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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 19 recordsLinked to original sources

Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.

The potent mesoderm-inducing factors activin and FGF are present as maternally synthesized proteins in embryos of X. laevis. We show that activin can act on explanted blastomeres to induce at least five different cell states ranging from posterolateral mesoderm to dorsoanterior organizer mesoderm. Each state is induced in a narrow dose range bounded by sharp thresholds. By contrast, FGF induces only posterolateral markers and does so over relatively broad dose ranges. FGF can modulate the actions of activin, potentiating them and broadening the threshold-bounded dose windows. Our results indicate that orthogonal gradients of activin and FGF would be sufficient to specify the main elements of the body plan.

Activins

Separation and identification of carotenoids and their oxidation products in the extracts of human plasma.

Eighteen carotenoids as well as vitamin A and two forms of vitamin E (gamma- and alpha-tocopherol) have been separated from extracts of human plasma by high-performance liquid chromatography (HPLC) on reversed-phase and sillca-based nitrile-bonded columns. In the order of chromatographic elution on a C18 reversed-phase column, the carotenoids were identified as (3R,3'R,6'R)-beta, epsilon-carotene-3,3'-diol [(3R,3'R,6'R)-lutein], (3R,3'R)-beta, beta-carotene-3,3'-diol [(3R,3'R)-zeaxanthin], 5,6-dihydroxy-5,6-dihydro-psi,psi-carotene, 3-hydroxy-2',3'-didehydro-beta,epsilon-caroten-3-ol, 3-hydroxy-beta-carotene,psi,psi-carotene, 7,8-dihydro-psi,psi-carotene, beta,psi-carotene, 7,8,7',8'-tetrahydro-psi,psi-carotene, beta,epsilon-carotene, beta,beta-carotene, 7,8,11,12,7',8'-hexahydro-psi,psi-carotene, and 7,8,11,12,7',8'-11',12'-octahydro-psi,psi-carotene. The polar carotenoids, which eluted in the vicinity of lutein and were unresolved on the C18 column, have been separated on a nitrile-bonded column employing isocratic HPLC conditions. In the order of elution, the carotenoids were epsilon,epsilon-carotene-3,3'-dione, 3'-hydroxy-epsilon,epsilon-caroten-3-one, 5,6-dihydroxy-5,6-dihydro-psi,psi-carotene, 3-hydroxy-beta,epsilon-caroten-3'-one, (all-E,3R,3'R,6'R)-lutein, (all-E,3R,3'R)-zeaxanthin, and (all-E,3R,3'S,6'R)-beta,epsilon-carotene-3,3'-diol (3'-epilutein) followed by several geometrical isomers of lutein and zeaxanthin.

Carotenoids

Abortion surveillance--United States, 1989.

Since 1980, the number of legal induced abortions reported to CDC has remained stable, varying each year by < 5%. In 1989, 1,396,658 abortions were reported--a 1.9% increase from 1988. The abortion ratio for 1989 was 346 legal induced abortions/1,000 live births, and the abortion rate was 24/1,000 women ages 15-44 years. The abortion ratio was highest for black women and women of other minority racial groups and for women < 15 years of age. Overall, women undergoing abortions tended to be young, white, and unmarried; to have had no previous live births; and to be having the procedure for the first time. Approximately half of all abortions were performed before the eighth week of gestation, and 87% were before the thirteenth week of gestation. Younger women tended to obtain abortions later in pregnancy than older women. This report also includes newly reported abortion-related deaths for 1986 and 1987, as well as an update on abortion-related deaths for the period 1978-1985. Ten deaths in 1986 and six deaths in 1987 were associated with legal induced abortion. The case-fatality rate in 1986 was 0.8 abortion-related deaths/100,000 legal induced abortions and 0.4/100,000 in 1987.

Abortion, Legal

Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue.

