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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

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

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

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

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

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

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

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

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

Antibody to myelin-associated glycoprotein produces central nervous system demyelination.

Antibodies to myelin-associated glycoprotein (MAG) have been implicated in certain human demyelinating diseases of the peripheral nervous system. In the present study, a monoclonal antibody to MAG with 20% guinea pig serum (GPS) was injected into mammalian optic nerves and produced in vivo demyelination associated with three ultrastructural patterns of myelin injury: (1) widened lamellae; (2) myelin vesiculation; and (3) cell-associated myelin damage. These patterns of myelin injury have been observed neuropathologically in MS and in a demyelinating peripheral neuropathy associated with plasma cell dyscrasias. Demyelination was not observed in nerves injected with anti-MAG and heated GPS or a monoclonal antibody to chick myoblasts and 20% GPS. These results establish the ability of anti-MAG to produce in vivo demyelination of mammalian CNS and indicate that a single antibody directed against a specific myelin component may initiate multiple types of myelin damage.

Animals

Clinical characteristics of women with chlamydial cervicitis.

Four hundred ninety-three women were examined, had a cervical culture done for Chlamydia trachomatis and completed a questionnaire. Sixty-one, or 12.4%, were positive for Chlamydia on culture. Infected women were more likely to be younger, to be unmarried, to have had more sexual partners, to have had past abnormal cytology, to have spotting or postcoital bleeding, to have a mucoid or purulent cervical discharge and to have signs of cervical inflammation, especially friability. No characteristic finding in the past history, symptoms or physical examination combined sufficient sensitivity and specificity to serve by itself as a basis for selective testing for C trachomatis. It appears that multiple characteristics--including history, symptoms, physical examination and cytologic results--must be utilized to select patients for testing.

Adolescent

Histopathologic study of ocular changes in a syndrome of multiple congenital anomalies.

We examined a 5-month-old boy who had an iris coloboma in the left eye, persistent hyaloid artery, macular hypoplasia, left aberrant nerve palsy, and bilateral blepharoptosis. He had microcephaly and bilateral corticospinal tract dysfunction. Additionally, he had brachycephaly, a high arched palate, hypospadias, a malformed left external ear, and bilateral finger contractures. Computed tomography showed agenesis of the corpus callosum. He died at age 5 months. On histologic examination the left eye showed an iris coloboma, ciliary epithelial differentiation to the retina, undifferentiated neuroepithelium beneath the equatorial retina, persistent hyaloid artery, and optic nerve coloboma and pit. These findings may result from failure of the fetal fissure of the optic cup to close, with redundant folds of neuroepithelium and focal aberrant differentiation. The constellation of developmental defects indicates that an insult occurred during the sixth week of gestation.

Abnormalities, Multiple

Equilibrium constants of several reactions involved in the fermentation of glutamate.

The equilibrium constants of the reactions catalysed by (S)-citramalate lyase and (R)-2-hydroxyglutarate dehydrogenase were determined using the purified enzymes from Clostridium tetanomorphum and Acidaminococcus fermentans, respectively. The former constant had to be determined at high ionic strength (I). Therefore it was corrected to I = 0.1 M by applying single-ion activity coefficients estimated from literature data. The result (Kapp = 4.31 +/- 0.07 M-1; direction of citramalate formation) agreed very well with the constant of the (2R,3S)-2,3-dimethylmalate lyase equilibrium when all optical isomers were taken into account. From these and other data values for the free energies of formation (delta Gzerof) of (2S,3S)-3-methylaspartate, mesaconate and (S)-citramalate were calculated. The constant of the (R)-2-hydroxyglutarate dehydrogenase equilibrium [Kapp = (1.47 +/- 0.12)10(-12) M, direction of 2-oxoglutarate formation, I = 0.1 M] was shown to lie between those for malate and lactate dehydrogenases as expected.

Alcohol Oxidoreductases

Energy yields for hydrogen cyanide and formaldehyde syntheses: the HCN and amino acid concentrations in the primitive ocean.

