Search PubMed⌕ Search

Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 325 records · Page 18Linked to original sources
PubMed1994

Home testing for HIV.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Crystallographic evidence for dual coordination around zinc in the T3R3 human insulin hexamer.

The T3R3 human insulin hexamer (T and R referring to extended and alpha-helical conformations, respectively, of the first eight residues of the B-chain), complexed to two zinc ions, crystallizes in space group R3 with hexagonal cell constants a = 80.64 and c = 37.78 A. The structure has been refined to a residual of 0.172 using 9225 independent data to 1.6-A resolution. The asymmetric unit consists of a TR dimer, and the insulin hexamer is generated by the action of the crystallographic 3-fold axis. The conformation of one insulin trimer is nearly identical to that of the T6 hexamer, while the other trimer approximates that of the R6 hexamer, except for the three N-terminal B-chain residues that adopt an extended rather than an alpha-helical conformation. Each of the two zinc ions, which lie on the crystallographic 3-fold axis and exhibit two different, disordered coordination geometries, is coordinated by the imidazole groups of three symmetry-related B10 histidine residues. The coordination sphere of the zinc in the T3 trimer is either tetrahedral, with the fourth site filled by a chloride ion, or octahedral, completed by three water molecules. The coordination of the zinc in the 12-A narrow channel in the R3 trimer is tetrahedral, with either a second chloride ion or a water molecule completing the coordination sphere. The putative off-axial zinc binding sites that result from the T-->R transition of monomer II do not contain zinc ion, but instead are filled with clusters of ordered water molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1994

Pre treatment with MK-801, a non-competitive NMDA antagonist, prevents development of mechanical hyperalgesia in a rat model of chronic neuropathy, but not in a model of chronic inflammation.

In the rat, loose ligation of the sciatic nerve results in behavioural signs of hyperalgesia reminiscent of neuropathy in man. A further rat model, of chronic inflammatory hyperalgesia, is produced by intraplantar administration of Freund's complete adjuvant (FCA). We report here that preemptive administration of a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, MK-801 (0.3 mg kg-1, s.c.) 30 min prior to and twice daily for a further 8 days following loose ligation of the sciatic nerve, blocks the development of mechanical hyperalgesia measured 27 days later. In contrast, MK-801 administration using the same dosing regimen did not significantly inhibit the hyperalgesia apparent 15 days following i.pl. administration of FCA. Our results suggest that the mechanisms responsible for the development of mechanical hyperalgesia associated with chronic nerve injury and chronic inflammation differ.

Animals↗
PubMed1994

In vivo determination of the anatomical axes of the ankle joint complex: an optimization approach.

This study investigates the feasibility of a subject-specific three-dimensional model of the ankle joint complex for kinematic and dynamic analysis of movement. The ankle joint complex was modelled as a three-segment system, connected by two ideal hinge joints: the talocrural and the subtalar joint. A mathematical formulation was developed to express the three-dimensional translation and rotation between the foot and shank segments as a function of the two joint angles, and 12 model parameters describing the locations of the joint axes. An optimization method was used to fit the model parameters to three-dimensional kinematic data of foot and shank markers, obtained during test movements throughout the entire physiological range of motion of the ankle joint. The movement of the talus segment, which cannot be measured non-invasively, is not necessary for the analysis. This optimization method was used to determine the position and orientation of the joint axes in 14 normal subjects. After optimization, the discrepancy between the best fitting model and actual marker kinematics was between 1 and 3 mm for all subjects. The predicted inclination of the subtalar joint axis from the horizontal plane was 37.4 +/- 2.7 degrees, and the medial deviation was 18.0 +/- 16.2 degrees. The lateral side of the talucrural axis was directed slightly posteriorly (6.8 +/- 8.1 degrees), and inclined downward by 7.0 +/- 5.4 degrees. These results are similar to previously reported typical results from anatomical, in vitro studies. Reproducibility was evaluated by repeated testing of one subject, which resulted in variations of about one-fifth of the standard deviation within the group, the inclination of the subtalar joint axis was significantly correlated to the arch height and a radiographic 'tarsal index'. It is concluded that this optimization method provides the opportunity to incorporate inter-individual anatomical differences into kinematic and dynamic analysis of the ankle joint complex. This allows a more functional interpretation of kinematic data, and more realistic estimates of internal forces.

Algorithms↗
PubMed1994

Short-term effects of mepacrine on serum lipids, lipoproteins, and apolipoproteins in patients with non-insulin-dependent diabetes mellitus.

