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Biomedical subjects

J Burton

Publications and source records attributed to J Burton.

At least 73 records · Page 4Linked to original sources

Three psychological treatments for bulimia nervosa. A comparative trial.

The specificity and magnitude of the effects of cognitive behavior therapy in the treatment of bulimia nervosa were evaluated. Seventy-five patients who met strict diagnostic criteria were treated with either cognitive behavior therapy, a simplified behavioral version of this treatment, or interpersonal psychotherapy. Assessment was by interview and self-report questionnaire, and many aspects of functioning were evaluated. All three treatments resulted in an improvement in the measures of the psychopathology. Cognitive behavior therapy was more effective than interpersonal psychotherapy in modifying the disturbed attitudes to shape and weight, extreme attempts to diet, and self-induced vomiting. Cognitive behavior therapy was more effective than behavior therapy in modifying the disturbed attitudes to shape and weight and extreme dieting, but it was equivalent in other respects. The findings suggest that cognitive behavior therapy, when applied to patients with bulimia nervosa, operates through mechanisms specific to this treatment and is more effective than both interpersonal psychotherapy and a simplified behavioral version of cognitive behavior therapy.

Adolescent↗

Conformation and inhibitory properties of peptides based on the tissue kallikrein-aprotinin complex.

A series of peptides encompassing the primary binding segment (residues 12-19) of aprotinin has been synthesized and tested for their ability to inhibit porcine pancreatic kallikrein. A minimum sequence of five amino acids spanning residues 12-16 of aprotinin is necessary for inhibition of porcine pancreatic kallikrein. An octapeptide homologous with the binding segment of aprotinin has a Ki-value of 1.2 x 10(-4) M. The solution structure of the octapeptide was studied by one- and two-dimensional NMR methods for comparison with the known structure of the segment of aprotinin that contacts tissue kallikrein. NMR experiments suggest that the peptide is either a random coil or that it samples several conformations on the NMR time scale. Analysis of the molecular dynamics trajectory of the octapeptide also suggests that the peptide is highly flexible. Thus, inhibition by the octapeptide occurs because of its homology with residues 12-19 of aprotinin. Moreover, the absence of a stable solution conformation similar to that of the binding segment of aprotinin is consistent with the 150,000-fold increase in Ki of the octapeptide compared to intact aprotinin.

Amino Acid Sequence↗

Synthetic peptide substrates for the immunoglobulin A1 protease from Neisseria gonorrhoeae (type 2).

Neisseria gonorrhoeae secretes protease which inactive human immunoglobulin A1 (IgA1) by cleavage of specific peptide bonds in the hinge region. The type 2 IgA1 protease (EC 3.4.24.13) is secreted as a 169-kDa precursor which undergoes autoproteolysis at three sites (A, B, and C) to release the 106-kDa active form of the enzyme (J. Pohlner, R. Halter, K. Beyreuther, and T. F. Meyer. Nature [London] 325:458-462, 1987). Synthetic decapeptides consisting of five residues on each side of the three autoproteolytic cleavage sites and their potential pentapeptide catabolites were prepared by solid-phase synthesis. Cleavage of the decapeptides by the type 2 IgA1 protease from N. gonorrhoeae was monitored by high-performance liquid chromatography. Peptides homologous with the amino acid sequences around the B and C sites are cleaved by the IgA1 protease. Amino acid analysis and Edman degradation show that the cleavage products have both the composition and amino acid sequence which would be expected from cleavage at the predicted sites. Km values of 1.35 mM and 3.43 mM and kcat values of 280 pmol/h/U and 439 pmol/h/U for the site B and site C peptides, respectively, were determined. The catalytic efficiency (kcat/Km) for the synthetic substrates is about 10% of that reported for intact IgA1. Cleavage of the peptides is inhibited by IgA1 protease inhibitors such as the tetrapeptide substrate analog inhibitor HRP-48, human colostrum, and a peptide-boronate transition state inhibitor. An extract from an N. gonorrhoeae construct lacking active IgA1 protease failed to cleave the synthetic substrate, while an extract from the control construct which secretes active enzyme completely hydrolyzed the synthetic peptide. Neither the site A peptide nor synthetic decapeptides encompassing cleavage sites in the hinge region of IgA1 are hydrolyzed by IgA1 protease. These are the first synthetic substrates to be reported for any IgA1 protease.

