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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 253 records · Page 14Linked to original sources

Fetal methylmercury study in a Peruvian fish-eating population.

Maternal consumption during pregnancy of methylmercury (MeHg)-contaminated fish in Japan and of MeHg-contaminated bread in Iraq caused psychomotor retardation in the offspring. Studies in Iraq suggested adverse fetal effects when maternal hair mercury concentrations were as low as 20 ppm. This prospective study involved 131 infant-mother pairs in Mancora, Peru with peak maternal hair MeHg levels during pregnancy from 1.2 ppm to 30.0 ppm, geometric mean 8.3. The MeHg was believed to be derived from marine fish in the diet. There was no increase in the frequency of neurodevelopmental abnormalities in early childhood. The possible role of selenium or other protective mechanisms in marine fish is discussed. This previously unpublished study was conducted between 1981 and 1984. Our report of August 1985 to the funding agencies has been circulated, and the data were presented at the Twelfth International Neurotoxicology Conference in Hot Spring, Arkansas, October 30 to November 2, 1994. The current account has not been modified or updated since 1985. For reference to interim publications on fetal MeHg studies in Iraq and New Zealand see Marsh et al., 1995.

Adult↗

Liquid-like side-chain dynamics in myoglobin.

At temperatures above approximately 200 K the motions of atoms in globular proteins contain a non-vibrational component that gives rise to characteristic elastic and quasi-elastic neutron scattering profiles. There is evidence that the non-vibrational dynamics is required for protein function. Here we show by analysing a molecular dynamics simulation of myoglobin that the neutron scattering results from liquid-like rigid-body motion of the protein side-chains.

Computer Simulation↗

Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction?

Activin and Vg1, two members of the TGF-beta family, are believed to play roles in mesoderm induction and axis formation in the amphibian embryo. Both molecules are provided maternally, either as protein (activin) or as RNA and protein (Vg1), and experiments with a truncated form of a type IIB activin receptor have led to the conclusion that activin is required for induction of mesoderm in vivo. In this paper we first show that truncated versions of two different Xenopus activin receptors also have severe effects on the activity of the mature region of Vg1, suggesting that such receptors may block the function of several members of the TGF-beta family. We go on to demonstrate that follistatin, a secreted protein which binds activin and blocks its activity, does not interfere with Vg1 signalling. Furthermore, overexpression of follistatin mRNA in Xenopus embryos does not perturb mesoderm formation. Taken together, our data show that the effects of truncated activin receptors on Xenopus development can be explained by the inhibition of Vg1 activity, while the lack of effect of follistatin argues against a function for activin in mesoderm induction.

Activin Receptors↗

Fatherhood without apparent spermatozoa after vasectomy.

Fatherhood after vasectomy is rare. We describe 6 cases of DNA-proven fatherhood after vasectomy in association with persistently negative semen examination. All vasectomy patients and their partners should be counselled about the small possibility of late failure, and warning of failure should be recorded.

Female↗

Specification of mesodermal pattern in Xenopus laevis by interactions between Brachyury, noggin and Xwnt-8.

We demonstrate that the nuclear, sequence-specific DNA-binding protein Xbra causes dorsal mesodermal differentiation of animal cap ectoderm when co-expressed with the secreted proteins noggin and Xwnt-8. None of these molecules causes dorsal mesoderm formation when expressed alone. Co-expression of Xenopus Brachyury (Xbra) mRNA with noggin mRNA in animal caps specifies the main dorsal tissues, namely muscle, notochord and neural tissue. Co-expression of Xbra with Xwnt-8, in contrast, converts animal caps to muscle masses. We have previously shown that expression of Xbra alone in animal caps is sufficient to specify ventral mesoderm which expresses Xhox3 and low levels of muscle-specific actin. We now conclude that the putative transcription factor Xbra defines a cell state in the vertebrate embryo which can respond to diffusible dorsal signals such as noggin and Xwnt-8, resulting in dorsal mesodermal differentiation. In the absence of such dorsal signals Xbra causes ventral mesodermal differentiation. This state is only partially maintained after the mid-blastula transition as it permits the dorsal response to zygotically expressed noggin but it does not allow a dorsal response to zygotically expressed Xwnt-8, which elicits only ventral mesodermal differentiation.

Animals↗

Control of somitic expression of tenascin in Xenopus embryos by myogenic factors and Brachyury.

