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Biomedical subjects

C Duffy

Publications and source records attributed to C Duffy.

At least 19 recordsLinked to original sources
PubMed2005

Redescription of Cetorhinicola acanthocapax Beveridge & Campbell, 1988 (Cestoda: Trypanorhyncha) from the basking shark Cetorhinus maximus (Gunnerus).

Cetorhinicola acanthocapax Beveridge & Campbell, 1988 is redescribed based on adult specimens collected from a basking shark Cetorhinus maximus (Gunnerus) off the east coast of New Zealand. Both the mature and gravid segments are described for the first time, and the first scanning electron micrographs of the armature and scolex microtriches are provided. Novel features include the opening of the vagina anterior to the cirrus-sac and the extension of the vagina anterior to the cirrus-sac. Pectinate microtriches are present on the anterior quarter of the pars pedunculus scolecis scattered between filiform microtriches; the bothrial margins are covered with tridigitate microtriches, while the adherent surface of the bothria have pectinate microtriches. The additional morphological features described are consistent with a close association between Cetorhinicola Beveridge & Campbell, 1988 and the Eutetrarhynchoidea Guiart, 1927.

Animals↗
PubMed2003

MSTd neuronal basis functions for the population encoding of heading direction.

Basis functions have been extensively used in models of neural computation because they can be combined linearly to approximate any nonlinear functions of the encoded variables. We investigated whether dorsal medial superior temporal (MSTd) area neurons use basis functions to simultaneously encode heading direction, eye position, and the velocity of ocular pursuit. Using optimal linear estimators, we first show that the head-centered and eye-centered position of a focus of expansion (FOE) in optic flow, pursuit direction, and eye position can all be estimated from the single-trial responses of 144 MSTd neurons with an average accuracy of 2-3 degrees, a value consistent with the discrimination thresholds measured in humans and monkeys. We then examined the format of the neural code for the head-centered position of the FOE, eye position, and pursuit direction. The basis function hypothesis predicts that a large majority of cells in MSTd should encode two or more signals simultaneously and combine these signals nonlinearly. Our analysis shows that 95% of the neurons encode two or more signals, whereas 76% code all three signals. Of the 95% of cells encoding two or more signals, 90% show nonlinear interactions between the encoded variables. These findings support the notion that MSTd may use basis functions to represent the FOE in optic flow, eye position, and pursuit.

Action Potentials↗
PubMed2003

Adult Hallervorden-Spatz syndrome simulating amyotrophic lateral sclerosis.

Hallervorden-Spatz syndrome (HSS) is a neurodegenerative disorder characterized by progressive dementia, dystonia, ataxia, and rigidity. An atypical form of adult-onset HSS was observed in a 36-year-old man presenting with progressive dysarthria. Markedly dysarthric speech and a weak atrophic tongue associated with a neurogenic pattern of motor unit recruitment in bulbar-supplied muscles on electromyography led to an initial impression of bulbar amyotrophic lateral sclerosis (ALS). Lack of expected progression of symptoms, however, prompted reinvestigation. Repeat brain magnetic resonance imaging demonstrated an "eye-of-the-tiger" pattern in the basal ganglia, characteristic of HSS, thus requiring genetic studies. DNA analyses of the pantothenate kinase gene (PANK2) was conducted and revealed two novel, disease-causing exon 3 missense mutations (Cys231Ser and Tyr251Cys). This case broadens the genotypic and phenotypic spectrum of HSS to include a late-onset syndrome resembling bulbar-onset ALS.

Adult↗
PubMed2002

Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine.

