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Biomedical subjects

J C Phillips

Publications and source records attributed to J C Phillips.

At least 19 recordsLinked to original sources

Predictive value of upper gastrointestinal studies versus clinical signs for gastrointestinal leaks after laparoscopic gastric bypass.

BACKGROUND: The utility of routine upper gastrointestinal (UGI) studies after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a matter of great debate. Because the morbidity and mortality rates associated with an unrecognized postoperative leak are high after LRYGB, diagnosis of a postoperative leak earlier would be of benefit. Clinical signs, however, may predict the diagnosis of a postoperative leak more often. This study explored the hypothesis that UGI studies are more predictive than clinical signs for the early diagnosis of a postoperative leak after LRYGB. METHODS: All patients who underwent LRYGB at the authors' institution were included in this study. Charts were reviewed to examine immediate clinical signs (heart rate, temperature, and white blood cell count within the first 24 h), UGI studies, and clinical course. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of clinical signs and UGI studies were calculated. RESULTS: This study included 245 patients with a 3% rate of leak. The positive and negative predictive value of UGI studies were 67% and 99%, respectively. Only an elevated white blood count had a better predictive value (100% for negative predictive value). The efficiency of UGI studies (98%) was better than that of heart rate (83%), white blood count (8%), or temperature (95%). CONCLUSIONS: According to our data, UGI studies are the most predictive of an early leak diagnosis. Clinical signs alone may not be as useful in predicting leaks early after laparoscopic gastric bypasses. Routine early postoperative UGI studies are a reasonable approach to predicting leaks after LRYGB.

Adolescent↗

Topological derivation of shape exponents for stretched exponential relaxation.

In homogeneous (ideal) glasses, the important dimensionless stretched-exponential shape parameter beta is described by magic (not adjusted) simple fractions derived from fractal configuration spaces of effective dimension d* determined by different topological axioms (rules) in the presence (absence) of a forcing electric field. The rules are based on a new central principle for defining glassy states: equal a priori distributions of fractal residual configurational entropy. Our approach and its beta estimates are fully supported by the results of relaxation measurements involving many different glassy materials and probe methods. The present unique topological predictions for beta typically agree with observed values to approximately 1% and indicate that for field-forced conditions beta should be constant for appreciable ranges of such exogenous variables as temperature and ionic concentration, as indeed observed using appropriate frequency-domain data analysis. The present approach can also be inverted and used to test sample homogeneity and quality.

Journal Article↗

The impact of hemolysis on Ortho-Clinical Diagnostic's ECi and Roche's elecsys immunoassay systems.

BACKGROUND: Hemolysis is regularly encountered in clinical specimens and often interferes with a variety of laboratory test methods. Although not widely recognized, immunoassays based on nonisotopic detection systems can also be affected by hemolysis. For this reason, we investigated the effect of differing amounts of hemolysis across a range of values for several immunoassays on the Ortho-Clinical Diagnostics ECi and Roche Elecsys platforms. METHODS: Hemolysate was prepared from whole blood and spiked at varying concentrations into pooled patient serum samples for different analytes. RESULTS: Out of the 21 analytes tested, six (28.6%) exhibited significant increases or decreases in measured concentrations with increasing amounts of hemolysis. CONCLUSIONS: Although immunoassays are generally thought to be impervious to hemolysis interference, hemolysis can interfere in immunoassay testing platforms. For these reasons, we recommend that laboratories conduct hemolysis interference studies for all laboratory test protocols.

Blood Specimen Collection↗

Universal intermediate phases of dilute electronic and molecular glasses.

Generic intermediate phases with anomalous properties exist over narrow composition ranges adjacent to connectivity transitions. Analysis of both simple classical and complex quantum percolation shows how topological concepts can be used to understand many mysterious properties of high temperature superconductors, including the remarkably similar phase diagrams of La(2-x)Sr(x)CuO4 and C60(+y). Predictions are made for novel threshold behavior of the impurity band metal-insulator transition in two dimensions.

Journal Article↗

Physician's guide to popular low-carbohydrate weight-loss diets.