Tenascin is a large glycoprotein which is expressed in a restricted pattern in the extracellular matrix (ECM) of vertebrate embryos. Tenascin interferes with cell-fibronectin interactions in vitro, and may play a role in the control of cell migration and differentiation during development. In Xenopus, tenascin immunoreactivity is first detected at the early tailbud stage in the ECM of the most anterior somite. Thereafter, it is distributed dorsally along neural crest cell migration pathways. In this paper, we report that tenascin mRNA is most abundant in dorsal mesoderm at the neurula stage and in somites at the early tailbud stage, indicating that the initial accumulation of tenascin in the ECM is due to secretion from paraxial mesoderm. To understand how tenascin expression in somitic mesoderm is controlled, we have expressed Xbra and the myogenic factors XMyoD and XMyf5 in blastula animal cap tissue. The tenascin gene is activated by all three transcription factors. Interestingly, expression of tenascin mRNA, and accumulation of the protein in the ECM, can occur without formation of muscle. Our results suggest that tenascin regionalization in early Xenopus embryos depends on tenascin RNA expression by somitic mesoderm, where it is likely to be activated by myogenic factors.

Animals↗

The kinetics of intravenously administered methyl mercury in man.

We describe a compartmental pharmacokinetic model for methyl mercury and its metabolite mercuric mercury in humans. A tracer dose of 203Hg-labeled methyl mercury was administered iv to seven healthy young adult male volunteers. Blood samples were obtained periodically and urine and feces were collected throughout the 70 days of the study. The blood contained predominantly methyl mercury, while the excreta contained principally inorganic mercury. The behavior of both methyl mercury and inorganic mercury in the body was modeled with the simplest compartmental model which fit the data. This five-compartment model shows that inorganic mercury accumulates in the body and at longer times is the predominant form of mercury present. The biological half-life of methyl mercury in the body is 44 days and 1.6% of the body burden is lost each day by both metabolism and excretion. This rate of loss is 60% greater than that currently accepted (1.0% per day). Thus, the risk associated with dietary methyl mercury may have been overestimated.

Adult↗

Abortion mortality, United States, 1972 through 1987.

OBJECTIVE: The aim of our study was to describe risk factors for legal abortion mortality and the characteristics of women who died of legal abortion complications for the period 1972 through 1987. STUDY DESIGN: We reviewed abortion mortality surveillance data collected by the Division of Reproductive Health, Centers for Disease Control and Prevention, and calculated rates by various demographic and reproductive health variables using the Center for Disease Control and Prevention's abortion surveillance data as denominators. Rates are reported as legal abortion deaths per 100,000 abortions. RESULTS: Between 1972 and 1987, 240 women died as a result of legal induced abortions. The case-fatality rate decreased 90% over time, from 4.1 deaths per 100,000 abortions in 1972 to 0.4 in 1987. Women > or = 40 years old had three times the risk of death as teenagers (relative risk 3.0, 95% confidence interval 1.5 to 6.0), and black women and those of other minority races had 2.5 times the risk of white women (relative risk 2.5, 95% confidence interval 1.9 to 3.2). Abortions at > or = 16 weeks were associated with a risk of death almost 15 times the risk of death from procedures at < or = 12 weeks' gestation. Women undergoing currettage procedures for abortion had a significantly lower risk of death than women undergoing other procedures. Whereas before 1977 infection and hemorrhage were the leading causes of death, during 1977 through 1982 anesthesia complications emerged as one of the leading causes of death and since 1983 have become the most frequent cause. CONCLUSIONS: Although legal induced abortion-related deaths are rare events, our findings suggest that more rigorous efforts are needed to increase the safety of anesthetic methods and anesthetic agents used for abortions and that efforts are still necessary to monitor serious complications of abortion aimed at further reducing risks of death associated with the procedure.

Abortion, Legal↗

Consistency of meal patterns in laboratory rats.

Meal pattern measures (e.g., bout length and bout number) provide a detailed description of the elements of ingestion, and as a result they are theoretically more sensitive to experimental manipulation than simple measurements of total consumption over a fixed time period. For this reason, meal pattern measures are often used as a way to infer how rodents respond to tastants or how pharmacological or surgical treatments modify ingestive behavior. This approach relies on the assumption that under normal conditions, the meal patterns of individual rats are consistent across consecutive light-dark (L-D) cycles. If these patterns are inconsistent, then experimental designs involving meal patterns would have limited power, and thus require relatively large sample sizes. The present study critically evaluates the consistency assumption in Sprague-Dawley and Fisher-344 rats by monitoring meal patterns over 10 consecutive L-D cycles. For each rat, the following feeding and drinking measures were determined: total daily intake, duration of night bouts, number of night bouts, and number of licks per night bout. The analysis excluded daytime ingestive measures owing to their infrequent occurrence. Ingestive measures were highly consistent across time in all Sprague-Dawleys, but in only a minority of the Fisher-344s. The distribution of feeding and drinking activity throughout each night was also determined in the same rats. Whereas Sprague-Dawleys displayed lights-off and lights-on peaks of ingestive activity, only a minority of Fisher-344s displayed a consistent lights-on peak of ingestive activity. It is concluded that rat strains can differ with respect to the consistency of meal patterning, and that such strain differences should be considered in future comparative studies of meal patterns in rats.

