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D L Miller

Publications and source records attributed to D L Miller.

At least 379 records · Page 21Linked to original sources

Polymorphism in the structure of the yeast mitochondrial tRNA synthesis locus.

Yeast mitochondrial DNA contains a genetic locus, called the tRNA synthesis locus, which codes for information necessary for mitochondrial tRNA biosynthesis. A 9S RNA molecule coded by this locus is thought to be the trans-acting element required for the removal of 5' extensions from tRNA precursors. The DNA coding for this RNA maps to a region of mitochondrial DNA known to contain strain specific restriction site polymorphisms. Comparison of the tRNA synthesis locus in two such strains by sequence analysis demonstrates that the restriction enzyme polymorphisms are due to the deletion/insertion of a 50 base pair GC-rich element in the 5' flanking sequence of the 9S RNA coding region. There are also several differences between the 9S RNA coding region of these two strains which do not interfere with the tRNA synthesis function.

Base Sequence↗

Structure of a precursor to the yeast mitochondrial tRNAMetf. Implications for the function of the tRNA synthesis locus.

A transcript from the yeast mitochondrial tRNAMetf gene has been isolated from a petite deletion mutant, ND40. RNA sequence analysis demonstrates that it has a 5' unprocessed extension of 28 nucleotides, and capping experiments with guanylyltransferase reveal that the first nucleotide has a 5' di- or triphosphate. A comparison of the RNA sequence with the tRNAMetf gene sequence reported here shows that transcription initiation occurs at a sequence homologous to a nonanucleotide segment implicated as a promoter element of yeast mitochondrial DNA. The 3' end of this transcript is identical to the mature tRNAMetf and carries a CCA sequence. The transcript can be processed in vitro to yield a mature tRNAMetf and thus appears to be a bona fide tRNA precursor. This tRNA precursor accumulates in the absence of the mitochondrial tRNA synthesis locus whereas mature tRNAMetf can be made from the same gene in the presence of the locus. This data provides clear and convincing evidence that the synthesis locus codes for a 5' tRNA processing function.

Base Sequence↗

Direct determination of the association constant between elongation factor Tu X GTP and aminoacyl-tRNA using fluorescence.

We have investigated the formation of the aa-tRNA X EF-Tu X GTP ternary complex spectroscopically by monitoring a fluorescence change that accompanies the association of EF-Tu X GTP with Phe-tRNAPhe-F8, a functionally active analogue of Phe-tRNAPhe with a fluorescein moiety covalently attached to the s4U-8 base. With this approach, the protein-nucleic acid interaction could be examined by direct means and at equilibrium. The fluorescence emission intensity of each Phe-tRNAPhe-F8 increased by 36-55% upon association with EF-Tu X GTP, depending on the solvent conditions. Thus, when Phe-tRNAPhe-F8 was titrated with EF-Tu X GTP, the extent of ternary complex formation was determined from the increase in emission intensity. A nonlinear least-squares analysis of the titration data yielded a dissociation constant of 0.85 nM for the ternary complex in 50 mM N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (pH 7.6), 10 mM MgCl2, and 50 mM NH4Cl, at 6 degrees C. The delta H degrees of this interaction, determined by the temperature dependence of Kd, was -16 kcal/mol; the delta S degrees was therefore -16 cal mol-1 deg-1 at 6 degrees C in this buffer. In a more physiological polycation-containing solvent ("polymix"), the Kd was 4.7 nM. The ionic strength dependence of ternary complex formation showed that a minimum of two salt bridges and a substantial nonelectrostatic contribution are involved in the binding of aa-tRNA to EF-Tu. The affinities of unmodified aa-tRNAs for EF-Tu X GTP were determined by their abilities to compete with the fluorescent aa-tRNA for binding to the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Escherichia coli↗

On the oscillation mode of gas-filled micropores.

Small pores in hydrophobic membranes trap gas when the membrane is immersed in aqueous media, and the resulting "gas bodies" may be used for studying biophysical effects of ultrasonic cavitation. In a previous study [D. L. Miller and W. L. Nyborg, J. Acoust. Soc. Am. 73, 1537-1544 (1983)], two modes of oscillation, a "pistonlike" and a "membranelike" mode, were described theoretically, and either model appears capable of qualitatively explaining observations of the linear behavior of the gas-filled micropores. In this study, low-amplitude nonlinear theory is employed with observations of second harmonic emissions to show that the membranelike model is the more appropriate model for the 3.4- and 4.0-microns-diam micropores tested at 0.81 and 1.62 MHz. In addition, this model is expanded to include the case for which the gas is asymmetrically situated in a pore, to discuss the motion of the three-phase line at the periphery of an air-water interface in a pore, and to suggest an explanation of the phenomenon of gas loss from the pores when the incident field intensity is raised. Knowledge of the behavior of the gas-filled micropores in an ultrasonic field should allow a more complete understanding of biological effects on cells exposed to this form of cavitation activity.

