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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 235 records · Page 13Linked to original sources
PubMed1995

New computational models of the respiratory oscillator in mammals.

Understanding how respiratory oscillations are generated and controlled in the mammalian brainstem requires synthesis of neural function at cellular, synaptic, and network levels. Modeling the respiratory network has entered a new era where simulations incorporating complex cellular properties and network interactions exhibited by respiratory neurons are possible. Given the complexity and unknowns of the real system, there are obvious limitations of the modeling in its present form. Nevertheless, if we are to produce neurobiologically satisfying, mechanistic explanations that synthesize cellular and network phenomena, the modeling approach outlined here should have distinct advantages. The approach allows a close interaction between experimental and computational studies, and will enable simulations with increasing neurobiological realism as additional experimental data becomes available. The modeling summarized here represents the initial stages of establishing a computational framework for storing information about neuron and network properties, and for exploring complex dynamical properties in ways not possible experimentally.

Animals↗
PubMed1995

Mesoderm-inducing factors and mesodermal patterning.

Identification of the signalling molecules involved in mesoderm formation in amphibian embryos still presents problems. None of the original candidates, such as activin, have been definitively ruled out, and new factors, such as the nodal-related genes, have come on to the scene. Of the original candidates, activin has been definitively shown to act as a morphogen, whereas bone morphogenetic protein (BMP)-4 has emerged as a ventral inducer and an inhibitor of neural differentiation. The effects of BMP-4 are antagonized by chordin, a molecule related to the product of the Drosophila gene short gastrulation.

Animals↗
PubMed1995

Functional interactions in bacteriorhodopsin: a theoretical analysis of retinal hydrogen bonding with water.

The light-driven proton pump, bacteriorhodopsin (bR) contains a retinal molecule with a Schiff base moiety that can participate in hydrogen-bonding interactions in an internal, water-containing channel. Here we combine quantum chemistry and molecular mechanics techniques to determine the geometries and energetics of retinal Schiff base-water interactions. Ab initio molecular orbital calculations are used to determine potential surfaces for water-Schiff base hydrogen-bonding and to characterize the energetics of rotation of the C-C single bond distal and adjacent to the Schiff base NH group. The ab initio results are combined with semiempirical quantum chemistry calculations to produce a data set used for the parameterization of a molecular mechanics energy function for retinal. Using the molecular mechanics force field the hydrated retinal and associated bR protein environment are energy-minimized and the resulting geometries examined. Two distinct sites are found in which water molecules can have hydrogen-bonding interactions with the Schiff base: one near the NH group of the Schiff base in a polar region directed towards the extracellular side, and the other near a retinal CH group in a relatively nonpolar region, directed towards the cytoplasmic side.

Bacteriorhodopsins↗
PubMed1995

Effect of pedal cadence on parameters of the hyperbolic power-time relationship.

The purpose of this study was to evaluate the effect of pedal cadence methodology on the relationship between power output and time to exhaustion. Twenty-four subjects each performed 12 all-out cycle ergometer tests (four at a constant 60 rpm, four at a constant 100 rpm, and four where they were allowed to select and, within each test, vary their cadence). The parameters of the hyperbolic power-time relationship, AWC (anaerobic work capacity) and CP (critical power), were estimated for each pedal cadence methodology using three regression models: nonlinear power-time, linear work-time, and linear power-time-1. In all cases, R2 was high and standard errors of the estimate of AWC and CP were low. With the two constant rpm methodologies, the estimates of AWC and CP were influenced by the choice of regression model. The estimates of AWC and CP were also influenced by the pedal cadence in the all-out tests. For example, the CP derived from the 100 rpm tests (mean +/- SD: 195 +/- 50 W) was lower (p < 0.05) than the CP from the other methodologies (207 +/- 50 W and 204 +/- 48 W), and the AWC from the variable cadence methodology (16.1 +/- 6.2 kJ) was greater than the AWC from constant rpm trials (14.5 +/- 5.9 kJ and 14.6 +/- 5.7 kJ). It is concluded that pedal cadence methodology influences the parameters of the power-time relationship.

Acceleration↗
PubMed1995

Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.

