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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 163 records · Page 9Linked to original sources
PubMed1998

Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm.

Brachyury, a member of the T-box gene family, is required for posterior mesoderm and notochord differentiation in vertebrate development, and mis-expression of Xenopus Brachyury causes ectopic mesoderm formation. Brachyury is a transcription activator, and its ability to activate transcription is essential for its biological function, but Brachyury target genes have proved difficult to identify. Here we employ a hormone-inducible Brachyury construct and subtractive hybridization to search for such targets. Using this approach we have isolated Bix1, a homeobox gene expressed both in the marginal zone of Xenopus and in the vegetal hemisphere. Expression of Bix1 is induced in an immediate-early fashion by mesoderm-inducing factors such as activin as well as by the products of the T-box genes Xbra and VegT (also known as Antipodean, Brat and Xombi). Activation of Bix1 in response to Xbra is direct in the sense that it does not require protein synthesis, and both Xbra and VegT activate expression of a reporter gene driven by the Bix 5' regulatory region, which contains an Xbra/VegT binding site. Mis-expression of low levels of Bix1 causes formation of ventral mesoderm, while high levels induce endodermal differentiation. These results suggest that Bix1 acts downstream of both VegT and Xbra to induce formation of mesoderm and endoderm.

Activins↗
PubMed1997

The Xenopus Brachyury promoter is activated by FGF and low concentrations of activin and suppressed by high concentrations of activin and by paired-type homeodomain proteins.

The mesoderm of Xenopus laevis arises through an inductive interaction in which signals from the vegetal hemisphere of the embryo act on overlying equatorial cells. One candidate for an endogenous mesoderm-inducing factor is activin, a member of the TGFbeta superfamily. Activin is of particular interest because it induces different mesodermal cell types in a concentration-dependent manner, suggesting that it acts as a morphogen. These concentration-dependent effects are exemplified by the response of Xbra, expression of which is induced in ectodermal tissue by low concentrations of activin but not by high concentrations. Xbra therefore offers an excellent paradigm for studying the way in which a morphogen gradient is interpreted in vertebrate embryos. In this paper we examine the trancriptional regulation of Xbra2, a pseudoallele of Xbra that shows an identical response to activin. Our results indicate that 381 bp 5' of the Xbra2 transcription start site are sufficient to confer responsiveness both to FGF and, in a concentration-dependent manner, to activin. We present evidence that the suppression of Xbra expression at high concentrations of activin is mediated by paired-type homeobox genes such as goosecoid, Mix.1, and Xotx2.

3T3 Cells↗
PubMed1997

Pregnancy-related mortality surveillance--United States, 1987-1990.

PROBLEM/CONDITION: The Healthy People 2000: National Health Promotion and Disease Prevention Objectives specifies goals of no more than 3.3 maternal deaths per 100,000 live births overall and no more than 5.0 maternal deaths per 100,000 live births among black women; as of 1990, these goals had not been met. In addition, race-specific differences between black women and white women persist in the risk for pregnancy-related death. REPORTING PERIOD COVERED: This report summarizes surveillance data for pregnancy-related deaths in the United States for 1987-1990. DESCRIPTION OF SYSTEM: The National Pregnancy Mortality Surveillance System was initiated in 1988 by CDC in collaboration with the CDC/American College of Obstetricians and Gynecologists Maternal Mortality Study Group. Health departments in the 50 states, the District of Columbia, and New York City provided CDC with copies of death certificates and available linked outcome records (i.e., birth certificates or fetal death records) of all identified pregnancy-related deaths. RESULTS: During 1987-1990, 1,459 deaths were determined to be pregnancy-related. The overall pregnancy-related mortality ratio was 9.2 deaths per 100,000 live births. The pregnancy-related mortality ratio for black women was consistently higher than for white women for every risk factor examined by race. The disparity between pregnancy-related mortality ratios for black women and white women increased from 3.4 times greater in 1987 to 4.1 times greater in 1990. Older women, particularly women aged > or =35 years, were at increased risk for pregnancy-related death. The gestational age-adjusted risk for pregnancy-related death was 7.7 times higher for women who received no prenatal care than for women who received "adequate" prenatal care. The distribution of the causes of death differed depending on the pregnancy outcome; for women who died following a live birth (i.e., 55% of the deaths), the leading causes of death were pregnancy-induced hypertension complications, pulmonary embolism, and hemorrhage. INTERPRETATION: Pregnancy-related mortality ratios for black women continued, as noted in previously published surveillance reports, to be three to four times higher than those for white women. The risk factors evaluated in this analysis confirmed the disparity in pregnancy-related mortality between white women and black women, but the reason(s) for this difference could not be determined from the available information. ACTIONS TAKEN: Continued surveillance and additional studies should be conducted to assess the magnitude of pregnancy-related mortality, to identify those differences that contribute to the continuing race-specific disparity in pregnancy-related mortality, and to provide information that policy makers can use to develop effective strategies to prevent pregnancy-related mortality for all women.

