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M A Wilson

Publications and source records attributed to M A Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Scattering of water from the glycerol liquid-vacuum interface.

Molecular dynamics calculations of the scattering of D2O from the glycerol surface at different collision energies are reported. The results for the trapping probabilities and energy transfer are in good agreement with experiments. The calculations demonstrate that the strong attractive forces between these two strongly hydrogen bonding molecules have only a minor effect on the initial collision dynamics. The trapping probability is influenced to a significant extent by the repulsive hard sphere-like initial encounter with the corrugated surface and, only at a later stage, by the efficiency of energy flow in the multiple interactions between the water and the surface molecules.

Chemical Phenomena↗
PubMed1995

A fungal actin-related protein involved in nuclear migration.

The ro-4 mutant of the filamentous fungus Neurospora crassa forms distinctive colonies in which hyphae grow into rope-like aggregates. This unusual morphology coincides with a defect in hyphal nuclear migration. The ro-4 gene was cloned from a cosmid library by complementation of the closely linked pab-2 gene. The deduced 380 amino acid protein is most similar to the vertebrate actin-related protein/centractin. The RO4 protein is not essential for cell viability, and new strains created by inducing point mutations at the ro-4 locus have a phenotype which is very similar to that of the original mutant. This study provides genetic evidence that an actin-related protein plays a role in nuclear motility. Since nuclear motility is believed to be a microtubule-dependent process, the ro-4 gene product may function as a component of the dynactin complex which activates force generation by cytoplasmic dynein.

Actins↗
PubMed1995

Haemophilus pneumonia is a common cause of early pulmonary dysfunction following trauma.

BACKGROUND: Haemophilus species are a common cause of community-acquired pneumonia; however, their significance in posttraumatic pneumonia is unclear. DESIGN: Case series. SETTING: University hospital, level I trauma center. PATIENTS: Two hundred fifty-seven consecutive patients with blunt and penetrating trauma treated for pneumonia. MAIN OUTCOME MEASURES: Length of stay in the intensive care unit, duration of ventilatory support, rate of recurrent or persistent pneumonia, and mortality. RESULTS: Ninety-six (37%) of 257 patients treated for pneumonia had a Haemophilus species isolated on sputum culture. Of these 96 patients, 49 (51%) had only Haemophilus species, while 33 (34%) had associated gram-positive organisms and 14 (15%) had gram-negative organisms. Seventeen pure cultures (29%) and seven mixed cultures (15%) (P < .05) were beta-lactamase-positive trains. Compared with patients who had pneumonia caused by other bacteria, patients with Haemophilus species were younger (mean +/- SE, 35 +/- 1.7 vs 42 +/- 1.6 years; P < .05) and more severely injured (Injury Severity Score, 20.7 +/- 1.1 vs 17.5 +/- 0.9; P < .05). There were no differences in any outcome variables between the two groups. Only one (1%) of 96 patients had persistent Haemophilus species on sputum cultures after 7 days of treatment. CONCLUSIONS: Haemophilus species are a frequent cause of pneumonia following traumatic injury. This occurs primarily in the early postinjury phase and therefore should be included in the differential diagnosis of early posttraumatic pulmonary insufficiency.

Adult↗
PubMed1995

Pentoxifylline attenuates pulmonary macromolecular leakage after intestinal ischemia-reperfusion.

