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Biomedical subjects

A D French

Publications and source records attributed to A D French.

At least 19 recordsLinked to original sources
PubMed2001

Modeling of deoxy- and dideoxyaldohexopyranosyl ring puckering with MM3(92).

Extensive variations of the ring structures of three deoxyaldohexopyranoses, L-fucose, D-quinovose, and L-rhamnose, and four dideoxyaldohexopyranoses, D-digitoxose, abequose, paratose, and tyvelose, were studied by energy minimization with the molecular mechanics algorithm MM3(92). Chair conformers, 4C(1) in D-quinovose and the equivalent 1C(4) in L-fucose and L-rhamnose, overwhelmingly dominate in the three deoxyhexoses; in the D-dideoxyhexoses, 4C(1) is again dominant, but with increased amounts of 1C(4) forms in the alpha anomers of the three 3,6-dideoxyhexoses, abequose, paratose, and tyvelose and in both alpha and beta anomers of the 2,6-dideoxyhexose D-digitoxose. In general, modeled proton-proton coupling constants agreed well with experimental values. Computed anomeric ratios strongly favor the beta configuration except for D-digitoxose, which is almost equally divided between alpha and beta configurations, and L-rhamnose, where the beta configuration is somewhat favored. MM3(92) appears to overstate the prevalence of the equatorial beta anomer in all three deoxyhexoses, as earlier found with fully oxygenated aldohexopyranoses.

Algorithms↗
PubMed2000

A QM/MM analysis of the conformations of crystalline sucrose moieties.

Both ab initio quantum mechanics (QM) and molecular mechanics (MM) were used to produce a hybrid energy surface for sucrose that simultaneously provides low energies for conformations that are observed in crystal structures and high energies for most unobserved structures. HF/6-31G* QM energies were calculated for an analogue based on tetrahydropyran (THP) and tetrahydrofuran (THF). Remaining contributions to the potential energy of sucrose were calculated with MM. To do this, the MM surface for the analogue was subtracted from the MM surface for the disaccharide, and the QM surface for the analogue was added. Prediction of the distribution of observable geometries was enhanced by reducing the strength of the hydrogen bonding. Reduced hydrogen-bonding strength is probably useful because many crystalline sucrose moieties do not have intramolecular hydrogen bonds between the fructose and glucose residues. Therefore, hydrogen bonding does not play a large role in determining the molecular conformation. On the hybrid energy surface that was constructed with a dielectric constant of 3.5, the average potential energy of 23 sucrose moieties from crystal structures is 1.16 kcal/mol, and the population of observed structures drops off exponentially as the energy increases.

Carbohydrate Conformation↗
PubMed2000

Constructing and evaluating energy surfaces of crystalline disaccharides.

This paper focuses on the methods used to construct Ramachandran plots for disaccharides. Our recent work based on a hybrid of molecular mechanics and quantum mechanics energies pointed to the need to take extra care when making these maps. Care is also important in the quantitative validation of these energy surfaces with linkage conformations that were determined by crystallography. To successfully predict conformations that have been observed experimentally, the calculation of the energy should include stereoelectronic effects and correctly weight the hydrogen bonding. Technical concerns include the method used to scan the range of conformations, starting geometries, and finding the zero of relative potential energy on a surface where the values were collected at regular intervals. The distributions of observed conformations on energy maps of sucrose, maltose, and laminarabiose at dielectric constants of 1.5 and 7.5 illustrate the effects of an elevated dielectric constant for the MM3 component of the hybrid energy calculations. At dielectric constants of 3.5 and 7.5, the overall average energies of observed conformations of sucrose and seven disaccharides of glucose were less than 1.0 kcal mol-1. The distribution of corresponding energies of the various crystalline conformations conformed well to a Boltzmann-like equation.

Carbohydrate Conformation↗
PubMed1999

Changing trends in South Wales fluoride prescription dispensing (1993-7).

OBJECTIVE: To observe patterns of fluoride preparation dispensing by primary care practitioners in a health authority. DESIGN: Observational study. SETTING: The Prescription Pricing Agency of the Welsh Health Common Services Authority (WHCSA). SUBJECTS: Individuals who had exchanged a prescription for a fluoride preparation at a pharmacy in Bro Taf Health Authority in the six months from 1 January 1997 to 30 June 1997. METHOD: Information from each prescription including a fluoride preparation, passed to WHCSA from pharmacists during the study, was entered onto a database, including the prescriber's postcode and profession, the recipient's postcode and product information. Numbers of dental prescriptions were correlated to local levels of NHS primary dental care provision and caries prevalence data. Comparisons were made with a similar study undertaken in 1993. RESULTS: 415 dentists' prescriptions were dispensed within the area, of which 38.8% originated from five dentists. At least one prescription had been made by 89 of the 253 local primary dental care providers (35%). Within the area monitored in both 1993 and 1997, dental prescribing rates had almost halved. Of the 122 doctors' prescriptions that were dispensed over the six-month period, 98 were mouthwash preparations for adult patients and four were for children. CONCLUSION: NHS provision of fluoride supplementation was low and remained related to prescribing patterns of individuals rather than to evidence on local variations in dental caries prevalence.

