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G D Smith

Publications and source records attributed to G D Smith.

At least 109 records · Page 6Linked to original sources
PubMed2000

Step-scan FTIR time-resolved spectroscopy study of excited-state dipole orientation in soluble metallopolymers.

Step-scan FTIR time-resolved spectroscopy (S2FTIR TRS) in acetonitrile-d3 has been used to probe the acceptor ligand in metal-to-ligand charge transfer (MLCT) excited states of amide-substituted polypyridyl complexes of RuII and in analogues appended to polystyrene. On the basis of ground-to-excited state shifts in v(C = O) of -31 cm-1 for the amide group in [RuII(bpy)2(bpyCONHEt')]2+ (bpyCONHEt' = 4'-methyl-2,2'-bipyridine-4-carboxamide-Et'; Et' = -CH2CH2BzCH2CH3) (1) and in the derivatized polystyrene abbreviated [PS-[CH2-CH2NHCObpy-RuII(bpy)2]20]40+ (3), the excited-state dipole is directed toward the amide-containing pyridyl group in the polymer side chain. Smaller shifts in v(C = O) of -17 cm-1 in [RuII(4,4'-(CONEt2)2bpy)2-(bpyCONHEt')]2+ (2) and in the derivatized polystyrene abbreviated [PS-[CH2CH2NHCObpy-RuII(4,4'-(CONEt2)2bpy)2]20]40+ (4) indicate that the excited-state dipole is directed toward one of the diamide bpy ligands. The nearly identical results for 1 and 3 and for 2 and 4 show that the molecular and electronic structures of the monomer excited states are largely retained in the polymer samples. These conclusions about dipole orientation in the polymers are potentially of importance in understanding intrastrand energy transfer dynamics. The excited-state dipole in 3 is oriented in the direction of the covalent link to the polymer backbone, and toward nearest neighbors. In 4, it is oriented away from the backbone.

Journal Article↗
PubMed2000

Life course accumulation of disadvantage: childhood health and hazard exposure during adulthood.

The present paper examines the association between physical and social disadvantage during childhood and lifetime exposure to health-damaging environments. Study members were participants of Boyd Orr's clinical, social and dietary survey conducted between 1937 and 1939 and were aged between 5 and 14 years at clinical examination. Study participants were traced and between 1997 and 1998 a random sample of 294 were interviewed. The lifegrid interview method was used to collect full occupational, residential and household histories, from which accumulated lifetime exposures to a range of environmental hazards were estimated. Age-adjusted height during childhood was found to be inversely related to subsequent exposure to all hazards combined (males p = 0.002; females p = 0.001). This relationship was found in males with manual fathers (p = 0.044) and females with non-manual fathers (p = 0.035). Chronic disease during childhood was also associated with greater subsequent hazard exposure in males with manual fathers (p = 0.008). Among females with non-manual fathers, in contrast, chronic disease during childhood was associated with reduced subsequent hazard exposure (p = 0.05). These findings suggest that exposure to health-damaging environments during adulthood may accumulate on top of health disadvantage during childhood and that this process of life course accumulation of disadvantage may vary by gender and childhood social class.

Adolescent↗
PubMed2000

Increasing mortality differentials by residential area level of poverty: Britain 1981-1997.

This paper considers mortality for ages 15-64 for the period 1981-97 in Britain according to population deciles defined by an area-based poverty measure. Over the study period there has been a polarization of life chances such that by 1994-97 almost one quarter of deaths in this age group can be attributed to unfavourable socioeconomic circumstances. Mortality differentials according to socioeconomic circumstances increased in tandem with increases in income inequality. A commitment to redistributive social policies is necessary if the trend of increasing inequality is to be reversed.

Adolescent↗
PubMed2000

The role of insulin dissociation from its endosomal receptor in insulin degradation.