OBJECTIVE: To assess the effects of pentoxifylline posttreatment on hemodynamic variables and acute pulmonary injury in the rat intestinal ischemia-reperfusion (I-R) model, using a recently developed method of fluorescent intravital pulmonary videomicroscopy. DESIGN: Anesthetized male Sprague-Dawley rats were cannulated for measurement of mean arterial pressure, heart rate, cardiac output, arterial blood gas values, and hematocrit. Rats underwent isolation of the superior mesenteric artery for intestinal I-R (45 minutes of ischemia, 120 minutes of reperfusion) and right lateral thoracotomy for pulmonary videomicroscopy. Epi-illumination fluorescent videomicroscopy was used to quantitate leakage of intravascular fluorescently labeled albumin into alveoli, while hemodynamic variables were simultaneously recorded. In the treatment groups, pentoxifylline was administered after 30 minutes of intestinal ischemia. Data (mean +/- SEM) were recorded before and during intestinal ischemia and after reperfusion at 30-minute intervals. MAIN OUTCOME MEASURE: The appearance of fluorescently labeled albumin into alveolar airspaces was quantitated off-line by computer and reported as the alveolar leak index. RESULTS: Intestinal I-R caused alveolar macromolecular leakage, marked by a 300% +/- 48% increase from baseline (P < .05) in the alveolar leak index. Intestinal I-R also produced systemic hemodynamic instability demonstrated by a decrease in the mean arterial blood pressure (-36% +/- 5% vs baseline, P < .05) and cardiac output (-42% +/- 6% vs baseline, P < .05), metabolic acidosis (final arterial pH of 7.17, P < .05 vs initial pH), and a 2.3-fold increase in the intravenous fluid requirement when compared with that in sham animals (P < .05). Treatment with pentoxifylline 30 minutes after intestinal ischemia attenuated pulmonary macromolecular leakage (P < .05 vs nontreated I-R) and reduced the decrease in cardiac output (-15% +/- 7% vs baseline, not statistically significant). Pentoxifylline treatment had no effect on the mean arterial blood pressure, heart rate, metabolic acidosis, or intravenous fluid requirement. CONCLUSIONS: Pentoxifylline reduces alveolar capillary membrane injury and subsequent protein leakage and improves cardiac output when administered after 30 minutes of intestinal ischemia. These data suggest that pentoxifylline may be a possible candidate as a future therapy for acute pulmonary dysfunction. Further studies in human patients are necessary.

Animals↗
PubMed1995

Platelet-activating factor and sepsis-induced small intestinal microvascular hypoperfusion.

Platelet-activating factor (PAF) and bacteremia both cause small intestinal (SI) hypoperfusion which may contribute to mucosal injury, and PAF has been postulated to mediate impaired SI microvascular blood flow during sepsis. Our previous studies demonstrate that sepsis-induced SI hypoperfusion is associated with both arteriolar and venular constriction, but the microvascular mechanisms by which PAF impairs SI blood flow are not well defined. Microcirculation studies in other tissues indicate that PAF is an arteriolar dilator, but this effect in the SI would not explain PAF-mediated hypoperfusion. We studied the effects of PAF on SI microvessels to characterize the microvascular mechanisms which mediate PAF-induced hypoperfusion. We also determined the role of PAF as a mediator of microvascular effects in the intestine during bacteremia by PAF receptor antagonism. Animals received either 10(9) live Escherichia coli IV or PAF applied topically to the SI (30, 80, and 300 nM). Arteriolar and venular diameters and red blood cell velocity (A1, V1) were measured with intravital microscopy and velocimetry. Both PAF and sepsis resulted in impaired SI blood flow (maximum decrease in blood flow -37 and 65%, respectively), but sepsis was associated with both arteriolar and venular constriction (20 and 30% diameter reduction each), whereas PAF produced only venular constriction (50% diameter reduction). Inhibition of PAF action prevented the microvascular alterations of bacteremia (blood flow unchanged, P < 0.05; venular diameter unchanged, P < 0.05), suggesting that PAF is an important mediator of these responses.

Animals↗
PubMed1995

The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability.

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pulmonary subpleural arteriolar diameters during intestinal ischemia/reperfusion.

