PubMed Health⌕ Search

Biomedical subjects

D M Guerin

Publications and source records attributed to D M Guerin.

9 recordsLinked to original sources
PubMed2000

Sweet's syndrome and polycythaemia rubra vera.

Sweet's syndrome is associated with haematological malignancy, particularly acute myelogenous leukaemia, but there are few reports of its association with polycythaemia rubra vera. We describe an 85-year-old man with polycythaemia rubra vera who developed Sweet's syndrome and review the literature of this association.

Aged↗
PubMed1999

Chronic lymphoedema and angiosarcoma.

Angiosarcoma has frequently been described arising within chronic lymphoedema of the upper limb following mastectomy and radiotherapy for carcinoma of the breast. We report a case of angiosarcoma arising in a lymphoedematous leg that had been subjected to radiotherapy 20 years previously for Hodgkin's disease. The diagnosis was expedited once the patient noticed the development of bleeding nodules. Prognosis of angiosarcoma is poor with treatment options being wide-excision surgery, palliative radiotherapy or chemotherapy. Unusual bruised areas or bleeding nodules developing within chronic lymphoedematous limbs should be biopsied to exclude the diagnosis.

Aged↗
PubMed1996

Structure-based design of achiral, nonpeptidic hydroxybenzamide as a novel P2/P2' replacement for the symmetry-based HIV protease inhibitors.

A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2,5-bis[N-(tert-butyloxycarbonyl)amino]-3,4-dihydroxy-1, 6-diphenylhexane (1) delineated a crucial water-mediated hydrogen bond between the tert-butyloxy group of the inhibitor and the amide hydrogen of Asp29 of the enzyme. Achiral, nonpeptidic 2-hydroxyphenylacetamide and 3-hydroxybenzamide groups were modeled as novel P2/P2' ligands to replace the crystallographic water molecules and to provide direct interactions with the NH groups of the Asp29/129 residues. Indeed, the symmetry-based inhibitors 7 and 19, possessing 3-hydroxy and 3-aminobenzamide, respectively, as a P2/P2' ligand, were potent inhibitors of HIV PR. The benzamides were superior in potency to the phenylacetamides and have four fewer rotatable bonds. An X-ray crystal structure of the HIV PR/7 complex at 2.1 A resolution revealed an asymmetric mode of binding, in which the 3-hydroxy group of the benzamide ring makes the predicted interaction with the backbone NH of Asp29 on one side of the active site only. An unexpected hydrogen bond with the Gly148 carbonyl group, resulting from rotation of the aromatic ring out of the amide plane, was observed on the other side. The inhibitory potencies of the benzamide compounds were found to be sensitive to the nature and position of substituents on the benzamide ring, and can be rationalized on the basis of the structure of the HIV PR/7 complex. These results partly confirm our initial hypothesis and suggest that optimal inhibitor designs should satisfy a requirement for providing polar interactions with Asp29 NH, and should minimize the conformational entropy loss on binding by reducing the number of freely rotatable bonds in inhibitors.

Benzamides↗
PubMed1988

Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.

The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.

Antiviral Agents↗
PubMed1983

Role of nocturnal feeding in the development of the diurnal rhythm of jejunal sucrase activity.

A diurnal rhythm of jejunal sucrase activity has been shown previously to make its developmental appearance in the rat at the time of weaning (Day 22). In this study we found that the rhythm was not present on Day 23 if the onset of feeding was not coordinated with the onset of darkness. Conversely, the sucrase rhythm appeared precociously (Day 19) in pups weaned onto chow on a schedule in which the onset of feeding is coordinated with the onset of the dark period. It is concluded that the normal developmental appearance of the sucrase rhythm is due, at least in part, to the fact that ad libitum feeding becomes nocturnal around Day 22.

Aging↗
PubMed1981

Role of diet in the determination of jejunal sucrase activity in the weanling rat.

This study was designed to determine the critical difference between rat milk and rat chow with respect ot their effects on jejunal sucrase activity during the fourth postnatal wk. Rats were weaned onto special diets on postnatal day 17, and jejunal sucrase was assayed on day 28. A pelleted diet containing lactose as sole carbohydrate did not cause depression of sucrase activity. Sucrase values (micromoles/hr/mg protein) were 10.49 +/- 0.81 (n = 15) for the lactose chow and 6.65 +/- 0.29 (n = 16) for the sucrose chow. This indicates that the nature of the dietary carbohydrate does not account for the sucrase differences of weaned and nonweaned animals. Likewise, the physical consistency of the diet is unimportant because sucrase values were just as high on liquid diet (10.91 +/- 0.77 micromoles/hr/mg protein; n = 8) as on he solid diets. However, when the relative proportions of carbohydrate and fat in the diet were varied, there were significant effects on sucrase activity; values on a low carbohydrate diet (4.30 +/- 0.33 micromoles/hr/mg protein; n = 8) being less than one-half those on a high carbohydrate diet (10.91 +/- 0.77 micromoles/hr/mg protein; n = 8).

Animals↗