Effect of visual display scale on duration estimates.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M A Davis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Tn10 rarely transposes, primarily because its IS10-encoded transposase protein is synthesized infrequently. Since the 5' end of the transposase gene is immediately adjacent to flanking host sequences, insertion of Tn10 into an actively transcribed operon could conceivably result in dramatically increased transposition. We show here that Tn10 is protected from such fortuitous activation; high levels of transcription from an upstream promoter actually decrease its rate of transposition. Protection operates at two levels. First, externally-initiated transcripts yield only a small amount of additional transposase protein, primarily because of inhibition at a posttranscriptional level. We suggest that the transposase gene start codon is sequestered in an mRNA secondary structure not present in transcripts initiated at the normal promoter. Second, transcription per se across an IS10 terminus inhibits its activity, thus negating any small transposase increase. These observations provide additional evidence that Tn10 has evolved specific mechanisms for keeping its transposition activity low.
Living arrangements and dietary patterns were examined for 3,477 adults aged 65 to 74 from the first National Health and Nutrition Examination Survey 1971 to 1974 (NHANES I). Several indicators of dietary variety, diet composition, and energy and nutrient intake from both the 24-hour recall, and the dietary frequency questionnaires were analyzed. Dietary patterns of older men were associated more strongly with type of living arrangement and income compared with older women. Men living with a spouse consistently had more favorable dietary patterns than either those living alone or those living with someone other than a spouse. Low income men who were not living with a spouse were at highest risk of poor dietary intake. Income was associated more consistently with the dietary indicators than type of living arrangement for women. Income, however, was still a less consistent influence on dietary patterns of older women compared to older men.
The present experiments were undertaken to assess hepatic lactate metabolism in the overnight-fasted, conscious dog after a physiological elevation in glucagon. Animals were given somatostatin plus intraportal insulin (243 microU . kg-1 . min-1) and glucagon (0.65 ng . kg-1 . min-1) to initially fix the pancreatic hormone levels at basal values. After a 40-min control period the glucagon level was increased to 527 +/- 27 pg/ml, while the insulin level was left unchanged (10 microU/ml). Fifteen minutes later blood lactate had increased by 215 +/- 24 mumol/l because of a marked increase in lactate output by the liver [2.4 +/- 2.0 to 10.0 +/- 3.8 mumol . kg . min (P less than 0.05)]. Subsequently, hepatic lactate output decreased, and after 3 h the liver was taking up lactate at a rate of 3.1 +/- 1.6 mumol . kg-1 . min-1 (P less than 0.05). Gut and renal lactate production were not significantly affected by glucagon. The rate of conversion of lactate and alanine to glucose had tripled after 3 h of hyperglucagonemia, while the efficiency with which the liver converted the incoming gluconeogenic precursors to glucose had doubled. The fractional extraction of alanine by the liver had more than doubled by 3 h, and net hepatic alanine uptake had increased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
We describe below several new variants of the tetracycline-resistance transposon Tn10 which are more useful than the wild-type transposon for many types of genetic and physical analysis of bacteria. These derivatives have one or more of the following new properties: (i) new drug resistance markers; (ii) high transposition frequencies; (iii) removal of the transposase gene to a position outside of the transposing segment; (iv) internal deletions which eliminate the ability of Tn10 to make adjacent deletion/inversions; or (v) addition of a trp-lac operon fusion segment just inside one terminus such that insertion can automatically generate a transcriptional fusion to the interrupted operon. Phage and plasmid vehicles carrying these new elements are described.
Large unilamellar phospholipid vesicles were prepared and loaded with various radiographic contrast media. Body CT following in vivo administration of these vesicles in the rat demonstrated opacification of organs associated with the reticuloendothelial system. Image enhancement in the spleen and liver was dose dependent and was linearly related within the dose range investigated. Contrast enhancement was observed within five minutes of intravenous administration, was maximal 60 minutes after injection, and declined during the second hour. Clearance of the radiographic contrast material was complete within 24 hours. Diffuse splenic lymphoma following intraperitoneal or intrasplenic injection of lymphoma cells, and solitary lymphoma nodules following intrahepatic injection were readily detected as nonenhanced areas following injection of liposomes.
