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Biomedical subjects

F Burns

Publications and source records attributed to F Burns.

At least 19 recordsLinked to original sources
PubMed2005

Factors associated with HIV testing among black Africans in Britain.

OBJECTIVE: To describe the factors associated with HIV testing among heterosexual black Africans aged 16-44 years living in Britain. DESIGN: We analysed data from the second British National Survey of Sexual Attitudes and Lifestyles (Natsal 2000)-a stratified national probability sample survey conducted between 1999-2001. Data from Natsal's main and ethnic minority boost (EMB) samples were analysed. Multivariate analysis was performed using complex survey functions to account for the clustered, stratified, and differential selection probabilities inherent within the survey. RESULTS: A total of 385 (216 women and 169 men) black African respondents were included in the study. 44.0% women and 36.4% men reported ever having had an HIV test. In univariate analysis, HIV testing was associated with being born abroad (OR 3.63), having a new partner(s) from abroad in past 5 years (OR 2.88), and attending a GUM clinic (OR 3.27) among men; and educational attainment (OR 3.50), perception of "not very much" personal risk of HIV (OR 2.75), and attending a GUM clinic (OR 2.91) among women. After adjusting for potential confounders, an increased likelihood of HIV testing was associated with being in the United Kingdom less than 5 years relative to being UK born (adjusted OR 9.49), and ever attending a GUM clinic (adj OR 5.53), for men; and educational attainment (adj OR 4.13), and low perception of HIV risk (adj OR 2.77) for women. CONCLUSIONS: Black Africans appear to have relatively high rates of HIV testing reflecting, at least partially, awareness of risk behaviours and potential exposure to HIV. Nevertheless, there remains substantial potential for health gain and innovative approaches are required to further increase timely HIV testing.

Adolescent↗
PubMed2001

Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.

INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients). OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome. METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses. RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features. CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.

Adult↗
PubMed2001

Sweet's syndrome in the setting of CD34-positive acute myelogenous leukemia treated with granulocyte colony stimulating factor: evidence for a clonal neutrophilic dermatosis.

BACKGROUND: Sweet's syndrome in the setting of hematologic dyscrasias can be categorized into paraneoplastic-associated SS, drug-induced SS, and SS with leukemia cutis. Apart from those cases demonstrating concomitant leukemic infiltrates, it has been surmised that SS is a reactive phenomenon induced by a specific cytokine milieu. METHODS: The authors present a patient with CD34+ acute myelogenous leukemia (AAML) who developed SS in the setting granulocyte colony stimulating factor (GCSF) therapy. Routine light microscopy and molecular studies were carried on the patient's skin biopsy specimen and post-treatment marrow. An X inactivation assay for clonality was employed. RESULTS: Routine light microscopic examination revealed differentiated myeloid precursors including myelocytes and metamyelocytes within the subcutis; myeloblasts were not identified. In addition, in the overlying skin, features typical of SS were observed. The neutrophils demonstrated dysplastic features including hypolobation compatible with a Pseudo Pelger-Huet anomaly. X inactivation studies showed clonality both within her post-treatment marrow and skin biopsy specimen. CONCLUSIONS: Sweet's syndrome developing in CD34+ AML patients following GCSF therapy likely reflects therapy induced differentiation of sequestered leukemic cells, hence indicative of a clonal neutrophilic dermatosis.

Acute Disease↗
PubMed2000

Sexual maturation and control issues among sexually abused and non-abused anorexia patients.

OBJECTIVES: To assess the relative salience of the maintenance of control and the avoidance of sexual maturation as sources of motivation for maintaining pathological eating behaviours among sexually abused anorexic patients. DESIGN/METHODS: A two-factor mixed experimental design was employed. Three independent groups (sexually abused anorexics (N = 12); non-abused anorexics (N = 9); non-anorexic/non-abused controls (N = 12)) constituted the between-subjects factor. Allocation to abuse/non-abuse group was dependent upon replies to a questionnaire-based measure of unwanted sexual experience. The within-subjects factor comprised three conditions in which words of various colours were presented to participants for colour-naming (Stroop, 1935). The conditions were represented by lists of neutral words, sexual maturation words, and control-related words. Two trials were carried out in each condition and mean response times were measured. RESULTS: Within-group analyses revealed that interference was greater from sexual maturation words than from control-related words among the sexually-abused anorexics, but of equal magnitude among non-abused counterparts. Between-groups analyses found that abused patients experienced marginally greater cognitive interference from sexual maturation words than the non-abused patients. CONCLUSION: Theoretically, support is offered for elaborated schematic models of cognitive processing. Clinically, treatment interventions may need to pay particular attention to issues of sexual maturation among sexually abused anorexic patients.

