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Biomedical subjects

S L Miller

Publications and source records attributed to S L Miller.

At least 19 recordsLinked to original sources
PubMed2000

Peptide nucleic acids rather than RNA may have been the first genetic molecule.

Numerous problems exist with the current thinking of RNA as the first genetic material. No plausible prebiotic processes have yet been demonstrated to produce the nucleosides or nucleotides or for efficient two-way nonenzymatic replication. Peptide nucleic acid (PNA) is a promising precursor to RNA, consisting of N-(2-aminoethyl)glycine (AEG) and the adenine, uracil, guanine, and cytosine-N-acetic acids. However, PNA has not yet been demonstrated to be prebiotic. We show here that AEG is produced directly in electric discharge reactions from CH(4), N(2), NH(3), and H(2)O. Electric discharges also produce ethylenediamine, as do NH(4)CN polymerizations. AEG is produced from the robust Strecker synthesis with ethylenediamine. The NH(4)CN polymerization in the presence of glycine leads to the adenine and guanine-N(9)-acetic acids, and the cytosine and uracil-N(1)-acetic acids are produced in high yield from the reaction of cyanoacetaldehyde with hydantoic acid, rather than urea. Preliminary experiments suggest that AEG may polymerize rapidly at 100 degrees C to give the polypeptide backbone of PNA. The ease of synthesis of the components of PNA and possibility of polymerization of AEG reinforce the possibility that PNA may have been the first genetic material.

Biopolymers↗
PubMed2000

An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise.

This study was designed to determine the response of muscle protein to the bolus ingestion of a drink containing essential amino acids and carbohydrate after resistance exercise. Six subjects (3 men, 3 women) randomly consumed a treatment drink (6 g essential amino acids, 35 g sucrose) or a flavored placebo drink 1 h or 3 h after a bout of resistance exercise on two separate occasions. We used a three-compartment model for determination of leg muscle protein kinetics. The model involves the infusion of ring-(2)H(5)-phenylalanine, femoral arterial and venous blood sampling, and muscle biopsies. Phenylalanine net balance and muscle protein synthesis were significantly increased above the predrink and corresponding placebo value (P < 0.05) when the drink was taken 1 or 3 h after exercise but not when the placebo was ingested at 1 or 3 h. The response to the amino acid-carbohydrate drink produced similar anabolic responses at 1 and 3 h. Muscle protein breakdown did not change in response to the drink. We conclude that essential amino acids with carbohydrates stimulate muscle protein anabolism by increasing muscle protein synthesis when ingested 1 or 3 h after resistance exercise.

Administration, Oral↗
PubMed1999

The prebiotic synthesis of modified purines and their potential role in the RNA world.

Modified purines are found in all organisms in the tRNA, rRNA, and even DNA, raising the possibility of an early role for these compounds in the evolution of life. These include N6-methyladenine, 1-methyladenine, N6,N6-dimethyladenine, 1-methylhypoxanthine, 1-methylguanine, and N2-methylguanine. We find that these bases as well as a number of nonbiological modified purines can be synthesized from adenine and guanine by the simple reaction of an amine or an amino group with adenine and guanine under the concentrated conditions of the drying-lagoon or drying-beach model of prebiotic synthesis with yields as high as 50%. These compounds are therefore as prebiotic as adenine and guanine and could have played an important role in the RNA world by providing additional functional groups in ribozymes, especially for the construction of hydrophobic binding pockets.

Adenine↗
PubMed1999

Production of guanine from NH(4)CN polymerizations.

The synthesis of adenine from the polymerization of concentrated ammonium cyanide solutions is well known. We show here that guanine is also produced by this reaction but at yields ranging from 10 to 40 times less than that of adenine. This synthesis is effective at both +80 and -20 degrees C. Since high concentrations of NH(4)CN are obtainable only by freezing, this prebiotic synthesis would be applicable to frozen regions of the primitive Earth, the Jovian satellite Europa and other icy satellites, and the parent body of the Murchison meteorite.

Cyanides↗
PubMed1999

Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe.