The present experiments were undertaken to assess lactate and gluconeogenic precursor metabolism in the 30 h following consumption of a mixed meal by the overnight-fasted, conscious dog. The arterial glucose level rose by a maximum of 13 mg/dl 4 h after the meal and had returned to control levels by 12 h. Hepatic glucose production was suppressed for 12 h after feeding, but net hepatic glucose uptake did not occur. The arterial lactate level rose from 0.55 +/- 0.10 to 1.28 +/- 0.14 mM within 1 h of feeding and remained elevated for 12 h. Net hepatic lactate production, measured with an A-V difference technique, rose from 3.5 +/- 2.8 to 19.4 +/- 3.1 mumol X kg-1 X min-1 h after the meal and declined slowly over the next 22 h. The liver then began to consume lactate so that at 30 h net hepatic uptake was 5.7 +/- 0.5 mumol X kg-1 X min-1. The total hepatic uptake of the gluconeogenic amino acids (alanine, glycine, serine, threonine) increased from 5.3 +/- 0.8 to 11.5 +/- 2.5 mumol X kg-1 X min-1 at 1 h and remained elevated for 4 h. The arterial alanine level rose from 0.36 +/- 0.03 to 0.51 +/- 0.04 mM at 2 h and remained elevated for 18 h. Insulin increased from 11 +/- 2 microU/ml to a maximum of 44 +/- 5 4 h after the meal, and the glucagon level rose from 59 +/- 8 pg/ml to a maximum of 150 +/- 22 1 h after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Losefamate, a hepatobiliary contrast agent, was encapsulated into liposomes to increase its ability to opacify the liver and spleen on computed tomographic (CT) images. Multilamellar lipid vesicles (lecithin, cholesterol, and stearylamine, in 4:1:1 molar ratio) containing iosefamate in their aqueous phase were prepared. Seven dogs received intravenous injections of 100-300 mg I/kg in one of three forms: encapsulated, unencapsulated, or a mixture of the two in equal parts. Animals that received the opaque vesicles had marked opacification of their livers, bile ducts, gallbladders, spleens (maximum 106 H enhancement), and gastrointestinal tracts. Spleen CT values (an indicator of encapsulated material uptake) were always higher in these dogs than in the animals receiving equivalent amounts of unencapsulated iosefamate alone. At the high-dose level, liver uptake of the encapsulated materials was also greater. Liposome-encapsulated hepatobiliary contrast agents are effective liver and spleen opacifiers for CT imaging in the dog.
A simple and efficient method of covalently coupling the strong chelator diethylenetriaminepentaacetic acid to proteins was developed for radiolabeling immunoglobulin G antibodies. After being coupled and labeled with indium-111, a monoclonal antibody to carcinoembryonic antigen retained its ability to bind to its antigen in vitro and in vivo. In nude mice with a human colorectal xenograft, 41 percent of the injected radioactivity became localized in each gram of xenograft at 24 hours compared with 9 percent for control antibody and 19 percent for radioiodinated antibody to carcinoembryonic antigen.
Unilamellar phospholipid vesicles loaded with the water-soluble, ionic X-ray contrast agent diatrizoate (Hypaque, Renografin) were manufactured by reverse-phase evaporation for use as organ-enhancing agents in X-ray computed tomography. Encapsulation efficiency was determined as a function of various diatrizoate concentrations in vesicles of varying lipid composition. Loss of encapsulated diatrizoate over 24 h was examined in vesicles composed of several egg phosphatidylcholine/cholesterol ratios. Size estimates for loaded vesicles were obtained by negative-stain electron microscopy, Millipore filtration and light microscopy. Intravenous in vivo injection of loaded vesicles in the rat resulted in significant enhancement of both spleen and liver on subsequent scans. Vesicles were similarly prepared with the water-soluble, nonionic agent metrizamide (Amipaque). Encapsulation efficiency was determined, and in vivo behavior was observed.
Complexes of ammine[103Ru]ruthenium(III) with L-histidine, beta-(4-pyridyl)-alpha-alanine, and S-[beta-(4-pyridyl)ethyl]-L-cysteine were synthesized in low specific activity and evaluated in mice as potential radiodiagnostic agents for pancreatic imaging. The biological distribution of each complex was determined in normal mice at 15 min, 1 h, and 2 h following intravenous administration. All four complexes were rapidly cleared through the kidneys, with 50% of the injected dose concentrated in the urine within 15 min. None of the complexes showed a tendency to accumulate in any major organ. Major differences in distribution were found in lungs, heart, spleen, stomach, intestine, bone, and soft tissues. A significant relative difference in pancreatic uptake was observed. Only the beta-(4-pyridyl)-alpha-alanine complex exhibited pancreas to liver ratios significantly greater than 1. The pancreas to liver ratio of 17 was reached 1 h following injection of this ruthenium complex, which is considerably higher than commonly reported values of 2.5 for [75Se]selenomethionine. The beta-(4-pyridyl)-alpha-alanine complex is therefore a promising candidate for evaluation as a pancreatic imaging agent when labeled with cyclotron-produced ruthenium-97.