Amino Acid Sequence↗

Transactivation of the transforming growth factor beta 1 (TGF-beta 1) gene by human T lymphotropic virus type 1 tax: a potential mechanism for the increased production of TGF-beta 1 in adult T cell leukemia.

We examined the effect of the human T lymphotropic virus type 1 (HTLV-I) Tax gene product on the human transforming growth factor beta 1 (TGF-beta 1) promoter. Transfection of deleted constructs of the TGF-beta 1 promoter revealed regions homologous with AP-1 binding sites that were required for Tax-induced transactivation of the TGF-beta 1 promoter. In addition, we examined the expression and secretion of TGF-beta in fresh leukemic cells isolated from patients with adult T cell leukemia (ATL) and in HTLV-1-infected T cell lines. We report that fresh leukemic cells from ATL patients constitutively produce high levels of TGF-beta 1 mRNA and secrete TGF-beta 1 but not TGF-beta 2 into the culture medium. In addition, long-term ATL cell lines expressed significant amounts of TGF-beta 1 mRNA as well as detectable levels of TGF-beta 1 protein. These results suggest a role for Tax in the upregulation of TGF-beta 1 in HTLV-I-infected cells.

Cell Line↗

Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor.

Previously, using flow cytometric resonance energy transfer and lateral diffusion measurements, we demonstrated that a 95-kDa protein identified by two monoclonal antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95-kDa protein (p95) was purified and amino acid sequence data were obtained that showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1). The identity of the p95 protein with ICAM-1 was confirmed by sequential immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells. In functional studies, the antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However, these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent T-cell line. Taken together with our previous observations, the present studies suggest that ICAM-1 is in proximity and interacts physically with the high-affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2 receptors by augmenting homotypic T-T-cell interaction, by receptor-directed focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the physically linked cells to the site of lymphocyte function-associated antigen 1-ICAM-1-IL-2 receptor interaction.

Amino Acid Sequence↗

Clinical efficacy of emergency bypass surgery for failed coronary angioplasty.

The clinical and angiographic variables of 26 coronary artery disease patients at the University of Alberta Hospitals requiring emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) were reviewed. Emergency CABG was judged necessary in 2% of 1300 consecutive patients undergoing PTCA. The most frequent indication for an emergency operation was dissection and acute closure of eccentric bend point target lesions associated with clinically severe, unremitting chest pain and ST-T abnormalities suggestive of impending myocardial infarction. The mortality rate for the combined procedures of failed PTCA and CABG was low (3.8%). The incidence of periprocedural infarction was high (61%); it was, however, associated with a benign clinical course and electrocardiographic evidence of significant reversibility of acute phase damage. Thus, overall, emergency CABG appears to be a clinically efficacious treatment for patients with threatened or impending infarction as a consequence of failed PTCA.

Aged↗

Herpes ophthalmicus.

Always ensure that patient consent is obtained before any type of photography is undertaken, as the patient has the right to decide what is to happen to the images.

Herpes Zoster Ophthalmicus↗

Medial mental sinus.

Lighting is an important tool of the photographer, since it can be used to create shadows to highlight the condition under study. For photographs such as the one shown, oblique lighting is essential.

Dental Fistula↗

In vivo inhibition of tissue kallikreins by kininogen sequence analogue peptides.

Kininogen sequence analogs containing amino acid residues around the Arg-Ser cleavage site of bovine kininogens were prepared with bulky aliphatic residues in P3 position. KKI-7 (containing a cyclohexylacetyl group) and KKI-8 (containing an adamantaneacetyl group) both inhibited human urinary kallikrein (HUK) with Ki of 4 microM. These inhibitors were 40 times more potent than the corresponding peptide containing the naturally occurring Pro at P3 and were one-seventh as susceptible to hydrolysis by HUK. Rat submaxillary kallikrein (RSK) and porcine pancreatic kallikrein (PPK) were also inhibited by these analogs. Both analogs were poor inhibitors of human plasma kallikrein, while their capacity to inhibit bovine trypsin was 1/3 and 1/17, respectively, that to inhibit HUK. In a rat blood flow study, KKI-7 infusion depressed the response to injected RSK. The response gradually returned toward normal 30 to 60 min after the infusion was terminated. Blood flow increase of dog jejunal artery in response to infused PPK was blunted by the simultaneous local infusion of Trasylol, KKI-7, or KKI-8, whereas these infusions did not alter the response to infused bradykinin. The vehicle infusion did not attenuate the response either to PPK or bradykinin. These analogs appear to have greater specificity and stability than those previously developed and to be appropriate for the in vivo inhibition of glandular kallikreins.

