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Biomedical subjects

T Clifford

Publications and source records attributed to T Clifford.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between personality and satisfaction with the dentition in tooth wear patients.

This study was undertaken to identify whether personality traits had any relationship with patients' satisfaction with their dentition in tooth wear cases. One hundred tooth wear patients and one hundred controls were recruited into the study. A Dental Impact on Daily Living questionnaire was used to assess impact of tooth wear on day to day life and satisfaction with the dentition. An ordinal scale was used to assess tooth wear severity in tooth wear patients. The NEO Five Factor inventory was used to assess personal profiles. Tooth wear patients were less satisfied with their dentition, had higher Neuroticism, lower Extraversion, and higher Openness than the controls.

Activities of Daily Living↗
PubMed2004

Photodynamic therapy using meta-tetrahydroxyphenylchlorin (Foscan) for the treatment of vulval intraepithelial neoplasia.

BACKGROUND: Photodynamic therapy (PDT) has unique properties which make it suitable for the local treatment of superficial epithelial disorders; it has been suggested as a useful treatment for carcinoma in situ of the vulva. OBJECTIVES: To evaluate the effect of the systemic photosensitizing agent meta-tetrahydroxyphenylchlorin (mTHPC or temoporfin; Foscan, Biolitec, Edinburgh, U.K.) in vulval intraepithelial neoplasia type III (VIN III). METHODS: PDT using mTHPC was performed in six patients with VIN III. A dose of 0.1 mg kg(-1) body weight mTHPC was injected intravenously and the area of VIN irradiated 96 h later with 652-nm light from a diode laser. Patients were reviewed 1 week, 6 months and 2 years following treatment. RESULTS: Patients experienced only minimal pain from the initial treatment but two patients subsequently developed severe pain at the treated site for up to 2 weeks following PDT. All patients developed oedema and slough formation at the treated site and one patient developed cellulitis. At 6 months two patients had developed small recurrences of VIN at the original site and one patient had an area of VIN at a new site. These were treated either with further PDT or with a small excision. At 2 years there was no recurrence of VIN at the original site in all patients reviewed. CONCLUSIONS: This small case series demonstrates that mTHPC-PDT is a useful initial treatment for VIN III. It is relatively selective, shows good cosmesis and conserves form and function. This is a major advantage over surgery. Repeat treatments are also possible, which is important in a condition such as VIN, which tends to be multifocal. Systemic mTHPC-PDT appears to have an advantage over topical 5-aminolaevulinic acid-PDT as the photosensitizer is distributed widely in areas of disease and consequently identifies foci which may not be apparent clinically but become evident when illuminated.

Adult↗
PubMed2001

Anion binding with two polyammonium macrocycles of different dimensionality.

A comparative study of the binding of nitrate and sulfate with a polyammonium monocycle L(1), (3,6,9,17,20,23-hexaazatricyclo[23.3.1.1(11,15)]-triaconta-1(29),11,13,15(30),25,27-hexaene), and the corollary bicycle L(2), (1,4,12,15,18,26,31,39-octaazapentacyclo-[13.13.13.1(6,10).1(20,24).1(33,37)]-tetratetraconta-6,7,9,20(43),21,23,33(42),34,36-nonaene), is reported. Potentiometric studies indicated negligible binding for L(1) and nitrate, but high affinity was observed for sulfate (log K(H5L(SO4)/H5L-SO4) = 3.53(1), log K(H6L(SO4)/H6L-SO4) = 4.36(1)). Stronger binding was observed for the cryptand L(2) with both nitrate and sulfate (log K(H6L(NO3)/H6L-NO3) = 3.11(5), log K(H7L(NO3)/H7L-NO3) = 3.55(5); log K(H6L(SO4)/H6L-SO4) = 4.43(1), log K(H7L(SO4)/H7L-SO4) = 4.97(5)). Five crystal structures are reported: the nitrate (1) and sulfate (2) salts of L(1), the free base (3) of L(2), and the nitrate (4) and tosylate (5) salts of L(2). Structural results for L(1) indicate relatively planar monocycles with cis and trans orientations of the phenyl groups for 2 and 1, respectively, with the anions above and below the monocycle rings. For L(2), key features include an encapsulated water and intricate water network in 3, two encapsulated and four external nitrates and two external water molecules in 4, and six external tosylates with sulfonate groups pointing into the cavity and eight external waters in 5.