Adult↗
PubMed1997

Abortion surveillance--United States, 1993 and 1994.

CONDITION: From 1991 through 1994, the number of legal induced abortions reported to CDC declined each year by < or =5% from the number reported for the preceding year. REPORTING PERIOD COVERED: This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1993 and 1994. This analysis also includes recently reported abortion-related deaths that occurred during 1991. DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City. RESULTS: In 1993, 1,330,414 legal abortions were reported to CDC, representing a 2.1% decrease from the number reported for 1992; in 1994, 1,267,415 abortions were reported, representing a 4.7% decrease from the number for 1993. In 1993 and 1994, the abortion ratio was 334 and 321 legal induced abortions per 1,000 live births, respectively. In 1993, the abortion rate was 22 per 1,000 women aged 15-44 years; in 1994, this rate declined to 21 per 1,000 women. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. More than half of all abortions (52%-54%) were performed at < or =8 weeks of gestation, and approximately 88% were before 13 weeks. Approximately 15%-16% of abortions were performed at < or =6 weeks of gestation, 16% were performed at 7 weeks, and 22% at 8 weeks. Younger women (i.e., women aged < or =19 years) were more likely to obtain abortions later in pregnancy than were older women. In 1991, 12 women died as a result of induced abortion: 11 of these deaths were related to legal abortion and one to illegal abortion. During 1991, the case-fatality rate of legal induced abortion was 0.8 abortion-related deaths per 100,000 legal induced abortions. INTERPRETATION: Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio also has declined; in 1994, it was the lowest recorded since 1977. This decrease in the abortion ratio reflected the lower proportion of pregnant women who obtained an induced abortion. As in previous years, deaths related to legal induced abortions occurred rarely (i.e., approximately one death per 100,000 legal induced abortions). ACTIONS TAKEN: The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.

Abortion, Legal↗
PubMed1997

Anteroposterior neural tissue specification by activin-induced mesoderm.

The transforming growth factor beta superfamily member, activin, is able to induce mesodermal tissues in animal cap explants from Xenopus laevis blastula stage embryos. Activin can act like a morphogen of the dorsoventral axis in that lower doses induce more ventral, and higher doses more dorsal, tissue types. Activin has also previously been reported to induce neural tissues in animal caps. From cell mixing experiments it was inferred that this might be an indirect effect of induced mesoderm signaling to uninduced ectoderm. Here we demonstrate directly that neural tissues do indeed arise by the action of induced mesoderm on uninduced ectoderm. Dorsal mesoderm is itself subdivided into posterior and anterior domains in vivo, but this had not been demonstrated for induced mesoderm. We therefore tested whether different concentrations of activin recreate these different anteroposterior properties as well. We show that the anteroposterior positional value of induced mesoderm, including its neuroinductive properties, depends on the dose of activin applied to the mesoderm, with lower doses inducing more posterior and higher doses giving more anterior markers. We discuss the implications of these results for patterning signals and the relationship between anteroposterior and dorsoventral axes.

Activins↗
PubMed1997

Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum.

