the possible influence of anticoagulant therapy in promoting peripheral cholesterol embolization. METHODS: Fourteen patients with mobile atheroma were treated with anticoagulation. A review of literature reporting results and complications of anticoagulation in the treatment of this condition was compared with our recent experience. RESULTS: Between 1994 and 1996, 14 patients with peripheral embolization and mobile atheroma confirmed by TEE were anticoagulated. Clinical follow-up between 6 to 30 months has demonstrated no further evidence of systemic embolization since anticoagulation. Furthermore, repeat TEE in 3 of 14 patients no longer visualized mobile atheroma. CONCLUSIONS: Mobile atheroma are recognized sources for embolization. Patients with generalized atherosclerosis should be screened for this condition in cases of systemic embolization. Anticoagulation may have therapeutic considerations in the management of this condition.

Aged↗
PubMed1997

Botulism.

Equine botulism is being recognized with increasing frequency by veterinarians throughout North America. Muscular weakness and dysphagia that progress during a period of 1 to 4 days, in the absence of laboratory derangements that indicate the presence of systemic disease, are suggestive of botulism. A tentative diagnosis usually is based on the presence of the following findings on physical examination: delayed pupillary light response, mydriasis, ptosis, generalized weakness, decreased tail tone, and slow prehension of feed. Definitive diagnosis requires detection of botulinum toxin in plasma, serum, gastrointestinal contents, or body tissues. Early treatment with antitoxin generally results in a favorable outcome. Botulism in foals and adult horses can be prevented by vaccination.

Animals↗
PubMed1997

Intensive nutritional counselling in bulimia nervosa: a role for supplementation with fluoxetine?

OBJECTIVE: The aims of the paper are to determine whether nutritional counselling is associated with an improvement in bulimic symptomatology, whether this improvement is maintained during post-treatment follow-up, and whether the addition of fluoxetine 3 x 20 mg/day confers additional benefit. METHOD: Psychological, pharmacological and combined psychopharmacological treatments of bulimia nervosa were reviewed briefly. Sixty-seven patients referred to specialist eating disorder services who fulfilled strict diagnostic criteria were treated with intensive nutritional counselling and randomly assigned to either fluoxetine 3 x 20 mg/day or placebo. After a 1-week 'wash-out', active treatment was given over 8 weeks, followed by post-treatment interviews at 12 and 20 weeks. RESULTS: Both groups of patients improved significantly during treatment. In some respects, the fluoxetine group did slightly better as demonstrated by the items 'restraint', 'weight concern' and 'shape concern' (p < 0.05 vs p < 0.0001) on the Eating Disorder Examination (EDE). Fluoxetine patients decreased their energy intake and lost a modest amount of weight. They went on to regain weight during the follow-up period, returning to levels higher than they were initially. These patients also appeared more likely to have a recurrence of symptoms, as shown by the fall in percentage of binge-free patients and by changes in the EDE. CONCLUSION: Nutritional counselling is an effective means of treating bulimia nervosa, with improvement maintained up to 3 months follow-up. The addition of fluoxetine may confer some benefit during active treatment, but its discontinuation may contribute to a higher rate of recurrence of symptoms post treatment. Of course, this study cannot be extrapolated to the efficacy of fluoxetine when used as the only form of treatment in patients for whom intensive nutritional counselling or other structured psychological programs are not available.

Adolescent↗
PubMed1996

Use of intravascular ultrasound in the endovascular management of atherosclerotic aortoiliac occlusive disease.

