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Biomedical subjects

M A Wilson

Publications and source records attributed to M A Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Adsorption and solvation of ethanol at the water liquid-vapor interface: a molecular dynamics study.

The free energy profiles of methanol and ethanol at the water liquid-vapor interface at 310K were calculated using molecular dynamics computer simulations. Both alcohols exhibit a pronounced free energy minimum at the interface and, therefore, have positive adsorption at this interface. The surface excess was computed from the Gibbs adsorption isotherm and was found to be in good agreement with experimental results. Neither compound exhibits a free energy barrier between the bulk and the surface adsorbed state. Scattering calculations of ethanol molecules from a gas phase thermal distribution indicate that the mass accommodation coefficient is 0.98, and the molecules become thermalized within 10 ps of striking the interface. It was determined that the formation of the solvation structure around the ethanol molecule at the interface is not the rate-determining step in its uptake into water droplets. The motion of an ethanol molecule in a water lamella was followed for 30 ns. The time evolution of the probability distribution of finding an ethanol molecule that was initially located at the interface is very well described by the diffusion equation on the free energy surface.

Adsorption↗
PubMed1997

Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression.

Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Interactions of anesthetics with the water-hexane interface. A molecular dynamics study.

The free energy profiles characterizing the transfer of nine solutes across the liquid-vapor interfaces of water and hexane and across the water-hexane interface were calculated from molecular dynamics simulations. Among the solutes were n-butane and three of its halogenated derivatives, as well as three halogenated cyclobutanes. The two remaining molecules, dichlorodifluoromethane and 1,2-dichloroperfluoroethane, belong to series of halo-substituted methanes and ethanes, described in previous studies (J. Chem. Phys. 1996, 104, 3760; Chem. Phys. 1996, 204, 337). Each series of molecules contains structurally similar compounds that differ greatly in anesthetic potency. The accuracy of the simulations was tested by comparing the calculated and the experimental free energies of solvation of all nine compounds in water and in hexane. In addition. the calculated and the measured surface excess concentrations of n-butane at the water liquid-vapor interface were compared. In all cases, good agreement with experimental results was found. At the water-hexane interface, the free energy profiles for polar molecules exhibited significant interfacial minima, whereas the profiles for nonpolar molecules did not. The existence of these minima was interpreted in terms of a balance between the free energy contribution arising from solute-solvent interactions and the work to form a cavity that accommodates the solute. These two contributions change monotonically, but oppositely, across the interface. The interfacial solubilities of the solutes, obtained from the free energy profiles, correlate very well with their anesthetic potencies. This is the case even when the Meyer-Overton hypothesis, which predicts a correlation between anesthetic potency and solubility in oil, fails.

Algorithms↗
PubMed1997

Differential intestinal microvascular dysfunction occurs during bacteremia.

Altered vascular responsiveness is the hallmark of septic shock. Recently, these changes have frequently been attributed to increased production of nitric oxide (NO). Continued exposure to high levels of NO may alter both endothelial and vascular smooth muscle cell function. Although ex vivo studies demonstrate hyporeactivity of large conduit arteries during established sepsis, it is unclear if the same phenomena exist during early sepsis. This is especially true in the small resistance arterioles of the viscera. We used in vivo microscopy of the rat small intestine to assess (1) endothelial-dependent relaxation and vasomotion (periodic contraction and relaxation of blood vessels) in response to acetylcholine (ACH; 10(-8) to 10(-5) M), (2) endothelial-independent relaxation to nitroprusside (NTP; 10(-5) M), and (3) vascular smooth muscle response to norepinephrine (NE; 10(-10) to 10(-7) M) in normal and bacteremic rats (Escherichia coli). There were no alterations in endothelial-dependent or -independent relaxation during bacteremia as measured by mean diameters. However, acute E. coli bacteremia severely impaired vasomotion in A1 (inflow) and A3 (premucosal) arterioles. Vasomotion was returned to baseline levels in A1 with low-dose ACH (10(-8) M) but only partially improved in A3 arterioles (P < 0.05). A1 response to NE was impaired, while A3 were minimally altered despite being more sensitive to E. coli-induced vasoconstriction. These data suggest that bacteremia causes a rapid, differential impairment of both endothelial-dependent (A3 vasomotion) and vascular smooth muscle cell (A1 constriction) functions. These microvascular impairments occur much earlier than previously described and may contribute to sepsis-induced mucosal ischemia of the intestines.

Acetylcholine↗
PubMed1997

Glucose-induced intestinal hyperemia is mediated by nitric oxide.