Thirty-four carotenoids, including 13 geometrical isomers and eight metabolites, in breast milk and serum of three lactating mothers have been separated, identified, quantified, and compared by high-performance liquid chromatography (HPLC)-photodiode array (PDA) detection-mass spectrometry (MS). Among the metabolites were two oxidation products of lycopene and four of lutein/ zeaxanthin. In addition, two metabolites of lutein, formed as a result of dehydration of this dihydroxycarotenoid under acidic conditions similar to those of the stomach, have also been identified in plasma and breast milk. The oxidative metabolites of lycopene with a novel five-membered-ring end group have been identified as epimeric 2,6-cyclolycopene-1,5-diols by comparison of their HPLC-UV/visible-MS profiles with those of fully characterized (1H- and 13C-NMR spectroscopy) synthetic compounds. The HPLC procedures employed also detected vitamin A, two forms of vitamin E (gamma- and alpha-tocopherol), and two non-carotenoid food components, i.e., piperine and caffeine, in serum and breast milk.

Adult↗
PubMed1997

L-2-chloropropionic acid-induced cerebellar granule cell necrosis is potentiated by L-type calcium channel antagonists.

We have used the model of L-2-chloropropionic acid (L-CPA)-induced selective cerebellar granule necrosis to study excitatory amino acid-induced necrotic cell death in vivo produced by the activation of N-methyl-D-aspartate (NMDA) receptors. However, the mechanism for the NMDA receptor activation and the biochemical events which dictate the anatomical selectivity for the L-CPA-induced lesion are as yet unknown. We examined whether blockade of sodium and calcium channels may reduce the neurotoxicity through a reduction of glutamate release from granule cells. None of the sodium channel antagonists examined, i.e. phenytoin, lamotrigine or rilazole nor the mixed sodium/calcium channel blocker, lifarazine, altered the L-CPA neurotoxicity. However, L-type calcium channel blockers, verapamil and nifedipine enhanced the L-CPA-induced granule cell necrosis, assessed by measuring the degree of L-CPA-induced reductions in cerebellar aspartate concentration, increases in cerebellar glycine concentrations and the development of cerebellar oedema. In addition, the locomotor activity of rats receiving both L-CPA and either verapamil or nifedipine was significantly lower than when rats received L-CPA alone, suggesting an enhancement of the neurotoxicity of L-CPA by L-type calcium channel blockade. The data suggest that L-CPA may interfere with non-L-type calcium channels located on granule cell bodies and nerve terminals leading to reduction of the calcium entry into the cells. We suggest that a combination of L-type channel blockade and non-L-type channels which are sensitive to L-CPA produces reductions in intracellular calcium concentrations below that required for neuronal survival.

Animals↗
PubMed1997

Small-angle neutron scattering by a strongly denatured protein: analysis using random polymer theory.

Small-angle neutron scattering profiles are presented from phosphoglycerate kinase, in the native form and strongly denatured in 4 M guanidinium chloride (GdnHCl) solution. The data are interpreted using a model in which the excess scattering density associated with the protein is represented as a finite freely jointed chain of spheres. The similarity of the model-derived scattering function to experiment increases asymptotically with the number of spheres. The improvement of the fit obtained with more than approximately 200 spheres (i.e., two residues per sphere) is insignificant. The effects of finite size of the scattering units and of scattering length variation along the polypeptide chain are examined. Improved agreement with experiment is obtained when these effects are taken into account. A method for rapid calculation of the scattering profile of a full, all-atom configuration is examined. It is found that a representation of the chain containing two scattering units per residue, placed at the backbone and side-chain scattering length centroids, reproduces the full, all-atom profile to within 2%.

Fourier Analysis↗
PubMed1997

Extinction of a conditioned taste aversion in rats: I. Behavioral effects.

