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Biomedical subjects

A E Clark

Publications and source records attributed to A E Clark.

At least 19 recordsLinked to original sources
PubMed2001

Model studies of hydrogen atom addition and abstraction processes involving ortho-, meta-, and para-benzynes.

H-atom addition and abstraction processes involving ortho-, meta-, and para-benzyne have been investigated by multiconfigurational self-consistent field methods. The H(A) + H(B)...H(C) reaction (where r(BC) is adjusted to mimic the appropriate singlet-triplet energy gap) is shown to effectively model H-atom addition to benzyne. The doublet multiconfiguration wave functions are shown to mix the "singlet" and "triplet" valence bond structures of H(B)...H(C) along the reaction coordinate; however, the extent of mixing is dependent on the singlet-triplet energy gap (DeltaE(ST)) of the H(B)...H(C) diradical. Early in the reaction, the ground-state wave function is essentially the "singlet" VB function, yet it gains significant "triplet" VB character along the reaction coordinate that allows H(A)-H(B) bond formation. Conversely, the wave function of the first excited state is predominantly the "triplet" VB configuration early in the reaction coordinate, but gains "singlet" VB character when the H-atom is close to a radical center. As a result, the potential energy surface (PES) for H-atom addition to triplet H(B)...H(C) diradical is repulsive! The H3 model predicts, in agreement with the actual calculations on benzyne, that the singlet diradical electrons are not coupled strongly enough to give rise to an activation barrier associated with C-H bond formation. Moreover, this model predicts that the PES for H-atom addition to triplet benzyne will be characterized by a repulsive curve early in the reaction coordinate, followed by a potential avoided crossing with the (pi)1(sigma*)1 state of the phenyl radical. In contrast to H-atom addition, large activation barriers characterize the abstraction process in both the singlet ground state and first triplet state. In the ground state, this barrier results from the weakly avoided crossing of the dominant VB configurations in the ground-state singlet (S0) and first excited singlet (S1) because of the large energy gap between S0 and S1 early in the reaction coordinate. Because the S1 state is best described as the combination of the triplet X-H bond and the triplet H(B)...H(C) spin couplings, the activation barrier along the S0 abstraction PES will have much less dependence on the DeltaE(ST) of H(B)...H(C) than previously speculated. For similar reasons, the T1 potential surface is quite comparable to the S0 PES.

Journal Article↗
PubMed2001

Novel sol-gel bioactive fibers.

Bioactive fibers were produced using a sol-gel method. The rheological properties of two different sol compositions prepared from a mixture of TEOS, phosphorous alkoxide and calcium nitrate, or calcium chloride in a water-ethanol solution, are reported. The sols were extruded through a spinneret to produce continuous 10 microm-diameter fibers. Discontinuous fibers and fibrous mats were prepared by air-spraying the multicomponent sols. The sol-gel fibers were converted to the bioactive fibers by three different thermal treatments at either 600 degrees, 700 degrees, or 900 degrees C for 3 h. SEM, BET, EDX, and FTIR were used to characterize the morphology and structure of the fibers. The BET measured surface area of the fibers sintered at 900 degrees C was 0 m(2)/gm compared to a value of 200 m(2)/gm for a typical sol-gel-derived particle of similar composition. Both the continuous and discontinuous fibers exhibited in vitro bioactivity in a simulated body fluid.

Biocompatible Materials↗
PubMed2001

A sol-gel derived bioactive fibrous mesh.

Nonwoven sheets of bioactive fibers were produced using a sol-gel process. A high velocity spray process was used to prepare fibers of two compositions in the SiO(2)-CaO-P(2)O(5) ternary system. Both discontinuous fibers and dispersed fibers were evaluated. Viscosity and pH of the sol were the two primary processing variables studied. The formation of hydroxy carbonate apatite (HCA) on the surface of the fibers was used to evaluate the kinetics of the bioactivity in a simulated body fluid (SBF). Diffuse reflection infrared fourier transform spectroscopic (DRIFTS) analysis confirmed the presence of HCA (P-O). A homogenous layer of HCA, as observed with SEM (scanning electron microscopy), typically formed after 3-h immersion in the SBF. The concentration of HCA formed was greater for samples richer in silica. The new bioactive fiber sheets produced by this process are chemically more stable than powders or monoliths prepared from similar precursors. Potential applications are as scaffold for both mineralized and nonmineralized structural tissues.

Biocompatible Materials↗
PubMed2001

UDFT and MCSCF descriptions of the photochemical Bergman cyclization of enediynes.