Amino Acid Sequence↗

Conformational preferences of sequential fragments of the hinge region of human IgA1 immunoglobulin molecule: II.

The mean solution conformation of tetrapeptide fragments of the hinge region of human IgA1 molecule was investigated by CD and 13C-NMR methods. Distinct conformational differences for the partial sequences were found. Tetrapeptides with the Thr-Pro-Ser-Pro sequence were found to show a clear preference for the beta-turn conformation. Conformational equilibria of these peptides are only slightly affected by acetylation or pH changes. In the case of Pro-Thr-Pro-Ser tetrapeptides conformational equilibria are dominated by unordered forms.

Amino Acid Sequence↗

Tetrapeptide inhibitors of the IgA1 proteinases from type I Neisseria gonorrhoeae.

The six series of unique tetrapeptides and their blocked N-acetyl, C-amide, and N-acetyl-C-amide analogues which comprise the hinge region of human IgA1 (Ser224 to Ser240) have been synthesized and tested as inhibitors of the type 1 IgA1 proteinase elaborated by Neisseria gonorrhoeae (EC 3.4.24.13). Most series had at least one member with an IC50 value less than 1 mM. The most effective inhibitors came from the series Ser-Thr-Pro-Pro (P4-P1) and Pro-Thr-Pro-Ser (P1-P3'). One member from each series had an IC50 value in the low microM range. Magnetic resonance studies (Siemion, I. Z.; et al. Biophys. Chem. 1988, 31, 35) indicate that the various tetrapeptide series appear to have different preferred solution conformations. However, these do not appear to be correlated with affinity for the neisserial proteinase. The most effective inhibitors tend to have a threonine residue adjacent to the N-terminus and the P1 or P1' residues at either the N- or the C-terminus. These relationships are not exclusive however, as other inhibitors, which do not meet these criteria, bind reasonably well. The most effective substrate analogues outlined here are about one-half the size and bind to the neisserial proteinase 2 orders of magnitude more tightly than previously reported inhibitors.

Amino Acid Sequence↗

Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response.

Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.

Adolescent↗

The amino-acid residues on the C-terminal side of the cleavage site of angiotensinogen influence the species specificity of reaction with renin.

The N-terminal sequences of human and canine angiotensinogen and two hybrid sequences were synthesized and used to determine whether the species specificity of renin is influenced by amino-acid residues adjacent to the cleavage site. kcat/Km for the generation of angiotensin I from the N-terminal tridecapeptide of human angiotensinogen by canine renin is 0.37% of that observed when the N-terminal tetradecapeptide from canine angiotensinogen is used as a substrate. Replacement of the valine residue at P'1 in the human tridecapeptide with the leucine residue from the canine sequence triples kcat and improves Km 4-fold. Replacement of isoleucine residue at P'2 with the valine residue from the canine sequence enhances Km 8-fold. Substitution of the histidine residue at P'3 with the tyrosine serine sequence of canine angiotensinogen increases kcat an order of magnitude. Results obtained with the synthetic substrate are similar to those observed with the protein substrates. Canine renin does not cleave human angiotensinogen. Also, kcat/Km of canine renin for its homologous substrate is about 6-times greater than the kcat/Km value for human renin acting on human angiotensinogen.

Amino Acid Sequence↗

Conformational preferences of the sequential fragments of the hinge region of the human IgA1 immunoglobulin molecule.

The mean solution conformation of tetrapeptide fragments spanning the hinge region of human IgA1 was investigated by CD and 13C-NMR methods. Distinct conformational differences for the partial sequences of IgA1 were found. In a series of tetrapeptides having the Thr-Pro-Pro-Thr sequence, the Pro-Pro fragment was ordered to the structure of a type II polyproline helix, but with unordered forms prevailing in the equilibria. In the case of the Pro-Pro-Thr-Pro sequence, a distinct preference for the beta-turn conformation was found. Acetylation of this tetrapeptide shifts the equilibrium towards unordered forms containing some elements of the type II polyproline helix. The peptide Thr-Pro-Ser-Pro exists predominantly in the beta-turn conformation whereas Pro-Ser-Pro-Ser-NH2 has, for the most part an unordered conformation.

Amino Acid Sequence↗