The literature is divided over whether a conditioned taste aversion (CTA) can be fully extinguished. In Experiment 1, we created a powerful aversion in 54 rats by pairing the taste of 0.0025 M NaSaccharin (CS) with intraperitoneal injections of 127 mg/kg LiCl (US) on 3 occasions. We then offered 23-h deprived rats NaSaccharin for 10 min/day to observe the course of recovery. Extinction occurred in three phases: static, dynamic, and asymptotic. During the static phase (mean = 9.6 days), rats consumed the CS at < 10% of their preconditioned rate. With dynamic recovery (6.0 days), they increased acceptance to > 80% of preconditioning levels. Finally, they achieved asymptote (3.1 days) at 100% acceptance. In Experiment 2, we used 8 additional conditioned rats and 8 unconditioned controls. We followed the same 1-bottle extinction procedure and, again, obtained 100% acceptance. Then we offered both NaSaccharin and water for 8 days at 23 h/day and monitored lick patterns every 6 s to determine taste preferences. The conditioned animals consumed less NaSaccharin than controls on Day 1, and less NaSaccharin as a percentage of total fluid as late as Day 3. For the last 5 days of 2-bottle preference testing, there were no significant differences between the groups with regard to 1. volume of NaSaccharin or water consumed, 2. percentage of total fluid taken as NaSaccharin, 3. consumption of each fluid associated with a meal or taken spontaneously, 4. intake during the light or dark periods, or 5. the characteristics of ingestion, including number of drinking bouts, duration of bouts, number of licks/bout, and rate of licking. Therefore, a robust CTA is subject to complete behavioral extinction.

Animals↗
PubMed1997

Structure of human annexin I: comparison of homology modelling and crystallographic experiment.

A model of domain II of annexin I has been built by homology modelling using an annexin V crystal structure as a template. The method used is based on that of Summers and Karplus (J Mol Biol (1989) 210, 785-811) and involves the calculation of torsion-angle rotational energy maps to position side chains. The RMS deviation of the backbone heavy atoms between the model and a crystal structure of annexin I is 1.1 A. Similarities and differences in the experimental and model-derived side-chain rotameric conformations and hydrogen-bonding interactions are examined. It is found that whereas many of the side chains are well positioned some of those placed using the 'entropy argument' in which the broadest of the available minima are preferred, are erroneous. The domain is subjected to molecular dynamics simulation in explicit solvent. The simulations are found to 'correct' some of the side-chain rotamer positions that were poorly placed in the homology modelling. Considerable helix instability is seen in the simulations, consistent with the requirement of domain interactions for the structural integrity of the protein.

Amino Acid Sequence↗
PubMed1997

Differential effects on Xenopus development of interference with type IIA and type IIB activin receptors.

One candidate for a mesoderm-inducing factor in early amphibian development is activin, a member of the TGF beta family. Overexpression of a truncated form of an activin receptor Type IIB abolishes activin responsiveness and mesoderm formation in vivo. The Xenopus Type IIA activin receptor XSTK9 differs from the Type IIB receptor by 43 and 25% in extracellular and intracellular domains respectively, suggesting the possibility of different functions in vivo. In this paper, we compare the Type IIA receptor with the Type IIB to test such a possibility. Simple overexpression of the wild-type receptors reveals minimal differences, but experiments with dominant negative mutants of each receptor show qualitatively distinct effects. We show that while truncated (kinase domain-deleted) Type IIB receptors cause axial defects as previously described, truncated type IIA receptors cause formation of secondary axes, similar to those seen by overexpression of truncated receptors for BMP-4, another TGF beta family member. Furthermore, in animal cap assays, truncated type IIB receptors inhibit induction of all mesodermal markers tested, while truncated type IIA receptors suppress induction only of ventral markers; the anterior/dorsal marker goosecoid is virtually unaffected. The suppression of ventral development by the type IIA truncated receptor suggests either that the truncated Type IIA receptor interferes with ventral BMP pathways, or that activin signaling through the Type IIA receptor is necessary for ventral patterning.

Activin Receptors↗
PubMed1997

Use of body mass index to monitor treatment of obese adolescents.