We report the immunological characterization of three colon carcinoma cell lines, COLO 205, SW620 and SW403, which we selected to combine with cytokine-secreting fibroblasts for the development of an allogeneic tumour cell vaccine. The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens. They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins. The lines presented TAAs in a manner recognized by immune effector cells, which was demonstrated by the lysis of SW620 by HLA-A2-restricted anti-p53 cytotoxic T lymphocytes (CTL). COLO 205 and SW620 were genetically modified to express the co-stimulatory molecule CD80 (B7.1), which increased the ability of the cells to stimulate CTL in vitro. CTL clones derived from HLA-A2+ peripheral blood mononuclear cells stimulated with the CD80-expressing lines lysed the stimulator cell and an HLA-A2+ colon cancer cell line, but did not lyse an isogeneic fibroblast line or an HLA-A2- colon cancer cell line. CTL clones derived from colon carcinoma patients immunized with an allogeneic vaccine containing these lines demonstrated killing of autologous tumour cells, the vaccine cell lines and other HLA-A2+ colon cancer cell lines, but not fibroblasts isogeneic to certain of the target cell lines. Our studies demonstrate that these colon carcinoma cell lines express shared TAAs that can induce CTLs which recognize and lyse other colon carcinoma cells, and support the continued clinical evaluation of the CD80 gene modified allogeneic colon cell/cytokine-secreting fibroblast carcinoma vaccine.

Antigen Presentation↗
PubMed2001

Dilated cardiomyopathy in two transgenic mouse lines expressing activated G protein alpha(q): lack of correlation between phospholipase C activation and the phenotype.

We previously described a transgenic mouse line (alpha(q)*52) in which cardiac-specific expression of activated G alpha(q)protein (HA alpha(q)*) leads to activation of phospholipase C beta (PLC beta), the immediate downstream target of HA alpha(q)*, with subsequent development of cardiac hypertrophy and dilation. We now describe a second, independent line in the same genetic background (alpha(q)*44h) with lower expression of HA alpha(q)* protein that ultimately results in the same phenotype: dilated cardiomyopathy (DCM) with severely impaired left ventricular systolic function (assessed by M-mode and 2D echocardiography), but with a much delayed disease onset. We asked if PLC activation correlates with the development of the phenotype. At 12-14 months, 65% of alpha(q)*44h mice still had normal cardiac function and ventricular weight/body weight ratios (VW/BW). However, their basal PLC activity, which began to increase in ventricles at 6 months, was threefold higher than in wild-type by 12 months. This increase was even more pronounced than in 2.5-month-old alpha(q)*52 mice, in which a twofold increase was accompanied by a 25% increase in VW/BW. Furthermore, at 12-14 months the increase in PLC activity in alpha(q)*44h mice with and without DCM was comparable. Thus, the delayed time course in alpha(q)*44h mice unmasked a lack of correlation between PLC activation and development of DCM in response to HA alpha(q)* expression, suggesting a role for additional pathways and/or mechanisms. It also revealed a differential temporal regulation of protein kinase C isoform expression. The markedly different ages of disease onset in these two mouse lines provide a model for studying both genetic modifying factors and potential environmental influences in DCM.

Aging↗
PubMed2001

A polymorphic modifier gene alters the hypertrophic response in a murine model of familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disorder caused by mutationally altered dominant-acting sarcomere proteins, exhibits significant clinical heterogeneity. To determine whether genetic background could influence the expression of this disease, we studied a murine model for this human condition. Hypertrophic responses to the Arg403Gln missense mutation in a cardiac myosin heavy chain gene were compared in 129SvEv (inbred; designated 129SvEv- alpha MHC403/+) and Black Swiss (outbred; designated BSw- alpha MHC403/+) strains. At 30-50 weeks of age all 129SvEv- alpha MHC403/+ showed left ventricular hypertrophy, while left ventricular wall thickness was increased in only half of BSw- alpha MHC403/+ mice demonstrating that a polymorphic modifier gene can determine the hypertrophic response to this dominant-acting sarcomere protein mutation. Further analysis suggests that SJL/J mice bear a recessive allele of this modifier gene that prevents a hypertrophic response to the Arg403Gln missense mutation. We conclude that genetic modifiers in mice, and presumably in man, can alter the hypertrophic response to sarcomere protein gene missense mutations.

Alleles↗
PubMed2001

The effects of an HIV-1 immunogen (Remune) on viral load, CD4 cell counts and HIV-specific immunity in a double-blind, randomized, adjuvant-controlled subset study in HIV infected subjects regardless of concomitant antiviral drugs.