Membranes, Artificial↗

Parathymic parathyroid: CT, US, and angiographic findings.

Six patients with primary hyperparathyroidism caused by an undescended parathymic adenoma are described. All glands were anterior to the common carotid artery at the level of the hyoid bone. Blood supply was from the superior thyroid artery, and venous drainage was into the superior thyroid vein. Ultrasound (one of five) and computed tomography (two of six) were rarely positive, but glands can be detected with both modalities if the examination is carried high enough. Glands within the carotid sheath are generally lower in the neck and have a blood supply from the inferior thyroid artery with drainage into the vertebral veins.

Adenoma↗

Lipid emulsions as contrast agents for hepatic sonography: an experimental study in rabbits.

An ultrasound contrast agent capable of increasing hepatic echogenicity would be useful for the detection of hepatic tumors and metastases. Fatty liver is known to produce increased liver echogenicity. Intravenously administered lipid emulsions are phagocytosed by cells of the reticuloendothelial system the liver with transient hepatic lipid accumulation. We examined the effectiveness of three lipid emulsions of differing particle size as potential ultrasound contrast agents using a rabbit liver model. None of the tested emulsions showed any consistent ability to alter liver echogenicity at maximum tolerable doses. Lipid emulsions do not appear to have potential as contrast agents for ultrasound examination of the liver.

Animals↗

The influence of perennial allergic rhinitis on facial type and a pilot study of the effect of allergy management on facial growth patterns.

Perennial rhinitis with an allergic component (PRAC) in association with chronic mouthbreathing has been thought to cause skeletal open-bite facial type and narrow transverse facial dimensions. The object of this study was to supply data for this theory and to determine if allergy management would alter the course of facial growth. When a group of children, aged 5 to 10 years, with PRAC was compared with a matched control sample, a significantly larger palatomandibular angle and lower anterior facial height were found for the PRAC group. Transverse cephalometric measurements showed significantly narrower bilateral orbital breadth, bizygomatic, and binasal dimensions (narrower face) of the PRAC patients compared with the control sample. A pilot study of twelve PRAC patients who received 2 1/2 years of allergy management revealed no significant dento-facial dimensional change. This study suggests that PRAC with chronic mouthbreathing can alter the development of the midface. Whether allergy therapy can prevent or change this is as yet uncertain.

Cephalometry↗

Improved detection of focal lesions with computerized tomographic examination of the liver using ethiodized oil emulsion (EOE-13) liver contrast.

A prospective study of computerized tomography (CT) of the liver using a liver contrast agent compared to conventional CT was undertaken. CT scanning without contrast agents (NC-CT), CT with water-soluble contrast (WSC-CT), and CT with ethiodized oil emulsion (EOE-CT) were performed on patients with possible or probable hepatic metastases. The findings on these three examinations were compared to the objective findings at surgery in 53 patients. Accuracy of these examinations was 80.7% for NC-CT, 77.1% for WSC-CT, and 84.9% for EOE-CT. The true-positive percentage for 129 hepatic lesions was 40.6% for the NC-CT, 33.6% for WSC-CT, and 76.7% for the EOE-CT. Eighty-three percent (44/53) of 1- to 2-cm liver lesions were detected by EOE-CT, whereas only 26.4% (14/53) lesions of this size were detected by the NC-CT and 20.4% (10/49) shown by WSC-CT. The likelihood that a lesion seen by CT scan was malignant was 84.6% for NC-CT, 89.4% for WSC-CT, and 81.8% for EOE-CT. The EOE contrast agent improves the sensitivity of liver CT for detecting hepatic metastases. The improvement occurs with lesions 1 cm and greater in diameter, but is particularly striking for lesions of 1 to 2 cm in diameter.

Ethiodized Oil↗

Rate of growth of intraabdominal metastases from colorectal cancer.