Mechanisms that terminate signals from activated receptors have potential to influence the magnitude and nature of cellular responses to insulin. The aims of this study were to determine in rat liver endosomes (the subcellular site of insulin signal termination) whether dissociation of insulin from its receptor was a pre-requisite for ligand degradation and whether the state of receptor phosphorylation influenced the dissociation and hence endosomal degradation of insulin and/or receptor recycling. Following in vivo administration of 125I-[A14]-insulin or analogues (native, X10 or H2, relative binding affinities 1:7:67) livers were removed and endosomes prepared. In the endosomal preparations a significantly greater percentage of both analogues were receptor-bound than native insulin with concomitantly less ligand degradation. When rats were injected with protein-tyrosine phosphatase inhibitors (peroxovanadium compounds bpV(phen) or bpV(pic)) before insulin, endosomal insulin receptor phosphotyrosine content, assessed by Western blotting, was increased as was receptor-bound 125I-[A14]-insulin, whilst insulin degradation was decreased. Peroxovanadiums also completely inhibited recycling of insulin receptors from endosomes. However, treatment of freshly isolated endosomes with acid phosphatase which completely dephosphorylated the insulin receptor, did not return the rate of insulin dissociation and degradation to control values, suggesting that peroxovanadium compounds elicit their effect on binding and degradation via a mechanism other than as protein-tyrosine phosphatase inhibitors. We conclude that promotion of sustained receptor binding decreases endosomal insulin degradation and extends the half-life of the activated endosomal receptor, which in turn would be expected to potentiate insulin signalling from this intracellular compartment.

Animals↗
PubMed2000

Investigation of functional and morphological integrity of freshly isolated and cryopreserved human hepatocytes.

There is a pressing need for alternative therapeutic methods effective in the treatment of patients with liver insufficiency. Isolated human hepatocytes may be a viable alternative or adjunct to orthotopic liver transplantation in such patients. The purpose of this study was to evaluate the viability and functional integrity of freshly isolated and cryopreserved human hepatocytes, in preparation for a multi-center human hepatocyte transplantation trial. We are currently processing transplant-grade human parenchymal liver cells from nondiseased human livers that are obtained through a network of organ procurement organizations (OPOs). Thus far, sixteen hepatocyte transplants have been performed using hepatocytes processed by our methods. At the time of referral all specimens were deemed unsuitable for transplantation due to anatomical anomalies, high fat content, medical history, etc. Hepatocytes were isolated from encapsulated liver sections by a modified two-step perfusion technique. Isolated cells were cryopreserved and stored in liquid nitrogen for one to twelve months. The total yield of freshly isolated hepatocytes averaged 3.7x10(7) cells per gram of wet tissue. Based on trypan blue exclusion, fresh preparations contained an average of 85% viable hepatocytes vs. 70% in cryopreserved samples. The plating efficiencies of cells seeded immediately after isolation ranged from 87% to 98%, while those of cryopreserved/thawed cells were markedly lower. Flow cytometry analysis of cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) showed that there was no significant difference in viability compared with trypan blue staining. Both freshly isolated hepatocytes and those recovered from cryopreservation showed typical and intact morphology as demonstrated by light and electron microscopy. The product of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reaction was always expressed more intensely in cultures of freshly isolated hepatocytes. Measurements of lactate dehydrogenase (LDH) leakage were inversely correlated with trypan blue exclusion and CFSE labeling. Energy status, evaluated by the intracellular ATP concentration measurements, and various liver-specific functions such as urea synthesis and metabolism of 7-ethoxycoumarin were maintained both in fresh and cryopreserved/thawed hepatocytes. However, the activities were expressed at different levels in thawed cells. These data illustrate the importance and feasibility of human hepatocyte banking. In addition, it is clear that further refinements in the methods of hepatocyte isolation and cryopreservation are needed to utilize more fully these valuable cells in the clinic.

Journal Article↗
PubMed2000

Height and cancer mortality: results from the Glasgow University student cohort.

The aim of the study was to examine the association between height and cancer mortality in a socially homogeneous group of subjects. The study was based on a cohort of students, 8397 men and 2329 women, aged 16-30 y, who attended the University of Glasgow between 1948 and 1968. Mean follow-up time was 40 y. Height was measured at a medical examination performed at the student health service. The outcome measures used in the study were all-cause mortality and mortality from: all cancers, smoking and non-smoking related cancers and cancers related to sex hormones. No substantial or statistically significant associations were seen between height and all-cause or all-cancer mortality in either sex. Neither were any significant associations found between height and any of the sub-types of cancer studied (ie those related to smoking, those not related to smoking, and those related to sex hormones). Previous observations which have shown positive associations between height and cancer mortality have generally been based on populations with diverse social origins, among whom the variation in height will reflect variation in health and nutrition in childhood. The relatively low level of such variation in the present study may account for the negative findings. Public Health (2000) 114, 451-455

Adolescent↗
PubMed2000

Consistency of histopathological reporting of laryngeal dysplasia. The Scottish Pathology Consistency Group.

