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Biomedical subjects

S L Miller

Publications and source records attributed to S L Miller.

At least 91 records · Page 5Linked to original sources
PubMed1993

Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A.

Pantoic acid can by synthesized in good prebiotic yield from isobutyraldehyde or alpha-ketoisovaleric acid + H2CO + HCN. Isobutyraldehyde is the Strecker precursor to valine and alpha-ketoisovaleric acid is the valine transamination product. Mg2+ and Ca2+ as well as several transition metals are catalysts for the alpha-ketoisovaleric acid reaction. Pantothenic acid is produced from pantoyl lactone (easily formed from pantoic acid) and the relatively high concentrations of beta-alanine that would be formed on drying prebiotic amino acid mixtures. There is no selectivity for this reaction over glycine, alanine, or gamma-amino butyric acid. The components of coenzyme A are discussed in terms of ease of prebiotic formation and stability and are shown to be plausible choices, but many other compounds are possible. The gamma-OH of pantoic acid needs to be capped to prevent decomposition of pantothenic acid. These results suggest that coenzyme A function was important in the earliest metabolic pathways and that the coenzyme A precursor contained most of the components of the present coenzyme.

4-Butyrolactone↗
PubMed1992

Cephalic migration of the bird's nest inferior vena caval filter: report of two cases.

The Bird's Nest inferior vena caval filter (Cook, Bloomington, Ind) has been approved for clinical use since 1989. The authors report two cases of cephalic migration of the filter. Both cases of migration occurred in association with a massive thromboembolism after placement of the filter. It appears that a massive thromboembolism can cause this filter to migrate cephalad. The authors suggest that there is potential for nonsurgical management of the migrated filter.

Aged↗
PubMed1991

Relationships between age and dental attrition in Australian aboriginals.

Tooth wear scores (ratios of exposed dentin to total crown area) were calculated from dental casts of Australian Aboriginal subjects of known age from three populations. Linear regression equations relating attrition scores to age were derived. The slope of the regression line reflects the rate of tooth wear, and the intercept is related to the timing of first exposure of dentin. Differences in morphology between anterior and posterior teeth are reflected in a linear relationship between attrition scores and age for anterior teeth but a logarithmic relationship for posterior teeth. Correlations between age and attrition range from less than 0.40 for third molars (where differences in the eruption and occlusion of the teeth resulted in different patterns of wear) to greater than 0.80 for the premolars and first molars. Because of the generally high correlations between age and attrition, it is possible to estimate age from the extent of tooth wear with confidence limits of the order of +/- 10 years.

Adolescent↗
PubMed1991

Maternal serum human chorionic gonadotropin levels in twin pregnancies.

Introduction of combined screening with maternal serum alpha-fetoprotein and human chorionic gonadotropin (MShCG) assays for fetal chromosome defects requires establishment of the normal range for twins. This report documents that the normal range for MShCG between 15 and 19 weeks in twin gestations was 1.84-2.41 multiples of the singleton median. Of the 192 twin pregnancies studied, 31.7 and 47.9 per cent had MShCG values greater than or equal to 2.5 and greater than or equal to 2.0 multiples of the singleton median, respectively.

Chorionic Gonadotropin↗
PubMed1991

Attempted nonenzymatic template-directed oligomerizations on a polyadenylic acid template: implications for the nature of the first genetic material.

Previous attempts to produce nonenzymatic template-directed oligomerizations of activated pyrimidines on polypurine templates have been unsuccessful. The only efficient reactions are those where the template is composed primarily of pyrimidines, especially cytosine. Because molecular evolution requires that a synthesized daughter polynucleotide be capable of acting as a template for the synthesis of the original polynucleotide, the one-way replication achieved thus far is inadequate to initiate an evolving system. Several uracil analogs were used in this investigation in order to search for possible replacements for uracil. The monomers used in this investigation were the imidazolides of UMP, xanthosine 5'-monophosphate, the bis-monophosphates of the acyclic nucleosides of uracil, and 2,4-quinazolinedione. The concentrations of various salts, buffers, pH, and temperature were among the different variables investigated in attempts to find conditions that would permit template-directed oligomerizations. Although the different monomers in this study demonstrated varying abilities to form very short oligomers, we were unable to detect any enhancement of this oligomerization that could be attributed to the poly(A) template. Although special conditions might be found that would allow purine-rich templates to work, these reactions cannot be considered robust. The results of our experiments suggest that pyrimidines were not part of the original replicating system on the primitive Earth. It has already been shown that ribose is an unlikely component of the first replicating systems, and we now suggest that phosphate was absent as well. This is due to the low solubility of phosphate in the present ocean (3 x 10(-6) M), as well as the difficulty of prebiotic activation of phosphates.