BACKGROUND: Intravascular ultrasound (IVUS) has been described as interesting technology in search of a clinical application by some and by others as a valuable diagnostic tool for many endovascular interventions. Its clinical usefulness has yet to be fully defined. When used during endovascular interventions, it can provide structural and diagnostic information, assess effectiveness of the therapy, and identify treatment-related complications. METHODS: Thirty-two consecutive patients with atherosclerotic aortoiliac occlusive disease who presented with 40 separate arterial lesions were evaluated with IVUS before and after balloon angioplasty and intraluminal stent placement. Information obtained from IVUS was compared with similar data obtained from simultaneous angiographic images. Both techniques were evaluated with respect to assessment of vessel size, lesion location, adequacy of therapy, and identification of complications. RESULTS: Real time IVUS imaging compared with angiographic imaging showed that in 62% of the patients, vessel diameter was underassessed using angiographic criteria alone. More importantly, 40% (16 of the 40 lesions) had underdeployed stents by IVUS evaluation that appeared adequately expanded by angiographic criteria. Further stent expansion with a larger balloon was necessary to achieve accurate stent to vessel wall apposition. This was found to be significant by an exact binomial 95% confidence interval. Incomplete stent deployment has been identified as a possible cause for restenosis and vessel occlusion. Information obtained from IVUS imaging substantially altered the endovascular therapy in approximately 40% of our patients and provided valuable vessel sizing and lesion composition information in 62% of the patients. CONCLUSION: Intravascular ultrasound can provide important diagnostic information that can alter the conduct of selected endovascular procedures. It is especially useful when the procedure requires deployment of arterial stents.

Adult↗
PubMed1996

Oxidized low-density lipoproteins inhibit endothelium-dependent relaxations in isolated large and small rabbit coronary arteries.

1. Previous studies suggest that oxidatively modified low-density lipoproteins (oxLDL) contribute to the impairment of endothelium-dependent vasodilation in the large arteries of hypercholesterolaemic animals, whereas this may not be the case with regard to the impairment of coronary resistance vessels. For this reason, the effect of lipoproteins on coronary resistance arteries has been examined in this study. 2. The influence of lipoproteins on endothelium-dependent relaxation induced by acetylcholine (ACh) or sodium nitroprusside in PGF2 alpha-preconstricted rings from the large (1st order branch) and small coronary arteries (3rd order branch) and the aorta of New Zealand White rabbits, was investigated. 3. The sensitivity to ACh was greater in the large compared with the small diameter coronary arteries. 4. Endothelium-dependent relaxations were unaffected by native LDL. Oxidized LDL (0.5 and 1 mg protein mL-1) caused a reversible inhibition of relaxations in both preconstricted small and large coronary arteries which was overcome at high ACh concentrations. Similar inhibitions were found in the aorta. 5. Endothelium-independent relaxations elicited by sodium nitroprusside in the large and small coronary arteries were unaffected by the oxidized lipoproteins, indicating that soluble guanylate cyclase activity was unaltered. 6. It is concluded that inhibition of endothelium-dependent relaxation in the small diameter coronary arteries in hypercholesterolaemia may arise from products of oxidative modification of LDL present in the artery itself or released upstream from proximal lesions.

Acetylcholine↗
PubMed1996

Immunohistological analysis of 'negative' patch test sites in atopic dermatitis.

BACKGROUND: Variable results have been obtained when patients with atopic dermatitis (AD),) have been patch tested with allergens known to produce a positive prick test. The significance of patch test results in our understanding of the pathogenesis of AD therefore remains questionable. OBJECTIVE: This study was designed to determine the relevance of either positive or negative patch test results in relation to the expression of cell mediated immunity to allergens in patients with AD. METHODS: Thirty-five patients with AD exhibiting patch test positivity to one or more aeroallergens on 'tape stripped' areas of the back were retested without prior tape stripping. Nine patients again showed positivity to one or more allergens while 26 failed to show positive reactions. In six of the positive patients both positive and negative patch tests were observed. Skin biopsies were taken from these matched positive and negative patch test sites as well as from an area of uninvolved skin. Samples were frozen and cryostat sections were analysed with immunohistological techniques using monoclonal antibodies to investigate the distribution of immunocompetent cells. RESULTS: All positive patch tests exhibited characteristics of a cell mediated immune response. The negative patch test sites were also found to contain evidence of mononuclear cell infiltration. Both negative and positive patch test sites showed significantly greater proportions of T cells compared to uninvolved skin. No increase in numbers of RFD1 positive and RFD7 positive macrophages were observed in either positive or negative patch test sites. Expression of CD23 by CD1 positive Langerhans cells was raised in both negative and positive patch tests compared to uninvolved areas. A significant increase in the population (RFD7+, CD23+) was seen in positive patch test sites compared to uninvolved skin. An increase in the proportion of RFD1 positive cells expressing CD23 was also seen in both negative and positive patch tests compared to uninvolved skin. CONCLUSIONS: This paper demonstrates that immunological reactions are promoted at 'non-tape stripped' patch test sites where no clinical evidence of reactivity is seen. Together the data demonstrate that the presence of systemic cell mediated immunity to specific allergens identified in patients by positive patch test, may also be present when no clinical signs are seen at the patch test site.

