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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 289 records · Page 16Linked to original sources
PubMed1993

Intercellular signalling in mesoderm formation during amphibian development.

The mesoderm of amphibian embryos arises through an inductive interaction in which a signal from the vegetal hemisphere of the blastula-stage embryo acts on overlying equatorial cells. Strong candidates for endogenous mesoderm-inducing signals include members of the fibroblast growth factor (FGF) and activin families. In this paper we show that cells form different mesodermal cell types in response to different concentrations of these factors, and that graded distributions of activin and FGF can, in principle, provide sufficient positional information to generate the body plan of the Xenopus embryo.

Activin Receptors↗
PubMed1993

Configurational distribution of denatured phosphoglycerate kinase.

Physiochemical characterization of the denatured states of proteins is important for a complete understanding of the factors stabilizing their folded conformations. Using a combination of small angle neutron scattering (SANS), statistical mechanical modelling and molecular mechanics calculations, we examine the configurational distribution of phosphoglycerate kinase denatured in 4 M guanidine hydrochloride solution. The denaturing of the protein produces a clear change in the form of the SANS profile and a large increase of the radius of gyration. In the statistical mechanical model, the region of contrast neutron scattering density associated with the protein is pictured as a chain of freely jointed spheres. The model is fitted to the SANS data for the denatured protein. It is found that a model with a small number of spheres cannot account for the higher resolution scattering, indicating an absence of detectable structuration; a good fit is found with 100 spheres of 8.5 A radius. Single configurations of the fitted chain of spheres are used as low-resolution bounds for model-building and molecular mechanics calculations to obtain plausible atomic-detail models of the denatured chain.

Computer Simulation↗
PubMed1993

Lattice vibrations in crystalline L-alanine.

Zwitterionic L-alanine forms crystals containing strong hydrogen-bonding and methylmethyl interactions. Well-defined low-frequency lattice vibrations exist in the crystals involving correlated intermolecular motions on the picosecond timescale. A characterization of these vibrations is expected to provide useful information on the nature of nonbonded interactions in peptides and proteins. We examine some of the vibrations using coherent inelastic neutron scattering and computer simulation techniques. The neutron scattering measurements are used to determine phonon dispersion relations for the acoustic and some low-frequency optic modes in the crystal. There is evidence for interaction between the two lowest frequency optical phonons and the longitudinal acoustic mode. The velocity of sound is anisotropic and can be correlated with the hydrogen-bonding arrangement in the crystal. Corresponding phonon dispersion relations are derived from normal mode analyses of the crystal using the program CHARMM. Although some calculated vibrational frequencies are somewhat too high, the form of the calculated dispersion relations are in good agreement with experiment.

Alanine↗
PubMed1993

Computer simulations of the flexibility of a series of synthetic cyclic peptide analogues.

The flexibility of a series of cyclic peptides derived from the epitope of a snake toxin is investigated using computer simulation techniques. Molecular dynamics (MD) simulations and vibrational analyses are performed on chemically constrained peptides modeled on the parent protein loop. In the 50 ps MD simulations, large variations in the atomic fluctuations are seen between the peptides, and can be related to the nature of the chemical constraints present in the molecules. Normal mode analyses are performed on energy-minimized configurations derived from the dynamics trajectories. The atomic fluctuations calculated from the normal modes are about 30% of those of the molecular dynamics for the more flexible peptides and 70% for the more constrained molecules. The calculated differences in flexibility between the molecules are much less significant in the harmonic approximation.

Amino Acid Sequence↗
PubMed1993

The Xenopus platelet-derived growth factor alpha receptor: cDNA cloning and demonstration that mesoderm induction establishes the lineage-specific pattern of ligand and receptor gene expression.

We have cloned the Xenopus PDGF alpha receptor cDNA and have used this clone, along with cDNA encoding PDGF A, to examine their expression pattern in Xenopus embryos and to determine the factors responsible for lineage specificity. Recombinant Xenopus alpha receptor expressed in COS cells exhibits PDGF-A-dependent tyrosine kinase activity. We find that receptor mRNA is present in cultured marginal zone tissue explants and in animal cap tissue induced to form mesoderm either by grafting to vegetal tissue or by treatment with recombinant activin A. In contrast, PDGF A mRNA is expressed in cultured, untreated animal cap tissue and is suppressed by mesoderm induction. These results suggest that ectodermally produced PDGF A may act on the mesoderm during gastrulation and that mesoderm induction establishes the tissue pattern of ligand and receptor expression.

