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Biomedical subjects

D Britton

Publications and source records attributed to D Britton.

13 recordsLinked to original sources

Growth factor signalling networks in breast cancer and resistance to endocrine agents: new therapeutic strategies.

Recent evidence demonstrates that growth factor networks are highly interactive with the estrogen receptor (ER) in the control of breast cancer growth and development. As such, tumor responses to anti-hormones are likely to be a composite of the ER and growth factor inhibitory activity of these agents, with alterations/aberrations in growth factor signalling providing a mechanism for the development of anti-hormone resistance. In this light, the current article focuses on illustrating the relationship between growth factor signalling and anti-hormone failure in our in-house tumor models of breast cancer and describes how we are now beginning to successfully target their actions to improve the effects of anti-hormonal drugs and to block aggressive disease progression.

Breast Neoplasms↗

Isomorphism and pseudosymmetry in 2,6-dichloro- and 2, 6-dibromobenzonitrile.

The title compounds are isomorphous, with two half-molecules in the asymmetric unit of a monoclinic unit cell in the space group C2/m. For the chloro compound: a = 18.0525 (8), b = 20.7374 (10), c = 3. 8334 (2) A, beta = 101.143 (1) degrees; for the bromo compound: a = 18.2269 (15), b = 21.349 (2), c = 3.9663 (3) A, beta = 101.446 (2) degrees. The dominant intermolecular interactions are between halogen atoms rather than between halogen and nitrile, as is the case in the corresponding 2,4,6-trihalobenzonitriles. The molecules pack into layers with a fourfold pseudosymmetry. The pseudosymmetry appears to be the consequence of halogen-halogen intermolecular interactions.

Journal Article↗

Two-dimensional packing and pseudosymmetry.

It is possible to understand, or at least rationalize, the occurrence of pseusosymmetry elements in some crystals as a consequence of a higher symmetry in a two-dimensional layer being obscured by the three-dimensional packing of the layers. Six examples, including both simple compounds and co-crystals and involving six different symmetries, are described.

Journal Article↗

2,4,6-Trichlorophenylisonitrile and 2,4,6-trichlorobenzonitrile

The molecular structures of the title compounds, 2,4, 6-trichlorophenylisonitrile (IUPAC name: 2,4,6-trichlorophenyl isocyanide), C(7)H(2)Cl(3)N, and 2,4,6-trichlorobenzonitrile, C(7)H(2)Cl(3)N, are normal. The two structures are not isomorphous, but do contain similar two-dimensional layers in which pairs of molecules are held together by pairs of Cl.CN [3.245 (3) A] or Cl.NC [3.153 (2) A] interactions. The two-dimensional isomorphism is lost through different layer-stacking modes.

Journal Article↗

A randomized trial of winged Vialon cannulae and metal butterfly needles.

The purpose of this parallel randomized study was to evaluate whether subcutaneous infusion sites initiated with winged vialon cannulae would have fewer skin reactions and longer site duration than metal butterfly needles and reduce needlestick injuries to staff. Data were collected on 42 hospice inpatients from the time of insertion of the first needle or cannula to the time of the first replacement of that device. A non-parametric survival plot for time (Kaplan-Meier method) was conducted and the survival time to replacement of the Vialon cannula was found to be longer than the metal butterfly needle. During the study period there were a total of four needlestick injuries to staff from metal butterfly needles. The authors conclude that Vialon cannulae reduce the frequency of site changes and are safer for staff to use because of the reduced risk of needlestick injuries.

Accidents, Occupational↗

Packing similarities of three isosteric molecules: 4,5-dichlorophthalic anhydride, 4,5-dibromophthalic anhydride and 5,6-dichlorobenzfurazan 1-oxide, including three polymorphs of 5,6-dichlorobenzfurazan 1-oxide.

