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Biomedical subjects

H I Miller

Publications and source records attributed to H I Miller.

At least 163 records · Page 9Linked to original sources
PubMed1981

Free fatty acid kinetics after burn shock in guinea pigs.

Extensive full-skin-thickness burn results in a change in the flux and utilization of the major metabolic fuels. Considerable work has been done on glucose metabolism after severe burn, but much less is known about free fatty acid (FFA) metabolism. Therefore, we studied the rate of appearance (Ra), the rate of disappearance (Rd), the metabolic clearance rate (MCR), and the plasma FFA concentration 0--6 hours after a 50% body surface area full-skin-thickness burn using a constant infusion of 14C-palmitate. We found that the plasma FFA concentration decreased from a control value of 0.60 +/- 0.05 microns/ml to 0.26 +/- 0.04 microns/ml of plasma at 2 hours postburn (P less than 0.05). This change appears to be due to a greater decrease in Ra than Rd. The MCR was unchanged during this period (26.7 ml/kg . min). In a second series of experiments, the plasma FFA concentration, Ra and Rd at 5.5--6 hours postburn did not differ from the preburn values. The rapid decline of plasma FFA 0--30 minutes postburn may relate to decreased blood flow to adipose tissue, which in the same guinea pig model had decreased about 80% at 15 minutes postburn, or to a shift toward esterification in the fat depots, decreasing FFA mobilization.

Animals↗
PubMed1981

The role of the Food and Drug Administration in the regulation of the products of recombinant DNA technology.

We emphasize again that the FDA will regulate each product according to the relevant statute and will apply those quality assurance standards necessary to assure safety for foods, and safety and efficacy for other products. We are also sensitive to continuing public concern about the environmental consequences of this technology. What-ever the outcome of our review, the FDA will attempt to regulate responsibly with appropriate concern for our two major constituencies--the public and the industry.

DNA, Recombinant↗
PubMed1981

Contribution of altered lipolysis and reesterification in perturbations of free fatty acid kinetics during burn shock.

We have previously shown that free fatty acid (FFA) mobilization is severely decreased during burn shock in the guinea pig. Glycerol mobilization was also decreased, indicating that decreased lipolysis was a major contributing factor to the impairment of FFA mobilization. In order to assess the contribution, if any, of increased FFA reesterification to the perturbations of FFA kinetics, we used the constant infusion technique, simultaneously infusing 14C-palmitate and 3H-glycerol. By this method we measured the rate of triglyceride hydrolysis (glycerol turnover) and the mobilization of FFA from adipose tissue (palmitate turnover). It was found that FFA turnover was decreased by 65% (39.4 +/- 4.1 to 16.7 +/- 1.4 mumole/kg . min, P less than 0.001), and glycerol turnover was decreased by 48% (23.6 +/- 2.5 to 12.3 +/- 1.1 mumole/kg . min, P less than 0.001) at 2 hr postburn. The FFA:glycerol ratio decreased from 1.87 +/- 0.20 to 1.43 +/- 0.15 (P less than 0.02), suggesting that increased FFA reesterification contributed to the decrease of FFA mobilization from adipose tissue during burn shock.

Animals↗
PubMed1980

An E. coli gene product required for lambda site-specific recombination.

We report characteristics of himA mutations of E. coli, selected for their inability to support the site-specific recombination reaction involved in the formation of lysogens by bacteriophage lambda. The himA allele lies at minute 38 on the chromosome. Three noncomplementing and closely linked mutations define the himA locus; one is a nonsense mutation which shows that the gene product is a protein. HimA mutations reduce both lambda integrative and excisive site-specific recombination. Since dominance tests demonstrate that himA mutations are recessive, it is probable that the himA protein is either a necessary component for site-specific recombination or, alternatively, regulates the expression of such a function. HimA mutations exhibit pleiotropic effects. They reduce integration of phages that have different attachment specificities from lambda and inhibit the growth of phage mu. In addition, himA mutations reduce precise excision of integrated phage mu as well as Tn elements. This pleiotropy suggests that the role of himA protein is nonspecific. Since all of the processes affected by himA mutations ultimately rely on protein-DNA interactions, we suggest that himA protein may act in an auxillary manner to facilitate these interactions.

Bacterial Proteins↗
PubMed1980

Body fluid compartment changes during burn shock in the guinea pig.

The alterations in body fluid compartments 1, 4, and 8 hours after a 70% full-skin thickness burn were studied in conscious guinea pigs. Concurrently, we measured hemodynamic changes associated with the burn. Cardiac output and heart rate were depressed one hour postburn, and mean arterial blood pressure was depressed eight hours postburn. A hemoconcentration one-hour postburn, as evidence by an increase in hematocrit, was due exclusively to a loss of plasma volume. Red blood cell (RBC) volume remained constant after the burn. As a consequence of decreased plasma volume, total blood volume was also depressed. Extracellular fluid was decreased on hour after the burn; how ever, four and eight hours postburn, extracellular fluid space was comparable to that in the control group. Total body water and body weights of burned animals did not differ from control values. This study has demonstrated the very rapid redistribution of fluids in burn shock without a loss of fluids from the body.

Animals↗
PubMed1980

The effect of heparin on cardiovascular and metabolic parameters following burn shock in guinea pigs.