Amino Acid Sequence↗
PubMed1993

Picosecond timescale rigid-helix and side-chain motions in deoxymyoglobin.

The contribution of rigid-body motions to the atomic trajectories in a 100 ps molecular dynamics simulation of deoxymyoglobin is examined. Two types of rigid-body motions are considered: one in which the helices are rigid units and one in which the side-chains are rigid units. Using a quaternion-based algorithm, fits of the rigid reference structures are made to each time frame of the simulation to derive trajectories of the rigid-body motions. The fitted trajectories are analysed in terms of atomic position fluctuations, mean-square displacements as a function of time, velocity autocorrelation functions and densities of states. The results are compared with the corresponding quantities calculated from the full trajectory. The relative contribution of the rigid helix motions to the helix atom dynamics depends on which quantity is examined and on which subset of atoms is chosen; rigid-helix motions contribute 86% of the rms helix backbone atomic position fluctuations, but 30% of the helix atom (backbone and side-chain) mean square displacements and only 1.1% of total kinetic energy. Only very low-frequency motions contribute to the rigid-helix dynamics; the rigid-body analysis allows characteristic rigid-helix vibrations to be identified and described. Treating the side-chains as rigid bodies is found to be an excellent approximation to both their diffusive and vibrational mean-square displacements: 96% of side-chain atom mean-square displacements originate from rigid side-chain motions. However, the errors in the side-chain atomic positional fits are not always small. An analysis is made of factors contributing to the positional error for different types of side-chain.

Computer Simulation↗
PubMed1993

Physiological model for the pharmacokinetics of methyl mercury in the growing rat.

We describe a physiological pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in the growing rat. Demethylation appears to occur in both host tissues and gastrointestinal flora with elimination dominated by biliary secretion of inorganic mercury and by transport of methyl mercury into the gut lumen followed by substantial bacterial metabolism. Biliary transport of both organic and inorganic mercury is modeled in terms of the known secretion of glutathione from the hepatic pool. At 98 days following an oral tracer dose of 203Hg-labeled methyl mercury chloride, 65% of the administered dose had been recovered in the feces as inorganic mercury and 15% as organic mercury. Urinary excretion is a minor elimination route, accounting for less than 4% of the dose as methyl mercury and 1% of the dose as inorganic mercury. Irreversible incorporation of the mercurials into hair is a significant route of elimination. Ten percent of the administered dose was contained in the hair shed during the 98 days and over 12% of the dose (almost 90% of the body burden) remained in the hair at the end of that time period. Apparent ingestion of hair by the rats during grooming represents a novel form of toxin recirculation. Transport of both chemical species between blood and tissues is bidirectional and symmetric with relatively slow movement into and out of the brain. Transport mechanisms for both mercurial species are discussed in the context of capillary transport physiology and the blood-brain barrier to small molecules and proteins.

Animals↗
PubMed1993

Pluripotent mesenchymal stem cells reside within avian connective tissue matrices.

Recent studies have noted the presence of putative stem cells derived from the connective tissues associated with skeletal muscle, heart, and dermis. Long-term continuous cultures of these cells from each tissue demonstrated five distinct phenotypes of mesodermal origin, i.e. muscle, fat, cartilage, bone, and connective tissue. Clonal analysis was performed to determine whether these morphologies were the result of a mixed population of lineage-committed stem cells or the differentiation of pluripotent stem cells or both. Putative stem cells from four tissues (skeletal muscle, dermis, atria, and ventricle) were isolated and cloned. Combined, 1158 clones were generated from the initial cloning and two subsequent subclonings. Plating efficiency approximated 5.8%. Approximately 70% of the 1158 clones displayed a pure stellate morphology, while the remaining clones contained a mixture of stellate, chondrogenic- or osteogenic-like morphologies or both. When cultured in the presence of dexamethasone, cells from all clones differentiated in a time- and concentration-dependent manner into muscle, fat, cartilage, and bone. These results suggest that pluripotent mesenchymal stem cells are present within the connective tissues of skeletal muscle, dermis, and heart and may prove useful for studies concerning the regulation of stem cell differentiation, wound healing, and tissue restoration, replacement and repair.