Aza Compounds↗
PubMed2001

Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2.

IL-1 is of utmost importance in the host response to immunological challenges. We identified and functionally characterized two novel IL-1 ligands termed IL-1delta and IL-1epsilon. Northern blot analyses show that these IL-1s are highly abundant in embryonic tissue and tissues containing epithelial cells (i.e., skin, lung, and stomach). In extension, quantitative real-time PCR revealed that of human skin-derived cells, only keratinocytes but not fibroblasts, endothelial cells, or melanocytes express IL-1delta and epsilon. Levels of keratinocyte IL-1delta are approximately 10-fold higher than those of IL-1epsilon. In vitro stimulation of keratinocytes with IL-1beta/TNF-alpha significantly up-regulates the expression of IL-1epsilon mRNA, and to a lesser extent of IL-1delta mRNA. In NF-kappaB-luciferase reporter assays, we demonstrated that IL-1delta and epsilon proteins do not initiate a functional response via classical IL-1R pairs, which confer responsiveness to IL-1alpha and beta or IL-18. However, IL-1epsilon activates NF-kappaB through the orphan IL-1R-related protein 2 (IL-1Rrp2), whereas IL-1delta, which shows striking homology to IL-1 receptor antagonist, specifically and potently inhibits this IL-1epsilon response. In lesional psoriasis skin, characterized by chronic cutaneous inflammation, the mRNA expression of both IL-1 ligands as well as IL-1Rrp2 are increased relative to normal healthy skin. In total, IL-1delta and epsilon and IL-1Rrp2 may constitute an independent signaling system, analogous to IL-1alphabeta/receptor agonist and IL-1R1, that is present in epithelial barriers of our body and takes part in local inflammatory responses.

Amino Acid Sequence↗
PubMed2001

Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.

The sequence of a novel hemopoietic cytokine was discovered in a computational screen of genomic databases, and its homology to mouse thymic stromal lymphopoietin (TSLP) suggests that it is the human orthologue. Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R alpha-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. Human TSLPR and IL-7Ralpha are principally coexpressed on monocytes and dendritic cell populations and to a much lesser extent on various lymphoid cells. In accord, we find that human TSLP functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells, as evidenced by the strong induction of the costimulatory molecules CD40 and CD80 and the enhanced capacity to elicit proliferation of naive T cells.

Amino Acid Sequence↗
PubMed2001

IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo.

We have characterized a cytokine produced by Th2 cells, designated as IL-25. Infusion of mice with IL-25 induced IL-4, IL-5, and IL-13 gene expression. The induction of these cytokines resulted in Th2-like responses marked by increased serum IgE, IgG(1), and IgA levels, blood eosinophilia, and pathological changes in the lungs and digestive tract that included eosinophilic infiltrates, increased mucus production, and epithelial cell hyperplasia/hypertrophy. In addition, our studies show that IL-25 induces Th2-type cytokine production by accessory cells that are MHC class II(high), CD11c(dull), and lineage(-). These results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types.

Amino Acid Sequence↗
PubMed2001

Influence of psychological factors on the acceptance of complete dentures.

OBJECTIVES: To assess the influence of psychological factors on the acceptance of complete dentures in a population wearing dentures judged to be clinically satisfactory. DESIGN: Subjects were asked to complete personality profiles and also to rate their dentures using a denture satisfaction questionnaire. SETTING: The survey was conducted in the prosthetics clinic of a teaching hospital. SUBJECTS: Patients were selected from those who had new complete dentures constructed in the department within the previous two years. INTERVENTION AND MAIN OUTCOME MEASURES: The personality inventory was a self-administered questionnaire comprising 240 items covering the five domains of personality. Denture satisfaction was scored on a nine item scale with four Likert type responses to each. RESULTS: A group of 16% consistently complained about their dentures. Statistical analysis showed that personality factors especially Neuroticism had a significant relationship with denture satisfaction. CONCLUSION: Psychological factors significantly influence denture satisfaction and profiles may provide useful in predicting potential difficult denture wearers.