Adult respiratory distress syndrome (ARDS) often occurs in response to sepsis, shock, or ischemia/reperfusion (I/R) of a remote organ and is a frequent cause of mortality in the ICU patient. Pulmonary vascular resistance (PVR) increases during ARDS, yet direct observations of the pulmonary microcirculation are needed to characterize the vascular response. The purpose of this study was to quantitate the changes in hemodynamic variables, subpleural arteriolar diameters (AD), and alveolar cross-sectional areas (ACSA) during intestinal I/R-induced lung injury in rats, using a new method of in vivo videomicroscopy. Sprague-Dawley rats were anesthetized and cannulated, and superior mesenteric arteries were looped. A thoracotomy was performed with animals ventilated with air with 1 cm PEEP. Hemodynamic and videomicroscopic data were obtained before and during 45 min of SMA occlusion and after reperfusion, up to 120 min. Maximal vessel dilation was measured using topical 10(-5) M nitroprusside. The ability of vessels to constrict was confirmed by applying topical 10(-6) M endothelin-1. Intestinal I/R produced decreases in arterial pH, mean arterial pressure, and cardiac output. Despite these alterations, subpleural AD remained maximally dilated. Arterioles maintained the ability to constrict as demonstrated by the response to topical endothelin-1. ACSA did not change, indicating a uniform inflation of the lung. Using a unique method of in vivo pulmonary videomicroscopy, we have shown that AD do not change following 120 min of intestinal I/R, despite systemic hemodynamic instability. It appears that pulmonary arteriolar vasoconstriction does not contribute to increased PVR during the early phase of lung injury.

Animals↗
PubMed1995

Alpha-adrenergic receptor antagonism prevents intestinal vasoconstriction but not hypoperfusion following resuscitated hemorrhage.

Resuscitation (RES) after hemorrhage (HEM) results in persistent arteriolar constriction and hypoperfusion of the small intestine (SI) despite restoration of mean arterial pressure (MAP) and cardiac output (CO) to normal values. We postulated that increased adrenergic activity contributes to this vasoconstriction and impairment of flow. A loop of SI from decerebrate rats was exteriorized and suffused with Krebs' solution (37 degrees C, pH 7.4). In initial experiments, the effectiveness of alpha-adrenergic receptor antagonism by phentolamine (PHEN) was assessed. Subsequent groups received either topical PHEN (10(-6) M, n = 6) or saline (n = 6) in the suffusion and were then bled to 50% baseline (BL) MAP for 60 min and resuscitated to BL with shed blood/lactated Ringer's. Intravital microscopy and optical Doppler velocimetry were used to measure large (A1) and small, premucosal (A3) arteriolar diameters and RBC velocity; microvascular blood flow was calculated. MAP and transpulmonary CO were measured. During HEM, control animals developed A1 constriction and hypoperfusion with A3 arteriolar dilation. PHEN treatment prevented A1 constriction and enhanced A3 dilation but did not improve flow. Immediately after RES in controls, microvascular diameters and A1 flow returned to BL; however, over the 2-hr post-RES period there was progressive A1 and A3 vasoconstriction and hypoperfusion despite maintenance of BL MAP and CO. After RES in PHEN-treated animals, A1 flow returned to BL, but progressive hypoperfusion was only partially prevented. alpha-Adrenergic-mediated vasoconstriction contributes to intestinal hypoperfusion after HEM, but other mechanisms are also involved in microvascular responses during RES.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1995

Probing the structure of cometary ice.

Computer simulations of bulk and vapor deposited amorphous ices are presented. The structure of the bulk low density amorphous ice is in good agreement with experiments on pressure disordered amorphous ice. Both the low density bulk ice and the vapor deposited ices exhibit strong ordering. Vapor deposition of hot (300 K) water molecules onto a cold (77 K) substrate yields less porous ices than deposition of cold (77 K) water molecules onto a cold substrate. Both vapor deposited ices are more porous than the bulk amorphous ice. The structure of bulk high density amorphous ice is only in fair agreement with experimental results. Attempts to simulate high density amorphous ice via vapor deposition were not successful. Electron diffraction results on vapor deposited amorphous ice indicate that the temperature of the nucleation of the cubic phase depends upon the amount of time between the deposition and the onset of crystallization, suggesting that freshly deposited ice layers reconstruct on times of the order of hours. The temperature dependence of the microporosity of the vapor deposited amorphous ices might affect laboratory experiments that are aimed at simulating astrophysical ices in the context of the origin of prebiotic organic material and its transport to the Earth.