UNLABELLED: Glucose-induced absorptive hyperemia of the intestine has been well demonstrated through microsphere blood flow experiments. We have previously demonstrated that glucose, when applied topically to rat ileal epithelium, restores microvascular vessel diameters and blood flow following Escherichia coli bacteremia or hemorrhage/resuscitation. However, the mechanisms of this hyperemia are not completely understood. We hypothesize that nitric oxide is a mediator of the microvascular response to glucose exposure on the rat intestinal epithelium. METHODS: Male Sprague-Dawley rats, 200-225 g, were monitored for hemodynamic stability with mean arterial blood pressure and heart rate. A 2-cm segment of the terminal ileum with intact neurovascular supply was exposed for intravital videomicroscopy. Intestinal arteriolar diameters (A1D, inflow; and A3D, premucosal arterioles) and microvascular blood flow (A1Q) were measured following topical application of isoosmotic glucose or saline, with or without l-NAME (LN, 100 mM), a competitive inhibitor of nitric oxide synthase. Statistical analysis was performed by ANOVA followed by Tukey-Kramer honestly significant difference test. RESULTS: All data are expressed as mean percentage changes from baseline +/- standard error of the mean. Hemodynamic variables did not change during the experimental procedure and there were no significant differences among group baselines. Addition of isotonic glucose to the bath solution caused a significant increase in A3D that persisted throughout the experiment (at 30 min, 19.2 +/- 4.2 vs -3.9 +/- 4.5, P < 0.05). This vasodilation was blocked by topical administration of LN (3.1 +/- 2.9, P < 0.05). A1D remained at baseline levels (saline and glucose) or constricted (LN) in all groups. Topical LN also attenuated A1Q in both the saline and glucose groups. CONCLUSIONS: These data demonstrate that glucose-induced intestinal hyperemia is primarily characterized by premucosal A3 arteriole dilation in this model and that nitric oxide is a mediator of glucose-induced intestinal hyperemia. These findings suggest that either (1) glucose directly causes endothelial nitric oxide production or (2) epithelial cells transduce a vasodilatory signal through vascular endothelial-derived nitric oxide during postprandial intestinal hyperemia.

Analysis of Variance↗
PubMed1997

Influence of gender and brain region on neurosteroid modulation of GABA responses in rats.

Neuroactive steroid derivatives of progesterone, testosterone and glucocorticoids can alter physiological responses to gamma-aminobutyric acid (GABA), apparently through direct, non-steroid receptor mechanisms. The present study examined gender-related differences and regional variations in the ability of tetrahydrodeoxycorticosterone (THDOC), 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-5alpha-THP, tetrahydroprogesterone), androsterone, and dihydroandrosterone (DHA) to alter physiological GABA responses. Steroid modulation of GABA-activated 36chloride influx into microsac preparations from cortex, hippocampus, amygdala, cerebellum and hypothalamus-preoptic area in adrenalectomized-gonadectomized rats of both sexes were tested. The effects of THDOC and 3alpha-5alpha-THP were also examined in groups of intact male and female rats. All four steroids increased GABA-activated chloride influx, although the maximal enhancement in GABA responses differed significantly among brain regions. The rank order of maximal THDOC and 3alpha-5alpha-THP effects was hippocampus > cortex approximately amygdala > hypothalamus-preoptic area approximately cerebellum. Regional differences in potentiation of GABA responses were seen with androsterone, but not dihydroandrosterone. The rank order of androgenic potentiation of GABA responses was amygdala approximately hippocampus > cortex approximately HPA > cerebellum. Slight gender-related differences in responses to steroids were seen with THDOC, with males showing greater maximal enhancement of GABA responses with THDOC than females in the amygdala and hypothalamus-preoptic area. Since sex differences were observed with the glucocorticoid derivative THDOC, but not the progesterone derivative 3alpha-5alpha-THP or androgenic steroids, it appears neuroactive steroid modulation of GABA responses can be differentially affected by the hormonal milieu in a regionally-specific manner.

Amygdala↗
PubMed1997

A comparison of surface roughness and composite/enamel bond strength of human enamel following the application of the Nd:YAG laser and etching with phosphoric acid.