Adolescent↗
PubMed1998

Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message.

During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Identification of key amino acids in a conserved cGMP-binding site of cGMP-binding phosphodiesterases. A putative NKXnD motif for cGMP binding.

cGMP-binding phosphodiesterases contain two kinetically distinct cGMP-binding sites (a and b), and each site contains a conserved N(K/R)XnFX3DE sequence. N276A, K277A, K277R, D289A, and E290A mutants in the N276KX7FX3DE290 sequence of site a (higher affinity site) of bovine cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE or PDE5A) were expressed in High Five cells and purified. The cGMP-binding affinities of three mutants [K277A (Kd approximately 12 microM), D289A (Kd approximately 24 microM), and N276A (Kd approximately 60 microM)] were decreased in comparison with wild-type enzyme (Kd = 1.3 microM), which suggested an important role for Asn276, Lys277, and Asp289 in cGMP binding. These residues could be presented as a putative NKXnD motif, and their functions were predicted based on analogy with the canonical NKXD motif in GTP-binding proteins. No marked differences in catalytic functions such as specific activity, Km for cGMP, and IC50 for zaprinast or 3-isobutyl-1-methylxanthine were found among wild-type and mutant cGB-PDEs. This suggested that cGMP binding to site a does not influence the catalytic properties of cGB-PDE.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

The identification of apparently novel cyclic AMP and cyclic GMP phosphodiesterase activities in guinea-pig tracheal smooth muscle.

Phosphodiesterase (PDE) activities that were capable of hydrolysing cyclic AMP (Km = 6.8 +/- 2 microM) and cyclic GMP (Km = 6.7 +/- 1.6 microM) were isolated from tracheal smooth muscle. These enzyme(s) activities were insensitive to stimulation by calcium/calmodulin and to inhibition by cyclic GMP, rolipram (type IV inhibitor) and siguazodan (type III inhibitor). Zaprinast was a relatively poor inhibitor of both cyclic AMP and cyclic GMP hydrolysis (IC50 = 46 +/- 9 microM and 45 +/- 14 microM respectively). These results suggest that tracheal smooth muscle may contain an apparently novel PDE. However, KCl (30 mM) which facilitates calcium entry in cells, depressed bradykinin-stimulated intracellular cyclic AMP formation, suggesting that the type I PDE may be functionally present. We suggest that considerable caution be exercised in identifying apparently novel PDE isoforms.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Lung phosphodiesterase isoenzymes.

The distinct phosphodiesterase isoenzyme activities in guinea-pig lung were identified and characterised. We demonstrate that protein kinase A catalyses the activation of lung Type V cyclic GMP phosphodiesterase. This occurs via a marked change in the Vmax for cyclic GMP hydrolysis. The sensitivity of the activated PDE to inhibition by zaprinast is also markedly reduced (zaprinast inhibits in PDE activity via a mixed mechanism). We suggest that activation of the PDE by protein kinase A involves a mechanism that leads to alteration in the regulatory action of a non-catalytic cyclic GMP binding site.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Interaction of the catalytic subunit of protein kinase A with the lung type V cyclic GMP phosphodiesterase: modulation of non-catalytic binding sites.

We have previously demonstrated that the catalytic sub-unit of protein kinase A can catalyse a potent activation of partially purified Type V cyclic GMP-specific phosphodiesterase activity (Burns et al., 1992, Biochem. J. 283, 487-491). We now demonstrate that this phosphodiesterase most likely has a sub-unit mass of 90kDa, based upon 32P-cyclic GMP photo-affinity labelling, that activation of the phosphodiesterase does not require the prior binding of cyclic GMP to the phosphodiesterase, and that alkaline phosphatase can reverse the protein kinase A-dependent activation of phosphodiesterase activity. Zaprinast is a mixed inhibitor of non-activated cyclic GMP phosphodiesterase activity. However, inhibition of the protein kinase A-activated phosphodiesterase is competitive. These results suggest that protein kinase A can modulate the inhibitory effects of zaprinast via perturbations of a non-catalytic binding site.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

The catalytic subunit of protein kinase A triggers activation of the type V cyclic GMP-specific phosphodiesterase from guinea-pig lung.