PURPOSE: Absolute weight loss may not always be the best measure of adherence and response to therapy in obese adolescents if weight gain owing to linear growth is not considered. We wished to compare short-term absolute weight and height changes with changes in body mass index (BMI) in a group of severely obese adolescents to determine the most meaningful measure of treatment response. METHODS: We analyzed weight, height, and BMI in 27 adolescents, 10-18 years of age, referred for management of severe obesity. Subjects attended clinic on at least three occasions within a 6-24-month period. Detailed profiles of usual daily food intakes, physical activities, and family and environmental structure/activities were obtained, and specific goals to achieve weight control were negotiated with adolescents and their families at each visit. Weight, height, and BMI at the initial visit and at the most recent visit were compared. RESULTS: While 48% of our population actually lost weight, 78% either had no change or a decrease in BMI during the observation period. Differences between initial and most recent heights and BMIs were statistically significant, but weight changes were not significant. CONCLUSIONS: In addition to weight, BMI should be routinely used and reported when monitoring the response to specific interventions in growing adolescents. Evaluation of weight alone may underestimate the adolescent's adherence to treatment goals.

Adolescent↗
PubMed1997

Polio eradication in the World Health Organization South-East Asia Region by the year 2000: midway assessment of progress and future challenges.

In the South-East Asia Region (SEAR) of WHO, paralytic poliomyelitis has decreased from 25,711 cases in 1988 to 3304 cases in 1995, representing an 87% reduction. By 1995, in 6 of 10 member countries--India, Bangladesh, Myanmar, Nepal, Indonesia, and Democratic People's Republic of Korea--polio remained endemic. Two countries, Sri Lanka and Thailand, appear close to polio eradication, and 2, Bhutan and Maldives, reported no cases during 1989-1995. Although reported rates of acute flaccid paralysis and the percentage of cases virologically investigated are low in some countries, no isolates of wild poliovirus type 2 have been reported outside India since 1993. By the end of 1996, all 8 countries in which polio is endemic will have conducted national immunization days for polio eradication. The major challenge for polio eradication in SEAR will be strengthening surveillance, because national immunization days alone cannot eradicate polio.

Asia, Southeastern↗
PubMed1997

Facial cooling-induced bradycardia: attenuating effect of central command at exercise onset.

Facial cooling (FC) elicits a marked bradycardia at rest that appears to be reduced during exercise. This study was done to delineate the effects of exercise mediated central command from those of muscle afferent feedback and sympathetic stimulation on the attenuation of the bradycardic effect of FC during the onset of exercise. Ten healthy subjects (26 +/- 2 yr) were exposed to FC under five different conditions: 1) seated rest on the cycle ergometer, 2) onset of mild exercise (resting HR + 20 beats.min-1), 3) onset of moderate exercise (resting HR + 50 beats.min-1), 4) seated rest on the ergometer during electrical stimulation, and 5) seated rest on the ergometer during a cold immersion test (CT) (one hand immersed in an ice slurry at 0 degree C). The two exercise intensities were presumed to provide different degrees of central command. Electrical stimulation of the quadriceps was assumed to provide isolated muscle afferent feedback, while the CT served as a sympathetic stimulus. Beat-by-beat data were recorded for HR and mean arterial blood pressure for the duration of each test (50 s), and a rating of perceived pain was taken after each FC. FC elicited significant increases in mean arterial pressure during mild and moderate exercise compared with resting control (P < 0.05) and during moderate exercise compared to exercise without FC (P < 0.05). Mean decreases in HR during FC were similar for resting control (-12 +/- 3 beats.min-1), electrical stimulation (-10 +/- 3 beats.min-1), and CT (-9 +/- 3 beats.min-1). The HR response to FC during mild exercise (-7 +/- 2 beats.min-1) was significantly different (P < 0.05) from the rest condition; however, there was no significant bradycardia (-2 +/- 2 beats.min-1; P > 0.05) during onset of moderate exercise. These findings suggest that the magnitude of cold face-induced bradycardia may be attenuated at exercise onset by neural signals related to the higher levels of central motor command associated with heavier exercise.

Adult↗
PubMed1997

Naturally occurring muscle pain during exercise: assessment and experimental evidence.