Low-carbohydrate weight-loss diets are very popular, but the recommendations of many of these diets are diametrically opposed to those put forth by the US Department of Agriculture, the American Heart Association, and other national organizations. Their focus on foods high in protein, fat, and cholesterol has potentially serious health implications. Physicians need to be knowledgeable about the efficacy of these programs and to talk to overweight patients about weight loss.

Diet Fads↗

Dose-response relationships for hepatic aflatoxin B1-DNA adduct formation in the rat in vivo and in vitro: the use of immunoslot blotting for adduct quantitation.

An immunoslot blotting (ISB) method for quantitating aflatoxin B1-DNA adduct levels has been developed and used to examine the relationship between dose and hepatic aflatoxin B1-DNA adduct levels in rats fed aflatoxin B1 (AFB1) in the diet at dose levels of between 0.5 and 10 micrograms/kg/day. The method has also been used to examine the dose-response relationship for adduct formation in precision-cut rat liver slices incubated with AFB1 at concentrations between 0.01 and 2 microM. For the feeding studies, groups of male Fisher F344 rats were given AFB1 in the diet for periods of 1 to 10 weeks and hepatic DNA adduct levels determined using ISB. The time for adduct levels to reach steady-state conditions was determined in animals given approximately 10 micrograms of AFB1/kg/day and steady-state levels at lower concentrations measured. The time course for the accumulation of AFB1-DNA adducts in rat liver slices incubated with AFB1 at 0.5 microM has been investigated and the relationship between adduct formation and AFB1 concentration over a wide concentration range in liver slices has been determined.

Aflatoxin B1↗

Slow algebraic relaxation in quartic potentials and related results.

We present a detailed report [see S. Sen et al., Phys. Rev. Lett. 77, 4855 (1996)] of our numerical and analytical studies on the relaxation of a classical particle in the potentials V(x)= +/-x(2)/2+x(4)/4. Both of the approaches confirm that at all temperatures, the relaxation functions (e.g., velocity relaxation function and position relaxation function) decay asymptotically in time t as sin(omega(0)t)/t. Numerically calculated power spectra of the relaxation functions show a gradual transition with increasing temperature from a single sharp peak located at the harmonic frequency omega(0) to a broad continuous band. The 1/t relaxation is also found when V(x) is a polynomial in powers of x(2) with a nonvanishing coefficient accompanying the x(4) term in V(x). Numerical calculations show that in the cases in which the leading term in V(x) behaves as x(2n) with integer n, the asymptotic relaxation exhibits 1/t(phi) decay where phi =1/(n-1). We briefly discuss the analytical approaches to relaxation studies in these strongly anharmonic systems using direct solution of the equation of motion and using the continued fraction formalism approach for relaxation studies. We show that the study of the dynamics of strongly anharmonic oscillators poses unique difficulties when studied via the continued fraction or any other time-series construction based approaches. We close with comments on the physical processes in which the insights presented in this work may be applicable.

Journal Article↗

Carbamoyl phosphate synthetase: caught in the act of glutamine hydrolysis.

Carbamoyl phosphate synthetase from Escherichia coli catalyzes the production of carbamoyl phosphate from two molecules of Mg2+ATP, one molecule of bicarbonate, and one molecule of glutamine. The enzyme consists of two polypeptide chains referred to as the large and small subunits. While the large subunit provides the active sites responsible for the binding of nucleotides and other effector ligands, the small subunit contains those amino acid residues that catalyze the hydrolysis of glutamine to glutamate and ammonia. From both amino acid sequence analyses and structural studies it is now known that the small subunit belongs to the class I amidotransferase family of enzymes. Numerous biochemical studies have suggested that the reaction mechanism of the small subunit proceeds through the formation of the glutamyl thioester intermediate and that both Cys 269 and His 353 are critical for catalysis. Here we describe the X-ray crystallographic structure of carbamoyl phosphate synthetase from E. coli in which His 353 has been replaced with an asparagine residue. Crystals employed in the investigation were grown in the presence of glutamine, and the model has been refined to a crystallographic R-factor of 19.1% for all measured X-ray data from 30 to 1.8 A resolution. The active site of the small subunit clearly contains a covalently bound thioester intermediate at Cys 269, and indeed, this investigation provides the first direct structural observation of an enzyme intermediate in the amidotransferase family.