OBJECTIVES: This study was conducted to evaluate enamel morphology after laser etching and acid etching and to determine the shear bond strength of composite to acid-etched and laser-treated enamel. METHODS: Enamel from freshly extracted permanent molar teeth was subjected to either laser treatment with an Nd:YAG laser in different laser parameters or was exposed to 37% phosphoric acid for 60 s (Gluma Gel, Bayer Dental). Surface profile analysis of the enamel was undertaken with a Perthometer (S8P, Feinpruif). The results were analyzed by SPSS/PC multiple range test and Student-Newman Keuls procedure. Specimens were examined in a scanning electron microscope (SEM). Shear bond strengths of acid-etched and laser-etched enamel/composite (Brilliant Dentin, Coltene AG and Pekalux, Bayer Dental) were also determined. These results were compared by SPSS/PC multiple range test. RESULTS: The acid-etched specimens exhibited a qualitatively different type of enamel surface morphology when compared with the laser-treated specimens. Laser treatment at higher exposures resulted in the formation of microcracks and fissures. No significant difference in surface roughness was observed between laser-treated enamel in three different parameters (10 pps, 0.8 W; 15 pps, 1.0 W; 20 pps, 1.25 W) and acid-etched specimens. However, the mean bond strengths of all laser-treated specimens, regardless of the test parameters, were significantly lower (p < 0.05) than the acid-etched enamel specimens. SIGNIFICANCE: Although the laser roughened the surface of the enamel, it did not provide a surface as retentive as a surface treated with conventional acid etching. It is concluded from this study that the Nd:YAG laser operated under the conditions described cannot be recommended as a viable alternative to acid etching.

Acid Etching, Dental↗
PubMed1997

Synaptic plasticity, place cells and spatial memory: study with second generation knockouts.

The use of genetically engineered mice has been a major development in neuroscience research. Genetic engineering is an undoubtedly powerful technique; however, the value of this approach has been debated, particularly in relation to its use to probe the underlying bases of complex behaviors, such as memory. A recent new development of the technique is the ability to target a specific gene knockout to a particular subregion or even to specific and limited cell types of the mouse brain. An example of this approach is the knockout of the NMDARI gene in only CAI-pyramidal cells of the hippocampus. The resulting animals can be tested by several methods, including in vivo multielectrode recording during behavioral tasks. The data provide strong evidence in favor of the notion that NMDA receptor-dependent synaptic plasticity at CAI synapses is required for both the acquisition of spatial memory and the formation of normal CAI place fields. This relationship suggests that robust place fields may be essential for spatial memory.

Animals↗
PubMed1997

Venous thromboembolism in the high-risk trauma patient: do risks justify aggressive screening and prophylaxis?

OBJECTIVE: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are considered to be a major source of morbidity and mortality among trauma patients. Several reports have identified high-risk patients with recommendations for management ranging from frequent duplex scanning to placement of prophylactic inferior vena cava (IVC) filters. We reviewed our experience with a large trauma population to determine whether such approaches are justified. METHODS: We analyzed 2,868 consecutive trauma admissions over 22 months and identified 280 patients (10%) in high-risk groups who survived > or = 48 hours: (1) severe closed head injury with mechanical ventilation > or = 72 hours, (2) closed head injury with lower extremity fractures, (3) spinal column/cord injury, (4) combined pelvic and lower extremity fractures, and (5) major infrarenal venous injuries. The remaining nonthermal injury patients constituted the low-risk group. RESULTS: There were 280 high-risk patients, 213 of whom (76%) received prophylaxis with compression therapy. There were 12 cases of DVT (5%) with four nonfatal PE (1.4%). Six patients (2%) had therapeutic IVC filters inserted and only one patient had prophylactic placement. There were 38 deaths in this group, attributable primarily to severe closed head injury or spine injuries, and none were caused by PE. In the 2,249 low-risk patients, there were three cases of DVT (0.1%, p < 0.05 vs. high risk) and no PE (p < 0.05 vs. high risk). CONCLUSIONS: Although these patients were at increased risk for thromboembolic events, the overall incidence of DVT was still extremely low with no apparent PE deaths. In our patient population, aggressive screening and prophylactic IVC filters would not have benefited 95% of "high-risk" patients without DVT and would not have prevented any deaths. We could not identify any population, except perhaps venous injuries, where such expensive and potentially harmful maneuvers seemed justified. Our experience with DVT and PE does not support either aggressive screening or prophylactic IVC filters as the standards of care.

Adolescent↗
PubMed1997

Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid causing Cushing's syndrome.

