PubMed Health⌕ Search

Biomedical subjects

P J Bond

Publications and source records attributed to P J Bond.

16 recordsLinked to original sources
PubMed2005

Simulation studies of the interactions between membrane proteins and detergents.

Interactions between membrane proteins and detergents are important in biophysical and structural studies and are also biologically relevant in the context of folding and transport. Despite a paucity of high-resolution data on protein-detergent interactions, novel methods and increased computational power enable simulations to provide a means of understanding such interactions in detail. Simulations have been used to compare the effect of lipid or detergent on the structure and dynamics of membrane proteins. Moreover, some of the longest and most complex simulations to date have been used to observe the spontaneous formation of membrane protein-detergent micelles. Common mechanistic steps in the micelle self-assembly process were identified for both alpha-helical and beta-barrel membrane proteins, and a simple kinetic mechanism was proposed. Recently, simplified (i.e. coarse-grained) models have been utilized to follow long timescale transitions in membrane protein-detergent assemblies.

Bacterial Outer Membrane Proteins↗
PubMed2005

Molecular simulations and lipid-protein interactions: potassium channels and other membrane proteins.

Molecular dynamics simulations may be used to probe the interactions of membrane proteins with lipids and with detergents at atomic resolution. Examples of such simulations for ion channels and for bacterial outer membrane proteins are described. Comparison of simulations of KcsA (an alpha-helical bundle) and OmpA (a beta-barrel) reveals the importance of two classes of side chains in stabilizing interactions with the head groups of lipid molecules: (i) tryptophan and tyrosine; and (ii) arginine and lysine. Arginine residues interacting with lipid phosphate groups play an important role in stabilizing the voltage-sensor domain of the KvAP channel within a bilayer. Simulations of the bacterial potassium channel KcsA reveal specific interactions of phosphatidylglycerol with an acidic lipid-binding site at the interface between adjacent protein monomers. A combination of molecular modelling and simulation reveals a potential phosphatidylinositol 4,5-bisphosphate-binding site on the surface of Kir6.2.

Computer Simulation↗
PubMed1995

Retrospective evaluation of admission criteria for paediatric electrical injuries.

In the medical community, the practice of admitting all electrical burns for 24-48 h of observation, monitoring and laboratory evaluation is widespread. This retrospective review of paediatric electrical burns was conducted to determine which patients may safely be treated as outpatients. Retrospective analysis of all paediatric burns admitted between 1980 and 1991 identified 35 patients with electrical injuries. Patients were divided into two groups for analysis: those burned by exposure to household voltages (120-240 V; n = 26) and those exposed to high voltages, in excess of 1000 V (n = 9). The majority of household electrical injuries occurred secondary to contact with the household 120 V (21/26). Contact with an extremity accounted for the largest number of these injuries (18/26). The mouth was the second most frequent site of injury (7/26). Most of these patients (20/26) had < 1 per cent BSA burn. No patient in the household-voltage group had an arrythmia that required treatment, nor were there any identified examples of compartment syndrome or other vascular complications. Seven patients did require minimal skin grafting. No deaths occurred in either group. The patients in the household-voltage group were significantly younger. High-voltage electrical injuries occurred in an older patient population and required more aggressive care and surgical intervention. This was evident at the time of initial evaluation. Based on these data, healthy children with small partial-thickness electrical burns and no initial evidence of cardiac or neurovascular injury do not appear to need hospital admission.

Adolescent↗
PubMed1980

Visualization of an unwound DNA duplex.

Certain dyes and drugs with planar aromatic components can intercalate these into stacks of base pairs and thereby bind tightly to DNA duplexes. Intercalation at one site usually precludes intercalation between the base pairs immediately adjacent. This exclusion implies that two distinct nucleoside conformations are needed in the dinucleoside phosphates which include the intercalation site. The simplest distinction would involve no more than quantitative differences in the (usually anti) conformations at the glycosidic bonds. This could be reinforced by additional, qualitative differences in the furanose ring puckerings (C-2'-endo and C-3'-endo). For the most pronounced difference there could be qualitative differences (syn and anti) in the conformations of the glycosidic bonds as well as in the conformations of the sugar rings. The model discussed here is an example of this most emphatic distinctiveness, as the nucleosides at the 5' ends of the intercalation sites are C-3'-endo and syn and at the 3' ends are C-2'-endo and anti. X-ray diffraction analysis suggests that a completely unwound allomorph of the DNA duplex can persist in oriented fibres when stabilized by certain platinum-containing intercalators. In the untwisting of (usually) right-handed DNA double helices, unwound duplexes are presumably fleeting intermediates.

Animals↗
PubMed1976

Stereochemical requirements for intercalation of platinum complexes into double-stranded DNA's.

