Biomedical subjects
Publications and source records attributed to D L Miller.
A microcomputer program for storage of qualitative patient data has been applied to CT and special procedures case data. Different vocabularies have been established and utilised for these two case categories. Experience over two years involving more than 10,000 cases is discussed. Utility for statistical, research, and patient care purposes is demonstrated.
Six patients with failed previous operations and anterior mediastinal parathyroid glands were evaluated with selective angiography and nonselective arterial digital arteriography. Selective angiography depicted two of nine mediastinal glands; nonselective arterial digital arteriography depicted only one of nine mediastinal glands and missed a sizable (4.5 cm) gland demonstrated by routine arteriography. Nonselective arterial digital arteriography did not demonstrate any additional mediastinal glands. From this preliminary experience, it was concluded that nonselective arterial digital arteriography is not a sensitive method for detecting mediastinal glands.
EOE-13 is an experimental liver-spleen-specific computed tomographic (CT) contrast agent developed at the National Institutes of Health. Experience with this agent in 225 clinical examinations is described. On average, use of EOE-13 increases the attenuation of normal liver by 32.5 H and that of normal spleen by 52.3 H. Tumors in these organs increase only 2.6 H, making them more easily detectable. Most of the iodine in EOE-13 appears to clear from the liver and spleen by 24 hr after injection. No deaths or permanent morbidity have been observed. The complication rate is 3.6%. EOE-13 is valuable for the detection of hepatic and splenic tumors.
Hepatic perfusion patterns were evaluated in five patients receiving hepatic artery infusion chemotherapy. All patients underwent 99mTc macroaggregated albumin (99mTc-MAA) scintigraphy and CT with EOE-13. In each case, the diagnostic agent was administered through the infusion catheter at 0.66 ml/min. Hepatic perfusion patterns were identified with both imaging methods, but CT with EOE-13 yielded more precise anatomic detail and was unique in demonstrating the perfusion status of each hepatic metastasis. Further evaluation of EOE-13 for this purpose is warranted.
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EOE-13 was infused directly into the hepatic artery through a surgically implanted hepatic artery infusion pump in a patient with liver metastases. A computed tomographic scan obtained after EOE-13 infusion accurately showed the perfusion pattern of the implanted catheter. It also demonstrated the hepatic metastases more clearly than scintigraphy with 99mTc-macroaggregated albumin. EOE-13 may prove useful for the evaluation of hepatic perfusion patterns in patients receiving hepatic artery infusion chemotherapy.
We report the pathologic and radiologic findings in a 13-year-old girl with malignant teratoma of the ovary. Extensive calcified intraperitoneal and mediastinal implants were demonstrated by plain film radiography and computed tomography.
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A variety of chemical agents that are known to induce erythrodifferentiation in the Friend virus-induced murine erythroleukemia (MEL) cell have been suggested to mediate DNA cleavage in cultured cells prior to differentiation. The activation of the nuclear enzyme, ADP-ribosyltransferase, depends upon the presence of single strand breaks in DNA. If dimethyl sulfoxide (Me2SO) causes DNA breakage, it would be expected that the activity of ADP-ribosyltransferase would increase. A study of ADP-ribosyltransferase activity during cell growth indicates that both Me2SO-treated and untreated MEL cells exhibit a similar increase in the enzyme activity but the increase in Me2SO-treated cells is delayed by a few hours. When examined at comparable stages of growth, both treated and untreated cells show almost identical levels of enzyme activity. The present data thus do not support the contention that Me2SO induces DNA breakage in the MEL cells.
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Escherichia coli Phe-tRNA, modified with the photoaffinity reagent 6-(2-nitro-4-azidophenylamino)caproate on the 3-(3-amino-3-carboxypropyl)uridine residue, was crosslinked to E. coli EFTu Section upon irradiation at 0 degree C with visible light at wavelengths greater than 400 nm. Crosslinking was dependent on irradiation, the photoaffinity probe, and was blocked by pre-photolysis. 1 mM-dithiothreitol completely quenched crosslinking. Binding of the tRNA to EFTu was a prerequisite for crosslinking, because neither EFTu . GDP nor AcPhe-tRNA could substitute; EFTu . GDPCP, however, was almost as active as EFTu . GTP. Crosslinking was complete in less than five minutes and was stable to at least 20 minutes of irradiation with a single 650 W tungsten lamp 4 cm away. The crosslinking yield ranged from 15% to 25%. The crosslinked complex possessed several remarkable properties. At 0.5 mM-Mg2+, the complex protected the AA-tRNA link to chemical hydrolysis, stabilized the bound GTP to dissociation or exchange, and was not adsorbed to cellulose nitrate filters. The purified crosslinked complex could be bound to ribosomes with concomitant hydrolysis of GTP. Extensive peptide bond formation with AcPhe-tRNA in the P site occurred despite the presence of the crosslinked EFTu. We conclude that hydrolysis of GTP is sufficient to release the 3' end of the Phe-tRNA from complexation with EFTu. Translocation of the A site bound complex did not occur. The crosslink site on EFTu is probably near the periphery of the molecule, because shortening the probe from 20 A to 14 A completely blocked crosslinking. A similar but shorter 8 A probe, p-azidophenacyl-4-thiouridine located on the opposite face of the tRNA, did not crosslink.
