Biomedical subjects
Publications and source records attributed to L J Wilson.
We report the nanoscale loading and confinement of aquated Gd3+n-ion clusters within ultra-short single-walled carbon nanotubes (US-tubes); these Gd3+n@US-tube species are linear superparamagnetic molecular magnets with Magnetic Resonance Imaging (MRI) efficacies 40 to 90 times larger than any Gd3+-based contrast agent (CA) in current clinical use.
The responses of Tetranychus urticae Koch from Australian cotton to chlorfenapyr has been monitored since the 1997--1998 growing season. Resistance was first detected in the 2001--2002 season and then increased quickly in both level and proportion of resistant strains detected. In response, the resistance management strategy for chlorfenapyr use in cotton was altered and now recommends a further restriction of use from two to one spray per season. There was no evidence of negative cross-resistance to the pyrethroid bifenthrin, but chlorfenapyr was associated with an undefined negative cross-resistance.
Knowledge of the sources and distribution of ammonia (NH3) emissions underpins our understanding of the nitrogen budget. Research has focused on quantifying NH3 emissions from anthropogenic sources, whilst those from natural sources have received little attention internationally. Seabirds excrete large quantities of nitrogen, making seabird colonies a major natural source of NH3. Ammonia emissions from each UK seabird species were estimated and combined with population distribution data to model their spatial distribution. Total NH3 emissions from UK seabirds were estimated at 2.7 kt per year. Seabird emissions are concentrated in remote parts of the UK where anthropogenic emissions are small, so that seabirds often represent the main source of NH3 emissions in these areas. Seabird NH3 emissions were found to have increased by 34% since the 1970s. This corresponds to population changes which may be influenced by human activities, showing that even this natural source can be anthropogenically modified.
Two new unsymmetrical picket-fence naphthylporphyrin ligands, 1 and 2, and several of their metalated porphyrinato complexes have been synthesized as precursor model compounds for the binuclear (Fe/Cu) cytochrome c oxidase (CcO) active site. 1 and 2 have a naphthylporphyrin superstructure that has been specifically incorporated to confer long-term configurational stability to the atropisomeric products. The two picket-fence porphyrin ligands also bear covalently linked, axially offset tris(heterocycle) coordination sites for a copper ion, much like that found in the native enzyme. Monometallic porphyrin complexes [M = Zn(II), Ni(II), Cu(II), and Fe(III)] of the pyridine-appended ligand 1 have been prepared and spectroscopically and magnetically characterized. An unusual monomeric iron(III) hydroxo porphyrin complex was isolated upon workup of the compound formed under ferrous sulfate/acetic acid reflux conditions. There is general difficulty in forming binuclear complexes of 1, which is attributed to the conformational flexibility of the benzyl ether type picket spacers. The potential of ligands such as 1 and 2 for future CcO active-site modeling studies is considered.
A series of outer-sphere cross-electron-transfer reactions involving the [Cu(bite)](2+/+) redox couple has been investigated in acetonitrile at 25 degrees C. In this complex, the bite ligand is a macrocyclic N(2)S(2) ligand with a 2,2'-biphenyl moiety as its backbone. The reaction of [Cu(II)(bite)](2+) with [Ru(hfac)(3)](-) produces [Cu(I)(bite)](+) and [Ru(hfac)(3)] reversibly with K = 1.9. The rate law is second order in both directions, with a rate constant of (8.22 +/- 0.27) x 10(2) M(-1) s(-1) in the forward direction. Rate constants were also obtained for the irreversible reactions of three Co(II) clathrochelates with [Cu(bite)](2+). The oxidation of [Cu(bite)](+) by [Fe(bpy)(3)](3+) was studied in order to obtain a rate constant for oxidation as well as reduction. Application of the Marcus cross relationship to these rate constants gives apparent self-exchange rate constants that are reasonably consistent yet unusually low, with an average value of 1.0 x 10(-2) M(-1) s(-1). The self-consistence of the apparent self-exchange rate constants implies that all of the cross reactions proceed through the same intermediate, and hence, the outer-sphere self-exchange reaction should have a second-order rate law with k = 1.0 x 10(-2) M(-1) s(-1). The much faster first-order self-exchange process reported previously for the [Cu(bite)](2+/+) couple in acetone implies a more efficient mechanism for the self-exchange reaction than for the cross reactions, such as an inner-sphere mechanism. Cyclic voltammograms of [Cu(bite)](n+) are strongly sensitive to the nature of the working electrode, thus precluding the use of these data in interpreting the homogeneous redox kinetics.
