Biomedical subjects
Publications and source records attributed to S L Miller.
Claims that modern hospitals are settings for human change and for religious ministry. Uses a pastoral care event in a Special Care Nursery to demonstrate the aspects of preparation, intervention, case development, crisis, and resolution. Details eleven salient features of the hospital chaplain in the modern hospital.
The discovery of hydrothermal vents at oceanic ridge crests and the appreciation of their importance in the element balance of the oceans is one of the main recent advances in marine geochemistry. It is likely that vents were present in the oceans of the primitive Earth because the process of hydrothermal circulation probably began early in the Earth's history. Here we examine the popular hypothesis that life arose in these vents. This proposal, however, is based on a number of misunderstandings concerning the organic chemistry involved. An example is the suggestion that organic compounds were destroyed on the surface of the early Earth by the impact of asteroids and comets, but at the same time assuming that organic syntheses can occur in hydrothermal vents. The high temperatures in the vents would not allow synthesis of organic compounds, but would decompose them, unless the exposure time at vent temperatures was short. Even if the essential organic molecules were available in the hot hydrothermal waters, the subsequent steps of polymerization and the conversion of these polymers into the first organisms would not occur as the vent waters were quenched to the colder temperatures of the primitive oceans.
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.
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.
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.
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.
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.
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.
HCN has been detected in the Jovian atmosphere at a column density of about 2.2 x 10(-7) moles cm-2. While photochemical synthesis from methylamine and aziridine, upwelling, and lightning have been proposed as possible sources of this HCN, corona discharge has not been previously considered. HCN energy yields (moles J-1) were measured using corona discharge for gas mixtures containing H2, CH4, NH3, with H2/CH4 ratios from 4.4 to 1585. The yields are approximately proportional to the mole fraction of methane in the gas mixture. Assuming that the 3/1 ratio of corona discharge to lightning energy on the Earth applies to Jupiter, HCN column densities from corona discharge could account for approximately 10% of the observed HCN. These estimates are very dependent on the values used for the energy available as lightning on Jupiter and the eddy diffusion coefficients in the region of synthesis.
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.
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.
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The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only sight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.
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.
The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only slight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.
Immunofluorescent staining was compared to cell culture for the diagnosis of Chlamydia trachomatis infections in the female genital tract. By culture, the incidence in the 496 patients in the study was 12.3%. Immunofluorescence demonstrated organisms in 90% of the culture-positive cases, with a specificity of 99.3%. This method appears to be a successful replacement for culture for general screening.
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The prebiotic synthesis of small molecules has been accomplished using various simulated atmospheres with CH4, N2, and NH3, H2O being the most effective, but H2, CO, N2, H2O and H2, CO2, N2, H2O also give good yields of organic compounds provided H2/CO > 1 and H2/CO2 > 2. The spark discharge is a very effective source of energy in such experiments, because it is a good source of HCN. Ultraviolet light would also have been important on the primitive earth. Almost all prebiotic amino acids are made by the hydrolysis of an amino nitrile formed from an aldehyde, NH3 and HCN (Strecker synthesis). There are reasonable prebiotic syntheses worked out for the twenty amino acids that occur in proteins, with the exception of lysine, arginine and histidine. The purines are derived from the polymerization of HCN, and the precursor of the pyrimidines is cyanoacetylene. The sugars (including ribose), would have been formed from the base catalyzed polymerization of formaldehyde. There is no good prebiotic synthesis of straight chain fatty acids. Of the vitamin coenzymes, only nicotinic acid has been synthesized under prebiotic conditions. Many of the molecules that are produced in these simulated primitive earth experiments are found in a group of meteorites that contain organic compounds, called the carbonaceous chondrites. Since such prebiotic syntheses took place on the parent body of the carbonaceous chondrites, generally thought to be an asteroid, it is plausible, but not proved, that such syntheses took place on the primitive earth, and that the first living organisms were formed out of these compounds.