Adult↗
PubMed1994

Relaxed-residue conformational mapping of the three linkage bonds of isomaltose and gentiobiose with MM3 (92).

Isoenergy surfaces were calculated for the alpha- and beta-anomers of isomaltose and gentiobiose, based on 46,656 conformers for each disaccharide. Low-energy regions exist for each of the three staggered positions about the C-5'-C-6' bonds, and known crystal structures lie in two of these regions. As expected, the molecular partition function showed greater flexibility for these three-bond-linked disaccharides than for comparable two-bond-linked structures. A model miniature crystal of gentiobiose accounts for most of the remaining structural differences between the modeled isolated molecule and the crystal structure. Based on models of isolated molecules of isomaltose and gentiobiose, the predicted Boltzmann-weighted nmr coupling constants were satisfactory, as were predicted optical rotations for gentiobiose.

Carbohydrate Conformation↗
PubMed1994

A study of the dietary fluoride supplementation prescribing pattern of south Glamorgan dentists.

Following the inclusion of dietary fluoride supplements in the Dental Practitioners Formulary on 1st January 1993, the aims of this study were to observe the fluoride supplementation prescribing pattern of South Glamorgan general dental practitioners and relate it to the latest caries prevalence data. The analysis was carried out on the prescribers and recipients of the prescriptions using post codes to locate all members of both groups into one of 26 dental planning areas (DPA) within the district. As the age of a minority of recipients could not be substantiated, an assumption that they were all 14 years or under was used to calculate a prescription to population ratio for each DPA. These ratios were correlated against the latest available caries prevalence data for each DPA to ascertain any relationship between the level of fluoride supplement prescription and the caries prevalence within South Glamorgan. Data were collected via the Prescription Pricing Division of Welsh Health Common Services Authority for the six month period, 1st January to 30th June 1993. Of 623 prescriptions dispensed within South Glamorgan, 581 were issued by dentists working in the District for patients living in the District. Of the 163 dentists registered within South Glamorgan FHSA, (boundary coterminous with the DHA) 49 made one or more prescription. Of these, 10 dentists wrote 20 prescriptions or more, totalling 401, during the study period, i.e. 6 per cent of the dentists made 69 per cent of the prescriptions. The correlation of the number of prescriptions issued per DPA (according to the dentists' location) with whole time equivalents in that DPA was 0.58 (P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Computer modeling of the tetrasaccharide nystose.

Nystose, O-beta-D-fructofuranosyl-(2-->1)-O-beta-D-fructofuranosyl-(2-->1)- beta-D-fructofuranosyl alpha-D-glucopyranoside, was modeled with the rigid-residue program PFOS and with MM3. The three furanose rings of crystalline nystose trihydrate all are within the 1 kcal.mol-1 contour on an MM3 energy surface that was calculated with a dielectric constant of 4. The calculations showed that in the extended conformation found in the crystal, there was a small influence of the remainder of the residues on the conformation of any given disaccharide segment. Even accounting for intramolecular, interresidue forces, however, the central inulobiose and the sucrose linkages appear to be distorted. These discrepancies are apparently due to crystal packing forces and, for the sucrose linkage, miscalculation of the energy of an overlapping exoanomeric effect, as indicated by studies of a model miniature crystal. The different conformations of the central and terminal inulobiose linkages in the crystal show that conformations in higher oligosaccharides will not always correspond to the global minima on conformational maps for isolated disaccharides.

Carbohydrate Conformation↗
PubMed1993

Overlapping anomeric effects in a sucrose analogue.

Previous calculations with the molecular mechanics program MM3 gave unusually high energies (as much as 5.5 kcal/mol) for sucrosyl geometries found in single-crystal diffraction studies of oligosaccharides. Comparable MM3 energies for observed interresidue linkage conformations of disaccharides such as maltose and cellobiose are all within 2.8 kcal/mol. These results suggest that some energies calculated by MM3 for the linkage between anomeric centers of a pyranose ring and a furanose ring are too high. In the present paper, ab initio calculations at the 4-21G level and MM3 were used to study the conformational energies and geometry of a sucrose analogue, tetrahydro-2-[(tetrahydro-2-furanyl)oxy]-2H-pyran. The range of energies of the observed structures was substantially reduced (to 2.4 kcal/mol) with the 4-21G calculations for the analogue despite an increase for the analogue (to 7.5 kcal/mol) based on new MM3 calculations. Besides the improved energy values, the 4-21G calculations also reproduced the observed variations in the endocyclic C-O bond lengths better than did MM3.