Computer Simulation↗
PubMed1995

Molecular dynamics studies of simple membrane-water interfaces: structure and functions in the beginnings of cellular life.

Molecular dynamics computer simulations of the structure and functions of a simple membrane are performed in order to examine whether membranes provide an environment capable of promoting protobiological evolution. Our model membrane is composed of glycerol 1-monooleate. It is found that the bilayer surface fluctuates in time and space, occasionally creating thinning defects in the membrane. These defects are essential for passive transport of simple ions across membranes because they reduce the Born barrier to this process by approximately 40%. Negative ions are transferred across the bilayer more readily than positive ions due to favorable interactions with the electric field at the membrane-water interface. Passive transport of neutral molecules is, in general, more complex than predicted by the solubility-diffusion model. In particular, molecules which exhibit sufficient hydrophilicity and lipophilicity concentrate near membrane surfaces and experience "interfacial resistance" to transport. The membrane-water interface forms an environment suitable for heterogeneous catalysis. Several possible mechanisms leading to an increase of reaction rates at the interface are discussed. We conclude that vesicles have many properties that make them very good candidates for earliest protocells. Some potentially fruitful directions of experimental and theoretical research on this subject are proposed.

Biophysical Phenomena↗
PubMed1995

Is the timing of fracture fixation important for the patient with multiple trauma?

OBJECTIVE: The effect of timing of femur fracture fixation for patients with multiple trauma was studied to determine the effect of operative timing on eventual outcome. METHODS: The relationship between timing of intramedullary rod (IMR) placement, degree of injury, and pulmonary complications was studied in 424 consecutive patients. The authors focused on 105 patients undergoing IMR placement with an Injury Severity score (ISS) of greater than or equal to 18. The effects of timing of IMR placement on various pulmonary complications, organ failure, intensive care unit (ICU) admission, and ventilatory assistance were studied for various time intervals. RESULTS: Of the 424 patients, pulmonary complications increased slightly in the more seriously injured group (ISS > 18) but were not influenced by the timing of IMR placement. Of the 105 patients undergoing IMR placement with an ISS > or = 18, only 2 patients died. Both patients had an IMR placed in less than 24 hours and died later of head injury and delayed hemorrhage. The incidence of organ failure, number of ventilator days, and length of ICU stay did not differ between the groups based on timing of fracture fixation. The incidence of severe head injuries was higher in the group undergoing delayed IMR placement (> 48 hours). CONCLUSIONS: Modest delays in IMR placement did not adversely affect patient outcome. Pulmonary complications were related to the severity of injury rather than to timing of fracture fixation. In a well-integrated trauma system, clinical judgment regarding the timing of IMR placement was the most important determinant of outcome. Delays that were made to stabilize the patient, treat associated injuries, and plan orthopedic reconstruction did not adversely affect patient outcome.

Adult↗
PubMed1995

Nitric oxide mediates redistribution of intrarenal blood flow during bacteremia.

The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described. Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including sepsis, and we hypothesized that alterations in nitric oxide contribute to redistribution of renal blood flow during sepsis. The current study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli bacteremia, with and without inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone during normal conditions and bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during sepsis.

Animals↗
PubMed1995

Nitric oxide mediates C5a-induced vasodilation in the small intestine.