OBJECTIVE: We examined the activity of an HIV-1 immunogen (Remune) on viral load, CD4 cells and HIV-1 specific immunity. METHODS: Plasma and peripheral blood mononuclear cells were obtained in a predefined random subset of subjects (n = 252) from a multicentre, double-blind, adjuvant-controlled phase III clinical endpoint study. RESULTS: The subjects treated with the HIV-1 immunogen had a significantly greater decline in viral load at multiple time points (P < 0.05), a trend towards increased CD4+ T cell counts and significantly enhanced HIV-1 specific immune responses as measured by HIV-1 lymphocyte proliferation (P < 0.001) compared to the adjuvant control group. Furthermore, in the HIV-1 immunogen treated group, enhanced HIV-1 specific lymphocyte proliferative immune responses were associated with decreased HIV-1 plasma RNA. CONCLUSION: These results suggest that, in a predefined, random subset of subjects, a beneficial effect of the HIV-1 immunogen was observed on viral load, CD4+ T cells, and HIV-specific immunity. These differences were observed in a background of multiple drug therapies. Ongoing trials are evaluating the effect of the combination of this HIV-1 specific, immune-based therapy with potent antiviral drug therapy on virological outcomes.

AIDS Vaccines↗
PubMed2001

Making faces: creating three-dimensional parameterized models of facial expression.

Previous studies of the perceptual processing and dynamics of emotional expression in faces have been limited by the lack of realistic yet controlled stimuli. The present work offers researchers a method for creating such stimuli for exploring these phenomena. We describe the creation of the stimuli and a series of experiments testing the validity of these stimuli with respect to emotional expressions in humans. Participants evaluated synthesized facial images and standardized photographs of six basic emotional expressions for intensity and accuracy of perceived emotion. Comparisons of these measures were qualitatively similar for synthesized and photographed faces. A manipulation of the magnitude of the synthesized expressions yielded a significant effect on the perceived intensity of expression. In a subsequent multidimensional scaling study, no systematic differences were uncovered in the derived configurations of the synthesized expressions and the photographs. These results are discussed in the context of possible future research applications.

Emotions↗
PubMed2000

Endonuclease and helicase activities of bacteriophage lambda terminase: changing nearby residue 515 restores activity to the gpA K497D mutant enzyme.

Terminase, the DNA packaging enzyme of bacteriophage lambda, is a heteromultimer of gpNu1 and gpA subunits. In an earlier investigation, a lethal mutation changing gpA residue 497 from lysine to aspartic acid (K497D) was found to cause a mild change in the high-affinity ATPase that resides in gpA and a severe defect in the endonuclease activity of terminase. The K497D terminase efficiently sponsored packaging of mature lambda DNA into proheads. In the present work, K497D terminase was found to have a severe defect in the cohesive end separation, or helicase, activity. Plaque-forming pseudorevertants of lambda A K497D were found to carry mutations in A that suppressed the lethality of the A K497D mutation. The two suppressor mutations identified, A E515G and A E515K, affected residue 515, which is located near the putative P-loop of gpA. A codon substitution study of codon 515 showed that hydrophobic and basic residues suppress the K497D defect, but hydrophilic and acidic residues do not. The E515G change was demonstrated to reverse the endonuclease and helicase defects caused by the K497D change. Moreover, the gpA K497D E515G enzyme was found to have kinetic constants for the high-affinity ATPase center similar to those of the wild type enzyme, and the endonuclease activity of the K497D E515G enzyme was stimulated by ATP to an extent similar to the ATP stimulation of the endonuclease activity of the wild type enzyme.

Amino Acid Sequence↗
PubMed2000

The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children.

BACKGROUND: Peanut-allergic patients are affected by a condition which forces them and their families to exercise extreme dietary vigilance and experience constant uncertainty throughout their lives. OBJECTIVE: To compare the quality of life and family relations of children and adults with a peanut allergy to that of children and adults with a rheumatological disease. METHODS: Patients with a confirmed diagnosis of peanut allergy or a rheumatological disease completed (for children less than 18 years, by proxy) self-report questionnaires regarding the impact of their condition on their quality of life and family relations. A vertical visual analogue scale and the Impact on Family Questionnaire (IFQ) served as outcome measures. RESULTS: One hundred and fifty-three peanut-allergic children were compared with 69 children with a rheumatological disease while 37 peanut-allergic adults were compared with 42 adults with a rheumatological disease. The parents of peanut-allergic children, compared to the parents of children with a rheumatological disease, reported that their children had significantly more disruption in their daily activities. Furthermore, the parents of peanut-allergic children reported more impairment in the familial-social dimension of the IFQ. Conversely, adults with a chronic rheumatological disease reported more disruption in their family relations than peanut-allergic adults. CONCLUSION: Given the considerable disruption in daily activities and family relations reported by the parents of peanut-allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut allergy more aware of the support that these families may require. Furthermore, we hope to motivate food industries to offer more 'peanut free' products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion.