AIMS: Clinical management of premalignant and malignant lesions of the larynx is dependent on histopathological evaluation. The Scottish Pathology Consistency Group assessed interobserver variation in the evaluation of laryngeal dysplasia. METHODS AND RESULTS: One hundred laryngeal biopsies ranging from normal to invasive carcinoma were assessed. The overall Kappa result of 0.32 was disappointing. However, agreement on those categories which dictate significantly different management was more favourable. The Kappa figure for mild dysplasia versus severe dysplasia/CIS was 0.7, the Kappa figure for mild dysplasia versus severe dysplasia/CIS and invasive carcinoma was 0.77. The Kappa figure for mild and moderate dysplasia versus severe dysplasia/ CIS and invasive carcinoma was 0.57. An attempt to use a two grade system gave a Kappa figure of 0.52. CONCLUSIONS: Our group had a satisfactory agreement on the distinction of mild from severe dysplasia and on microinvasive carcinoma without any discussion as to histopathological criteria to be used. Clinical management--review endoscopy, repeat cord stripping, radiotherapy and laryngectomy--is in general dependent on histological assessment. Thus the agreement on categories which underpin clinical management is reassuring. However, assessment of moderate dysplasia remains problematic. An attempt to utilize a two grade system--low grade from high grade dysplasia/CIS--may have merit. The implications of the terminology used must be agreed among pathologists and clinicians working closely within clinicopathological cancer groups.

Adenocarcinoma↗
PubMed2000

Divergence in murine myometrium spontaneous and oxytocin-stimulated contractile responses to serine/threonine protein phosphatase-1 inhibition.

Reversible phosphorylation is essential in regulating uterine contractions. Identification, characterization, and functional understanding of myometrium protein phosphatase(s) are lacking. Okadaic acid (OA), which inhibits protein phosphatase-1 (PP1) and PP2A, has been shown to alter uterine contractions. Experiments were conducted to determine the 1) identity of the myometrial OA-sensitive PP, 2) influence of OA on spontaneous and oxytocin (OT)-stimulated myometrial contractions, and 3) expression of uterine PPs during sexual development. Western blot analysis indicated the presence of PP1(alpha) and PP2A in immature and mature mice. As determined by immunohistochemistry, gonadotropin-stimulated adult mouse uteri contain PP1(alpha) in longitudinal and circular myometrial layers and endometrial epithelium. Conversely, PP2A was localized to the endometrial stroma. Cumulative addition of OA (n = 9; 10, 100, 250, 500, 1000 nM) did not significantly alter spontaneous contractions of mouse uterine horns in comparison to vehicle-treated controls (n = 9). By the end of the test period OA- and vehicle-treated uteri displayed a comparable decline in uterine contractions to 79.2% and 63.7%, respectively, of basal contractile activity. Pretreatment of uterine tissue with OA (1 microM; n = 7) significantly reduced contractile response to increasing concentrations of OT (8, 16, 32, 64 nM) in comparison to vehicle pretreatment (dimethyl sulfoxide; n = 7). At the end of the OT-administration period, contractile activity was 160.4% and 67.3% of basal contractile activity for vehicle (no OA) and OA-pretreated groups, respectively. During the early prepubertal period PP1(alpha) was expressed in longitudinal myometrium and absent in circular myometrium; whereas, during the transition to sexual maturity PP1(alpha) was observed in both the longitudinal and circular myometrium. In summary, these studies have indicated 1) that PP1 is the primary myometrial OA-sensitive PP; 2) that inhibition of PP1 had no effect on spontaneous contractions, whereas it markedly inhibited OT-stimulated uterine contractions; and 3) that PP1 is differentially expressed in the circular and longitudinal myometrium in relation to sexual development.

Animals↗
PubMed2000

Radiation safety role in institutional disaster planning.

United States Nuclear Regulatory Commission (NRC) materials license applicants (non-nuclear power) must submit spill procedures with their application. While our counterparts in the nuclear power industry historically have concerned themselves with disaster drills and evacuation plans as a result of fire, explosion, or an act of terrorism, other licensees are looking only at minor spills of unsealed radioactive material and only at tile radiation hazard. Beyond NRC regulations, various oversight and accrediting organizations require, or at a minimum encourage, a written disaster plan outlining actions to be taken for events likely to occur in the region of the institution. Some of these organizations require drills to practice implementation of the written plan. On 5 May 1999, Mayo Clinic performed a wide-scale disaster drill involving Rochester City and Olmsted County response organizations, and several Mayo Clinic departments. Planning took several months; the drill took approximately three hours. Participants gathered at several meetings post-drill for "debriefing" sessions to discuss successes, areas for improvement, and lessons learned. There were three overriding lessons learned: critical responders need special identification to allow access to the disaster site; initial victim surveys are for gross contamination only; and access to the potentially contaminated disaster site might take weeks or months following a real event.