Asparagine↗

Broken symmetry and strangeness of the semiconductor impurity band metal-insulator transition.

The filamentary model of the metal-insulator transition in randomly doped semiconductor impurity bands is geometrically equivalent to similar models for continuous transitions in dilute antiferromagnets and even to the lambda transition in liquid He, but the critical behaviors are different. The origin of these differences lies in two factors: quantum statistics and the presence of long range Coulomb forces on both sides of the transition in the electrical case. In the latter case, in addition to the main transition, there are two satellite transitions associated with disappearance of the filamentary structure in both insulating and metallic phases. These two satellite transitions were first identified by Fritzsche in 1958, and their physical origin is explained here in geometrical and topological terms that facilitate calculation of critical exponents.

Journal Article↗

Quantum dynamics of the femtosecond photoisomerization of retinal in bacteriorhodopsin.

The membrane protein bacteriorhodopsin contains all-trans-retinal in a binding site lined by amino acid side groups and water molecules that guide the photodynamics of retinal. Upon absorption of light, retinal undergoes a subpicosecond all-trans-->13-cis phototransformation involving torsion around a double bond. The main reaction product triggers later events in the protein that induce pumping of a proton through bacteriorhodopsin. Quantum-chemical calculations suggest that three coupled electronic states, the ground state and two closely lying excited states, are involved in the motion along the torsional reaction coordinate phi. The evolution of the protein-retinal system on these three electronic surfaces has been modelled using the multiple spawning method for non-adiabatic dynamics. We find that, although most of the population transfer occurs on a timescale of 300 fs, some population transfer occurs on a longer timescale, occasionally extending well beyond 1 ps.

Bacterial Proteins↗

Filamentary microstructure and linear temperature dependence of normal state transport in optimized high temperature superconductors.

A filamentary model of "metallic" conduction in layered high temperature superconductive cuprates explains the concurrence of normal state resistivities (Hall mobilities) linear in T (T-2) with optimized superconductivity. The model predicts the lowest temperature T0 for which linearity holds and it also predicts the maximum superconductive transition temperature Tc. The theory abandons the effective medium approximation that includes Fermi liquid as well as all other nonpercolative models in favor of countable smart basis states.

Journal Article↗

Broken symmetry and critical transport properties of random metals.

Recent experimental data on the conductivity final sigma+(T), T --> 0, on the metallic side of the metal-insulator transition in ideally random (neutron transmutation-doped) 70Ge:Ga have shown that final sigma+(0) ~ (N - Nc)mu with mu = (1/2), confirming earlier ultra-low-temperature results for Si:P. This value is inconsistent with theoretical predictions based on diffusive classical scaling models, but it can be understood by a quantum-directed percolative filamentary amplitude model in which electronic basis states exist which have a well-defined momentum parallel but not normal to the applied electric field. The model, which is based on a new kind of broken symmetry, also explains the anomalous sign reversal of the derivative of the temperature dependence in the critical regime.

Journal Article↗

Critical transport properties of random metals in large magnetic fields.

The threshold behavior of the transport properties of a random metal in the critical region near a metal-insulator transition is strongly affected by the measuring electromagnetic fields. In spite of the randomness, the electrical conductivity exhibits striking phase-coherent effects due to broken symmetry, which greatly sharpen the transition compared with the predictions of effective medium theories, as previously explained for electrical conductivities. Here broken symmetry explains the sign reversal of the T --> 0 magnetoconductance of the metal-insulator transition in Si(B,P), also previously not understood by effective medium theories. Finally, the symmetry-breaking features of quantum percolation theory explain the unexpectedly very small electrical conductivity temperature exponent alpha = 0.22(2) recently observed in Ni(S,Se)2 alloys at the antiferromagnetic metal-insulator transition below T = 0.8 K.

Journal Article↗

Effect of piperonyl butoxide on cell replication and xenobiotic metabolism in the livers of CD-1 mice and F344 rats.