The Brachyrury (T) gene is required cell-autonomously for mesoderm formation in the posterior of the mouse embryo, and both is complementary DNA sequence and expression pattern closely resemble those of a Xenopus homologue (Xbra), suggesting that these genes have an evolutionarily conserved function in vertebrate development. Strong expression of Xbra messenger RNA is found in the ring of involuting mesoderm during Xenopus gastrulation, and the expression of Xbra is an immediate-early response of animal pole blastomeres to mesoderm-inducing factors. To assess the role of Xbra in mesoderm formation, we increased its domain of expression in the embryo by microinjection of Xbra transcripts into the animal pole of Xenopus embryos at the one-cell stage. We show that expression of Xbra by cells of the early embryo is sufficient to direct their development into differentiated mesodermal tissues. At the molecular level this response shows a sharp threshold of sensitivity to the dose of Xbra RNA delivered, and we suggest that Xbra may act as a genetic switch initiating posterior mesodermal specification during embryogenesis.

Animals

Keloid fibroblasts are refractory to inhibition of DNA synthesis by phorbol esters. Altered response is accompanied by reduced sensitivity to prostaglandin E2 and altered down-regulation of phorbol ester binding sites.

To investigate abnormal growth regulation in keloid fibroblasts, responses to phorbol esters were examined. Treatment of quiescent cultures with phorbol 12-myristate 13-acetate (PMA) blocked a normally occurring (20-24 h) peak of serum-stimulated thymidine incorporation in normal and keloid cells. In keloid fibroblasts PMA induced a delayed peak of DNA synthesis. When indomethacin was added with PMA the delayed peak appeared in normal fibroblasts. The ED50 for inhibition of the 20-24-h peak was 1 nM, whereas the delayed peak required a 50-fold-higher PMA concentration. In both cell types PMA induced prostaglandin E2 (PGE2) synthesis, and exogenous PGE2 caused 50% inhibition of the 20-24-h peak. When PMA and indomethacin were added with PGE2 the delayed peak was inhibited 90% in normal fibroblasts, whereas inhibition of keloid cells was the same as with PGE2 alone. Normal and keloid fibroblasts had the same number of phorbol ester binding sites. However, in normal cells, phorbol 12,13-dibutyrate bound with greater affinity, and down-regulation of phorbol ester binding occurred to a greater extent. These findings suggest that altered expression of protein kinase C isozymes or another molecule that binds phorbol esters may play a role in abnormal growth regulation of keloid cells.

Binding Sites

Glutamate release and presynaptic action of AP4 during inspiratory drive to phrenic motoneurons.

High-performance liquid chromatography (HPLC) was used to detect the presence of excitatory amino acids released from bulbospinal axon terminals projecting to cervical spinal respiratory motoneurons during transmission of inspiratory drive in an in vitro neonatal rat brainstem-spinal cord preparation. Measurements were then repeated under paradigms where transmitter release was decreased by either depression of bulbospinal respiratory drive, or by adding DL-2-amino-4-phosphonobutyrate (AP4) to the solution bathing the spinal cord. The amounts of glutamate, but not aspartate, released decreased significantly with depressed brainstem inspiratory drive or the activation of AP4-sensitive receptors within the cervical (C) spinal cord.

6-Cyano-7-nitroquinoxaline-2,3-dione

Whole-cell patch-clamp recordings from respiratory neurons in neonatal rat brainstem in vitro.

Whole-cell recordings were obtained from respiratory neurons by applying patch-clamp techniques in the en bloc medulla of in vitro neonatal rat brainstem-spinal cord preparations. Stable voltage-clamp recordings of excitatory or inhibitory synaptic drive currents and current-clamp recordings of spike discharge of inspiratory and expiratory neurons could be maintained for periods of 1-2 h. Parameters of whole-cell recording, including membrane seal resistances and series resistances, obtained in the en bloc medulla were similar to those obtained in corresponding regions of thin slices where neurons were directly visualized to optimize conditions for whole-cell patch clamp.

Animals

Maternal origin of deletion 15q11-13 in 25/25 cases of Angelman syndrome.

About half of the cases of Angelman syndrome arise from deletions of chromosome band 15q12. In 25 cases we have been able to determine the parental origin of the deletion and, in line with other reported cases, we have found the deletion to be of maternal origin. There were no exceptions. The parental origin was determined using cytogenetic markers in 13 of the cases, in nine by using the pattern of inheritance of restriction fragment length polymorphisms, and in three using both techniques.

