Computed tomographic enterography adds information to clinical management in small bowel Crohn's disease

Background: CT enterography yields striking findings in the bowel wall in Crohn's disease. These images may help to evaluate whether small bowel narrowing results from active disease requiring anti-inflammatory therapy. However, the clinical relevance of these images is unknown. It is also not known if these radiologic findings correlate with objective biomarkers of inflammation. Methods: In a blinded and independent evaluation, IBD subspecialty gastroenterologists reviewed clinical data, and CT radiologists reviewed CT enterography scans of 67 consecutive patients with Crohn's disease and suspicion of either small bowel inflammation or stricture. Comparisons were made between (1) clinical and radiologic assessments of inflammation and stricture, (2) clinical assessments before and after computed tomographic enterography (CTE) reports were revealed, and (3) radiologic findings and objective biomarkers of inflammation. Results: (1) Individual CTE findings correlated poorly (Spearman's rho < 0.30) with clinical assessment; (2) clinicians did not suspect 16% of radiologic strictures, and more than half the cases of clinically suspected strictures did not have them on CTE; (3) CTE data changed clinicians' perceptions of the likelihood of steroid benefit in 41 of 67 cases; (4) specific CTE findings correlated with CRP, and a distinct set of CTE findings correlated with ESR in the subset of patients who had these biomarkers measured. Conclusions: CTE seems to add unique information to clinical assessment, both in detecting additional strictures and in changing clinicians' perceptions of the likelihood of steroids benefiting patients. The biomarker correlations suggest that CTE is measuring real biologic phenomena that correlate with inflammation, providing information distinct from that in a standard clinical assessment. (Inflamm Bowel Dis 2006)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55965/1/20013_ftp.pd

Site and risk assessment in Providence, Rhode Island

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2000."June 2000."Includes bibliographical references (leaves 86-88).by Marnie A. Bell and Beth A. Manoogian.M.Eng

Structure-activity relationships of FMRF-NH2 peptides demonstrate A role for the conserved C terminus and unique N-terminal extension in modulating cardiac contractility.

FMRF-NH2 peptides which contain a conserved, identical C-terminal tetrapeptide but unique N terminus modulate cardiac contractility; yet, little is known about the mechanisms involved in signaling. Here, the structure-activity relationships (SARs) of the Drosophila melanogaster FMRF-NH2 peptides, PDNFMRF-NH2, SDNFMRF-NH2, DPKQDFMRF-NH2, SPKQDFMRF-NH2, and TPAEDFMRF-NH2, which bind FMRFa-R, were investigated. The hypothesis tested was the C-terminal tetrapeptide FMRF-NH2, particularly F1, makes extensive, strong ligand-receptor contacts, yet the unique N terminus influences docking and activity. To test this hypothesis, docking, binding, and bioactivity of the C-terminal tetrapeptide and analogs, and the FMRF-NH2 peptides were compared. Results for FMRF-NH2 and analogs were consistent with the hypothesis; F1 made extensive, strong ligand-receptor contacts with FMRFa-R; Y → F (YMRF-NH2) retained binding, yet A → F (AMRF-NH2) did not. These findings reflected amino acid physicochemical properties; the bulky, aromatic residues F and Y formed strong pi-stacking and hydrophobic contacts to anchor the ligand, interactions which could not be maintained in diversity or number by the small, aliphatic A. The FMRF-NH2 peptides modulated heart rate in larva, pupa, and adult distinctly, representative of the contact sites influenced by their unique N-terminal structures. Based on physicochemical properties, the peptides each docked to FMRFa-R with one best pose, except FMRF-NH2 which docked with two equally favorable poses, consistent with the N terminus influencing docking to define specific ligand-receptor contacts. Furthermore, SDNAMRF-NH2 was designed and, despite lacking the aromatic properties of one F, it binds FMRFa-R and demonstrated a unique SAR, consistent with the N terminus influencing docking and conferring binding and activity; thus, supporting our hypothesis

SDNAMRF-NH₂ applied to heart.

<p>The effect of the analog SDNAMRF-NH₂ on heart rate is reported as mean values ± S.E.M.</p

FMRF-NH₂ docked to FMRFa-R yielded two best poses.

<p>Two best poses (A and B) were generated in docking FMRF-NH₂ to FMRFa-R. Contacts made between the amino acids in FMRF-NH₂ are shown as F1 (orange), M (green), R (red), and F4 (blue) and the receptor, FMRFa-R, whose transmembrane regions are labeled TM# where # is 1–7. The C-terminal F was amidated, -NH₂.</p

FMRF-NH₂ applied to heart.

<p>The effect of the conserved tetrapeptide FMRF-NH₂ on heart rate is reported as mean values ± S.E.M. The effects are shown in adult (A), pupal (B), and larval (C) heart.</p

Cardioexcitatory effects of a <i>D. melanogaster</i> FMRF-NH₂ analog ^{a, b}.

a<p>The effects of SDNAMRF-NH₂ on adult heart are reported as mean values ± S.E.M. calculated as percent increase in heart rate with p values relative to saline.</p>b<p>Basal heart rate is equal to 100%.</p

YMRF-NH₂ ligand-receptor contact sites ^a.

a<p>One-letter amino acid codes followed by 1–4 are in the peptide; other numbers are in the receptor.</p

SDNAMRF-NH₂ docked to FMRFa-R.

<p>Contacts between the amino acids in SDNAMRF-NH₂ are shown as S (brick red), D (tan), N (yellow), A (sky blue), M (green), R (red), and F7 (blue) and the receptor, FMRFa-R, whose transmembrane regions are labeled TM# where # is 1–7. The C-terminal F was amidated, -NH₂.</p

WMDF-NH₂ docked to CCK-R1.

<p>Contacts between the amino acids inWMDF-NH₂ are shown as W (purple), M (green), D (brown), and F (dark blue) and the receptor, FMRFa-R, whose transmembrane regions are labeled TM# where # is 1–7. The C-terminal F was amidated, -NH₂.</p