Proteins in the TGF-beta superfamily transduce their effects through binding to type I and type II serine/threonine kinase receptors. Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 or BMP-7), a member of the TGF-beta superfamily which belongs to the BMP subfamily, was found to bind activin receptor type I (ActR-I), and BMP receptors type IA (BMPR-IA) and type IB (BMPR-IB) in the presence of activin receptors type II (ActR-II) and type IIB (ActR-IIB). The binding affinity of OP-1 to ActR-II was two- to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR-II. These results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins. Some of the known biological effects of activin were observed for OP-1, including growth inhibition and erythroid differentiation induction. Compared to activin, OP-1 was shown to be a poor inducer of mesoderm in Xenopus embryos. Moreover, follistatin, an inhibitor of activins, was found to inhibit the effects of OP-1, if added at a 10-fold excess. However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. OP-1 has overlapping binding specificities with activins, and shares certain but not all of the functional effects of activins. Thus, OP-1 may have broader effects in vivo than hitherto recognized.

Activin Receptors↗
PubMed1995

Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells.

Differentiated cultures of Caco-2 human colonic cells were used to examine the importance of reduction of nonheme ferric iron, Fe(III), for transport across the brush border surface. Cultures accumulated approximately 100 pmol Fe/(h.mg protein) when 10 mumol Fe(III) as the nitrilotriacetic acid complex (1Fe:2NTA) was added to the apical compartment. Ascorbic acid enhanced cellular acquisition of iron in a dose-dependent manner, with a concentration as low as 8 mumol/L ascorbate increasing iron uptake by 50%. Similarly, the rate of iron transport from the apical to the basolateral compartment increased 5.6- and 30-fold when 100 and 1000 mumol/L ascorbic acid, respectively, were present in the apical chamber. Ascorbate-mediated stimulation of iron uptake was temperature dependent and required the reduction of Fe(III) to Fe(II), because it was inhibited by ascorbate oxidase and chelators of Fe(II). Moreover, Caco-2 cells recycled dehydroascorbic acid to ascorbic acid. Ferricyanide and Fe(II) chelators also partially inhibited iron uptake from a medium devoid of ascorbic acid. Intact Caco-2 cells exhibited a ferrireductase activity on the apical surface that accounted for the majority of iron accumulated by cells incubated in the absence of exogenous reductant. These data suggest that reduction of Fe(III) within the lumen or at the cell surface is required for transfer of this essential micronutrient across the intestinal brush border surface.

Ascorbic Acid↗
PubMed1995

Epidemiology of cleft lip and cleft palate in Mississippi.

We present an epidemiologic study of the cases of cleft lip and cleft palate in Mississippi from 1980 through 1989. Cases were stratified by race (white and nonwhite) but not by association with a major malformation. During this period, a total of 457 new patients with cleft lip or cleft palate were identified from a population of approximately 439,354 live births. The incidence of total clefts in live-born infants was 1.36/1,000 for whites and 0.54/1,000 for nonwhites. White boys had a higher incidence of cleft lip and palate than white girls; black boys had an extremely low incidence of cleft lip, whereas black girls showed a higher incidence of cleft palate alone. Examination of the rate of cleft malformations for each county in Mississippi revealed no clearly defined pattern, nor were we able to demonstrate that rates were increased in a major agricultural area of the state, in which use of potentially toxic products is high.

Cleft Lip↗
PubMed1995

Periodic carbohydrate replacement during 50 min of high-intensity cycling improves subsequent sprint performance.

The purpose of this study was to investigate the effect of 7% carbohydrate-electrolyte (CE) drink on sprint capacity immediately following 50 min of high-intensity cycling. After an overnight 12-hr fast, 8 trained male cyclists performed two 50-min simulated time trials on a Monark stationary cycle ergometer. Subjects consumed either the CE or a flavored water placebo (PL) at 10, 20, 30, and 40 min during the time trial. At the conclusion of each 50-min time trial, subjects immediately performed a Wingate Anaerobic Power Test. Peak power, mean power, and minimum power were significantly higher for the CE trials, whereas mean RPE was significantly lower. Mean heart rate and fatigue index were not different between trials. These results suggest that sprint performance following a high-intensity simulated time trial of only 50 min can be improved with periodic consumption of CE during the ride, particularly following an overnight fast, when liver glycogen is likely to be low. These findings have implications for competitive cycling, where sprint capacity at the conclusion of a race is an important determinant of success.