The purpose of the present study was to determine whether an ischemic index--expressed as the product of flow deprivation (FD) and the duration of occlusion (T), FD X T--correlated with biochemical and early morphologic alterations of the subendocardial myocardium and could predict ultimate development of irreversible injury after coronary reperfusion. Myocardial biopsy specimens for measurement of ATP and other purines and for ultrastructure studies were obtained in vivo during coronary occlusion in a canine model and were considered relative to development of necrosis after coronary reperfusion. FD X T correlated negatively with ATP content [ATP, nmol/mg of cardiac protein = 23.6 - 0.24(FD X T) + 0.0007(FD X T)2; r = -0.81] and with a semiquantitative early histologic index of damage (r = 0.70). Values of (FD X T) less than 18 were associated with reversible injury--i.e., complete salvage after coronary reperfusion. (FD X T) greater than 18 was associated with varying degrees of necrosis; necrosis was severe (78 +/- 12% of subendocardial biopsy specimens) when ATP less than 10 nmol/mg of protein and total purine pool was decreased by 50%. FD X T correlated with the eventual percentage of subendocardial necrosis (r = 0.85). Accordingly, as an index of ischemic injury, FD X T may be useful in assessing whether ischemic myocardial tissue will benefit from early restoration of blood flow to the ischemic area.
The 59Fe-iron(II) chelates of 2-formylpyridine thiosemicarbazone (I), 5-dimethylamino-2-formylpyridine thiosemicarbazone (II), and 5-hydroxy-2-formylpyridine thiosemicarbazone (III) were prepared and their biodistribution determined in normal rats. Early accumulation of these complexes occurred in the liver, muscle and pelt with lesser amounts in the blood, kidneys and other organs. The tissue levels decreased with a 1 to 2-h half-life with the exception of the liver and intestines. The liver level tended to remain constant over the 2-h period. Accumulation in the gut resulting from hepatobiliary excretion increased over the first 60 min and then leveled off. In rats bearing a subcutaneous glioblastoma the uptake of compound I increased during the first 24 h after administration, and tumor to normal tissue ratios of 2 to 3.3 were obtained.
Data from the first National Health and Nutrition Examination Survey were examined for individual 24-h dietary intakes of protein, vitamin A, thiamin, riboflavin, and iron, and for laboratory indices of the same nutrients in blood and urine. Mean intake values were close to or above reference standards for all nutrients except iron. Substandard laboratory values were recorded for: serum albumin and vitamin A--less than 3% of subjects; urinary thiamin/creatinine excretion--3 and 8% of white and Black subjects, respectively; Hb, hematocrit, and percentage transferrin saturation--5 to 15% of whites and 18 to 27% of Black subjects; serum iron--less than 6% of subjects. Individual dietary recall data were of limited value in predicting the laboratory indices; regression analyses indicated that sociodemographic variables may be of greater predictive value.
The 75Se-labeled 4-substituted-1,2,3-selenadiazole analogs of two drugs that inhibit the adrenocorticosteroid 11 beta- and 17 alpha-hydroxylase enzymes were prepared by the [75Se]selenious acid oxidation of the appropriate methyl ketone semicarbazones. The concentration of the radiolabeled compounds in the adrenal glands of rats over a 0.25--24-hr period was determined and compared with that in the blood, liver, and kidneys. The concentration in the adrenal glands and the target to nontarget ratios were much lower than those reported for other adrenocorticosteroid inhibitors. Therefore, these 1,2,3-selenadiazole agents do not have potential as adrenocorticosteroid imaging agents.
Transposon Tn10 is 9300 bp in length, with 1400 bp inverted repeats at its ends. The inverted repeats are structurally intact IS-like sequences (Ross et al., 1979). Analysis of deletion mutants and structural variants of Tn10, reported below, shows that the two IS10 segments contain all of the Tn10-encoded genetic determinants, both sites and functions, that are required for transposition. Furthermore, the two repeats (IS10-Right and IS10-Left) are not functionally equivalent: IS10-Right is fully functional and is capable by itself of promoting normal levels of Tn10 transposition; IS10-Left functions only poorly by itself, promoting transposition at a very low level when IS10-Right is inactivated. Complementation analysis shows that IS10-Right encodes at least one function, required for Tn10 transposition, which can act in trans and which works at the ends of the element. Also, all of the sites specifically required for normal Tn10 transposition have been localized to the outermost 70 bp at each end of the element; there is no evidence that specific sites internal to the element play an essential role. Finally, Tn10 modulates its own transposition in such a way that transposition-defective point mutants, unlike deletion mutants, are not complemented by functions provided in trans; and wild-type Tn10, unlike deletion mutants, is not affected by functions provided in trans from a "high hopper" Tn10 element.
Explore the source record for details and available documents.