Biomedical subjects
Publications and source records attributed to G A Webb.
The 15N results reveal a difference in the extent of intramolecular hydrogen bond formation exhibited by the Schiffs base, compound 2, in solution and the solid state. Comparison of the 15N shielding changes observed, with those arising from protonation, provides the basis for a quantitative estimate of the strength of the hydrogen bonds formed.
15N NMR data are reported for two Di-(alpha-pyridyl) derivatives in various stages of protonation. A combination of 15N NMR measurements taken, on a number of solutions, and on the solid state provide a quantitative overall view of the progress of protonation of these compounds. 15N shieldings, J(15N-1H) and 2J (15N-1H) interactions all provide information indicative of unsymmetrical monoprotonation in the solid state and producing both the monoprotonated [N-H-N]+ structure and the diprotonated structure in the presence of an excess of TFA.
A model of angiogenin has been prepared by homology modelling, based upon the structure of ribonuclease A. This model has been used to postulate an inhibitor based upon the angiostatic agent TAN1120. The complex of ribonuclease A with a dinucleotide has been modelled and used as a guide to the binding orientation of daunomycin--the closest TAN1120 analogue for which the crystal structure and stereochemistry are available.
31P Cross-polarization magic-angle spinning nuclear magnetic resonance (CP-MAS NMR) spectra of eight monophospha-lambda 5-azenes were measured at room temperature. Three of these compounds, with 2-OH substituents, are in principle capable of taking part in the equilibrium process. However, only the open form, tautomer A, is found in the present study. 15N CP-MAS NMR spectra support the results. The most shielded component of the 31P chemical shift tensor lies in the direction of the P = N bond.
A series of monocationic complexes of N-substituted-3-hydroxy-2-methyl-4-pyridinones labeled with technetium(IV)-99m have been evaluated in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the ring nitrogen atom: ethyl, i-propyl, i-butyl, benzyl, phenyl, p-methoxyphenyl, 3-butoxypropyl and cyclohexyl. Biodistribution studies of the 99mTc complexes have been carried out in rabbits and mice. High kidney uptake and retention of the radionuclide has been shown in rabbits and mice with the cationic complexes of 3-hydroxy-1-(p-methoxyphenyl)-2-methyl-4-pyridinone and 1-(cyclohexyl)-3-hydroxy-2-methyl-4-pyridinone. These 99mTcL3+ compounds appear to be morphologic renal agents.
A series of highly lipophilic complexes of 1-aryl-3-hydroxy-2-methyl-4-pyridinones with gallium(III)-67 has been evaluated in vitro and in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the para-position of the phenyl ring: R = H, CH3, OCH3 and NO2. Biodistribution studies of 67Ga complexes have been carried out in rabbits, mice, rats and a dog. High heart uptake of the radionuclide has been shown in rabbits and the dog. The different biodistribution patterns in mice and rats indicate that there is a species difference in the biodistribution of these complexes. Rabbits and the dog show rapid heart uptake and blood clearance. The speciation of the Ga3+ ion in vivo is simulated in vitro with a simple blood plasma model based on the available thermodynamic data.
A model of the beta 2-adrenergic receptor binding site is built from the primary structure of the receptor, experimental evidence for key binding residues and analogy with a homologous protein of partially determined structure. It is suggested that residues Trp-109, Thr-110 and Asp-113 are involved in ligand binding. Noradrenaline is successfully docked into this model, and the results of an INDO molecular orbital calculation on the complex indicate that a charge transfer interaction between Trp-109 and noradrenaline is possible.
INDO molecular orbital calculations are reported for 35 selected angiotensin-converting enzyme inhibitors. QSARs are developed between pI50 data and molecular electronic indices. The QSARs obtained reflect the importance of both charge-charge interactions between inhibitor and receptor and of specific interactions between groups on the inhibitor with points around the molecule which are postulated to correspond to binding sites at the receptor.
In a clinical-pathologic review of 825 cases of endometrial carcinoma diagnosed between 1955 and 1984, 735 cases were confirmed as endometrial carcinoma. From this group 29 cases of clear cell carcinoma of the endometrium were found representing a 4% frequency. Clear cell carcinoma of the endometrium was found in an older group of women, all postmenopausal. No relationship to the use of estrogen could be demonstrated. The frequency of clear cell carcinoma of the endometrium dropped from 6% in the group diagnosed between 1955 and 1969 to 3% in the group diagnosed between 1970 and 1984, although the numbers of cases of endometrial cancer rose from 194 to 525 in the comparative time span. Clear cell carcinoma of the endometrium has a poorer prognosis, with a 64% 5-year survival rate compared with an 80% 5-year survival rate for adenocarcinoma, not otherwise stated. Three patients died after 5 years of disease. Treatment is still not satisfactory, but the proved therapy remains total abdominal hysterectomy plus salpingo-oophorectomy. The role of adjunctive therapy has not been established.
New advice from the National Radiological Protection Board gives a range of monetary values for the unit collective dose, depending in part on the annual individual dose. In this paper the special factors in medical radiodiagnosis are described and a valuation for the man-sievert in this field is suggested. The harm to children from ionising radiation may be appreciably larger than in adults, and a different value for children and in obstetrics is suggested.
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The objective of this brief paper is to highlight the way in which we assess and control the impact of environmentally dispersed radionuclides. It touches on the assessment of dispersion of radionuclides in the environment, their transfer to man, the resultant dose to man and the presumed health consequences, the control of releases based on such assessments and some perspective against which to judge the results of control policies.
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Some significant correlations are observed between the CNS activities of a series of 59 benzodiazepines and some calculated electronic indices. The parameters concerned are the net charge on the carbonyl oxygen atom of the lactam ring and the total molecular dipole moment, correlations with the latter index being superior. The utility of the observed relationships is discussed.
This paper is an analysis of 95 cases treated surgically at the University of California Hospitals and at Children's Hospital between 1949 and 1971; 92 had abdominal radical surgery and three were done vaginally. Figures are analyzed by age, cell type, pregnancy status, and survival data. The numbers surviving for 5 years were 27 in the control group (26 living five years and over) and 50 in the study group.
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