Abnormalities, Multiple

A system for studying the microstructure of ingestive behavior in mice.

A system for long-term monitoring of mouse eating and drinking behavior with 6-s resolution is described. The apparatus utilizes infrared beams to monitor activity at a single feeding port and electronic contact detector circuitry to record individual licks at two drinking ports. Eight SWR/J mice were monitored using this system and data from the last day of testing with food and water were analyzed. Mice ate an average of 4.54 +/- 0.40 g of powdered food and drank an average of 5.81 +/- 0.65 ml of water. Mice had an average of 36.25 +/- 3.96 food bouts and 32.25 +/- 7.56 water bouts lasting 3.00 +/- 0.48 and 0.88 +/- 0.35 min, respectively. Information regarding the temporal association between eating and drinking and the circadian patterns of ingestion was provided, utilizing customized software that augments the system. Important implications for the use of mice in ingestion pattern research are discussed.

Animals

Thirst and salt appetite induced by hypovolemia in rats: analysis of drinking behavior.

A detailed description of the increased intake of water and 0.5 M NaCl solution by rats after colloid-induced hypovolemia was obtained by measuring drinking activity every 6 s for 23 h. After an initial phase of largely single-bout water drinking that reflected hypovolemic thirst, there was a marked increase in saline drinking in multiple-bout episodes. This salt appetite developed while rats were volume depleted but persisted for hours even after the plasma volume deficits were repaired. Their drinking episodes then seemed to reflect osmoregulation, since cumulative intakes of water and saline were in appropriate proportions to produce a near-isotonic NaCl solution. Remarkably, rats concocted a 1% NaCl solution within 29% of the drinking episodes, by alternating intakes of water and saline every 30-90 s. This alternation was too rapid to allow significant absorption of ingested fluids from the intestines and changes in plasma osmolality, and thereby to permit central osmoreceptors to influence ongoing consumption. Instead, we propose that, in these episodes, rats are guided by gustatory receptors to obtain the desired NaCl in a palatable solution.

Angiotensin II

Salt appetite induced by DOCA treatment or adrenalectomy in rats: analysis of ingestive behavior.

A detailed description of the increased intake of 0.5 M NaCl solution by rats after systemic treatment with desoxycorticosterone acetate (DOCA) or after adrenalectomy was obtained by measuring feeding and drinking activity every 6 s for 23 h. In both models of salt appetite, the induced increase in saline intake occurred mostly at night and in close temporal association with bouts of eating and water drinking rather than in isolation. Consequently, there was no significant change in the total number of ingestive episodes, despite the substantial increase in the number of saline bouts. Saline drinking was in small draughts that usually were preceded by food bouts and followed promptly by water bouts. These and other observations indicate that under standard maintenance conditions of ad lib access to food and fluids, adrenalectomy and DOCA treatment each produce a relatively weak stimulus of salt appetite, and large daily intakes accrue because the animals do not remain satiated and the appetite recurs repeatedly.

Adrenal Glands

Lack of an order effect in brief contact taste tests with closely spaced test trials.

The number of licks during 30-s exposures to a range of concentrations of sucrose, glucose, fructose, maltose, and Polycose were recorded. A complete series of concentrations of each carbohydrate was offered in ascending, descending, or random order with 30-s intertrial intervals. The order of presentation differed on different days. For sucrose, glucose, fructose, and maltose the number of licks in the 30-s periods was an increasing monotonic function of concentration regardless of the order of stimulus presentation. For Polycose, the lick rate-concentration function was an inverted U-shaped function of concentration with a peak on the 0.1 M to 0.2 M range. In all cases the rate of licking declined during the 30-s exposure period, suggesting the development of gustatory sensory adaptation. The results indicate that it is possible to obtain a rapid assessment of the taste sensitivity of the rat to a variety of carbohydrate solutions on a single day with very brief intertrial intervals.

Animals

Are beta 1 integrins involved in Xenopus gastrulation?