4,5-Dichlorophthalic anhydride (CPA) lies on a twofold axis in space group C2/c; the molecules pack as stacks of two-dimensional sheets. Polymorph A of 5,6-dichlorobenzfurazan 1-oxide (CBF; systematic name 5,6-dichloro-2,1,3-benzoxadiazole 1-oxide) is isomorphous with CPA with disordered CBF molecules being pseudo-isosteric with the CPA molecule. Polymorph C of CBF has similar unit-cell dimensions but the arrangement of the molecules in the cell is different. 4,5-Dibromophthalic anhydride occurs in space group P1; in a structure derived from the CPA structure. The four structures all have similar two-dimensional sheets of molecules, but differ, in addition to the disorder of the CBF molecules, in the stacking of successive sheets. There are three polymorphs of 5,6-dichlorobenzfurazan 1-oxide. In all three the molecules are disordered about twofold or pseudo-twofold axes. In all three the molecules form chains involving similar Cl.O contacts along the direction of the twofold axis. In polymorphs A and C these chains form virtually identical two-dimensional sheets with inter-chain C-H.O, C-H.N and Cl.Cl contacts, but with different stacking arrangements between the sheets. In polymorph B the chains are associated in face-to-face pairs with the same face-to-face overlap as in A, at an average distance of 3.42 Å compared to an average distance of 3.38 Å in A (cf. Table 8); there are no two-dimensional sheets.

Journal Article↗

Tris[(2-pyridinium)methyl]amine perchlorate.

Nitrilotrismethylenetri-2-pyridinium perchlorate, C18H21N4(3+).3C1O4-, Mr = 591.74, cubic, P2(1)3, a = 13.289 (3) A, V = 2347 (2) A 3, Z = 4, Dx = 1.675 (2) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 4.60 cm-1, F(000) = 1216, T = 189 (3) K, R = 0.056 for 1073 unique observed reflections with I greater than sigma(I). All four ions lie on threefold axes. The perchlorate ions are nearly regular tetrahedra. The bond lengths and angles in the ions are normal. As the name implies, the cation is protonated on the pyridine N atoms and not on the amine N atom. Each H atom attached to an N atom is part of a three-centered hydrogen bond in which the H-atom acceptors are O atoms on two different perchlorate ions.

Models, Molecular↗

Structures of N-acetylbenzamide, N-propionylbenzamide and N-butyrylbenzamide and analysis of imide hydrogen-bond patterns.

N-Acetylbenzamide, C9H9NO2 (I) Mr = 163.18, orthorhombic, Pbca, a = 8.990 (2), b = 9.208 (3), c = 19.619 (3) A, V = 1624 (1) A3, Z = 8, Dx = 1.335 (1) g cm-3, lambda(Mo K alpha) = 0.710569 A, mu = 0.89 cm-1, F(000) = 688, T = 295 K, R = 0.031 for 865 observed reflections. N-Propionylbenzamide, C10H11NO2 (II), Mr = 177.20, monoclinic, P2(1)/c, a = 10.485 (2), b = 23.236 (4), c = 8.132 (2) A, beta = 108.43 (2) degrees, V = 1880 (1) A3, Z = 8, Dx = 1.252 (1) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.82 cm-1, F(000) = 752, T = 297 K, R = 0.044 for 1407 observed reflections. N-Butyrylbenzamide, C11H13NO2 (III), Mr = 191.23, monoclinic, P2(1)/n, a = 8.270 (4), b = 12.600 (3), c = 10.459 (3) A, beta = 108.16 (3) degrees, V = 1040 (1) A3, Z = 4, Dx = 1.221 (1) g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.79 cm-1, F(000) = 408, T = 298 K, R = 0.038 for 1060 observed reflections. Compound (I) crystallizes in the Z,Z(trans-trans) conformation in chains linked by N-H...O hydrogen bonds. (I): N...O = 2.910 (2) A, NH...O = 170 (3) degrees. Compounds (II) and (III) crystallize in the E,Z(cis-trans) conformation and are linked by N-H...O hydrogen bonds forming eight-membered ring dimers. (II): N...O = 3.019 (4) A, NH...O = 167 (3) degrees and N...O = 2.982 (4) A, NH...O = 170 (3) degrees; (III): N...O = 2.990 (2) A, NH...O = 165 (2) degrees.

Benzamides↗

A dye-photosensitized reaction that generates stable protein-protein crosslinks.

Irradiation of fibrinogen with visible light for 30 s in the presence of 1-1000 microM fluorescein was found to crosslink fibrinogen both inter- and intramolecularly. Optimum crosslinking was achieved at dye concentrations of around 100 microM and the amount of crosslinking was shown to increase with pH. Crosslinking was inhibited in the presence of 50 microM tryptophan or tyrosine and enhanced in the presence of 5 mM histidine. Twice as much crosslinking was found to take place under anaerobic conditions. These observations are consistent with a dye-photosensitized reaction following the hydrogen abstraction pathway. The subunits of eukaryotic ribosomes and those of phosphorylase a were also crosslinked by the method described.