The objectives were: (i) to present a method for assessing muscle pain during exercise, (ii) to provide reliability and validity data in support of the measurement tool, (iii) to test whether leg muscle pain threshold during exercise was related to a commonly used measure of pain threshold pain during test, (iv) to examine the relationship between pain and exertion ratings, (v) to test whether leg muscle pain is related to performance, and (vi) to test whether a large dose of aspirin would delay leg muscle pain threshold and/or reduce pain ratings during exercise. In study 1, seven females and seven males completed three 1-min cycling bouts at three different randomly ordered power outputs. Pain was assessed using a 10-point pain scale. High intraclass correlations (R from 0.88 to 0.98) indicated that pain intensity could be rated reliably using the scale. In study 2, 11 college-aged males (age 21.3 +/- 1.3 yr) performed a ramped (24 W.min-1) maximal cycle ergometry test. A button was depressed when leg muscle pain threshold was reached. Pain threshold occurred near 50% of maximal capacity: 50.3 (+/- 12.9% Wmax), 48.6 (+/- 14.8% VO2max), and 55.8 (+/- 12.9% RPEmax). Pain intensity ratings obtained following pain threshold were positively accelerating function of the relative exercise intensity. Volitional exhaustion was associated with pain ratings of 8.2 (+/- 2.5), a value most closely associated with the verbal anchor "very strong pain." In study 3, participants completed the same maximal exercise test as in study 2 as well as leg cycling at 60 rpm for 8 s at four randomly ordered power outputs (100, 150, 200, and 250 W) on a separate day. Pain and RPE ratings were significantly lower during the 8-s bouts compared to those obtained at the same power outputs during the maximal cycle test. The results suggest that noxious metabolites of muscle contraction play a role in leg muscle pain during exercise. In study 4, moderately active male subjects (N = 19) completed two ramped maximal cycle ergometry tests. Subjects drank a water and Kool-Aid mixture, that either was or was not (placebo) combined with a 20 mg.kg-1 dose of powdered aspirin 60 min before exercise. Paired t-tests revealed no differences between conditions for the measures of exercise intensity at pain threshold [aspirin vs placebo mean (+/- SD)]: power output: 150 (+/- 60.3 W) versus 153.5 (+/- 64.8 W); VO2: 21.3 (+/- 8.6 mL.kg-1.min-1) versus 22.1 (+/- 10.0 mL.kg-1.min-1); and RPE: 10.9 (+/- 3.1) versus 11.4 (+/- 2.9). Repeated measures ANOVA revealed no significant condition main effect or condition by trial interaction for pain responses during recovery or during exercise at 60, 70, 80, 90, and 100% of each condition's peak power output. It is concluded that the perception of leg muscle pain intensity during cycle ergometry: (i) is reliably and validly measured using the developed 10-point pain scale, (ii) covaries as a function of objective exercise stimuli such as power output, (iii) is distinct from RPE, (iv) is unrelated to performance of the type employed here, and (v) is not altered by the ingestion of 20 mg.kg-1 acetylsalicylic acid 1 h prior to the exercise bout.

Adolescent↗
PubMed1997

Outcome of pregnancy in women with Marfan's syndrome.

OBJECTIVE: To improve life expectancy and prevent premature mortality in women with Marfan's syndrome. METHODS: During the development of a regional genetic register for Marfan's Syndrome the outcome of 91 pregnancies in 36 women with this condition was established retrospectively and the cardiovascular and obstetric complications documented. RESULTS: No patient had a significant cardiovascular abnormality limiting function before her pregnancy. Of 36 women, four had an aortic dissection relating to pregnancy and two others required aortic surgery following delivery. Thirty women had uncomplicated gestational histories. The incidence of obstetric complications did not exceed expectation. CONCLUSIONS: Women with Marfan's syndrome are at significant risk of aortic dissection in pregnancy even in the absence of preconceptional cardiovascular abnormality. Aortic root dilatation may be a predictor of risk but dissection may occur without significant dilatation. Guidelines for obstetric care are suggested and preconceptional assessment recommended.

Adult↗