Evolution, Molecular↗
PubMed1991

Template-directed synthesis of oligonucleotides under eutectic conditions.

One of the most important sets of model prebiotic experiments consists of reactions that synthesize complementary oligonucleotides from preformed templates under nonenzymatic conditions. Most of these experiments are conducted at 4 degrees C using 0.01-0.1 M concentrations of activated nucleotide monomer and template (monomer equivalent). In an attempt to extend the conditions under which this type of reaction can occur, we have concentrated the reactants by freezing at -18 degrees C, which is close to the NaCl-H2O eutectic at -21 degrees C. The results from this set of experiments suggest that successful syntheses can occur with poly(C) concentrations as low at 5 x 10(-4) M and 2MeImpG concentrations at 10(-3) M. It was also anticipated that this mechanism might allow the previously unsuccessful poly(A)-directed synthesis of oligo(U)s to occur. However, no template effect was seen with the poly(A) and ImpU system. The failure of these conditions to allow template-directed synthesis of oligo(U)s supports the previously proposed idea that pyrimidines may not have been part of the earliest genetic material. Because of the low concentrations of monomer and template that would be expected from prebiotic syntheses, this lower temperature could be considered a more plausible geologic setting for template-directed synthesis than the standard reaction conditions.

Chromatography, High Pressure Liquid↗
PubMed1991

Reliability and validity of infant speech-sound discrimination-in-noise thresholds.

Infants were tested on a speech-sound discrimination-in-noise task using the visual reinforcement infant speech discrimination (VRISD) procedure with an adaptive (up-down) threshold protocol. An adult control group was tested using the same stimuli and apparatus. The speech sounds were synthetic magnitude of ba and magnitude of ga. The masker was band-passed presented continuously at 48 dB SPL. Test-retest reliability was good for both groups, although test-retest differences were smaller for adults. For infants the mean of the absolute values of the differences between tests was only 5.2 dB, and there was less than a 10-dB difference between the two tests of 14 (87.5%) of the 16 infants completing the study. The infant-adult difference in discrimination threshold in noise was 6.9 dB, which agrees well with detection-in-noise thresholds from earlier studies and with discrimination-in-noise thresholds obtained on a subset of subjects in our earlier work. Advantages of the adaptive threshold procedure and its possible applications both in research studies and in the clinic are discussed.

Adult↗
PubMed1991

Two-dimensional life?

A model [Wächtershäuser, G. (1988) Microbiol. Rev. 52, 452-484], according to which life started in the form of a monomolecular layer of interacting anionic metabolites electrostatically bound to a positively charged surface, is examined critically. The model raises a number of thermodynamic and kinetic difficulties.

Animals↗
PubMed1991

Effect of interferon on a primary conjunctival epithelial cell model of trachoma.

An in vitro human primary conjunctival epithelial system was adapted to determine if the effects of interferon-gamma (IFN-gamma), as described in cultured cell lines, were applicable to human ocular infection with Chlamydia trachomatis, Primary human epithelial cell cultures were exposed to varying concentrations of IFN-gamma. The treatment resulted in the induction of the tryptophan decyclizing enzyme indolamine 2,3-deoxygenase (IDO) in a dose-dependent manner as determined by assaying the conversion of tryptophan to its metabolites using reversed-phase high-performance liquid chromatography. Little IDO induction occurred in the presence of IFN-alpha or IFN-beta. Catabolism of up to 38% of available tryptophan occurred in IFN-gamma-treated cells in contrast to controls that showed only baseline activity. Cells cultured with IFN-gamma and then infected with an ocular isolate of C. trachomatis (TW-5), had a reduction in the percentage of inclusion-containing cells by over 80% in a dose-dependent manner. Reversal by the addition of exogenous tryptophan substantiated that IFN-gamma-mediated induction of IDO and catabolism of tryptophan were responsible for inhibition of intracellular growth of C. trachomatis.