Animals↗
PubMed1993

Human basal ganglia volume asymmetries on magnetic resonance images.

The brains of 19 healthy adults, ages 18-49, were imaged on a GE Signa 1.5 T MR scanner. Basal ganglia were circumscribed on sequential axial proton density-weighted images (TR 1700, TE 20) and submitted for 3-dimensional reconstruction and volumetric analysis at a computer graphics workstation. The 15 right-handed patients (12 men, 3 women) had significantly larger left total basal ganglia volumes, which included larger globus pallidus and lenticular nuclei on the left, but larger caudate nuclei on the right. In contrast, basal ganglia asymmetries were not seen in four left-handers. No sex differences were detected. The basal ganglia appear to belong to an increasing number of CNS structures that display anatomical hemispheric lateralization.

Adult↗
PubMed1993

Analysis of gastrulation: different types of gastrulation movement are induced by different mesoderm-inducing factors in Xenopus laevis.

In this paper we analyze the control of gastrulation in Xenopus laevis. Our approach takes advantage of the observation that mesoderm-inducing factors such as activin, FGF and BMP-4 induce presumptive ectodermal cells to undergo gastrulation-like movements. Activin, for example, makes intact animal pole regions undergo convergent extension and causes individual cells to spread and migrate on a fibronectin-coated substrate. By varying the concentrations of the growth factors to which animal pole cells are exposed, and by applying them in different combinations, we show how graded distributions of a combination of factors could establish the correct spatial and temporal patterns of gastrulation in the Xenopus embryo. The distributions we propose support and develop the model previously suggested by Green et al. (1992) to account for the spatial patterns of gene activation in the early embryo.

Activins↗
PubMed1993

Control of vertebrate gastrulation: inducing signals and responding genes.

Recently, genes with similar expression patterns in the early gastrulae of several different vertebrate species have been identified. The remarkable conservation of these expression patterns suggests that fundamental similarities exist within the vertebrates at remarkably early stages. It has yet to be established exactly how these genes are activated in the correct spatial patterns and what their functions might be.

Animals↗
PubMed1993

Axillofemoral bypass with externally supported, knitted Dacron grafts: a follow-up through twelve years.

PURPOSE: The purpose of this study was to review our experience with externally supported, knitted Dacron grafts used for axillofemoral bypass. METHODS: Retrospective analysis was performed on records of 79 consecutive axillofemoral bypass graft operations performed on 77 patients from January 1978 to April 1990. RESULTS: The mortality rate within 30 days of operation was 5% (four of 79); 36 patients died in the follow-up period; none died of graft causes. During this 12-year period (mean follow-up 42 months) three patients were unavailable for follow-up. The primary patency rate was 78% at 5 years and 73% at 7 years, with no change thereafter. Neither the graft configuration (i.e., axillounifemoral [n = 50] vs axillobifemoral [n = 29]) nor patency of the superficial femoral artery had an impact on the primary patency rate. Patients who underwent surgery for disabling claudication (n = 30 grafts) had a primary patency rate of 80% at 6 years compared with 65% at 6 years for those who required surgery for limb salvage (n = 49 grafts); the difference was not significant (p = 0.37). Actuarial survival of patients with axillofemoral grafts was 23% at 10 years compared with 72% in a concurrent population of patients with aortofemoral bypass (p < 0.001). CONCLUSION: These findings indicate that axillofemoral bypass grafts may be appropriate for high-risk patients with severe aortoiliac disease who require revascularization for either limb salvage or incapacitating claudication.

Adult↗
PubMed1993

A comparison of methods of estimating anaerobic work capacity.