An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.
[reaction: see text] The solid-phase synthesis of 2,4-diaminoquinazolines is presented. The chemistry involves the sequential condensation of 2-aminobenzonitriles and amines starting from an acyl isothiocyanate resin via a traceless cleavage and cyclization. The alpha-1 antagonist prazosin was synthesized, as well as several other examples, in good yields and purity.
Bifenthrin (Talstar) was registered at the beginning of the 1993/94 season for control of Helicoverpa spp. and Tetranychus urticae in Australian cotton. Resistance was monitored in T. urticae following registration but despite the implementation of resistance management, resistance evolved in the 1996/97 cotton-growing season after only four seasons use. During the following three seasons resistance increased progressively both in level (from 1.2- to 109-fold at LC50) and abundance (from 20 to 90% strains) and was linked to field control failures. The evolution of resistance has now reduced the reliability of bifenthrin for T. urticae control in Australian cotton. The impact of bifenthrin resistance in T urticae and its continued management in Australian cotton is discussed.
Chiral HPLC methods were developed and utilized for the simultaneous determination of plasma protein binding of enantiomers of two racemic aminohydantoin compounds. Reversed-phase HPLC with the use of a polysaccharide-type chiral stationary phase column was employed for the separation and quantitation of the enantiomers of the two compounds with detection limits in the range 5-10 ng/ml in the plasma matrix. The chiral HPLC methods were selective, sensitive and reproducible. The R and S enantiomers of both compounds were baseline-resolved under the chromatographic conditions employed. Ultrafiltration techniques were applied to determining the plasma protein binding for each enantiomer in rat, dog and human plasma. The results clearly show stereoselective binding of the two enantiomers of each compound with higher protein binding of the R enantiomer than the S enantiomer in rat, dog and human plasma. Binding association constants were also determined to be in the range 1.01-14.0 x 10(4) M(-1) at 37 degrees C. Both the protein binding percentage and binding association constant were enantioselective and species-dependent. Such information is important for a clear understanding of the differences in biological activity as well as in pharmacokinetic and pharmacodynamic properties between the two enantiomers of each compound in the drug discovery and development process.
Biodistribution studies of a water-soluble radioactive metallofullerene compound have been conducted using BALB/c mice. To this end, a sample containing Hox@C82 (x = 1, 2) was purified and derivatized to prepare the water-soluble metallofullerol, Hox@C82(OH)y. This metallofullerol was then neutron-activated (165Ho[n,gamma]166Ho) to prepare the 166Hox@C82(OH)y analog as a radiotracer, which was monitored, after intravenous administration, for up to 48 hours by using dissection radioanalysis, and its biodistribution was compared with a control compound, Na2[166Ho(DTPA)(H2O)]. Results showed selective localization of the 166Hox@C82(OH)y tracer in the liver but with slow clearance, as well as uptake by bone without clearance. In contrast, excretion of the control compound was nearly quantitative after 1 hour. The fate of 166Ho was also explored by a metabolism study of 166Hox@C82(OH)y in Fischer rats. Results indicated 20% excretion of intact 166Hox@C82(OH)y within 5 days. The present findings demonstrate the feasibility of using water-solubilized metallofullerene radiotracers to monitor the fate of fullerene-based materials in animals, and suggest that water-solubilized fullerene materials, in general, may be useful components in drug design.