Cells, Cultured↗
PubMed1990

Abnormal maternal serum levels of human chorionic gonadotropin free subunits in trisomy 18.

We have measured maternal serum levels of free alpha and beta subunits of human chorionic gonadotropin between 8 and 12 weeks of gestation in 704 women at increased risk for trisomy. This group was studied because of advanced maternal age or a previous birth with chromosomal abnormality. All sera had been collected prior to chorion villus biopsy for prenatal diagnosis. Serum levels of free alpha and beta hCG were determined by specific monoclonal antibody-based immunoradiometric assays. Analysis of chorionic tissue showed that in 38 of 704 (5.4%) pregnancies the fetus had a chromosome abnormality. There were 8 fetuses with trisomy 18 (1.1%) and 9 (1.3%) with trisomy 21. In all pregnancies carrying a trisomy 18 fetus, we observed either high levels of free alpha hCG or low levels of free beta hCG or both. More importantly, the calculated ratio of free beta hCG/alpha hCG was less than 0.25 multiples of the median (MoM) in 6 of 8 (75%) trisomy 18 cases. Only 21 of 666 mothers (3.2%) carrying a normal fetus had a ratio less than 0.25 MoM (P less than 0.0001). There was no difference between this ratio in trisomy 21 and normal pregnancy. Thus, when adjusted for gestational age, a low free beta hCG/alpha hCG ratio in maternal serum indicates a pregnancy at high risk [RR = 72 (95% CI 32, 162)] for trisomy 18.

Chorionic Gonadotropin↗
PubMed1990

Prebiotic synthesis of histidine.

The prebiotic formation of histidine (His) has been accomplished experimentally by the reaction of erythrose with formamidine followed by a Strecker synthesis. In the first step of this reaction sequence, the formation of imidazole-4-acetaldehyde took place by the condensation of erythrose and formamidine, two compounds that are known to be formed under prebiotic conditions. In a second step, the imidazole-4-acetaldehyde was converted to His, without isolation of the reaction products by adding HCN and ammonia to the reaction mixture. LC, HPLC, thermospray liquid chromatography-mass spectrometry, and tandem mass spectrometry were used to identify the product, which was obtained in a yield of 3.5% based on the ratio of His/erythrose. This is a new chemical synthesis of one of the basic amino acids which had not been synthesized prebiotically until now.

Aldehydes↗
PubMed1990

Infant speech-sound discrimination in noise.

The effects of noise on 7- to 11-month-old infants' speech-sound discrimination (/ba/vs/ga/) were determined using a conditioned head-turn procedure. Variation in performance as a function of signal-to-noise ratio (S/N) was estimated by testing each infant at four S/N's (-8, 0, 8, and 16 dB). Adults were tested for comparison at four S/N's (-12, -8, -4, and 0 dB). The S/N's were chosen based on pilot data. Performance varied monotonically with S/N for both age groups, but infants required greater S/N than adults to achieve comparable levels of performance. Both groups were also tested using an adaptive (1-up, 1-down) threshold procedure with a 3-dB step size. There was a group mean difference in threshold of 5.8-dB S/N favoring the adults. Weighted group psychometric functions, derived from the responses obtained in the adaptive runs, showed good correspondence with the data points at the four S/N's. The slopes of these functions were the same (7.5%/dB) for infants and adults. The results suggest that infants are at a greater disadvantage than adults when processing speech in noise and that concern over the effects of a noisy environment on the acquisition of language is justified. In addition, the adaptive threshold procedure can be used as an efficient way to estimate the limits of discrimination ability as a function of S/N or intensity, both for individual subjects and for groups of subjects, in developmental research.

Auditory Pathways↗
PubMed1989

Detection and partial biochemical characterization of a novel 57,500 dalton protein in rat brain myelin.