OBJECTIVES: We studied the role of nitric oxide in the maintenance of uterine vascular tone during pregnancy. STUDY DESIGN: Late-pregnant ewes were instrumented with ultrasonographic flow probes on the left and right main uterine arteries. A catheter was passed retrogradely into 1 uterine artery from a tributary. In 14 animals nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME) was infused at 2 or 20 mg/kg during a 1-minute period into either the main left or right uterine artery. RESULTS: The nitric oxide synthase inhibitor (20 mg/kg), infused into 1 uterine artery, significantly decreased uterine blood flow (P <.001) bilaterally, increased (P <.05) mean arterial pressure, and decreased heart rate (P <.05). The compound (when infused at 2 mg/kg) also significantly (P <.05) decreased uterine blood flow in the artery ipsilateral to, but not contralateral to, the infusion, with no change in mean arterial pressure and a decrease (P <.05) in heart rate. CONCLUSION: During ovine pregnancy, endogenous nitric oxide production contributes to uterine vasodilatation.

Animals↗
PubMed1999

Does formate reduce alpha-ketoglutarate and ammonia to glutamate?

The reported reduction of alpha-ketoglutarate and ammonia by formate is much slower than described (Morowitz et al., 1995). The formate reduction if any is small under these conditions. Glutamate is produced from a reduction by a second molecule of alpha-ketoglutarate involving an oxidative decarboxylation.

Ammonia↗
PubMed1999

Physical exercise as a modulator of adaptation to low and high carbohydrate and low and high fat intakes.

Quantification of the metabolic response aids in ascertaining the nature and extent of the energy requirements imposed by exercise. During high intensity exercise, virtually all of the energy is supplied by the net oxidation of glycogen while fat oxidation plays a more prominent role during lower intensity exercise. Therefore, the lower limit of carbohydrate required above resting needs is equal to the portion of the total energy cost derived from carbohydrate sources. There is no upper limit of additional carbohydrate intake that could be eaten to satisfy the extra caloric requirement since carbohydrate intake will restore any endogenous energy stores that were used during exercise, regardless of the intensity of exercise. The recommendation of a high carbohydrate intake to provide caloric balance in exercising individuals is supported by the observation that exercise performance at high intensity is improved by a high carbohydrate diet, and exercise performance at low intensity is relatively insensitive to the source of the caloric intake. Limited dietary studies are consistent with predictions based on the metabolic response. At exercise intensities below 65% VO2 max, the percent fat and carbohydrate in the diet makes little difference on exercise performance, provided adequate time is allowed to adapt to a high-fat diet. On the other hand, exercise ability during high-intensity exercise is significantly limited by a high-fat diet. A consideration of importance beyond the aspect of energy balance is the anabolic effect of insulin on muscle protein synthesis after exercise. Provision of carbohydrate after exercise is likely to stimulate muscle protein synthesis to a greater extent than a corresponding amount of fat. Dietary fats may offer practical advantages to the athlete but if fats are consumed at the expense of carbohydrate intake, many established benefits of high carbohydrate intake in terms of performance may be sacrified.

Adaptation, Physiological↗
PubMed1999

A multi-zone model evaluation of the efficacy of upper-room air ultraviolet germicidal irradiation.

Engineering controls can be used to reduce the spread of airborne infectious disease, particularly tuberculosis (TB), in high-risk settings. This article evaluates published data on the efficacy of upper-room air ultraviolet germicidal irradiation (UVGI). A three-zone representation of a TB patient room equipped with a germicidal UV lamp is developed. The lamp irradiates the upper-room zone and inactivates airborne mycobacteria; the unirradiated lower-room zone also contains a near-field zone surrounding the TB patient. Infectious particles are generated in the near-field zone and transported throughout the room by air flow between zones. Each zone is independently well-mixed; the whole room, however, is not well-mixed. The three-zone model is applied to a previously published study of UVGI against airborne mycobacteria in a test room. Based on the estimated slopes of the semi-log concentration decay curves for viable mycobacteria, and on the assumption that the test room was essentially well-mixed, the published study reported that UVGI provided 10 to 25 equivalent air changes per hour. However, when the same decay curve slopes are interpreted in the context of the three-zone model, UVGI is seen to be far less effective in reducing exposure intensity near the TB patient. Near-field exposure intensity is relevant because health care workers are usually in close proximity to the TB patients they attend. In general, the interpretation of concentration decay data depends on the specific model of room air mixing that is assumed appropriate. It is recommended that tests of the efficacy of UVGI and other control devices against airborne microorganisms be based on steady-state concentration measurements rather than concentration decay measurements, because the former measurements do not require inferences based on a particular model.