The possible roles of pertussis immunisation and of other factors in the aetiology of infantile spasms were investigated by analysis of 269 cases reported to the National Childhood Encephalopathy Study. In 34% of the cases an antecedent factor which may have caused infantile spasms was identified; the commonest of these were perinatal hypoxia (38 cases) and tuberous sclerosis (16 cases). Case-control analyses showed no significant association between infantile spasms and pertussis immunisation in the 28 days before onset. There was, however, some clustering of cases immunised with either diphtheria-tetanuspertussis or diphtheria-tetanus vaccines in the 7 days before onset. The excess compared with controls was compensated for by a corresponding deficit over the remaining period up to 28 days. It is suggested that these vaccines do not cause infantile spasms but may trigger their onset in those children in whom the disorder is destined to develop.
We have characterized a mutation affecting the yeast mitochondrial tRNASerUCX. The mutation is a single nucleotide substitution located within the structural portion of the tRNASerUCX gene which causes the strain to be respiratory deficient. The substitution is a G leads to A transition located in the dihydrouridine arm. The tRNASerUCX transcripts from the mutant gene are present in the same amount and are the same size as transcripts from the wild-type gene. The mutant tRNASerUCX can be charged in vitro with mitochondrial aminoacyl-tRNA synthetase. Mitochondrial protein synthesis does occur in the mutant, but the amount of cytochrome oxidase subunit I is significantly decreased relative to other mitochondrial translation products.
The association of aminoacyl-tRNA (aa-tRNA) with elongation factor Tu.GTP to form an aa-tRNA.EF-Tu.GTP ternary complex was investigated by using two different fluorescent probes, both of which monitored structural changes near the juncture of the two arms of the L-shaped tRNA. Aminoacylation of tRNAPhe-F8, a functionally active analogue of tRNAPhe with a fluorescein moiety covalently attached to the s4U-8 base, did not cause a change in the fluorescence emission intensity. However, when EF-Tu.GTP bound to Phe-tRNAPhe-F8, the emission intensity increased by approximately 30%, depending upon the solvent conditions. About half of this increase in fluorescence was due to an increase in the molar absorptivity of the fluorescein dye. Ternary complex formation did not alter the rate of iodide ion quenching of the Phe-tRNAPhe-F8 fluorescence. Since solvent access to fluorescein was not reduced when EF-Tu.GTP was bound to Phe-tRNAPhe-F8, the fluorescence intensity change noted above was not caused by a direct interaction between fluorescein and EF-Tu. Instead, the binding of EF-Tu.GTP to the aa-tRNA resulted in a conformational change in the aa-tRNA near s4U-8. Ternary complex formation also altered the nature of the single strong binding site for ethidium in unfractionated and unmodified aa-tRNA. However, ethidium binding to its strong site was not blocked. These results indicate that only the acceptor-T psi C arm of aa-tRNA interacts directly with EF-Tu.GTP and that the anticodon-D arm is available for direct interaction with the ribosome during recognition. Our data also suggest that EF-Tu facilitates protein biosynthesis by ensuring that every aa-tRNA is in a particular (possibly the same) conformation prior to initiation of the recognition process at the ribosomal complex.
Hepatocytes can be maintained in culture for periods of a few hours to many days. This review summarizes the metabolic characteristics of these cultures and describes their use in studying the regulation of plasma protein synthesis. Hormones selectively stimulate the synthesis of certain proteins. Cortisol stimulates the synthesis of fibrinogen and other acute-phase proteins; whereas, insulin stimulates albumin synthesis. In the latter case insulin increases the rate of a nuclear process. Mediators elaborated by leukocytes stimulate acute-phase protein synthesis in hepatocytes. Plasmin-generated fibrin peptides stimulate fibrinogen synthesis via a leukocytic mediator. Lipoprotein synthesis is stimulated by fatty acids and is inhibited by albumin and other macromolecules. These and other processes are susceptible to detailed analysis using sub-cellular fractions (mRNA, nuclei, transcription factors, etc.) isolated from hepatocytes. Studies on fetal or embryonic hepatocytes and hepatomas are yielding information on the regulation of secretory protein synthesis during development and following neoplastic transformation.
Yeast mitochondrial DNA codes for a complete set of tRNAs. Although most components necessary for the biosynthesis of mitochondrial tRNA are coded by nuclear genes, there is one genetic locus on mitochondrial DNA necessary for the synthesis of mitochondrial tRNAs other than the mitochondrial tRNA genes themselves. Characterization of mutants by deletion mapping and restriction enzyme mapping studies has provided a precise location of this yeast mitochondrial tRNA synthesis locus. Deletion mutants retaining various segments of mitochondrial DNA were examined for their ability to synthesize tRNAs from the genes they retain. A subset of these strains was also tested for the ability to provide the tRNA synthesis function in complementation tests with deletion mutants unable to synthesize mature mitochondrial tRNAs. By correlating the tRNA synthetic ability with the presence or absence of certain wild-type restriction fragments, we have confined the locus to within 780 base pairs of DNA located between the tRNAMetf gene and tRNAPro gene, at 29 units on the wild-type map. Heretofore, no genetic function or gene product had been localized in this area of the yeast mitochondrial genome.
We treated 31 patients with ragweed conjunctivitis in an eight-week, double-masked parallel-group study with cromolyn sodium 4% ophthalmic solution. Analysis of data showed preseason serum IgE antibody to ragweed level was a significant predictor of drug response. Of 16 patients with ragweed IgE values of less than 100 ng/ml, the nine treated with cromolyn had significantly fewer symptoms during the course of treatment than the seven in the placebo group. Of the 15 remaining patients, who had IgE levels of more than 100 ng/ml, the eight treated with cromolyn improved but the difference between their symptom scores and those of the seven patients treated with placebo was not statistically significant.