A 57-year-old man presented with clinical features of hypercortisolism and was diagnosed with ACTH-dependent Cushing's syndrome. Biochemical testing showed partial suppression of urinary free cortisol with high dose dexamethasone. Initial computed tomography (CT) of the chest and abdomen, and magnetic resonance imaging of the pituitary were negative. In-111 pentetreotide scintigraphy with single photon emission computerized tomography revealed two 'hot' lesions in the abdomen which were then confirmed by subsequent directed thin-slice abdominal CT and small bowel barium study. At surgery, two segments of ileum, adjoining mesentery and lymph nodes were resected. Histopathology was consistent with a malignant carcinoid tumor of the ileum which stained intensely for ACTH. Plasma ACTH, and serum and urinary cortisol normalized postoperatively. To our knowledge, this is the first reported case of ileal carcinoid tumor causing Cushing's syndrome with premortem diagnosis. Another unique feature of this case is that In-111 pentetreotide scan provided the decisive clue to localization of the tumor.

Carcinoid Tumor↗
PubMed1997

Lazaroid improves intestinal blood flow in the rat during hyperdynamic bacteraemia.

BACKGROUND: Intestinal mucosal hypoperfusion and loss of barrier function during sepsis may contribute to maintaining the septic state. Free radicals are produced during sepsis and antioxidants improve survival from experimental sepsis. It is unclear whether endothelial cell injury from free radicals results in altered microvascular reactivity. Lazaroids are antioxidants which scavenge radicals and block lipid radical chain reactions. The authors sought to determine whether lazaroids altered the intestinal microvascular responses to sepsis. METHODS: In vivo video microscopy was used to study the ileal microcirculation of the rat. A1 (inflow) arteriolar diameter and flow, A3 (premucosal) arteriolar diameters, and cardiac output were measured. Lazaroid or vehicle was infused before a bolus injection of live Escherichia coli or saline. RESULTS: Lazaroid alone had no effect on the intestinal vessels or haemodynamics. E. coli caused vasoconstriction (A1, -21 per cent, A3, -19 per cent of baseline) and hypoperfusion (-36 per cent) despite increased cardiac output (+31 per cent). Lazaroid significantly attenuated both constriction (A1, -11 per cent; A3, 10 to -1 per cent) and hypoperfusion (-15 per cent), but did not increase cardiac output (30 per cent). CONCLUSION: E. coli bacteraemia led to intestinal vasoconstriction and hypoperfusion. Lazaroid reduced this effect without altering central haemodynamic responses, suggesting that free radicals have a deleterious effect on the intestinal microcirculation during bacteraemia.

Animals↗
PubMed1996

Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice.

To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell-specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity of individual place fields. We have also found a striking deficit in the coordinated firing of pairs of neurons tuned to similar spatial locations. Pairs have uncorrelated firing even if their fields overlap. These results demonstrate that NMDA receptor-mediated synaptic plasticity is necessary for the proper representation of space in the CA1 region of the hippocampus.

Action Potentials↗
PubMed1996

Haida perspectives on living with non-insulin-dependent diabetes.

OBJECTIVE: To understand the experience of Haida people living with non-insulin-dependent diabetes mellitus (NIDDM), in order to provide a basis for a culturally sensitive community-based approach to managing NIDDM. DESIGN: Qualitative study using grounded theory. SETTING: The villages of Skidegate and Old Massett in Haida Gwaii (Queen Charlotte Islands), British Columbia. PARTICIPANTS: Nine focus groups met at the beginning and six at the end of the project. The focus groups had 8 to 12 members each and roughly the same number of men and women overall. The groups included people with diabetes, family members of people with diabetes, community leaders and elders. FINDINGS: Conceptual findings related to the participants' views on the impact of NIDDM on their lives, their views on what life was like before the effects of NIDDM were felt and their beliefs about the prevention and treatment of NIDDM. Six themes recurred in the discussions: fear; grief and loss; the loss of and desire to regain control; food and eating; physical and personal strength; and traditional ways. CONCLUSIONS: Insights into the illness experience of different cultural groups can inform program development and the creation of culturally sensitive health care interventions.

Adult↗
PubMed1996

Endothelial cell-based cytokine gene delivery inhibits 9L glioma growth in vivo.