The effect of heparin intravenous (IV) infusion (1,200 IV/kg day) on the cardiovascular and metabolic responses to scalding was studied. The burn was produced by immersing an anesthetized guinea pig into 100 degrees C water for 3 seconds, resulting in a full-skin-thickness burn that covered 50% of the body surface area. We found that heparin-treated animals had lower cardiac outputs and carotid artery temperatures 24 hours after the burn than did control animals receiving saline. Heart rates and mean arterial blood pressures did not differ in the heparin-plus-saline and saline-infused animals. The hematocrits and plasma protein concentrations decreased similarly in both groups 8 and 24 hours after the burn. Free fatty acid levels were increased in heparin treated animals, whereas glucose concentrations were comparable. The 48 hour mortality was higher in the heparin-treated group. It appears that in our model, heparin was not of benefit in the immediate recovery after a full-skin-thickness burn.

Animals↗
PubMed1978

Metabolic and hemodynamic aspects of the hypothermia of early burn shock.

Guinea pigs briefly anesthetized with Halothane were burned over 70% of their body surface area. Core temperature progressively decreased over an 8 hour period reaching its lowest level just before death. Heart rate, cardiac output, and oxygen consumption also diminished over this period. The fractional distribution of the cardiac output to the pancreas, adipose tissue, burned and unburned skin and muscles fell sharply. Actual volume flow to the heart and brain also decreased while plasma FFA concentration exhibited little change. However, hyperglycemia was noted due in part to peripheral insulin resistance. Although plasma catecholamines increased during this trauma, their effect was muted by a low plasma pH and a rising lactic acid concentration. It is postulated that the destroyed peripheral temperature receptors, hypoxic areas of the brain, decreased blood flow through high metabolic areas and low oxygen and substrate utilization in the periphery brought about the hypometabolism.

Animals↗
PubMed1978

Comparison of cloned mouse alpha- and beta-globin genes: conservation of intervening sequence locations and extragenic homology.

We have cloned and characterized a 9.7-kilobase EcoRI fragment of mouse DNA that contains an alpha-globin gene. The gene is encoded in at least three discontinous segments of DNA interrupted by two small intervening sequences that can be visualized as R-loop structures in the electron miscroscope. The size of the gene and its small intervening sequences fits well with the known size of the alpha-globin mRNA precursor, suggesting that these intervening sequences, like those of beta-globin, are transcribed. Partial sequence analysis indicates that the larger intervening sequence interrupts the alpha-globin gene at a site exactly corresponding to that interrupted by the larger intervening sequences in both the beta-globin major and minor genes. This observation suggests that these sequences were present when the alpha- and beta-globin genes diverged in early vertebrate evolution, more than 500 million years ago. Furthermore, though alpha and betamaj genes are encoded on different chromosomes, when their sequences are compared directly by visualization of heteroduplex structures, only one 150- to 200-base-pair segment of homology is recognized. These homologous sequences are located on the 3'-flanking segments of both genes, about 1.5 kilobases from each.

Animals↗
PubMed1977

Glucose and lactate kinetics in burn shock.

We studied the glucose and lactate kinetics during burn shock by means of the primed constant infusion of [6-3H]glucose and Na-L-(+)-[U-14C]lactate. We found an early postburn hyperglycemia that was due to an increased rate of appearance (Ra) of glucose. Later, the ability of the tissues to extract glucose became impaired, and the plasma glucose concentration increased even more in spite of the return of Ra of glucose to the control level. The Ra of lactate rose rapidly postburn, whereas the rate of disappearance (Rd) of lactate stayed at the control level for 30 min. Consequently, plasma lactate rose approximately 350%. After 30 min, Rd of lactate increased to the same level as Ra; and Ra, Rd, plasma lactate concentration, and the percent of glucose derived from lactate remained elevated for the duration of the experiment. These results indicate an important role of lactate in burn shock metabolism and substrate kinetics.

Animals↗
PubMed1977

Regional blood flow redistribution during early burn shock in the guinea pig.

The distribution of blood flow was determined with radioactive microspheres following scald injury in guinea pigs. Burn was induced in halothane-anesthetized guinea pigs by a 3-sec immersion to the xiphoid process in 100 degree C water. Cardiac output and fractional blood flow measurements were made at preburn, 15-min postburn, and 75-min post-burn. In the scalded animals cardiac output decreased 58% by 75 min postburn. Three different blood flow responses to burn were noted: a) Brain, heart, hepatic artery, and adrenals received an increased fraction of the cardiac output; b) the fractional distribution of the diaphragm, liver (portal), spleen, gastrointestinal tract, muscle (from burned portion of the body), and bone remained constant; while c) the pancreas, burned skin, nonburned skin, and adipose tissue received a reduced fraction of the cardiac output. Although some regions of the body (i.e., brain and heart) received a greater percentage of the total cardiac output after burn injury, the cardiac output decrease was sufficient to cause a depression in absolute blood flow to all but two sites (adrenals and hepatic artery).

Animals↗
PubMed1977

Effect of burn injury on glucose turnover in guinea pigs.

Using our guinea pig model, we found the rate of appearance of glucose was elevated during the three phases following burn injury: the burn shock phase, the hypermetabolic phase and the septic phase. The rate of disappearance of glucose initially was not elevated, resulting in hyperglycemia during burn shock, but eventually, the rate of disappearance of glucose increased to the same extent as the rate of appearance of glucose. During the hypermetabolic and septic phases, the glucose turnover rate was elevated, but the plasma glucose concentration was normal. Glucose turnover was poorly correlated with total body oxygen consumption, suggesting that not all of the increased turnover of glucose was due to increased glucose oxidation.

Animals↗