The molecular basis of vertebrate gastrulation is poorly understood. Work on urodele amphibians has implicated beta 1-containing integrins, but the limited information available for Xenopus indicates otherwise: peptides containing the RGD sequence do not inhibit gastrulation and induction of cell spreading in presumptive ectodermal cells by activin is not accompanied by an increase in synthesis of integrin beta 1. Here we report that beta 1-containing integrins are, nevertheless, the principal fibronectin receptors in the Xenopus gastrula, although their cell surface levels are low. Antibodies recognizing the external domain of the molecule can, unlike peptides containing the RGD site, block gastrulation when introduced into the blastocoel. These results allow us to propose a model to explain the role of integrin beta 1 in Xenopus gastrulation.

Activins

Organ donation in intensive care--a look at the ethical issues.

This paper is based on consideration of the ethical issues surrounding organ donation. This emotive subject has far-reaching implications concerning both donation and transplantation but the purpose in this paper is to deal specifically with issues related to cadaveric organ donation and how they concern nurses in an intensive care unit (ICU). A brief, general description of both ethics and organ donation is followed by a discussion of the issues surrounding the donor himself, including the diagnosis of brainstem death, the donor's family, and the nursing and medical implications. Legal, social and economic factors are considered with the aim of highlighting ethical areas but not necessarily providing answers to the questions raised.

Brain Death

Hydration-dependent far-infrared absorption in lysozyme detected using synchrotron radiation.

Using the National Synchrotron Light Source (NSLS) at Brookhaven far-infrared absorption in the frequency range 15-45 cm-1 was detected in samples of lysozyme at different hydrations and in water. The absorption is due to the presence of low-frequency (picosecond timescale) motion in the samples, such as are calculated in molecular dynamics simulations. The form of the transmission profile is temperature independent but varies significantly with the degree of hydration of the protein. At higher hydrations the profile resembles closely that of pure water in the region 20-45 cm-1. At a low hydration marked differences are seen with, in particular, the appearance of a transmission minimum at 19 cm-1. The possible origins of the hydration dependence are discussed. The results demonstrate the usefulness of long-wavelength synchrotron radiation for the characterisation of biologically-important low-frequency motions in protein samples.

Animals

Mortality, morbidity and complications following transurethral resection of the prostate for benign prostatic hypertrophy.

A total of 388 men undergoing transurethral resection of the prostate for benign prostatic hypertrophy during 1988 entered a prospective cohort study designed to examine the outcome of surgery during postoperative year 1. Self-administered questionnaires were completed preoperatively, and at 3, 6 and 12 months postoperatively. The surgeons completed 1 questionnaire shortly after surgery and another questionnaire 3, 6 or 12 months later. The mortality rate during the 12 months of followup was 2.8% (11 deaths). The surgeons reported perioperative complications in 14% of the patients and immediate postoperative complications, excluding urinary tract infections, in 17%. During the first 3 months postoperatively 38% of the patients reported incontinence and 25% had a urinary tract infection. Between 6 and 12 months postoperatively only 12% of the patients were troubled by either condition. The postoperative prevalence of impotence (24%) did not alter during followup and was similar to that reported preoperatively (22%). Of the patients 74% reported feeling better and 78% experienced a decrease in the overall level of symptoms postoperatively. The improvement in symptom levels was greatest in those with the most severe preoperative symptoms, and obstructive symptoms were alleviated slightly more than irritative symptoms.

Adult

Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men.

We determined serial changes in four major plasma carotenoid fractions (alpha-carotene, beta-carotene, lutein/zeaxanthin, and lycopene) in 30 men consuming defined daily doses of carotenoids from foods (broccoli, carrots, or tomato juice) or from purified beta-carotene in capsules (12 or 30 mg) for 6 wk while fed a controlled diet. Compared with baseline, beta-carotene increased in the 30- and 12-mg-capsule and carrot groups whereas alpha-carotene increased in the carrot group and lutein increased in the broccoli group. Lower lutein concentrations in recipients of beta-carotene capsules suggested an interaction between these two carotenoids. Lycopene declined in all groups except the tomato-juice group. Total carotenoid concentration changes only reflected the large increases in beta-carotene concentrations and not the smaller changes observed in other individual carotenoids. Overall, purified beta-carotene produced a greater plasma response than did similar quantities of carotenoids from foods sources. However, some foods increased plasma concentrations of certain carotenoids.

Adult