The complexes 1,10-phenanthrolineethylenediamineplatinum(II) and 2,2'-bipyridineethylenediamineplatinum(II) have a planar, aromatic ligand system that facilitates intercalation, as shown by their ability to unwind closed circular duplex DNA. Nonbonded steric interactions can rotate the pryidine ligands out of the coordination plane in bis(pyridine)ethylenediamineplatinum(II), thus preventing intercalation. Fiber x-ray diffraction patterns of the two metallointeracalators indicate that the binding is governed by the neighbor exclusion principle.

DNA↗
PubMed1976

Models of triple-stranded polynucleotides with optimised stereochemistry.

Detailed models are presented for the triple-stranded polynucleotide helices of poly (U)-poly (A)-poly (U) (two forms), poly (U)-poly d (A) -poly (U), poly d(C)-poly d(I)-poly d(C), poly d(T)-polyd(A)-poly d(T) and poly (I)-poly (A)-poly (I). The models were genrated using a computerized, linked-atom procedure which preserves standard bond lengths, bond anglesand sugar ring conformations, constrains the helices to have the pitches and symmetries observed in X-ray diffraction experiments, and optimises the non-bonded interatomic contacts including hydrogen bonds. The possible biological sigificance of such complexes is discussed.

Computers↗
PubMed1975

X-ray fiber diffraction evidence for neighbor exclusion binding of a platinum metallointercalation reagent to DNA.

Good quality x-ray diffraction patterns have been obtained of polycrystalline fibers containing 2-hydroxyethanethiolato(2,2'2"-terpyridine)platinum(II) bound to calf thymus DNA by intercalation. The photographs strongly support the neighbor exclusion binding model in which electron-dense platinum atoms are regularly distributed at 10.2 A intervals, every other interbase pair site.

Animals↗
PubMed1973

Triple-stranded polynucleotide helix containing only purine bases.

The structure of the complex involving one polyadenylic acid and two polyinosinic acid chains has been determined by x-ray diffraction. The three coaxial, helical chains have conformations like conventional RNA double helices despite the absence of purine-pyrimidine pairing. Formation of hypoxanthine pairs in codon-anticodon interactions therefore requires only trivial changes in the conformation of a standard nucleotide. Evolution of the contemporary genetic code involving purine-pyrimidine complementarity from a primeval code with only adenine-hypoxanthine pairing would have been possible without major discontinuities in molecular geometry.

Adenine Nucleotides↗
PubMedDate not supplied

Absence of postburn hypermetabolism in a group of children with serious burns.

Hypermetabolism proportional to wound size is the expected response in patients who sustain large burns. This metabolic response persists until wound closure is achieved. The value of this response to the injured host remains unproven. Between 1978 and 1991, 104 patients with burns covering 30% or more of the body surface area underwent partitional calorimetry as a component of various research protocols. Thirteen of these patients failed to demonstrate an increase in metabolic rate as compared with a control group. These patients without hypermetabolism were compared with case-matched patients who demonstrated the expected increase in metabolic rate. Although they were not hypermetabolic in response to the burn injury, five of these patients were exposed to a cold stress and were able to increase their metabolic rate appropriately. The failure to mount a hypermetabolic response did not impact the clinical course as measured by survival, length of hospital stay, or maximum weight loss.

Body Surface Area↗
PubMedDate not supplied

Alteration in gastrointestinal peptides after thermal injury in humans.

Alterations in gastrointestinal function are common after thermal injury in humans. The peptide hormones gastrin and cholecystokinin are known to exert effects on gastric and biliary motility and on secretory function and to induce trophic changes in gut mucosa. The effect of injury on these hormones has received little attention. Six patients with burns were studied while receiving a combination of regular diet and continuous enteral feeding. Four healthy members of the nursing staff served as the control group. Blood was drawn every 4 hours for 24 hours. Gastrin and cholecystokinin were analyzed by radioimmunoassay. Patients with burns demonstrated significantly higher levels of gastrin and lower levels of cholecystokinin when compared with the control group. Patients with burns also failed to demonstrate the normal circadian variation in these peptides.

Adult↗
PubMedDate not supplied

The pharmacokinetics of ibuprofen after burn injury.

Ibuprofen is an effective antipyretic in the postburn period and produces associated decrements in the hypermetabolic response. Burn injury is capable of altering the kinetics of many drugs, making the predictable use of agents such as ibuprofen difficult. Ten patients with serious burns were studied after the administration of 10 mg/kg ibuprofen suspension. The half-life varied from 1.4 to 5.1 hours, depending on the site of administration and/or the presence of solid food. The reported half-life for ibuprofen suspension is 1.8 to 2 hours. Burn size did not alter ibuprofen half-life or area under the time-concentration curve. Maximum ibuprofen concentration varied greatly, depending on route of administration. Time to maximal temperature reduction was between 2 and 3 hours after drug administration. Although the precise level of ibuprofen needed for cyclooxygenase inhibition is unknown, enteral administration results in levels below the targeted 10 to 20 mcg/ml for much of the traditional 6-hour dosing interval. Future studies with ibuprofen in the burn population must standardize more than just total dose.

Adult↗