Aged↗
PubMed2000

Varying coordination modes and magnetic properties of copper(II) complexes with diazamesocyclic ligands by altering additional donor pendants on 1,5-diazacyclooctane.

A series of new diazamesocyclic ligands based on a diazamesocycle, 1,5-diazacyclooctane (DACO), functionalized by additional donor groups--1,5-bis(N-1-methylimidazol-2-ylmethyl)-1,5- diazacyclooctane (L1), 1-(2-hydroxybenzyl)-1,5-diazacyclooctane (HL2), 1,5-bis(2-hydroxybenzyl)-1,5-diazacyclooctane (H2L3), and 1-(N-1-methylimidazol-2-ylmethyl)-1,5-diazacyclooctane (L4)--and their Cu(II) complexes have been synthesized and characterized. Single-crystal X-ray diffraction analysis of the four Cu(II) complexes revealed that L1 forms a five-coordinate mononuclear complex, HL2 a N3- mu-bridged binuclear complex, H2L3 an oxygen mu-bridged trinuclear complex, and L4 a one-dimensional zigzag coordination polymeric complex with Cu(II). [CuL1ClO4](ClO4) (I): a = 12.194(2) A, b = 13.351(3) A, c = 14.473(3) A, beta = 107.10(3) degrees, Z = 4. [CuL2(N3)]2 (II): a = 8.1864(6) A, b = 18.141(2) A, c = 9.3307(7) A, beta = 103.662(6) degrees, Z = 2. [Cu3(L3)2Cl2] (III): a = 10.7296(13) A, b = 13.7707(17) A, c = 13.5523(17) A, beta = 106.350(3) degrees, Z = 2. ([CuL4Cl]2ClO4) infinity (IV): a = 7.279(1) A, b = 23.695(5) A, c = 19.308(4) A, beta = 100.28(3) degrees, Z = 8. All four complexes crystallize in the monoclinic crystal system with the P2(1)/c space group, and each Cu(II) center coordinated with DACO is pentacoordinated with a distorted square-pyramidal or trigonal-bipyrimidal coordination environment. In complex IV, the binuclear cation unit [CuL4Cl]2(2+) constitutes the fundamental building block of an infinite alternating zigzag chain structure, and the binuclear unit contains two types of geometries around the Cu(II) centers: the Cu(1) center is a distorted square-pyramidal environment, while the Cu(2) is a distorted trigonal-bipyramidal coordination environment. To the best of our knowledge, this is the first Cu(II) complex of a diazamesocyclic ligand with an infinite polymeric structure. The magnetic properties of complexes II, III, and IV have been investigated by variable-temperature magnetic susceptibility measurements in the solid state. The obtained parameters are 2J = 2.06 cm-1 (II), -345.56 cm-1 (III), and -2.60 cm-1 (IV), which differ greatly from ferromagnetic to weak and strong antiferromagnetic coupling. These results unequivocally indicate that the nature of the pendant arms is a key factor governing the structure and properties of the complexes; therefore, the coordination modes and properties of the metal complexes of a diazamesocycle can be controlled by altering the pendant donors on it. Magneto-structural correlation has been precisely analyzed, and the solution properties of these complexes have also been described.

Journal Article↗
PubMed1999

Mobilization of the A-kinase N-myristate through an isoform-specific intermolecular switch.