Monitoring the progression or regression of intraabdominal metastatic disease is required for knowledgeable management of chemotherapeutic regimens designed to treat metastases. Computerized tomography (CT) and CT with EOE-13, a liver contrast agent, allowed precise measurement of metastatic disease. The tumor doubling time of colorectal metastases in four patients was determined from serial CT scans of individual patients. Tumor doubling times of untreated patients varied from 50 to 95 days, and were in the same range for hepatic, lymph node, or intraperitoneal metastatic disease. These data may indicate that metastatic disease of colorectal cancer progresses at a faster rate in the peritoneal cavity than is reported for colorectal cancer metastatic to the lungs. The response to chemotherapy or progression of disease was also determined in treated patients. High resolution CT scanning with EOE-13 allowed calculation of tumor doubling times, and therefore more precise management of cancer patients with metastases.

Cell Division↗

Isolation and regional localization by in situ hybridization of a unique gene segment to chromosome 21.

V chromosome 21 (ch. 21) flow-sorted library was screened for the presence of unique DNA segments which are specific for the 21st chromosome. By combining the techniques of somatic cell genetics and in situ hybridization, we have identified several of these recombinant probes and have regionally mapped one of them to the distal half of the long arm of chromosome 21 (q22.1- greater than qter). This represents the first report of the sublocalization of a unique DNA segment to chromosome 21 by in situ hybridization.

Animals↗

Acoustic cavitation series: part six. Gas body activation.

A small body of gas which is stabilized against dissolution in a liquid by a supportive structure may oscillate in response to an ultrasonic field and this form of cavitation is termed gas body activation. Linear theory describes the response of gas-filled intercellular channels in plant tissue and of gas-filled micropores in thin sheets of plastic. Calculations from this theory yield good agreement with indirect observations of resonance frequencies and rough agreement with direct measures of aggregate response (transmission and reflection coefficients). Studies of gas body activation in biological systems should allow quantitative analysis of cavitation bioeffects for relatively low-intensity ultrasound applications.

Cell Survival↗

Immunisation practice and policy.

Immunisation has proved to be a generally safe and effective means of disease control, particularly where environmental approaches are impractical. Recent developments in vaccine production, aimed at selecting or synthesising in pure form the antigens needed to evoke a protective response, give hope of more effective and less toxic vaccines in future. Adequate trials of improved vaccines may, however, be difficult to carry out under modern conditions. Policies for the use of vaccines are sometimes controversial, particularly when there is concern about reactions, as with pertussis vaccine. Acceptance rates for measles and rubella vaccines in the UK have hitherto been disappointingly low and need to be increased if the aims of elimination of measles and congenital rubella are to be achieved. Cost-benefit analyses generally support the use of immunisation in disease control.

Drug Evaluation↗

Calcium and sodium transport and vitamin D metabolism in the spontaneously hypertensive rat.

Serum ionized calcium levels are lower and immunoreactive parathyroid hormone levels are higher in the spontaneously hypertensive (SH) rat than in the normotensive Wistar-Kyoto (WKy) control. We postulated that there is either a defect in the regulation of vitamin D metabolism by parathyroid hormone or that the gut target organ for vitamin D in the SH rat is unresponsive. To test these hypotheses we measured serum concentrations of vitamin D metabolites and intestinal transport of calcium and sodium. Compared with that of WKy controls, in vitro calcium transport by duodenal sacs of the SH rat was decreased (P less than 0.001) at 5 wk, before the development of hypertension, and at 12 wk, after hypertension was well established. When measured in vivo in the most proximal 20 cm of small intestine, maximum velocity (Vmax) for calcium transport was decreased (P less than 0.05) and net absorption of sodium and water was increased (P less than 0.05) in SH rats as compared with WKy rats. Vmax for calcium transport was also decreased (P less than 0.05) in the most distal 20 cm of small intestine of SH rats, but net sodium and water transport were the same in SH and WKy rats. At 12 wk, serum concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] was the same in both SH and WKy groups, but its precursor, 25-hydroxycholecalciferol, was increased (P less than 0.05) in the SH rat. We conclude that in the SH rat: (a) the concentration of 1,25-(OH)2D3 is inappropriately low in relation to the elevated immunoreactive parathyroid hormone and the depressed calcium absorption, suggesting a defect in the regulation of vitamin D metabolism; and (b) the depressed calcium absorption, in the setting of normal concentrations of [1,25-(OH)2D3], demonstrates unresponsiveness of the gut to vitamin D and may explain in part the low serum ionized calcium found in earlier studies. The presence of these abnormalities before we found a significant difference in blood pressure suggests that they may be causal, not secondary, to the hypertension.

Animals↗