OBJECTIVE: Although weight loss is commonly recommended for symptoms of gastroesophageal reflux, a relationship between excessive body weight and esophageal reflux has not been established. The aim of this study was to determine whether obesity is associated with the presence of a hiatal hernia (HH) and/or an endoscopic diagnosis of esophagitis. METHODS: Retrospective case control studies were done using 1389 patients who underwent gastric analysis and upper GI endoscopy between 1974 and 1995. After excluding patients with Zollinger-Ellison syndrome, 189 cases of esophagitis with 1024 controls were identified. In a separate analysis of the database, 151 cases of HH with 1053 controls were also identified. Patients were classified by body mass index (BMI) as: thin (BMI <20 kg/m2), normal (BMI 20-25), mildly obese (BMI 25-30), and obese (BMI >30). RESULTS: Excessive body weight was significantly associated with the presence of HH, the probability of HH increasing with each level of BMI (p < 0.01), as well as with esophagitis (OR 1.8; 95% CI 1.4-2.1). HH was independently associated with esophagitis (OR 4.2 95% CI 2.9-6.1); when controlled for the effect of HH, the association between BMI and esophagitis diminished but remained significant. In the population as a whole, for the presence of esophagitis multiple logistic regression indicates BMI and hiatal hernia were significant factors but gender and race did not appear to be. CONCLUSIONS: Excessive body weight is a significant independent risk factor for hiatal hernia and is significantly associated with esophagitis, largely through an increased incidence of hiatal hernia. Whites are more likely to have the combination of esophagitis and hiatal hernia than are blacks.
Glutaraldehyde cross-linking followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis has been used to detect aggregates of isozyme in solutions which lead to crystals. In solutions of varying NaCl content, the number of aggregates was found to be related to the ionic strength of the solution. Solutions of 1% NaCl, pH 4.0 were monomeric while those containing 7-15% NaCl, pH 4.0 were shown to be as much as 36% aggregated and 64% monomeric. The aggregates detected at the highest salt and protein concentration studied were composed of dimers, trimers and tetramers. The aggregates increased by addition of single units suggesting the aggregation pathway to be that of monomer addition. The kinetics of the cross-linking reaction were slow preventing a study of either the time dependence of aggregation or the effect of temperature on aggregate distributions. Comparison of the total aggregate concentrations for NaCl and Na(2)SO(4) showed that the concentration of aggregates was related to the ionic strength of the solution suggesting that in both crystallization and precipitation, electrostatic shielding of like-charged protein molecules is necessary in order for aggregation to occur.
Dialysis kinetics measurements have been made to study the effect of ionic strength on the dimerization of lysozyme in acidic solutions that lead to the growth of tetragonal lysozyme crystals. Using glutaraldehyde cross-linked dimers of lysozyme, we have determined that both monomers and dimers can escape from 25,000 molecular weight cutoff dialysis membranes with velocity constants of 5.1 x 10(-7) and 1.0 x 10(-7) s(-1) for the monomer and dimer species, respectively. The flux from 25K MWCO membranes has been measured for lysozyme in pH 4.0 buffered solutions of 1, 3, 4, 5, and 7% NaCl over a wide range of protein concentrations. Assuming that dimerization is the first step in crystallization, a simple monomer to dimer equilibrium was used to model the flux rates. Dimerization constants calculated at low protein concentrations were 265, 750, 1212, and 7879 M(-1) for 3, 4, 5, and 7% NaCl, respectively. These values indicate that dimerization increases with the ionic strength of the solution suggesting that aggregation is moderated by electrostatic interactions. At high protein concentrations and high supersaturation, the dimerization model does not describe the data well. However, the Li model that uses a pathway of monomer <-> dimer <-> tetramer <-> octamer <-> 16-mer fits the measured flux data remarkably well suggesting the presence of higher order aggregates in crystallizing solutions.