Although the catalytic (C) subunit of cAMP-dependent protein kinase is N-myristylated, it is a soluble protein, and no physiological role has been identified for its myristyl moiety. To determine whether the interaction of the two regulatory (R) subunit isoforms (R(I) and R(II)) with the N-myristylated C subunit affects its ability to target membranes, the effect of N-myristylation and the R(I) and R(II) subunit isoforms on C subunit binding to phosphatidylcholine/phosphatidylserine liposomes was examined. Only the combination of N-myristylation and R(II) subunit interaction produced a dramatic increase in the rate of liposomal binding. To assess whether the R(II) subunit also increased the conformational flexibility of the C subunit N terminus, the effect of N-myristylation and the R(I) and R(II) subunits on the rotational freedom of the C subunit N terminus was measured. Specifically, fluorescein maleimide was conjugated to Cys-16 in the N-terminal domain of a K16C mutant of the C subunit, and the time-resolved emission anisotropy was determined. The interaction of the R(II) subunit, but not the R(I) subunit, significantly increased the backbone flexibility around the site of mutation and labeling, strongly suggesting that R(II) subunit binding to the myristylated C subunit induced a unique conformation of the C subunit that is associated with an increase in both the N-terminal flexibility and the exposure of the N-myristate. R(II) subunit thus appears to serve as an intermolecular switch that disrupts of the link between the N-terminal and core catalytic domains of the C subunit to expose the N-myristate and poise the holoenzyme for interaction with membranes.

Cyclic AMP-Dependent Protein Kinases↗
PubMed1999

Microdecompressive percutaneous endoscopy: spinal discectomy with new laser thermodiskoplasty for non-extruded herniated nucleosus pulposus.

Open spinal discectomy, at times with spinal fusion, is associated with significant local morbidity and long-term convalescence, requires general anesthesia, and involves dissection of muscle, removal of bone, ligament and disc, which are all at greater financial cost. Therefore, the search for a less traumatic spinal discectomy began, including micro-discectomy, and percutaneous techniques and endoscopic discectomy. Lyman Smith reported intradiscal injection of chymopapain in 1964. Onik et al. developed the automated percutaneous discectomy device for continuous aspiration/irrigation of disc tissue in 1985. Hijikata et al also described nucleotomy independently in 1985. In 1986, Ascher and Choy first reported laser discectomy to decrease intradiscal pressure.

Journal Article↗
PubMed1998

Backbone flexibility of five sites on the catalytic subunit of cAMP-dependent protein kinase in the open and closed conformations.

To develop an alternative approach to measure peptidyl backbone flexibility and to expand our understanding of the segmental flexibility of cAMP-dependent protein kinase (cAPK), the effect of protein kinase inhibitor peptide, PKIalpha(5-24), and MgATP on the mobility of fluorescein selectively conjugated to five sites on the catalytic subunit of cAPK was examined. Specifically, five full-length, single-site catalytic subunit mutants (K16C, K81C, I244C, C199A, and N326C) were prepared, and fluorescein maleimide was selectively attached to the side chains of each substituted cysteine or, in the case of the C199A mutant, to the unprotected native C343. The time-resolved anisotropy decay profiles of the five fluorescein maleimide-conjugated mutants were well fit to a biexponential equation. The fast rotational correlation times of the fluorescein conjugates ranged between 1.9 and 2.8 ns and were inversely correlated (r = -0.87) to the averaged crystallographic main-chain atom B factors around each site of conjugation. The slow correlation times ranged between 25 and 28 ns and were about the same magnitude as the value of 21 ns estimated from the Stokes-Einstein equation. The presence of MgATP and PKIalpha(5-24), which induces the closed conformation of cAPK, was associated with a reduction of the fast rotational correlation time of the K81C conjugate, indicating that the peptidyl backbone around K81 is measurably less flexible when the C subunit is in the closed compared with the open conformation. The results suggest (i) that time-resolved fluorescence anisotropy can assess the nanosecond flexibility of short segments of the peptidyl backbone around each site of labeling and (ii) that the substrate/pseudosubstrate binding differentially affects the backbone flexibility of cAPK.

Animals↗
PubMed1996

Mandibular tori, migraine and temporomandibular disorders.

In this study the presence of mandibular tori was related to conditions associated with parafunctional activity. Parafunction in the form of tooth clenching or grinding has been associated with temporomandibular disorders (TMD) and recently migraine. Patients attending a facial pain clinic in Belfast were assessed for the presence of tori and results compared to age and gender matched controls. The findings were that mandibular tori were present significantly more commonly in both migraineurs and TMD patients. The results support an association with parafunction in the aetiology of mandibular tori and suggest that tori are a useful marker of past or present parafunction in some patients.