Air Pollution, Indoor↗
PubMed1999

Home-based multisystemic therapy as an alternative to the hospitalization of youths in psychiatric crisis: clinical outcomes.

OBJECTIVE: The primary purpose of this study was to determine whether multisystemic therapy (MST), modified for use with youths presenting psychiatric emergencies, can serve as a clinically viable alternative to inpatient psychiatric hospitalization. METHOD: One hundred sixteen children and adolescents approved for emergency psychiatric hospitalization were randomly assigned to home-based MST or inpatient hospitalization. Assessments examining symptomatology, antisocial behavior, self-esteem, family relations, peer relations, school attendance, and consumer satisfaction were conducted at 3 times: within 24 hours of recruitment into the project, shortly after the hospitalized youth was released from the hospital (1-2 weeks after recruitment), and at the completion of MST home-based services (average of 4 months postrecruitment). RESULTS: MST was more effective than emergency hospitalization at decreasing youths' externalizing symptoms and improving their family functioning and school attendance. Hospitalization was more effective than MST at improving youths' self-esteem. Consumer satisfaction scores were higher in the MST condition. CONCLUSIONS: The findings support the view that an intensive, well-specified, and empirically supported treatment model, with judicious access to placement, can effectively serve as a family- and community-based alternative to the emergency psychiatric hospitalization of children and adolescents.

Activities of Daily Living↗
PubMed1999

Dosimetry of room-air germicidal (254 nm) radiation using spherical actinometry.

A method is demonstrated for measuring germicidal (254 nm) ultraviolet radiation (GUVR) in an omnidirectional manner. This method has application for those situations in which GUVR from more than one direction or source impinges on a three-dimensional object, and when it is of interest to determine the radiant fluence experienced by the object. For this purpose spherical quartz vessels were constructed varying from 0.8 to 1.25 cm in outside diameter. The vessels were filled with an actinometric solution consisting of KI and KIO3. This solution is optically opaque at 254 nm and is insensitive to room light. Upon exposure to GUVR this solution, which counts all of the 254 nm photons, forms triiodide. Following radiation, the contents of the vessel are removed, the absorbance of triiodide measured and the fluence rate determined based on a relationship that takes the volume to cross-sectional area of the actinometer into account. It is demonstrated that, in accordance with theory, the area of the sphere that intercepts the radiant energy is equal to the cross-sectional area of the sphere. A demonstration of the utility of this method was carried out in a test facility 90 m3 equipped with five GUVR lamps, one in each corner and one in the center of the room, arranged so as to irradiate the air in the upper portion of the room. Twenty spherical actinometers were evenly distributed around the room and exposed for either 30 or 90 min. The fluence rate varied from one part of the room to another, peaking near the GUVR lamps at 65-85 microW per cm2. By averaging over all 20 points, a pseudoaverage fluence rate for the room was found to be 42 and 44 microW per cm2 for the 30 and 90 min exposures, respectively. The similarities in the values for this metric demonstrates that the actinometric response is linear over this exposure range.

Disinfection↗
PubMed1999

On the origin of metabolic pathways.

The heterotrophic theory of the origin of life is the only proposal available with experimental support. This comes from the ease of prebiotic synthesis under strongly reducing conditions. The prebiotic synthesis of organic compounds by reduction of CO(2) to monomers used by the first organisms would also be considered an heterotrophic origin. Autotrophy means that the first organisms biosynthesized their cell constituents as well as assembling them. Prebiotic synthetic pathways are all different from the biosynthetic pathways of the last common ancestor (LCA). The steps leading to the origin of the metabolic pathways are closer to prebiotic chemistry than to those in the LCA. There may have been different biosynthetic routes between the prebiotic and the LCAs that played an early role in metabolism but have disappeared from extant organisms. The semienzymatic theory of the origin of metabolism proposed here is similar to the Horowitz hypothesis but includes the use of compounds leaking from preexisting pathways as well as prebiotic compounds from the environment.