OBJECTIVE: This study was designed to investigate the microvascular responses of the small intestine to complement C5a and to define the role of nitric oxide in the C5a-induced response. METHODS: Male Sprague-Dawley rats were anesthetized with pentobarbital, and a loop of small intestine was exteriorized and suffused with Krebs solution. The diameters of large and small arterioles of the small intestinal wall were measured with in vivo videomicroscopy following the application of experimental mediators. Four 1-hr C5a dose-response trials were performed (10(-14) M, 10(-12) M, 10(-10) M, and 10(-8) M). Then, we completed acetylcholine dose-response curves with and without N omega-nitro-L-arginine (N-Arg) to document the adequacy of nitric oxide synthase inhibition. The microvascular response to the topical application of C5a (10(-12) M) was recorded in the presence of 2 x 10(-4) M N-Arg. Additionally, experiments of C5a-induced response with N-Arg were repeated in the presence of L-arginine (L-Arg; the precursor of nitric oxide synthesis) or with systemic administration of superoxide dismutase (SOD). RESULTS: (1) C5a induces a dose-dependent vasodilation in the small intestine, and the maximal vasodilation occurs in A3 arterioles at C5a concentration of 10(-12) M; (2) N-Arg inhibits the Ach-induced vasodilation in the rat small intestine; and (3) L-Arg or SOD partially reverses the inhibitory effect of N-Arg. CONCLUSIONS: Nitric oxide mediates the C5a-induced vasodilation in small intestinal microvessels. Superoxide is, at least partially, responsible for the vasoconstrictor response to C5a in the presence of N-Arg.

Animals↗
PubMed1995

The outcome of a clinical trial of a dentin bonding system. Justice or injustice?

PURPOSE: To review the findings and to question the outcome of a clinical evaluation of a dentin bonding system. MATERIALS AND METHODS: The study was a split mouth, single blind (to patient), randomised within patient, clinical trial of Tripton used in conjunction with Opalux and the ultrafine compact-filled, experimental visible light cured resin composite M221784 (ICI Dental) in the restoration of mixed (enamel/dentin), caries free buccal-surface cervical lesions in vital, permanent canine and premolar teeth. The design of the trial was based on the then current American Dental Association (ADA) Clinical Protocol Guidelines for Dentin and Enamel Adhesive Materials. Restorations were placed as dictated by a predetermined randomised number scheme with each patient recruited to the study receiving at least one pair of matched restorations, comprising one restoration of each resin composite. RESULTS: The study reported was discontinued at 1 year subsequent to a 17% loss rate between 6 and 12 months after placement, with most of the restorations lost having been placed in what has subsequently become shown to be relatively unfavorable situations. It is suggested that the outcome of clinical trials of the type considered may warrant review in the light of new knowledge and understanding, and that regulatory bodies setting clinical protocol guidelines must give careful consideration as to whether the criteria for this type of trial should be more restrictive or required to include a representative range of clinically relevant situations.

Adolescent↗
PubMed1995

Altered microvascular responses to C5a in rat striated muscle during two-kidney, one clip renovascular hypertension.

OBJECTIVE: To determine how two-kidney, one clip (2-K,1C) renovascular hypertension alters microvascular responses in rat striated muscle to complement C5a, one of the most important inflammatory mediators. METHODS: 2-K,1C hypertension was induced in male Sprague-Dawley rats. Under anesthesia with pentobarbital (50 mg/kg, intraperitoneally) the cremaster muscle microcirculatory preparation with intact neurovascular connections was studied in vivo by closed-circuit videomicroscopy. Recombinant human C5a was applied topically in the tissue bath at concentrations of 10(-12), 10(-10) and 10(-8) mol/l, consecutively. Changes in the microvessel diameters in small arterioles, large arterioles and venules were measured. RESULTS: In normotensive rats complement C5a induces a significant dilation in small arterioles at low bath concentrations (10(-12) or 10(-10) mol/l), but the dilation is attenuated at a higher concentration (10(-8) mol/l). In contrast, in 2-K,1C hypertensive rats C5a constricts small arterioles at low concentrations (< 10(-10) mol/l) but dilates them at a higher concentration (10(-8) mol/l). Large arterioles and venules have minimal responses to C5a in either normotensive or 2-K,1C hypertensive rats. CONCLUSION: 2-K,1C hypertension dramatically alters C5a-induced microvascular responses in small arterioles. The alteration might be attributable to the enhanced vasoconstrictor mechanisms and impaired vasodilator mechanisms during 2-K,1C renovascular hypertension.

Animals↗