Adolescent↗
PubMed2000

An audit of subcutaneous syringe drivers in a non-specialist hospital.

The use of syringe drivers as a method of drug delivery to control symptoms in palliative care is a common and accepted practice, but one which has evolved rather than been subject to close multiprofessional scrutiny and guideline formation. There is evidence that adverse incidents may arise as a result of syringe driver use (Medical Devices Agency (MDA), 1998), for example, errors in drug calculations, drug stability, equipment failure (including disconnection) and the wrong rate of infusion. Inadequate user training, poor servicing of equipment and inadequate documentation and record keeping are all thought to be contributing factors (MDA, 1998). In the hospital where this audit was carried out, syringe drivers are used to administer drugs to patients with cancer during the palliative phase of illness. The purpose of this clinical audit was to establish the standard of current practice in wards where syringe drivers were being used. A retrospective study of 13 cases of syringe driver use is presented. The results highlight many areas of unregulated practice with regard to setting up, monitoring and maintenance of syringe drivers. The choice of drugs and doses prescribed, evaluation of treatment responses and review of treatment regimens were also areas of concern. Guidelines for the use of syringe drivers in non-specialist hospitals are put forward.

Adult↗
PubMed1999

Magnetic resonance imaging of intercranial plasmocytic granuloma.

The objective of this study is to determine characteristic magnetic resonance imaging (MRI) features of intracranial plasmocytic granulomas. Pathological confirmation of three patients with intracranial pathologically confirmed plasmocytic granuloma are presented. Clinical records as well pre- and postgadolinium-enhanced images from each patient are reviewed. The location of the abnormalities is compared with previous reported cases of plasmocytic granulomas, to determine if there is a characteristic finding in this disense. The predominance of this abnormality in the pediatric and young adult patient was striking. On T(1)-weighted MRI, plasmocytic granulomas appear as hypointense lesions, with isointense appearance on T(2) images, and significant, variable patterns of enhancement after the infusion of gadolinium. Typically, the lesion is infiltrating, and causes little mass effect. A dural based lesion, as well as a sellar region abnormality and an infiltrating cortical lesion with little mass effect in the pediatric or young adult age group may lead the observer to suspect the diagnosis of plasmocytic granuloma.

Journal Article↗
PubMed1998

N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity.

Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3-(aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2-furanylamidine (77) (Ki-nNOS = 0.006 microM; Ki-eNOS = 0.35 microM; Ki-iNOS = 0.16 microM). Finally, alpha-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (Ki-nNOS = 0. 011 microM; Ki-eNOS = 1.1 microM; Ki-iNOS = 0.48 microM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.

Amidines↗
PubMed1998

Telepsychiatry: an island pilot project.

A telemedicine link was established in 1996 between the island of Inishmore and the department of psychiatry in University College Hospital, Galway. The link was mainly used to facilitate emergency consultations between patients on the island and the duty psychiatrist, always at the request of the island's general practitioner. Nine patients were referred for assessment in this manner over eight months. Three patients had their first psychiatric contact and assessment through the video-link, and were followed up as outpatients via the link to eventual resolution of the episode of illness and discharge at the outpatient clinic. Our experience has been that videoconferencing systems are acceptable and satisfactory for patients and staff alike.

Adult↗
PubMed1997

Effect of immunization with an inactivated gp120-depleted HIV-1 immunogen on beta-chemokine and cytokine production in subjects with HIV-1 infection.