Decontamination↗
PubMed2000

Optimizing DREAR and SnB parameters for determining Se-atom substructures.

The determination of the anomalous scattering substructure is the first essential step in any successful macromolecular structure determination using the multiwavelength anomalous diffraction (MAD) technique. The diffE method of calculating difference Es in conjunction with SnB has had considerable success in determining large Se-atom substructures. An investigation of the parameters used in both the data-reduction and error-analysis routines (DREAR) as well as the SnB phasing process itself was undertaken to optimize these parameters for more efficient use of the procedure. Two sets of selenomethionyl S-adenosylhomocysteine hydrolase MAD data were used as test data. The elimination of all erroneously large differences prior to phasing was found to be critical and the best results were obtained from accurate highly redundant intensity measurements. The high-resolution data collected in the typical MAD experiment are sufficient, but the inclusion of low-resolution data below 20 A improved the success rate considerably. Although the best results have been obtained from single-wavelength peak anomalous diffraction data alone, independent SnB analysis of data measured at other wavelengths can provide confirmation for questionable sites.

Computer Simulation↗
PubMed2000

R6 hexameric insulin complexed with m-cresol or resorcinol.

The structures of three R(6) human insulin hexamers have been determined. Crystals of monoclinic m-cresol-insulin, monoclinic resorcinol-insulin and rhombohedral m-cresol-insulin diffracted to 1. 9, 1.9 and 1.78 A, respectively, and have been refined to residuals of 0.195, 0.179 and 0.200, respectively. In all three structures, a phenolic derivative is found to occupy the phenolic binding site, where it forms hydrogen bonds to the carbonyl O atom of CysA6 and the N atom of CysA11. Two additional phenolic derivative binding sites were identified within or between hexamers. The structures of all three hexamers are nearly identical, although a large displacement of the N-terminus of one B chain in both monoclinic structures results from coordination to a sodium ion which is located between symmetry-related hexamers. Other minor differences in structure arise from differences in packing in the monoclinic cell compared with the rhombohedral cell. Based upon the differences in conformation of the GluB13 side chains in T(6), T(3)R(f)(3) and R(6) hexamers, the deprotonation of these side chains appears to be associated with the T-->R conformational transition.

Cresols↗
PubMed2000

The first protein crystal structure determined from high-resolution X-ray powder diffraction data: a variant of T3R3 human insulin-zinc complex produced by grinding.

X-ray diffraction analysis of protein structure is often limited by the availability of suitable crystals. However, the absence of single crystals need not present an insurmountable obstacle in protein crystallography any more than it does in materials science, where powder diffraction techniques have developed to the point where complex oxide, zeolite and small organic molecular structures can often be solved from powder data alone. Here, that fact is demonstrated with the structure solution and refinement of a new variant of the T(3)R(3) Zn-human insulin complex produced by mechanical grinding of a polycrystalline sample. High-resolution synchrotron X-ray powder diffraction data were used to solve this crystal structure by molecular replacement adapted for Rietveld refinement. A complete Rietveld refinement of the 1630-atom protein was achieved by combining 7981 stereochemical restraints with a 4800-step (d(min) = 3.24 A) powder diffraction pattern and yielded the residuals R(wp) = 3.73%, R(p) = 2.84%, R(F)(2) = 8.25%. It was determined that the grinding-induced phase change is accompanied by 9.5 and 17.2 degrees rotations of the two T(3)R(3) complexes that comprise the crystal structure. The material reverts over 2-3 d to recover the original T(3)R(3) crystal structure. A Rietveld refinement of this 815-atom protein by combining 3886 stereochemical restraints with a 6000-step (d(min) = 3.06 A) powder diffraction pattern yielded the residuals R(wp) = 3.46%, R(p) = 2.64%, R(F)(2) = 7.10%. The demonstrated ability to solve and refine a protein crystal structure from powder diffraction data suggests that this approach can be employed, for example, to examine structural changes in a series of protein derivatives in which the structure of one member is known from a single-crystal study.

Humans↗