Adult↗
PubMed1995

Pre-Bötzinger complex in the cat.

1. Patterns of respiratory neuronal activity were examined in pentobarbitone anesthetized adult cats in a circumscribed area of the ventrolateral medulla, which has previously been defined as the pre-Bötzinger complex (pre-BOTC) from electrophysiological and morphological criteria in the brain stem-spinal cord preparation of the neonatal rat. The pre-BOTC has been proposed to play a critical role in respiratory rhythm generation in mammals, but electrophysiological properties of the region have not been thoroughly characterized in the adult brain stem in vivo. 2. From intra- and extracellular recordings, we verified the existence of a well-defined zone with a distinct profile of neuronal activity between the rostral Bötzinger complex containing expiratory neurons and the more caudal medullary pool of inspiratory neurons of the ventral respiratory group (VRG) in the para-ambigual region. This zone corresponds to the pre-BOTC. It was characterized by a concentration of the various types of respiratory neurons, particularly those proposed to be involved in respiratory phase transitions, including neurons discharging immediately before the onset of inspiratory phase activity (pre-inspiratory neurons), early-inspiratory, and postinspiratory neurons. The majority of these neurons were presumed interneurons because they were not antidromically activated by spinal cord or cranial nerve stimulation. 3. The locus of the pre-BOTC corresponded histologically to the rostral part of the nucleus ambiguus and ventrolateral reticular formation. It was located caudal to the retrofacial nucleus and rostral to the lateral reticular nucleus, extending 3.0-3.5 mm rostral to the obex, and 3.2-4.0 mm lateral from the midline. This location was homologous to that established in the neonatal rat. 4. Pre-inspiratory neurons (pre-I neurons) were specifically found in the pre-BOTC. Intracellular recordings from these neurons revealed two types of activity patterns. Type 1 of pre-I neurons exhibited a steady membrane depolarization during expiration and a steep membrane depolarization with a high-frequency burst of action-potential discharge during the phase transition from expiration to inspiration. This was followed by a decline of depolarization and spike discharge during the remainder of the inspiratory phase. A second type of pre-I neurons exhibited a secondary graded membrane depolarization and burst discharge during the late-inspiratory period. 5. Synaptic events were examined in other respiratory neurons during the 40-160 ms preceding the onset of phrenic nerve activity when pre-I neurons exhibited peak spike discharge. Early-inspiratory, throughout-respiratory, and postinspiratory neurons were disinhibited during this period, whereas stage-2 expiratory neurons exhibited a decrease in spike activity and repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1995

Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation.

Mouse embryos homozygous for a null mutation in nodal arrest development at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodal-related genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first within the vegetal region of late blastulae and later in the marginal zone during gastrulation, with enrichment in the dorsal lip. Xnrs and mouse nodal function as dose-dependent dorsoanterior and ventral mesoderm inducers in whole embryos and explanted animal caps. Using a plasmid vector to produce Xnr proteins during gastrulation, we show that, in contrast to activin and other TGF beta-like molecules, Xnr-1 and Xnr-2 can dorsalize ventral marginal zone explants and induce muscle differentiation. Xnr signalling also rescues a complete embryonic axis in UV-ventralized embryos. The patterns of Xnr expression, the activities of the proteins and the phenotype of mouse nodal mutants, all argue strongly that a signaling pathway involving nodal, or nodal-related peptides, is an essential conserved element in mesoderm differentiation associated with vertebrate gastrulation and axial patterning.

Amino Acid Sequence↗
PubMed1995

Patterning of the mesoderm in Xenopus: dose-dependent and synergistic effects of Brachyury and Pintallavis.