OBJECTIVE: To measure beta-chemokine and cytokine production in HIV-1-infected subjects undergoing treatment with HIV-1 immunogen (REMUNE). DESIGN: Open label treatment study. METHODS: beta-Chemokine and cytokine production in peripheral blood mononuclear cell (PBMC) culture. RESULTS: Interferon-gamma production (p = 0.04) and lymphocyte proliferation (p = 0.001) to HIV-1 antigen-stimulated PBMCs increased after immunization with the HIV-1 immunogen. A correlation was demonstrated after immunization between HIV-1 antigen-stimulated lymphocyte proliferation and interferon-gamma levels (r = 0.53, p = 0.04). No significant change after immunization was seen for interleukin-4 production. A significant increase in mean levels of HIV-1 antigen-stimulated RANTES (i.e., regulated upon, activation normal T-cell expressed and secreted), was evident 1 month after immunization (p = 0.002) and remained elevated 3 months after immunization. RANTES production was decreased in CD8-depleted PBMC cultures. Mean serum HIV-1 RNA copy numbers and CD4 cell counts remained stable after immunization (p > 0.5). A correlation was demonstrated between HIV-1 antigen-stimulated interferon-gamma and RANTES production (r = 0.54, p = 0.002). CONCLUSIONS: This report describes an augmentation of beta-chemokines and TH1-type cytokines from PBMCs after immunization with the HIV-1 immunogen.

CD4 Lymphocyte Count↗
PubMed1997

Immunity to cartilage link protein in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To determine whether children with juvenile rheumatoid arthritis (JRA) express cellular immunity to cartilage link protein. METHODS: Link protein was purified from human fetal epiphyseal and bovine adult nasal cartilage. It was used in proliferation assays with the peripheral blood lymphocytes isolated from 54 children with JRA and 22 nonarthritic controls. RESULTS: Patients with JRA expressed a significantly higher prevalence of cellular proliferation to human link protein compared with the control group, independent of whether they had pauciarticular, polyarticular, or systemic disease. In the case of bovine link protein, significant differences were only noted for the polyarticular group. There was significant correlation between the immunity to bovine and to human link proteins. Furthermore, immune responses to both molecules correlated with measures of joint disease activity. CONCLUSION: These results suggest that immunity to link protein may play a role in the pathogenesis of JRA.

Adolescent↗
PubMed1996

The nitric oxide-cyclic GMP pathway is required for nociceptive signalling at specific loci within the somatosensory pathway.

The involvement of nitric oxide in nociceptive processing was examined at the main loci of synaptic transmission within the rat somatosensory pathway from the caudal sural cutaneous nerve. Intrathecal (lumbar 1-3) administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (30 micrograms), inhibited nitric oxide synthase in this region of the spinal cord by greater than 80% but had no significant effect on nitric oxide synthase in parietal cerebral cortex, thalamus or medulla/pons. In a rat model of peripheral neuropathy (one to two week ligation of the caudal sural cutaneous nerve), intrathecal administration of the same dose of N omega-nitro-L-arginine methyl ester prevented the hyperalgesic response to thermal stimuli. Administration of 30 micrograms N omega-nitro-L-arginine methyl ester into the lateral ventricle had no effect on nitric oxide synthase in the lumbar 1-3 region of the spinal cord but gave substantial inhibition in higher areas of the somatosensory pathway (parietal cerebral cortex, thalamus and medulla/pons). Nitric oxide synthase in the parietal cerebral cortex (but not thalamus) was inhibited to a greater extent in the hemisphere ipsilateral to the site of administration. Administration of 30 micrograms N omega-nitro-L-arginine methyl ester into the lateral ventricle decreased thermal hyperalgesia, but only when N omega-nitro-L-arginine methyl ester was administered contralateral to the ligated caudal sural cutaneous nerve and therefore ipsilateral to the cortical nociceptive processing from this nerve. Intrathecal and intracerebroventricular administration of the selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1-H-[1,2,4]oxadiazalo[4,3-a]quinoxalin-1-one, also decreased the hyperalgesic response to thermal stimuli. These data demonstrate that, in a model of neuropathic pain, nitric oxide is involved in nociceptive processing at spinal and cerebrocortical synaptic loci of the somatosensory pathway and that its actions appear to be mediated through guanylyl cyclase.

Animals↗