Malignant brain neoplasms present great therapeutic challenges due to their extremely aggressive behavior and relative isolation by the blood-brain and blood-tumor barriers. Endothelial cells may be versatile platforms for delivering genes to solid tumors by virtue of their location at blood-tissue interfaces and their proliferation in response to endothelial mitogens produced by tumors. Immortalized rat brain endothelial cells that express the E. coli lacZ reporter gene and the gene for murine interleukin-2 (RBEZ-IL2) were co-inoculated with 9L glioma cells to Fisher rats to examine the effects of endothelial cell-based cytokine delivery on glioma growth in vivo. 9L glioma growth was not affected by the implantation of control RBEZ cells. The growth of subcutaneous and intracranial 9L gliomas was significantly inhibited by RBEZ-IL2 cells (P < 0.005 and P < 0.01, respectively) when compared to control transfected RBEZ cells. Rats receiving intracranial 9L glioma cells with RBEZ-IL2 cells showed increased survival (P < 0.001). Histologic and immunohistologic analysis showed enhanced activation of microglia/macrophages and CD8-positive T lymphocytes and/or natural killer cells within brain at sites of 9L inoculation with RBEZ-IL2 cells. This report establishes that immortalized endothelial cells can be used for cytokine gene delivery and to activate anti-tumor host responses to experimental gliomas within the central nervous system.

Animals↗
PubMed1996

Mechanism of unassisted ion transport across membrane bilayers.

To establish how charged species move from water to the nonpolar membrane interior and to determine the energetic and structural effects accompanying this process, we performed molecular dynamics simulations of the transport of Na+ and Cl- across a lipid bilayer located between two water lamellae. The total length of molecular dynamics trajectories generated for each ion was 10 ns. Our simulations demonstrate that permeation of ions into the membrane is accompanied by the formation of deep, asymmetric thinning defects in the bilayer, whereby polar lipid head groups and water penetrate the nonpolar membrane interior. Once the ion crosses the midplane of the bilayer the deformation "switches sides"; the initial defect slowly relaxes, and a defect forms in the outgoing side of the bilayer. As a result, the ion remains well solvated during the process; the total number of oxygen atoms from water and lipid head groups in the first solvation shell remains constant. A similar membrane deformation is formed when the ion is instantaneously inserted into the interior of the bilayer. The formation of defects considerably lowers the free energy barrier to transfer of the ion across the bilayer and, consequently, increases the permeabilities of the membrane to ions, compared to the rigid, planar structure, by approximately 14 orders of magnitude. Our results have implications for drug delivery using liposomes and peptide insertion into membranes.

Cell Membrane Permeability↗
PubMed1996

Interactions of anesthetics with the membrane-water interface.

Although the potency of conventional anesthetics correlates with lipophilicity, an affinity to water also is essential. It was recently found that compounds with very low affinities to water do not produce anesthesia regardless of their lipophilicity. This finding implies that clinical anesthesia might arise because of interactions at molecular sites near the interface of neuronal membranes with the aqueous environment and, therefore, might require increased concentrations of anesthetic molecules at membrane interfaces. As an initial test of this hypothesis, we calculated in molecular dynamics simulations the free energy profiles for the transfer of anesthetic 1,1,2-trifluoroethane and nonanesthetic perfluoroethane across water-membrane and water-hexane interfaces. Consistent with the hypothesis, it was found that trifluoroethane, but not perfluoroethane, exhibits a free energy minimum and, therefore, increased concentrations at both interfaces. The transfer of trifluoroethane from water to the nonpolar hexane or interior of the membrane is accompanied by a considerable, solvent-induced shift in the conformational equilibrium around the C-C bond.

Anesthetics↗
PubMed1996

Excess chemical potential of small solutes across water--membrane and water--hexane interfaces.

The excess chemical potentials of five small, structurally related solutes, CH4, CH3F, CH2F2, CHF3, and CF4, across the water-glycerol 1-monooleate bilayer and water-hexane interfaces were calculated at 300, 310, and 340 K using the particle insertion method. The excess chemical potentials of nonpolar molecules (CH4 and CF4) decrease monotonically or nearly monotonically from water to a nonpolar phase. In contrast, for molecules that possess permanent dipole moments (CH3F, CH2F, and CHF3), the excess chemical potentials exhibit an interfacial minimum that arises from superposition of two monotonically and oppositely changing contributions: electrostatic and nonelectrostatic. The nonelectrostatic term, dominated by the reversible work of creating a cavity that accommodates the solute, decreases, whereas the electrostatic term increases across the interface from water to the membrane interior. In water, the dependence of this term on the dipole moment is accurately described by second order perturbation theory. To achieve the same accuracy at the interface, third order terms must also be included. In the interfacial region, the molecular structure of the solvent influences both the excess chemical potential and solute orientations. The excess chemical potential across the interface increases with temperature, but this effect is rather small. Our analysis indicates that a broad range of small, moderately polar molecules should be surface active at the water-membrane and water-oil interfaces. The biological and medical significance of this result, especially in relation to the mechanism of anesthetic action, is discussed.

Anesthetics↗