The type V cyclic GMP phosphodiesterase was partially purified from the high-speed supernatant of guinea-pig lung. The isoenzyme displayed linear kinetics for cyclic GMP hydrolysis, with Km = 2.2 +/- 0.2 microM and Vmax. = 1.2 +/- 0.08 nmol/min per mg. The selective type V phosphodiesterase inhibitor Zaprinast inhibited cyclic GMP hydrolysis with IC50 (concn. giving 50% inhibition) = 0.45 +/- 0.08 microM. Isobutylmethylxanthine promoted a 3-fold increase in the binding of cyclic GMP to the isoenzyme. The addition of the catalytic subunit of protein kinase A to an activation cocktail containing the partially purified type V phosphodiesterase resulted in a marked increase in Vmax. for cyclic GMP hydrolysis (approximately 10-fold at 40 units of protein kinase A). We have suggested that protein kinase A triggers phosphorylation of the phosphodiesterase, which results in activation of phosphodiesterase activity. In addition, the sensitivity to inhibition by Zaprinast is severely decreased (the IC50 for inhibition is 7.5 +/- 1.1 microM), suggesting that the potency of phosphodiesterase inhibitors is effected by phosphorylation of the enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Differential effects of electrical stimulation, blockade of neuronal amine uptake and activation of alpha 2-adrenoceptors on the release of endogenous noradrenaline and 5-hydroxytryptamine from the isolated rat pineal gland.

Isolated rat pineal glands were incubated in vitro and the release of endogenous noradrenaline or 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was determined by HPLC with electrochemical detection. In the absence of test drugs, the spontaneous outflow of noradrenaline was about 10 fmol/10 min and electrical stimulation (5 Hz, 1500 pulses) evoked the release of about 70 fmol noradrenaline. Nomifensine enhanced the spontaneous outflow of noradrenaline about threefold and the electrically evoked release of noradrenaline about sixfold. In the presence of nomifensine, the alpha 2-adrenoceptor antagonist yohimbine markedly increased the electrically evoked release of noradrenaline, whereas the alpha 1-adrenoceptor antagonist prazosin had no effect. Clonidine inhibited the electrically evoked release of noradrenaline by about 65%, and this was antagonized by yohimbine in a competitive manner. In the absence of drugs, the initial spontaneous outflow of 5-HT was (compared with noradrenaline) very high 64 pmol/10 min). It declined by 80% within 1 h of incubation in vitro. The outflow of 5-HIAA amounted initially to 38 pmol 10 min and declined by 40% within 1 h of incubation. Addition of L-tryptophan (10 mumol/l) after 1 h of incubation in vitro largely enhanced the outflow of 5-HT and 5-HIAA within 30 min of incubation (about ten- and fourfold, respectively). When L-tryptophan was present from the onset of incubation the initial outflow of 5-HT and 5-HIAA was only slightly elevated, but the decline was largely attenuated. Neither omission of calcium nor addition of nomifensine, clonidine or yohimbine significantly affected the spontaneous outflow of 5-HT or 5-HIAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease.

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.

Adult↗
PubMed1989

Frequency-dependent effects of activation and inhibition of protein kinase C on neurohypophysial release of oxytocin and vasopressin.

Isolated rat neurohypophyses were superfused in vitro and the release of vasopressin and oxytocin into the medium was determined by specific radioimmunoassays. Hormone secretion was increased by electrical stimulation of the pituitary stalk at different frequencies. The effects of several phorbol esters, known to activate phorbol 12,13-dibutyrate, PDB) or not to affect (4 alpha-phorbol 12,13-dideconate and phorbol 12-monoacetate) protein kinase C, and of the direct protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) were tested. Electrical stimulation with 450 pulses caused the release of about 45 microU vasopressin and 55 microU oxytocin, when a frequency of 3 Hz was applied, and of about 500 microU vasopressin and oxytocin, when a frequency of 15 Hz was used. PDB (1 mumol/l) increased the release of vasopressin evoked by 15 Hz stimulation maximally by about 40-50% and that evoked by 3 Hz stimulation by about 150%. The release of oxytocin evoked by 15 Hz stimulation was increased by about 150% and that evoked by 3 Hz stimulation by about 400-500% in the presence of PDB. Both inactive phorbol esters had no effects on the evoked release of vasopressin or oxytocin. The effect of PDB on the release of vasopressin and oxytocin was blocked by H7 (10-30 mumol/l). H7 (30 mumol/l) alone reduced the release of vasopressin evoked by stimulation at 15 Hz by 50%. The release of oxytocin was not significantly affected by H7. In the presence of naloxone (1 mumol/l) the release of oxytocin evoked by 3 and 15 Hz stimulation was increased by about 175 and 105%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