Widespread expression of the DNA-binding protein Brachyury in Xenopus animal caps causes ectopic mesoderm formation. In this paper, we first show that two types of mesoderm are induced by different concentrations of Brachyury. Animal pole explants from embryos injected with low doses of Xbra RNA differentiate into vesicles containing mesothelial smooth muscle and mesenchyme. At higher concentrations somitic muscle is formed. The transition from smooth muscle formation to that of somitic muscle occurs over a two-fold increase in Brachyury concentration. Brachyury is required for differentiation of notochord in mouse and fish embryos, but even the highest concentrations of Brachyury do not induce this tissue in Xenopus animal caps. Co-expression of Brachyury with the secreted glycoprotein noggin does cause notochord formation, but it is difficult to understand the molecular basis of this phenomenon without knowing more about the noggin signal transduction pathway. To overcome this difficulty, we have now tested mesoderm-specific transcription factors for the ability to synergize with Brachyury. We find that co-expression of Pintallavis, but not goosecoid, with Brachyury causes formation of dorsal mesoderm, including notochord. Furthermore, the effect of Pintallavis, like that of Brachyury, is dose-dependent: a two-fold increase in Pintallavis RNA causes a transition from ventral mesoderm formation to that of muscle, and a further two-fold increase induces notochord and neural tissue. These results suggest that Pintallavis cooperates with Brachyury to pattern the mesoderm in Xenopus.

Animals↗
PubMed1995

A capitated payment system for involuntary mental health clients.

This DataWatch examines an outpatient capitated payment system, in the state of Oregon, designed to enhance community services for persons with chronic mental illness who had repeatedly been hospitalized involuntarily. Special state funds and Medicaid dollars were used to pay providers prospectively on a risk-adjusted basis for the delivery of outpatient mental health services. During the three-year study period clients were able to be discharged from the state hospital. Although the data are not straightforward, capitated clients' use of the state mental hospital seems to have declined somewhat more than that of comparison subjects. Outpatient service use was modest and appeared to have little relationship to a client's level of illness severity. Indeed, it was not possible to predict prospectively these clients' outpatient mental health services expenditures.

Capitation Fee↗
PubMed1995

Vasectomy in the United States, 1991.

OBJECTIVES: Recent conflicting findings on possible health risks related to vasectomy have underscored the need for reliable and representative estimates of numbers and rates of vasectomies in the United States. The purpose of this study was to estimate the annual US number, rate, and characteristics of vasectomies in 1991. METHODS: A national survey of urology, general surgery, and family practice physician practices was conducted with probability sampling methods (n = 1685 physicians). RESULTS: An estimated 493,487 (95% confidence interval = 450,480, 536,494) vasectomies were performed in 1991, for a rate of 10.3 procedures per 1000 men aged 25 through 49 years. Most vasectomies were performed by urologists, and most were done in physicians' offices with local anesthesia and ligation as the method of occlusion. The rate of vasectomies was highest in the Midwest. CONCLUSIONS: This survey provides the first national estimates of the number and rate of vasectomies in the United States, as well as the first estimates of occlusion method used. Results confirm previous findings that urologists perform most vasectomies and that most vasectomies are performed with local anesthesia. Recommendations include the monitoring of vasectomy numbers and rates as well as demographic studies of men obtaining vasectomies.

Adult↗
PubMed1995

Ascorbate offsets the inhibitory effect of inositol phosphates on iron uptake and transport by Caco-2 cells.

Differentiated monolayer cultures of Caco-2 human intestinal cells were used as a model to examine interactions between various dietary factors related to the intestinal uptake and absorption of nonheme Fe. Caco-2 cells accumulated 91-98 pmol Fe/mg protein from uptake buffer containing 12 nmol of Fe(III)-nitrilotriacetate during a 1-hr incubation at 37 degrees C. Addition of a 10-fold molar excess of inositol hexaphosphate (IP6) and its lesser phosphorylated derivatives (IP3, IP4, and IP5) decreased cellular uptake and transport of Fe from the lumenal compartment. Addition of ascorbic acid (AA) to the solution containing IPs stimulated Fe uptake and transport in a manner dependent upon the ratio of AA to IP and inversely proportional to the degree of phosphorylation of inositol (i.e., IP3 > IP4 > IP5 > IP6). A mixture of essential amino acids had minimal impact on Fe uptake in either the absence or presence of IPs. Cellular acquisition of Fe from solutions containing IPs was further enhanced by simultaneous addition of essential amino acids and AA. The stimulatory influence of ascorbic acid on Fe uptake from solutions containing IP6 was associated with an increase in the level of ferrous ion. These data further support the usefulness of Caco-2 cells as a model for investigating the effects of various dietary factors on mineral bioavailability.