The hyperbolic relationship between power output (P) and time to exhaustion (t) is described as: (P-theta PA).t = W', where theta PA is the power asymptote (or 'critical power'), which theoretically represents the highest sustainable power output, and W' is a constant which represents a limited amount of work which can be performed above theta PA (or 'anaerobic capacity'). The purpose of this study was to determine the validity of W' as anaerobic capacity, using maximal oxygen deficit as the criterion measure. Thirteen women (mean (+/- SD) age 23 +/- 2 years, height 1.67 +/- 0.07 m and mass 60.8 +/- 8 kg) and 13 men (mean age 23 +/- 2 years, height 1.74 +/- 0.1 m and mass 71.3 +/- 14 kg) performed two sets of five bouts of high-intensity cycling exercise to exhaustion, each bout on a separate day and at a different relative power. Individual W' were calculated by nonlinear regression of time with power, with time as the dependent variable. Oxygen deficit was determined during each bout, and the mean of the values obtained from the power output which elicited the highest values was used as the criterion for anaerobic capacity. Mean (+/- SE) values for anaerobic capacity for women were 179 +/- 10 J.kg-1 (W') and 177 +/- 10 J.kg-1 (oxygen deficit) and for men, 224 +/- 10 J.kg-1 (W') and 235 +/- 9 J.kg-1 (oxygen deficit). The W' estimates and criterion measures were the same (F1,24 = 0.61, p = 0.44), and there was no method-gender interaction (F1,24 = 0.26, p = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The correlation between two dietary assessments of carotenoid intake and plasma carotenoid concentrations: application of a carotenoid food-composition database.

A newly available carotenoid food-composition database providing specific carotenoid values for > 2300 foods was linked to dietary data on 57 male nonsmokers to examine the association between dietary carotenoid intake and plasma carotenoid concentrations over 3 wk when free-living. Carotenoid intake was estimated from a food-frequency questionnaire (FFQ) and 7 d of food diaries with concurrent analysis of plasma carotenoid concentrations. After adjustment for energy intake, percentage of energy from alcohol, and plasma lipid concentrations, significant diet-plasma correlations for the FFQ and the food diaries (FD) included alpha-carotene (r = 0.29 and 0.43), beta-carotene (r = 0.36 FFQ only), beta-cryptoxanthin (r = 0.46 and 0.44), lutein (r = 0.44 FD only), and lycopene (r = 0.53 FD only). Dietary carotenoid intakes were associated with plasma carotenoid concentrations for all the carotenoids except for beta-carotene when food diaries were used whereas the diet-plasma correlation for the provitamin A carotenoids were consistently significant when the FFQ was used.

Adult↗
PubMed1993

Lymphocyte responsiveness of children supplemented with vitamin A and zinc.

We sought to determine the effect of supplementation with zinc, vitamin A, or a combination of the two on proliferation of T lymphocytes to concanavalin A (ConA), tetanus toxoid (TT), or tuberculin (PPD) of children living in a region endemic for suboptimal vitamin A and zinc intake. The children (n = 140, aged 6-13 y) were randomly assigned and supplemented with either zinc (25 mg/d), vitamin A (1500 mg RE/d), zinc + vitamin A, or placebo for 6 mo. After a baseline blood collection, subjects were boosted with diphtheria-tetanus antigen. Proliferative responsiveness of T lymphocytes to ConA and TT in each treatment group (n = 35) was not different at baseline or postsupplementation. Children supplemented with zinc + vitamin A tended to show higher proliferative responsiveness of T lymphocytes to PPD than did those treated with placebo (P = 0.08). This tendency was observed in females but not in males. Increased zinc and vitamin A intake could result in health benefits for children living in regions endemic for suboptimal micronutrient nutriture.

Adolescent↗
PubMed1993

Differences in outcome of transurethral resection of the prostate for benign prostatic hypertrophy between three diagnostic categories.

As part of a prospective cohort study of 388 men undergoing transurethral resection of the prostate (TURP) for benign prostatic hypertrophy, pre-operative factors and the outcome of surgery during the first post-operative year were compared between patients in whom their surgeon felt the principal reason for operating was chronic retention (37%), acute retention (with no chronic retention) (28%), or symptomatic prostatism (with no history of chronic or acute retention) (35%). Although in many respects the patients in the 3 diagnostic categories were similar, patients with chronic retention were more likely to be younger, of higher social class and to have worse general health. Patients with acute retention were more likely to present with a urinary tract infection and to have electrocardiographic abnormalities, and symptomatic patients presented with more severe urinary symptoms. Minor differences between the categories with regard to post-operative morbidity and mortality were not statistically significant at the 5% level. However, some significant differences did exist. Patients with acute retention were more likely to experience urinary and non-urinary infections and impotence after surgery, while symptomatic patients reported less improvement in their health status as regards pain and social isolation. These results suggest that the method of categorisation is clinically valid and a necessary distinction to make when auditing TURP.

Acute Disease↗