Acclimatization↗

How random is a highly denatured protein?

There has been renewed interest in determining the physicochemical properties of denatured states of proteins. In many denatured states there is evidence for the existence of nonrandom configurational distributions. Here we examine the small-angle neutron scattering profile of yeast phosphoglycerate kinase in the native state and in highly denaturing conditions. We show that the denatured protein scattering profile can be interpreted using a model developed for synthetic polymers in which the chain behaves as a random coil in a good solvent, i.e. with excluded volume interactions. The implications of this result for our appreciation of the protein folding process are discussed.

Journal Article↗

Protein interactions and dynamics probed by quantum chemistry, computer simulations and neutron experiments.

We review some recent experiments and calculations on aspects of the structure and dynamics of proteins and related systems. The use of quantum chemical techniques to determine geometries and energies of supramolecular complexes of biological interest is illustrated, and the concomitant development of empirical energy functions for use in protein simulations outlined. We describe how simulations of crystalline peptides and amino-acids using an empirical force field can be combined with appropriate coherent and incoherent inelastic neutron scattering experiments to elucidate the characteristics of lattice vibrations and diffusive atomic motions in the crystals. The application of molecular dynamics simulations to the interpretation of incoherent neutron scattering experiments on proteins is examined and the resulting ideas on the general characteristics of protein motion discussed in terms of their functional implications.

Journal Article↗

Stress and coping in the context of psychoneuroimmunology: a holistic framework for nursing practice and research.

Nurses who specialize in mental health routinely deal with stress and coping as priority issues. Yet there has been no consensus on an overriding framework for organizing and interpreting knowledge concerning the influences of stress on health and well-being. In addition, stress-management interventions have often been piecemeal. This article surveys traditional and emerging conceptualizations of stress and stress management, with a special focus on the transactional model and psychoneuroimmunology as complementary integrative frameworks. The authors recommend a comprehensive approach for stress management that includes behavioral, cognitive, and combination strategies for active coping as well as cognitive-behavioral techniques for relaxation.

Adaptation, Psychological↗

Femoropopliteal bypass with externally supported knitted Dacron grafts: a follow-up of 200 grafts for one to twelve years.

PURPOSE: This article reports our experience with externally supported, preclotted knitted Dacron grafts in femoropopliteal bypass. METHODS: This is a retrospective analysis of a consecutive series of 154 patients who received 200 grafts (175 above knee and 25 below knee). Follow-up extended to 12 years (mean 59 1/2 months). RESULTS: Primary patency rates for the entire series were 75%, 70%, and 47% at 3, 5, and 10 years, respectively. Above-knee grafts had 76%, 71%, and 50% rates and 3, 5, and 10 years, respectively. Below-knee grafts had 65% and 57% at 3 and 5 years, respectively. Limb-salvage rates were 87%, 79%, and 73% at 3, 5, and 10 years, respectively, for the 57 limbs operated on because of critical ischemia. The most significant predictor of graft failure was poor runoff as determined by preoperative arteriography. The effect of poor runoff was most pronounced in the first 3 months. CONCLUSION: Externally supported, preclotted knitted Dacron grafts provide encouraging primary patency rates for above-knee femoropopliteal bypass. Poor leg vessel runoff is a major determinant of early graft failure.

Adult↗

Correlated intramolecular motions and diffuse X-ray scattering in lysozyme.

Correlated motions of protein atoms are of biological significance in processes involving ligand binding, conformational change and information transmission. X-ray scattering patterns from protein crystals contain diffuse scattering that originates from correlated displacements of atoms. Here we present experimental data on diffuse X-ray scattering from lysozyme crystals. We show that the diffuse scattering is similar in form to scattering derived from molecular dynamics simulation and normal mode analysis of the isolated protein, the normal modes giving the closest agreement with experiment.

Animals↗

Loss of sensitivity to low concentrations of NaCl following bilateral chorda tympani nerve sections in rats.

A reliable short-term NaCl taste test was developed for rats which resulted in differential responding to a variety of concentrations. The rats were required to exist on a low sodium diet for 8-10 days prior to the initiation of testing. The peak response in this test was to isotonic NaCl with lesser responding to hyper- and hypotonic solutions. After stable responding was obtained, bilateral sections were made of the chorda tympani nerves. This surgery resulted in a loss of sensitivity to the lowest hypotonic solutions (0.03 and 0.06 M NaCl). Little, if any, effect was noted in the perception of sucrose following these nerve sections.

Animals↗