Adolescent↗
PubMed1995

Gastrin sensitivity of primary human colorectal cancer: the effect of gastrin receptor antagonism.

The purpose of this study was to determine the effect of the gastrin receptor antagonist, CR2093, on basal and gastrin-stimulated growth of primary human colorectal adenocarcinomas and to relate this to gastrin receptor expression. Tumour cells, derived from surgical specimens by enzymatic disaggregation, were grown on matrices of type I collagen and irradiated fibroblasts. Gastrin receptor expression was measured by using a mouse monoclonal antibody directed against the gastrin receptor and an avidin-biotin immunocytochemical method. Increased growth in the presence of gastrin-17 (used at physiological concentrations and as assessed by [3H] thymidine uptake) was shown in 16/34 (47%) tumours. CR2093 significantly reversed this stimulated growth (P < 0.05, one way analysis of variance) in 9/16 (56.3%) of the tumours and inhibited the basal growth of 11/34 (32.4%). Basal growth inhibition was reversed by gastrin-17 in 82% (9/11) of tumours. Gastrin receptor expression was widespread, but was not related to the degree of growth response to gastrin, and there was no significant correlation between intensity of receptor expression and inhibition of basal growth by CR2093. In conclusion, both gastrin-stimulated and basal growth of primary human colorectal can be inhibited by gastrin receptor antagonism, but gastrin receptor expression does not predict the sensitivity of tumours to (i) the proliferative effects of gastrin or (ii) the inhibitory effects of a gastrin receptor antagonist on basal growth. Antigastrin agents may have clinical value in the treatment of gastrin-sensitive colorectal tumours, and gastrin receptor expression may be related to endogenous gastrin production by colorectal tumour cells.

Amino Acids↗
PubMed1995

The dental awareness and needs of a Parkinson's disease population.

The dental awareness and needs of a population with Parkinson's disease were assessed by means of postal questionnaires sent to members of Parkinson's disease societies of Belfast and London. A total of 228 valid replies were received representing a response rate of 31%. Results showed that dental problems were reported often, xerostomia and burning sensation being at least twice that of the general population. Satisfaction with dental care was high although it was significantly reduced in those with loose dentures and burning sensation. The results of this study support a greater participation by dentists in the planning and provision of healthcare for sufferer of Parkinson's disease.

Aged↗
PubMed1995

Occlusal splint prescription in the management of temporomandibular disorders.

The case records of 159 patients who had been treated for temporomandibular disorders at the School of Clinical Dentistry Queen's University of Belfast were analysed retrospectively to determine which type of occlusal splint had been prescribed. Full maxillary occlusal coverage polycarbonate vacuum formed splints were prescribed most frequently, being used in 45% of cases, whilst lower splints were rarely constructed. After treatment 54% were asymptomatic which is slightly greater than that described by others as a placebo effect in splint therapy. This low success rate was, at least, in part attributable to a poor overall management strategy. The study highlights the need for a structured management strategy in treating patients with temporomandibular disorders and suggests a need for continuing postgraduate education in the care of these patients.

Humans↗
PubMed1990

Elevated T cell subpopulations in dental students.

The absolute numbers of circulating white cells and lymphocyte subpopulations were studied in 25 final-year dental students and compared with a control group of 28 medical students. The total lymphocyte count, total T cell numbers (CD3), T helper/inducer (CD4), and T suppressor/cytotoxic (CD8) numbers were significantly elevated in the dental students as compared with the control group. There was no significant difference in the T helper/inducer to T suppressor/cytotoxic cell ratios or the circulating B cell (CD21) and natural killer cell (CD16) numbers between the study and control groups. Patch testing to mercury and mercuric compounds in both the study and control groups showed no evidence of cutaneous hypersensitivity to mercury. The reason for the observed elevations in T cell subpopulations in dental students is not clear. However, one possible explanation is the dental student's occupational exposure to mercury. Further work is underway to examine this possible relationship and it is suggested that dental personnel take adequate measures to reduce their exposure to mercury until the results of these studies are available.

Adult↗