We investigated the effects of 7 days' treatment with oral mepacrine hydrochloride 100 mg three times daily on fasting serum levels of glucose, insulin, lipids, lipoproteins, and apolipoproteins in 16 patients with non-insulin-dependent diabetes mellitus (NIDDM) in a double-blind placebo-controlled study. Mepacrine treatment decreased fasting levels of total cholesterol (7.0 +/- 0.6 to 5.6 +/- 0.4 mmol/L, P < .01), low-density lipoprotein (LDL) cholesterol (4.7 +/- 0.5 to 3.5 +/- 0.3 mmol/L, P < .01), and apolipoprotein (apo) B (1.20 +/- 0.14 to 1.02 +/- 0.08 g/L, P < .05), and the ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol (P < .05). There was no change in fasting levels of serum glucose, insulin, C-peptide, nonesterified free fatty acids, triglycerides, or lipoprotein(a). In conclusion, a short course of oral mepacrine treatment has a potentially beneficial effect on LDL cholesterol and apo B levels in patients with NIDDM and warrants further investigation in this situation.

Adult↗
PubMed1994

Increased sensitivity to the antinociceptive activity of (+/-)-baclofen in an animal model of chronic neuropathic, but not chronic inflammatory hyperalgesia.

Modulation of sensory afferent inputs to the spinal cord by GABA appears to be an important physiological mechanism and may provide an antinociceptive control system. In the present study we have evaluated the antinociceptive activity of the GABAB receptor agonist, (+/-)-baclofen, in rats with unilateral chronic inflammatory or neuropathic hyperalgesia. (+/-)-Baclofen was antinociceptive in untreated control animals and both animal models. In the neuropathic model the sensitivity to (+/-)-baclofen was significantly increased by 3-fold in the ipsilateral limb. By contrast, in animals with chronic inflammation no difference in sensitivity between ipsilateral and contralateral limbs to (+/-)-baclofen was observed. Receptor autoradiographic analysis in spinal cord sections revealed no increase in the density of GABAB receptor binding sites and no change in receptor affinity in the neuropathic model.

Analgesics↗
PubMed1994

Social patterning of medical mortality in youth and early adulthood.

It has been suggested that socio-economic gradients in health reduce or disappear during youth, to be re-created during early adulthood through a process of health-related social mobility. The present analysis tests this hypothesis in relation to 'medical mortality', using a data set which is free of numerator-denominator bias. The sample consists of the appropriate age groups in the OPCS Longitudinal Study; 62,647 males and 59,644 females aged 0-14 at the 1971 census. 'Medical mortality' during 1971-1985, calculated as standardised mortality ratios, is analysed by parental social class, housing tenure and car access in 1971. 'Medical mortality' during 1981-1985 is analysed by own social class in 1981. The results suggest that 'medical mortality' is inversely related to social advantage at ages of death 0-9 years, that this gradient flattens or disappears at ages 10-14 and that it re-emerges at ages 15-29. Within the present analysis this apparent re-emergence could not have been due to health-related social mobility. It is concluded that the apparent absence of socio-economic gradients in 'medical mortality' during youth may be an artefact of the high levels of health enjoyed by this age group and its consequent low levels of non-accidental death.

Adolescent↗
PubMed1994

Vibrational circular dichroism measurements of ligand vibrations in haem and non-haem metalloenzymes.

We have measured the vibrational circular dichroism (VCD) spectra of the stretching vibrations of azide and cyanide ligated to the Fe3+ atoms of haemoglobin (Hb) and myoglobin (Mb). The antisymmetric azide-stretch of the low-spin haems have an anomalously large g-value of ca. -1 x 10(-3). In contrast, CN- has a g-value of ca. +2.4 x 10(-3). We also show, for the first time, that a significant VCD occurs for the azide ligand antisymmetric stretches of non-haem proteins; we measure a g-value of ca. -1 x 10(-4) for azide bound to haemerythrin. We have examined the mechanism of the VCD phenomenon by: (1) reconstituting Mb with haems substituted such that they insert differently in the haem pocket; (2) replacing the Fe3+ with Mn3+; (3) examining proteins where replacements occur for E-7 His and E-11 Val distal amino acids close to the haem and (4) examining an Mb mutant where the proximal F-8 His is replaced by Gly, and where an imidazole ligand inserts into the resulting crevice and binds to the haem in a way similar to that of the proximal histidine in the native protein. The VCD anisotropy appears insensitive to the haem substituent replacements used in this study. Exchange of the E-7 distal His or the E-11 Val has a dramatic effect on the g-value. Exchange of the F-8 proximal His reverses the sign of the g-value for the azide complex, but not for the cyanide complex. The work to date indicates that VCD has the potential to become a sensitive technique for examining the structure of metalloenzymes. Work is needed to determine the mechanism giving rise to the large g-values and to correlate the VCD spectrum with the metalloenzyme structure at the active site.