Amino Acids↗
PubMed1998

The stability of the RNA bases: implications for the origin of life.

High-temperature origin-of-life theories require that the components of the first genetic material are stable. We therefore have measured the half-lives for the decomposition of the nucleobases. They have been found to be short on the geologic time scale. At 100 degreesC, the growth temperatures of the hyperthermophiles, the half-lives are too short to allow for the adequate accumulation of these compounds (t1/2 for A and G approximately 1 yr; U = 12 yr; C = 19 days). Therefore, unless the origin of life took place extremely rapidly (<100 yr), we conclude that a high-temperature origin of life may be possible, but it cannot involve adenine, uracil, guanine, or cytosine. The rates of hydrolysis at 100 degreesC also suggest that an ocean-boiling asteroid impact would reset the prebiotic clock, requiring prebiotic synthetic processes to begin again. At 0 degreesC, A, U, G, and T appear to be sufficiently stable (t1/2 >/= 10(6) yr) to be involved in a low-temperature origin of life. However, the lack of stability of cytosine at 0 degreesC (t1/2 = 17, 000 yr) raises the possibility that the GC base pair may not have been used in the first genetic material unless life arose quickly (<10(6) yr) after a sterilization event. A two-letter code or an alternative base pair may have been used instead.

Animals↗
PubMed1998

Oceanic protection of prebiotic organic compounds from UV radiation.

It is frequently stated that UV light would cause massive destruction of prebiotic organic compounds because of the absence of an ozone layer. The elevated UV flux of the early sun compounds this problem. This applies to organic compounds of both terrestrial and extraterrestrial origin. Attempts to deal with this problem generally involve atmospheric absorbers. We show here that prebiotic organic polymers as well as several inorganic compounds are sufficient to protect oceanic organic molecules from UV degradation. This aqueous protection is in addition to any atmospheric UV absorbers and should be a ubiquitous planetary phenomenon serving to increase the size of planetary habitable zones.

Oceans and Seas↗
PubMed1998

Cycloserine-induced decrease of cerebroside in myelin.

L-Cycloserine has been shown specifically to lower brain cerebroside levels in vivo, but the extent to which the decrease in whole brain cerebroside content reflects lower myelin cerebroside levels is not known since a substantial portion of cerebroside is found in nonmyelin membranes. The present report demonstrates that chronically administered cycloserine lowers the proportion of cerebroside in rat brain myelin. Cycloserine-induced decrease of myelin cerebroside should provide a useful tool in investigating the role of cerebroside in maintaining myelin stability.

Animals↗
PubMed1998

Hydrogen consumption by methanogens on the early Earth.

It is possible that the first autotroph used chemical energy rather than light. This could have been the main source of primary production after the initial inventory of abiotic organic material had been depleted. The electron acceptor most readily available for use by this first chemoautotroph would have been CO2. The most abundant electron donor may have been H2 that would have been outgassing from volcanoes at a rate estimated to be as large as 10(12) moles yr-1, as well as from photo-oxidation of Fe+2. We report here that certain methanogens will consume H2 down to partial pressures as low as 4 Pa (4 x 10(-5) atm) with CO2 as the sole carbon source at a rate of 0.7 ng H2 min-1 microgram-1 cell protein. The lower limit of pH2 for growth of methanogens can be understood on the basis that the pH2 needs to be high enough for one ATP to be synthesized per CO2 reduced. The pH2 values needed for growth measured here are consistent with those measured by Stevens and McKinley for growth of methanogens in deep basalt aquifers. H2-consuming autotrophs are likely to have had a profound effect on the chemistry of the early atmosphere and to have been a dominant sink for H2 on the early Earth after life began rather than escape from the Earth's atmosphere to space.

Carbon Dioxide↗