Using a monoclonal antibody (P6C3) derived from mice immunized with partially delipidated rat myelin, we detected a single 57.5 kDa protein species (BT57.5) positioned between alpha- and beta-tubulin on nitrocellulose containing electrophoretically separated rat brain myelin proteins. The kinetics of incorporation of 14C-labeled BT57.5 and myelin basic protein into myelin was similar in rats injected intracranially with [14C]amino acids to radioactively label these proteins. Immunoblotting of the separated proteins of the myelinlike fraction of rat brain with the anti-BT57.5 monoclonal antibody occasionally revealed a faint band corresponding to BT57.5 but consistently showed a more prominent protein band that migrated slightly ahead of BT57.5. When the myelin and myelinlike fraction were isolated from rats injected with [14C] amino acids, labeling of the prominent anti-BT57.5 binding protein in the myelinlike fraction preceded that of BT57.5 in myelin, reaching a peak of labeling and then decreasing before BT57.5 reached its peak level. Thus, the prominent anti-BT57.5 protein in the myelinlike fraction might be a metabolic precursor of BT57.5 in myelin or the myelinlike fraction is simply turning over more rapidly and is distinct from the myelin fraction. BT57.5 was detectable in rat, mouse, guinea pig, bovine, and human CNS myelin but not rabbit and was detectable in the peripheral nervous system only in myelin of rats and humans. Finally, in extensively purified myelin, BT57.5 appeared to copurify with myelin basic protein, suggesting that BT57.5 is a constituent of myelin rather than an artifact arising during brain homogenization procedures.

Animals↗
PubMed1989

Production of organic compounds in plasmas: a comparison among electric sparks, laser-induced plasmas, and UV light.

The chemistry in planetary atmospheres that is induced by processes associated with high-temperature plasmas is of broad interest because such processes may explain many of the chemical species observed. There are at least two important phenomena that are known to generate plasmas (and shocks) in planetary atmospheres: lightning and meteor impacts. For both phenomena, rapid heating of atmospheric gases leads to formation of a high-temperature plasma which emits radiation and produces shock waves that propagate through the surrounding atmosphere. These processes initiate chemical reactions that can transform simple gases into more complex compounds. In order to study the production of organic compounds in plasmas (shocks), various mixtures of N2, CH4, and H2, modeling the atmosphere of Titan, were exposed to discrete sparks, laser-induced plasmas (LIP), an ultraviolet radiation. The yields of HCN and several simple hydrocarbons were measured by gas chromatography and compared to those calculated from a simple quenched thermodynamic equilibrium model. The agreement between experiment and theory was fair for HCN and C2H2. However, the agreement for C2H6 and the other hydrocarbons was poor, indicating that a more comprehensive theory is needed. Our experiments suggest that photolysis by ultraviolet light from the plasma is an important process in the synthesis. This was confirmed by the photolysis of gas samples exposed to the light but not to the shock waves emitted by the sparks. Hence, the results of these experiments demonstrate that the thermodynamic equilibrium theory does not adequately model lightning and meteor impacts and that photolysis must be included. Finally, the similarity in yields between the spark and the LIP experiments suggest that LIP provide valid and clean simulations of lightning and meteor impacts and that photolysis must be included. Finally, the similarity in yields between the spark and the LIP experiments suggests that LIP provide valid and clean simulations of lightning in planetary atmospheres.

Atmosphere↗
PubMed1989

Temporal allocation of (14)C to extramatrical hyphae of ectomycorrhizal ponderosa pine seedlings.

Ponderosa pine seedlings were inoculated with Hebeloma crustuliniforme either in growth pouches before they were transplanted to root-mycocosms (P seedlings), or at the time of transfer to root-mycocosms (V seedlings). Uninoculated seedlings served as controls (U seedlings). The use of root-mycocosms allowed examination of portions of hyphae separate from roots and rooting substrate but still in symbiosis with the host. The results thus provided a quantitative basis for estimating hyphal mass and carbon allocation to extramatrical hyphae. The amount of (14)CO(2) fixed after a 2-h exposure was greatest for P seedlings and least for uninoculated seedlings. Four and nine days after exposure, (14)C content was greatest in uninoculated seedlings and least in inoculated seedlings. In isotope distribution and dry mass accumulation, V seedlings were more similar to U than to P seedlings. Calculated on a dry weight basis, the allocation of isotope to mycelium suggested that extramatrical hyphae of P seedlings were a stronger sink for carbon than extramatrical hyphae of V seedlings. Differences in inoculation methods resulted in differences in carbon allocation and physiology of extramatrical hyphae that could affect seedling establishment and survival. Seedlings inoculated by one method cannot serve as surrogates for mycorrhizal seedlings produced by other inoculation techniques.

Journal Article↗