Azides↗
PubMed1994

Helicobacter pylori and chronic antral gastritis in elderly patients.

Fifty-five elderly patients with chronic antral gastritis (CAG) were studied to assess the relationship between Helicobacter pylori (H. pylori) status and CAG subtypes as specified in the Sydney System for Gastritis Classification. Twenty-eight patients (51%) were H. pylori positive and 27 (49%) H. pylori negative. H. pylori-positive patients had a significantly greater association with features of severe active CAG (chronic inflammation and polymorph activity) than H. pylori-negative patients. No association was apparent between H. pylori and more advanced stages of CAG (atrophy and intestinal metaplasia) thought to carry pre-malignant potential. The recognized association between dyspeptic symptoms in elderly people and an H. pylori-positive gastritis was confirmed. Use of NSAIDs correlated with a predominantly H. pylori-negative gastritis which was relatively asymptomatic.

Aged↗
PubMed1994

Cigarette smoking as a potential cause of cervical cancer: has confounding been controlled?

It is widely believed that some sexually transmitted pathogen plays a key role in the aetiology of cervical cancer. However, although certain human papilloma viruses are strongly implicated, the pathogen responsible and its mechanism of action remain to be finally characterized. The correlation between cigarette smoking and sexual activity that exists in most cultures therefore makes evaluation of the potential additional role of smoking difficult, due to confounding with the presence of the aetiological pathogen. Epidemiological studies of the association between smoking and cervical cancer have adjusted for the lifetime number of sexual partners as a proxy measure of the presence of the pathogen and, in most cases, the association has diminished but remained statistically significant. Since the use of a proxy will tend to result in underestimation of the effect of the aetiological pathogen on risk of cervical cancer, however, the adjustment is likely to be insufficient, thus resulting in overestimation of the adjusted or 'independent' effect of smoking. In an attempt to address this concern we used a simulation approach to investigate whether a substantial 'independent' association between smoking and cervical cancer might be expected as a result of the use of a poor proxy for the aetiological pathogen, even if there is no true effect of smoking. Using realistic estimates of the association between the presence of the aetiological pathogen and both smoking and risk of cervical cancer, 'independent' relative risks for cigarette smoking of two and above were generated. It is therefore plausible that the observed 'independent' effect of cigarette smoking on cervical cancer is due to residual confounding.

Confounding Factors, Epidemiologic↗
PubMed1994

Survival in HIV infection: do sex and category of transmission matter? Swiss HIV Cohort Study.

OBJECTIVE: To examine survival differences in HIV-infected individuals between the sexes and the categories of transmission. PATIENTS AND SETTING: Subjects assumed to have been infected by injecting drug use, by male homosexual contact or by heterosexual contact and enrolled in the Swiss HIV Cohort Study, a national multicentre cohort study of adult HIV-infected patients. METHODS: Kaplan-Meier lifetable and Cox regression analyses were performed (time 0 = date of study entry) and survivors were censored at their last follow-up visit. RESULTS: A total of 4428 patients (mean duration of follow-up, 2.1 years) were considered. At entry, men were older and had lower CD4+ counts than women (P < 0.0001). Homosexual men were the oldest group with the lowest CD4+ counts and the most advanced disease at study entry (P < 0.0001). Crude hazard ratios indicated a 28% lower mortality from all causes in women compared with men (P < 0.0001) and, among men but not in women, a 28 and 32% higher mortality in homosexuals and heterosexuals compared with injecting drug users (IDU) (P = 0.0002 and P = 0.008, respectively). After adjusting for differences at entry, the mortality difference between the sexes disappeared (P = 0.5) and differences across transmission categories were reversed. Mortality in homosexual men was an estimated 13% (P = 0.057) lower than in male IDU; mortality was 22% lower in heterosexual women than in female IDU (P = 0.098). In stratified analysis the increased risk in IDU was confined to subjects with CD4+ cell counts > 500 x 10(6)/l cells at study entry. CONCLUSIONS: These results indicate a uniform mortality risk across the sexes but indicate an increased risk in IDU without CD4+ cell depletion at entry, the latter probably attributable to causes not related to progression of HIV infection. This study underscores the importance of adjusting for prognostic factors when comparing survival between different patient groups.

Adult↗