Amino Acids↗

Augmented pituitary corticotropin response to a threshold dosage of human corticotropin-releasing hormone in depressives pretreated with metyrapone.

We studied pituitary corticotropin response to exogenous corticotropin-releasing hormone infusion and attempted to control for the confounding effect of variable serum cortisol levels between depressed and control subjects. If metyrapone was given during the time of day when hypothalamic pituitary adrenal activity was otherwise low, the relative increase in the corticotropin concentration was small. Pituitary response to exogenous corticotropin-releasing hormone can be defined under conditions in which the amount of glucocorticoid-mediated negative feedback present at the level of the pituitary gland is equal in all subjects. When the ambient cortisol level was equalized (and suppressed) in all subjects at the time of study with a threshold dosage of corticotropin-releasing hormone, we found an augmented response to corticotropin-releasing hormone in depressives. This raises the possibility that either increased pituitary sensitivity to corticotropin-releasing hormone or an increased intracellular pool of corticotropin is available for release in subjects with major depressive illness.

Adrenocorticotropic Hormone↗

Elective and emergency surgery for colorectal cancer in a district general hospital: impact of surgical training on patient survival.

A total of 640 patients were studied retrospectively after surgery for colorectal cancer over a 5-year period at a district general hospital. The complications, perioperative survival figures, and 5-year survival figures were recorded with particular reference to the grade of surgeon carrying out the original operation. The number and type of complications were similar for consultants and for surgeons-in-training with the exception of operative injury to the ureters and postoperative anastomotic strictures, which were more common in cases operated on by consultants. Perioperative mortality rates were similar after elective and emergency operations, but emergency surgery was associated with a significant increase in mortality when compared with elective surgery if the operation was undertaken by a trainee. Although the 5-year survival rate rose when a consultant surgeon carried out the original operation, the difference was not significant.

Adult↗

Crystal structures of a family of silver cyanide complexes of thiourea and substituted thioureas.

The syntheses and crystal structures of a family of silver cyanide complexes of thiourea and substituted thioureas are reported. The sulfur ligands include thiourea (tu), 1-methyl-2-thiourea (mtu), 1,3-dimethyl-2-thiourea (dmtu), 1,1,3,3-tetramethyl-2-thiourea (tmtu), and 2-imidazolidinethione (N,N'-ethylenethiourea, etu). Synthesis was effected by dissolving AgCN in an aqueous solution of ligand. Two different complexes were obtained by the reaction of AgCN with tu. Complex 1a: (AgCN)(tu), monoclinic, P2(1)/c, a = 9.3851 (6) A, b = 8.2782 (5) A, c = 7.1178 (5) A, beta = 94.591 (1) degree, and Z = 4. Complex 1b: (AgCN)(tu)2, triclinic, P1, a = 7.9485 (14) A, b = 9.431 (2) A, c = 12.771 (2) A, alpha = 85.695 (3) degrees, beta = 81.210 (4) degrees, gamma = 77.987 (2) degrees, and Z = 4. Complex 2: (AgCN)(mtu), triclinic, P1, a = 4.113 (2) A, b = 9.472 (4) A, c = 9.679 (4) A, alpha = 113.918 (5) degrees, beta = 98.188 (6) degrees, gamma = 97.725 (6) degrees, and Z = 2. Complex 3 (AgCN)2(dmtu)2, monoclinic, P2(1)/m, a = 7.1482 (7) A, b = 14.776 (2) A, c = 7.3366 (7) A, beta = 92.418 (2) degrees, and Z = 2. Complex 4: (AgCN)(tmtu), orthorhombic, P2(1)2(1)2(1), a = 8.823(6) A, b = 10.209 (2) A, c = 10.362 (2) A, and Z = 4. Complex 5: (AgCN)2(etu)2, triclinic, P1, a = 6.8001 (2) A, b = 8.6154 (1) A, c = 13.4747 (3) A, alpha = 71.720 (1) degree, beta = 79.906 (1) degree, gamma = 75.885 (2) degrees, and Z = 2. All of the structures involve either one- or two-dimensional polymeric arrays held together by bridging S and CN groups. There is, however, no similarity between any two of the arrays. Four of the five ligands used also form similar complexes with CuCN. For one ligand, tmtu, the structures are isomorphous. For the other three, not only are the structures not isomorphous, the m/n ratio in (MCN)mLn when M is Ag is different from that when M is Cu.

Journal Article↗