Adolescent↗
PubMed1995

Mapping the homotypic binding sites in CD31 and the role of CD31 adhesion in the formation of interendothelial cell contacts.

CD31 is a member of the immunoglobulin superfamily consisting of six Ig-related domains. It is constitutively expressed by platelets, monocytes, and some lymphocytes, but at tenfold higher levels on vascular endothelial cells. CD31 has both homotypic and heterotypic adhesive properties. We have mapped the homotypic binding sites using a deletion series of CD31-Fc chimeras and a panel of anti-CD31 monoclonal antibodies. An extensive surface of CD31 is involved in homotypic binding with domains 2 and 3 and domains 5 and 6 playing key roles. A model consistent with the experimental data is that CD31 on one cell binds to CD31 on an apposing cell in an antiparallel interdigitating mode requiring full alignment of the six domains of each molecule. In addition to establishing intercellular homotypic contacts. CD31 binding leads to augmented adhesion via beta 1 integrins. The positive cooperation between CD31 and beta 1 integrins can occur in heterologous primate cells (COS cells). The interaction is specific to both CD31 and beta 1 integrins. Neither intercellular adhesion molecule-1 (ICAM-1)/leukocyte function-associated antigen-1 (LCAM-1) nor neural cell adhesion molecule (NCAM)/NCAM adhesion leads to recruitment of beta 1 integrin adhesion pathways. Establishment of CD31 contacts have effects on the growth and morphology of endothelial cells. CD31(D1-D6)Fc inhibits the growth of endothelial cells in culture. In addition, papain fragments of anti-CD31 antibodies (Fab fragments) disrupt interendothelial contact formation and monolayer integrity when intercellular contacts are being formed. The same reagents are without effect once these contacts have been established, suggesting that CD31-CD31 interactions are critically important only in the initial phases of intercellular adhesion.

Antigens, Differentiation, Myelomonocytic↗
PubMed1995

Differentiation and CD23 expression of peripheral blood monocytes in patients with atopic dermatitis.

In this study we investigate the expression of the low affinity immunoglobulin E (IgE) receptor (Fc epsilon RII) on plastic-adherent leucocytes from patients with atopic dermatitis (AD). Peripheral blood mononuclear cells were obtained from patients with AD, normal controls (and in one study from a group of atopic asthmatic patients). Monocytes were separated by 2-h adherence to plastic. These cells were then cultured for up to 7 days. Cells were harvested at time 0 (after adherence), and after 5 and 7 days culture, and cytospins were prepared. The proportion of cells expressing the phenotype of antigen presenting cells (monoclonal antibodies (mAb) RFD1+), and mature phagocytes (mAb RFD7+) together with CD23, were evaluated using combination staining with immunoperoxidase and alkaline phosphatase anti-alkaline phosphatase methods. It was found that a significantly larger proportion of circulating adherent cells in AD patients expressed the RFD1 antigen, and that increases in the proportion of these adherent cells expressing RFD1 or RFD7 occurred faster as cells matured in culture, when compared with cells obtained from normal controls. By day 7, however, equivalent proportions of RFD1+ and RFD7+ cells were present in AD and control cultures. None the less, expression of the CD23 molecule was consistently present on a larger proportion of both RFD1+ and RFD7+ cells from AD patients compared with controls. The raised proportion of circulating RFD1+ cells found in AD was not present in samples from atopic asthmatics, while the raised expression of CD23 on these cells occurred in samples from both these groups. These data support the suggestion that abnormalities in peripheral blood adherent cell phenotype, maturation, and CD23 expression, occur in AD patients. Some of these observations may be related to atopy in general rather than being specific for this skin disease.

Antigen-Presenting Cells↗