Ascorbic Acid↗
PubMed1995

Technology assessment at the Institute for Clinical Systems Integration and HealthPartners.

The Technology Assessment Committee of the Institute for Clinical Systems Integration (ICSI) draws upon the resources of many different groups and in turn, keeps the groups informed about new medical treatments, devices, and procedures. This new Minneapolis-based technology assessment committee uses a collaborative effort to serve the information needs of many employer groups, patients, providers, and health care organizations in the area. This committee serves as the principal mechanism by which new medical and surgical procedures, devices, and treatments, as well as new applications of old but unproved or doubtful applications of existing technologies are reviewed for medical appropriateness at ICSI (a nonprofit quality improvement organization) and at HealthPartners (a combined staff and group model HMO in Minnesota).

Academies and Institutes↗
PubMed1995

Cost-effectiveness analysis of a rotavirus immunization program for the United States.

OBJECTIVE: To estimate the economic consequences in the United States of routine childhood immunization of children younger than 1 year of age with a rotavirus (RV) vaccine. DESIGN: Cost-effectiveness analysis of a national RV immunization program from the perspective of the health care system and the perspective of society. Estimates of disease incidence, medical expenditures, productivity costs, vaccine efficacy, and vaccine coverage rates were derived from published literature and unpublished vaccine trial reports. The impact of changes in estimates of vaccine efficacy and medical costs was determined by sensitivity analysis. MAIN OUTCOME MEASURES: Incremental cost effectiveness, expressed as savings per case of RV diarrhea prevented. RESULTS: Given a vaccine efficacy rate of 50% and a vaccine cost of $30 per dose, an RV immunization program would prevent more than 1 million cases of RV diarrhea, 58,000 hospitalizations, and 82 deaths per year. A vaccine program would cost $243 million per year but would yield net savings of $79 million from the perspective of the health care system and $466 million from the perspective of society. The incremental cost effectiveness was a savings of $459 per case prevented from the societal perspective and $78 per case prevented from the health care system perspective. Sensitivity analyses substantiated net savings over a wide range of variables, and cost effectiveness increased with greater vaccine efficacy or decreased vaccine cost. CONCLUSIONS: Economic and disease reduction benefits would be realized from the use of an RV vaccine that is partially protective against severe RV diarrhea. These findings suggest that immunization with an RV vaccine would be cost effective and cost saving.

Child, Preschool↗
PubMed1995

Modulation of neural network activity in vitro by cyclothiazide, a drug that blocks desensitization of AMPA receptors.

To determine whether AMPA receptor channel desensitization has a physiological role in shaping network activity by modulating signal transmission through excitatory circuits, we examined the effects of cyclothiazide (CYT), the most potent known blocker of AMPA receptor desensitization, on the behavior of an endogenously active neural system in vitro, the brainstem network generating rhythmic respiratory oscillations in neonatal rat medullary slices. Bath application of 100 microM CYT significantly increased the frequency of endogenously generated rhythm and increased the amplitude of the circuit output [i.e., discharge of hypoglossal (XII) respiratory motoneurons]. Local application of CYT within the XII motor nucleus produced a concentration-dependent increase (up to 35%) in amplitude of the motoneuron population discharge as well as an increase in the peak current (23%) and total charge transfer of the rhythmic inspiratory synaptic drive (33%) to individual XII motoneurons. CYT also acted postsynaptically to increase the amplitude of spontaneous EPSCs in motoneurons. In addition, CYT produced a profound, long-term augmentation of network frequency and motor output that may be secondary to block of desensitization. These results suggest that AMPA receptor desensitization has functionally significant effects on the temporal behavior and output of the rhythmic, respiratory neural network, and, by extrapolation, on other integrative actions of the mammalian CNS.

Animals↗