Carbohydrate Conformation↗
PubMed1993

Miniature crystal models of cellulose polymorphs and other carbohydrates.

Miniature crystal models of cellulose and other carbohydrates were evaluated with the molecular mechanics program MM3. The models consisted of groups of 24 to 32 monosaccharide residues, with the models of mono- and disaccharides based on well-established, single-crystal work. Structures of the cellulose forms and cellotetraose were based on published work using fibre diffraction methods. A structure for the single-chain I alpha cellulose unit cell was also tested. A dielectric constant of about 4 was best for this type of work. Calculated intra- and intermolecular energy for glucose agreed with literature values for the heat of combustion. Cellulose II had the lowest calculated energy for a cellulose form, followed by I alpha, cellulose III(I), ramie I, IV(II) and IV(I). Optimization of cellulose IV caused larger mean atomic movements from the original crystallographic positions than the other cellulose forms, and cellotetraose had larger movements than any of the other structures. Lattice energies for the cellulose forms were about 20 kcal/mol of glucose residues, with a dominant van der Waals component.

Carbohydrates↗
PubMed1992

Conformational analysis of the anomeric forms of sophorose, laminarabiose, and cellobiose using MM3.

Relaxed-residue energy maps based on the MM3 force-field were computed for relative orientations of the pyranosyl rings of sophorose, laminarabiose, and cellobiose, respectively the (1----2)-beta-; (1----3)-beta-; and (1----4)-beta-linked D-glucosyl disaccharides. Sixteen starting conformations of the rotatable exocyclic side-groups were considered for each molecule. All of the energy surfaces have two intersecting low-energy troughs and illustrate the importance of exo-anomeric effects in determining disaccharide conformation. Local minima were found by relaxed minimization without restriction. The energy surfaces of these disaccharides are very similar to the energy surfaces of their corresponding 6-methyltetrahydropyran analogues. There is good agreement between disaccharide structures having minimal MM3 energy and those found by crystallography.

Carbohydrate Conformation↗
PubMed1992

Conformational analysis of the anomeric forms of kojibiose, nigerose, and maltose using MM3.

Energy surfaces were computed for relative orientations of the relaxed pyranosyl rings of the two anomeric forms of kojibiose, nigerose, and maltose, the (1----2)-alpha, (1----3)-alpha, and (1----4)-alpha-linked D-glucosyl disaccharides, respectively. Twenty-four combinations of starting conformations of the rotatable side-groups were considered for each disaccharide. Optimized structures were calculated using MM3 on a 20 degree grid spacing of the torsional angles about the glycosidic bonds. The energy surfaces of the six disaccharides were similar in many respects but differed in detail within the low-energy regions. The maps also illustrate the importance of the exo-anomeric effect and linkage type in determining the conformational flexibility of disaccharides. Torsional conformations of known crystal structures of maltosyl-containing molecules lie in a lower MM3 energy range than previously reported.

Carbohydrate Conformation↗
PubMed1992

Agglutination of lung surfactant with glucan.

Respirable cotton dust, implicated in the pathogenesis of byssinosis, contains a number of bioactive compounds. These include lipopolysaccharide (LPS), tannins, bacterial peptides, byssinosin, iacinilene C, and 1,3-beta-D-glucan. The exact aetiological agent of byssinosis in such dust has not been definitively identified nor has its mechanism of action on lower lung surfaces been determined. In the present study 1,3-beta-D-glucan, Enterobacter agglomerans LPS, and ovine pulmonary surfactant were mixed in varying combinations. After incubation, their characteristics were determined by sucrose density centrifugation, TLC, and carbohydrate analysis. Precipitates were found in mixtures containing surfactant-glucan and surfactant-glucan-LPS, but not in surfactant-LPS. Precipitates were not seen in the surfactant, LPS, and glucan controls. The formation of a precipitate did not increase the density of the surfactant glucan mixture when compared by density gradient centrifugation with the surfactant control. The interaction between surfactant and glucan was analysed by molecular modelling. The energy of a surfactant-glucan complex (60.07 kcal/mol) was calculated to be much lower than the sum of glucan (47.09 kcal/mol) and surfactant (30.98 kcal/mol) when added separately. The results indicate that 1,3-beta-D-glucan does interact with surfactant and this complex may play a part in the pathogenesis of byssinosis by altering lung physiology maintained by pulmonary surfactant.