(meso-Tetraphenylporphinato)(trifluoroacetato)iron(III), [Fe(C2F3O2)(C44H28N4)], consists of a central Fe atom equatorially coordinated to four pyrrole N atoms and axially coordinated th an O atom of the trifluoroacetate group. The average Fe--N bond distance is 2.054(5)A and the Fe atom is displaced 0.483 (1) A from the porphinato plane. The Fe--O distance is 1.921 (4) A. The out-of-plane displacement and the Fe--N bond lengths indicate that the Fe atom is in a high-spin state.
OBJECTIVE: Currently recommended rates of weight loss for obese persons are not based on demonstrated health risks. The authors attempt to determine a medically safe rate of weight loss based on currently available data on the risk of gallstone formation during active weight loss. METHODS: All prospective studies published in the English language on the formation of gallstones in obese persons during active weight loss were reviewed and evaluated. A statistical analysis was performed using studies of at least 4 weeks' duration that included information on diet composition, rates of weight loss, length of follow-up, and incidence of gallstone formation. A statistical model was fit to the data from the studies that met the criteria. RESULTS: Nine subject groups derived from five published reports met the criteria for inclusion in the analysis. When the results of these groups were evaluated statistically, a curvilinear relationship between incidence of gallstone formation and rate of weight loss was demonstrated. The relationship was best described by an exponential regression curve, with an adjusted r2 of 0.98 and a dramatically increasing risk of gallstone formation at rates of weight loss above 1.5 kg per week. CONCLUSION: Risk of gallstone formation in obese persons during active weight loss seems to increase in an exponential fashion. The data suggest that rates of weight loss should not exceed an average of 1.5 kg per week.
Primary sensory neurons that are motoneuron-like in morphology and often nonspiking (transmit afferent signals as graded depolarizations) characterize an unusual type of stretch receptor in decapod crustaceans. Nonspiking and spiking receptors occur in similar positions at homologous joints in different species and have been presumed to be homologous, the spiking one considered "primitive". To better understand the evolutionary origin of these stretch receptors and why some are nonspiking, we examined the spiking telson-uropod stretch receptors in the spiny sand crab Blepharipoda occidentalis (Albuneidae) and the squat lobster Munida quadrispina (Galatheidae) and compared them with the nonspking telson-uropod stretch receptor of the mole sand crab Emerita analoga (Hippidae). The position, morphology and responses to stretch of the sensory neurons, and the ultrastructure of the elastic strand portion of the receptor are similar in M. quadrispina and B. occidentalis, except that in B. occidentalis the receptor muscles are substantially smaller and the extracellular matrix of the elastic receptor strand is both more extensive and more organized, reminiscent of the ultrastructure of E. analoga's nonspiking receptor. We conclude that the spiking telson-uropod stretch receptors of albuneids and galatheids are homologous. The differences in the ultrastructure of their receptor strands imply that the efficiency of coupling receptor length change to deformation of the dendritic termini increases in the order M. quadrispina < B. occidentalis < E. analoga. The spiking and nonspiking telson-uropod stretch receptors differ anatomically in three major respects that appear to preclude their homology. (1) The receptor strands are on opposite sides of a conserved muscle. (2) The sensory somata are in different regions of the sixth abdominal ganglion: a lateral cluster of somata for the spiking sensory neurons and two medial clusters, one anterior, one posterior, for the nonspiking sensory neurons. (3) The neuropil projections of the sensory neurons are different. We conclude that the hippid's nonspiking telson-uropod stretch receptor evolved de novo and not by modification of the ancestral anomuran telson-uropod stretch receptor (which Hippidae have lost).
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An innovative educational program on developmental care of the neonate was successfully implemented within the high-tech environment of a Level III NICU. Devised by a multidisciplinary team, the program provided appropriate levels of education to all personnel--from neonatologists to housekeeping staff--involved on a day-to-day basis with the infants. To assist those wishing to implement a similar program in their institution, details of program development, content, implementation, evaluation, and future goals are discussed.