Prebiotic electric discharge and ultraviolet light experiments are usually reported in terms of carbon yields and involve a large input of energy to maximize yields. Experiments using lower energy inputs are more realistic prebiotic models and give energy yields which can be used to estimate the relative importance of the different energy sources on the primitive earth. Simulated prebiotic atmospheres containing either CH4, CO or CO2 with N2, H2O and variable amounts of H2 were subjected to the spark from a high frequency Tesla coil. The energy yields for the synthesis of HCN and H2CO were estimated. CH4 mixtures give the highest yields of HCN while H2CO is most efficiently produced with the CO mixtures. These results are a model for atmospheric corona discharges, which are more abundant than lightning and different in character. Preliminary experiments using artificial lightning are also reported. The energy yields from these experiments combined with the corona discharge available on the earth, allows a yearly production rate to be estimated. These are compared with other experiments and model calculations. From these production rates of HCN (e.g. 100 nmoles cm-2 yr-1) and the experimental hydrolysis rates, the steady state concentration in the primitive ocean can be calculated (e.g., 4 X 10(-6) M at pH 8 and 0 degrees). A steady state amino acid concentration of 3 X 10(-4) M is estimated from the HCN production rate and the rate of decomposition of the amino acids by passage through the submarine vents.

Amino Acids

Prebiotic synthesis of imidazole-4-acetaldehyde and histidine.

The prebiotic synthesis of imidazole-4-acetaldehyde and imidazole-4-glycol from erythrose and formamidine has been demonstrated as well as the prebiotic synthesis of imidazole-4-ethanol and imidazole-4-glycol from erythrose, formaldehyde and ammonia. The products were identified by TLC, HPLC, and LC-MS by comparison with authentic samples. The maximum yields of imidazole-4-acetaldehyde, imidazole-4-ethanol, and imidazole-4-glycol obtained in these reactions are 1.6, 5.4, 6.8% respectively, based on the erythrose. Imidazole-4-acetaldehyde would have been converted to histidine on the primitive earth by a Strecker synthesis, and several prebiotic reactions would convert imidazole-4-glycol and imidazole-4-ethanol to imidazole-4-acetaldehyde.

Aldehydes

Comparison of scrape, swab, and cytobrush samples for the diagnosis of cervical chlamydial infection by immunofluorescence.

An endocervical swab, cytologic scraper, and endocervical cytobrush were used to prepare simultaneous full-slide smears for immunofluorescence for the diagnosis of cervical chlamydial infection. The cytobrush produced the best sample, with significantly higher numbers of organisms. Most of the false negative results were obtained with the cytologic scraper. The optimum technique appears to be to use a cytobrush sample; however, a swab should be used with pregnant patients.

Chlamydia Infections

The case for an ancestral genetic system involving simple analogues of the nucleotides.

The idea that the first living systems on earth were based on self-replicating RNA molecules has recently become popular as a result of the discovery of ribozymes. However, there are several major problems associated with the prebiotic synthesis of ribonucleotides. In addition, there is the newly recognized problem of enantiomeric cross-inhibition, whereby template-directed polymerization involving one enantiomer of RNA is inhibited strongly by the presence of the other enantiomer. Here we propose that RNA was preceded in the evolution of life by a polymer constructed from flexible, acyclic, probably prochiral nucleotide analogues that were synthesized readily on the primitive earth. Several potentially prebiotic nucleotide analogues are considered in this context, and some of the consequences of this proposal are discussed.

Models, Genetic

Type beta transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro.

To investigate the potential role of platelets in the inhibition of megakaryocytopoiesis, freeze-thawed extracts of human platelets were added to serumless liquid cultures of murine marrow. When acetylcholinesterase (AchE), a marker of megakaryocytic differentiation in mice, was assayed, a significant inhibition of enzymatic activity was noted in cultures containing the equivalent of greater than 5 X 10(6) solubilized platelets per milliliter. Freeze-thawed extracts of granulocytes had significantly less inhibitory effect than did platelets. Transforming growth factor beta (TGF-beta), a growth factor known to be inhibitory to some cell lineages and to be found at relatively high concentrations in platelets, was then added to liquid marrow cultures. A similar inhibition of AchE activity was detected when cultures were stimulated with mitogen-stimulated conditioned medium. The effect was potent with 50% inhibition of AchE activity observed at 4 pmol TGF-beta/L. To determine if TGF-beta inhibited specifically one aspect of megakaryocytic differentiation, the factor was added to isolated single megakaryocytes in serumless culture induced by interleukin 3 (IL3) to increase in size. The number of megakaryocytes increasing in size in response to IL 3 exposure was reduced from 68% to 20% when both factors were simultaneously added to cultures. Colony assays showed that megakaryocytic and granulocyte-macrophage colony detection was inhibited at picomolar concentrations of the factor. These data suggest that TGF-beta is a potent in vitro inhibitor of the murine megakaryocytic lineage, although its effects are not limited to this lineage.

Acetylcholinesterase