Agglutination↗
PubMed1991

Conformational analysis of 1-kestose by molecular mechanics and by n.m.r. spectroscopy.

Models of the trisaccharide, 1-kestose [beta-D-fructofuranosyl-(2----1)-beta-D-fructofuranosyl-(2 in equilibrium with 1)-alpha-D -glucopyranoside], were analyzed with the molecular mechanics computer program MM2(87) to ascertain their inter-ring torsion angles, primary alcohol side-group orientations, and ring puckering. The most striking result was that the modeling predicted and n.m.r. spectroscopy corroborated that the central fructofuranose ring takes a different form from that previously observed in the crystal. No other studies of fructofuranoses have observed that crystallographic form, thus suggesting that the 18 hydrogen bonds created upon crystallization of 1-kestose support the ring deformation. Because this trisaccharide is too complex for a complete study of conformation space, only structures having inter-ring conformations that were at energetic valleys in previous studies of the constituent disaccharides were analyzed. The model of the model disaccharides, although they were generally close to the linkage conformations observed in the crystal structure, differing by an average of 19 degrees.

Carbohydrate Conformation↗
PubMed1991

A study of the dental health of children and young adults attending special schools in South Glamorgan.

An epidemiological study was carried out involving 677 children and young adults aged between 3 and 19 years who were attending special schools in South Glamorgan. The children and young adults were examined for caries and periodontal disease. Their dental attendance pattern and the dental service they used were recorded, and their mobility and posture, and comprehension and cooperation, were assessed. The results showed that the majority were receiving regular dental care and that the caries experience of 12- and 14-year-old children was lower than that of children of the same ages in other state schools. Five-year-old children were found to have a dmft of 4.18, which was significantly higher than that of similar-aged children attending state schools. Forty-seven per cent of the children and young adults were found to have periodontal disease; the greatest percentage (60%) was found in the young adults in the 15-19-year-old age group. Caries experience and gingival health were not related to the subjects' mobility and posture but caries experience was greater and gingival health was poorer in subjects who had reduced comprehension and cooperation. The study highlighted deficiencies in the service provided for this group, especially for pre-school children.

Adolescent↗
PubMed1991

Differential fermentation of cellulose allomorphs by ruminal cellulolytic bacteria.

In addition to its usual native crystalline form (cellulose I), cellulose can exist in a variety of alternative crystalline forms (allomorphs) which differ in their unit cell dimensions, chain packing schemes, and hydrogen bonding relationships. We prepared, by various chemical treatments, four different alternative allomorphs, along with an amorphous (noncrystalline) cellulose which retained its original molecular weight. We then examined the kinetics of degradation of these materials by two species of ruminal bacteria and by inocula from two bovine rumens. Ruminococcus flavefaciens FD-1 and Fibrobacter succinogenes S85 were similar to one another in their relative rates of digestion of the different celluloses, which proceeded in the following order: amorphous > III(I) > IV(I) > III(II) > I > II. Unlike F. succinogenes, R. flavefaciens did not degrade cellulose II, even after an incubation of 3 weeks. Comparisons of the structural features of these allomorphs with their digestion kinetics suggest that degradation is enhanced by skewing of adjacent sheets in the microfibril, but is inhibited by intersheet hydrogen bonding and by antiparallelism in adjacent sheets. Mixed microflora from the bovine rumens showed in vitro digestion rates quite different from one another and from those of both of the two pure bacterial cultures, suggesting that R. flavefaciens and F. succinogenes (purportedly among the most active of the cellulolytic bacteria in the rumen) either behave differently in the ruminal ecosystem from the way they do in pure culture or did not play a major role in cellulose digestion in these ruminal samples.

Journal Article↗
PubMed1990

Conformational analysis of inulobiose by molecular mechanics.

Conformational energies for inulobiose [beta-D-fructofuranosyl-(2----1)-beta-D-fructofuranoside], a model for inulin, were computed with the molecular mechanics program MMP2(85). The torsion angles of the three linkage bonds were driven in 20 degree increments, and the steric energy of all other parameters was minimized. The linkage torsion angles defined by C-1'-C-2'-O-C-1 (phi) and O-C-1-C-2-O-2 (omega) have minima at +60 degrees and -60 degrees, respectively, regardless of side group orientation; accessible minima exist at other staggered conformations. The torsion angle at the central bond C-2'-O-1-C-1-C-2 (psi) was approximately 180 degrees in all the low-energy conformers. This appears to be generally true for rings linked by three bonds. The fructofuranose rings initially had low-energy 4/3T conformations (angle of pseudorotation, phi 2 = 265 degrees) that were retained except when the linkage conformations created severe inter-residue conflicts. In those cases, almost all puckerings of the furanose rings were found.

Carbohydrate Conformation↗