Male CD- 1 mice were fed diets containing 0 (control), 10, 30, 100, and 300 mg/kg/day piperonyl butoxide (PBO) and 0.05% sodium phenobarbital (NaPB) and male F344 rats were fed diets containing 0 (control), 100, 550, 1050, and 1850 mg/kg/day PBO and 0.5% NaPB for periods of 7 and 42 days. In both species PBO and NaPB increased relative liver weight and whereas PBO produced a midzonal (mouse) or periportal/midzonal (rat) hypertrophy, NaPB produced a centrilobular hypertrophy. In the rat, individual cell necrosis was also observed at 42 days after high doses of PBO. Replicative DNA synthesis, assessed as the hepatocyte labeling index following implantation of 7-day osmotic pumps containing 5-bromo-2'-deoxyuridine during Study Days 0-7 and 35-42, was increased in mice given 300 mg/kg/day PBO and NaPB for 7 days and in rats given 550 and 1050 mg/kg/day PBO and NaPB for 7 days and 1050 mg/kg/day PBO for 42 days. While PBO had no effect on body weights in mice, the body weights of rats given 550, 1050, and 1850 mg/kg/day PBO for 42 days were reduced to 92, 89, and 70% of control, respectively. PBO induced microsomal cytochrome P450 content and mixed function oxidase activities in the mouse and rat, although the effects were less marked than those produced by NaPB. In summary, this data demonstrates that PBO can produce liver enlargement in the mouse and the rat which is associated with induction of xenobiotic metabolism, hypertrophy, and hyperplasia. The hepatic effects of PBO in the mouse were similar to but less marked than those produced by NaPB. In the rat high doses of PBO were hepatotoxic and resulted in a marked reduction in body weight. Thus while the reported formation of eosinophilic nodules in mouse liver by PBO may occur by a mechanism(s) similar to that of NaPB and other nongenotoxic enzyme inducers, the reported tumor formation in rats at greater than the maximum tolerated dose is most likely associated with marked enzyme induction in conjunction with a regenerative hyperplasia resulting from PBO-induced hepatotoxicity.

Administration, Oral↗

Predicting the structure of apolipoprotein A-I in reconstituted high-density lipoprotein disks.

In reconstituted high-density lipoproteins, apolipoprotein A-I and phosphatidylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-1 bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high-density lipoprotein disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoylphosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8-A shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of a reconstituted high-density lipoprotein were simulated. In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails.

Amino Acid Sequence↗

Lack of effect of piperonyl butoxide on unscheduled DNA synthesis in precision-cut human liver slices.

In this study the effect of piperonyl butoxide (PBO) on unscheduled DNA synthesis in precision-cut human liver slices has been examined. Liver slices prepared from tissue samples from five human donors were cultured in medium containing [3H]thymidine and 0-2.5 mM PBO using a dynamic organ culture system. After 24 h the liver slices were processed for autoradiographic examination of UDS. As positive controls, liver slices were also cultured with three known genotoxic agents, namely 2-acetylaminofluorene (2-AAF), aflatoxin B1 (AFB1) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). UDS was quantified as the net grain count in centrilobular hepatocytes and as the percentage of centrilobular hepatocyte nuclei with > 5 and > 10 net grains. Compared to control liver slice cultures PBO had no effect on UDS. In contrast, treatment with 0.02 and 0.05 mM 2-AAF, 0.002 and 0.02 mM AFB1 and 0.005 and 0.05 mM PhIP produced significant increases in net grain counts of centrilobular hepatocytes. The greatest induction of UDS was observed in liver slices treated with 0.05 mM PhIP. Treatment with 2-AAF, AFB1 and PhIP also produced increases in the number of centrilobular hepatocyte nuclei with > 5 and > 10 net grains. At the concentrations examined neither PBO, 2-AAF nor PhIP had any significant effect on replicative DNA synthesis in 24 h cultured human liver slices. In cultured liver slices treated with 0.02, but not 0.002, mM AFB1 a significant reduction in the rate of replicative DNA synthesis was observed. These results demonstrate that PBO does not induce UDS in cultured human liver slices. However, all three positive control compounds produced marked significant increases in UDS, thus confirming the functional viability of the human liver slice preparations used in this study. In conclusion, these results provide further evidence that PBO is a non-genotoxic agent which does not damage DNA in human liver.

DNA Repair↗