Several singlet and triplet potential energy surfaces (PES) for the Bergman cyclization of cis-1,5-hexadiyne-3-ene (1a) have been computed by UDFT, CI, CASCI, CASSCF, and CASMP2 methods. It is found that the first six excited states of 1a can be qualitatively described as linear combinations of the configurations of weakly interacting ethylene and acetylene units. Although the symmetry relaxation from C2nu to C2 makes cyclization of the 13B state Woodward-Hoffmann allowed, it also increases the probability of competing cis-trans isomerization. Hydrogen atom abstraction is another plausible pathway because the terminal alkyne carbons possess a large radical character. In view of the competing processes, we conclude that the Bergman cyclization along the 13B path is unlikely despite its exothermicity (Delta = -42 kcal/mol). Calculations on cyclic analogues of 1a lead to similar conclusions. A less exothermic, but more plausible pathway for photochemical cyclization lies on the 2(1)A PES (Delta = -18 kcal/mol). Compared to the 1(1)A(1) and 1(3)B states, the 2(1)A state has less in-plane electron repulsion which may facilitate cyclization. The resulting p-benzyne intermediate has an unusual electronic structure combining singlet carbene and open-shell diradical features. Deactivation of the 2(1)A state of 1a is a competing pathway.

Journal Article↗
PubMed2001

Pulp capping with a modified bioglass formula (#A68-modified).

PURPOSE: To evaluate a modified Bioglass (Formula #68 (MBF68) when used as a pulp capping agent. MATERIALS AND METHODS: After exposure, the pulps were contaminated with saliva for 60s, rinsed, dried and treated with Consepsis, acting as a hemostatic and bactericidal agent. After drying the Consepsis, the MFB68, having been pre-mixed in sterile saline, was carefully deposited over the pulp exposure, covered with polycarboxylate cement and restored with the ProBond bonding resin system. A calcium hydroxide group was used as control. RESULTS: There was no evidence of mummification, the incidence of properly positioned dentin bridge formation was higher and the incidence of extruded dentin bridge formation was reduced.

Animals↗
PubMed2000

Chronic insulin effects on insulin signalling and GLUT4 endocytosis are reversed by metformin.

Decreases in insulin-responsive glucose transport and associated levels of cell surface GLUT4 occur in rat adipocytes maintained in culture for 20 h under hyperinsulinaemic and hyperglycaemic conditions. We have investigated whether this defect is due to reduced signalling from the insulin receptor, GLUT4 expression or impaired GLUT4 trafficking. The effects of chronic insulin treatment on glucose transport and GLUT4 trafficking were ameliorated by inclusion of metformin in the culture medium. In comparison with the ic insulin treatment attenuated changes in signalling processes leading to glucose transport. These included insulin receptor tyrosine phosphorylation, phosphoinositide 3-kinase activity and Akt activity, which were all reduced by 60-70%. Inclusion of metformin in the culture medium prevented the effects of the chronic insulin treatment on these signalling processes. In comparison with cells maintained in culture without insulin, the total expression of GLUT4 protein was not significantly altered by chronic insulin treatment, although the level of GLUT1 expression was increased. Trafficking rate constants for wortmannin-induced cell-surface loss of GLUT4 and GLUT1 were assessed by 2-N-4-(1-azi-2, 2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannose-4-yloxy)-2-propyla min e (ATB-BMPA) photolabelling. In comparison with cells acutely treated with insulin, chronic insulin treatment resulted in a doubling of the rate constants for GLUT4 endocytosis. These results suggest that the GLUT4 endocytosis process is very sensitive to the perturbations in signalling that occur under hyperinsulinaemic and hyperglycaemic conditions, and that the resulting elevation of endocytosis accounts for the reduced levels of net GLUT4 translocation observed.

Adipocytes↗
PubMed2000

Effectiveness of metal surface treatments in controlling microleakage of the acrylic resin-metal framework interface.

STATEMENT OF PROBLEM: Microleakage at the junction between the metal alloy and acrylic resin in a removable partial denture may result in discoloration, fluid percolation, and acrylic resin deterioration. The junction between a metal alloy and acrylic resin is an area of clinical concern. Failure of a removable partial denture may be linked to this interface. Enhancing resistance to microleakage at this interface may improve the long-term union between the 2 materials. PURPOSE: This investigation was designed to determine the effects of various metal surface treatment protocols on microleakage and bond strength between the metal alloy and acrylic resin used in the fabrication of a removable partial denture. MATERIAL AND METHODS: Ninety-six nickel-chromium-beryllium alloy specimens were randomly divided into 8 groups. After adaptation of baseplate wax, each specimen was invested. Subsequent to wax removal, each specimen was divided into a control half and an experimental half. Air abrasion, tinplating/oxidation, and silanation were evaluated individually and in all combinations. Heat-polymerized acrylic resin was processed against all specimens before storage in distilled water at 37 degrees C for 72 hours. Each specimen then was thermocycled in distilled water (3000 cycles) before immersion in sodium fluorescein dye for 24 hours. Counting grids that exhibited dye penetration under ultraviolet light exposure allowed assessment of microleakage. RESULTS: Air abrasion resulted in a significant decrease in microleakage when used individually and in all combinations (P<0.05). All experimental combinations that did not involve air abrasion demonstrated no significant reduction in measured microleakage between the experimental and control sides. Tukey's pair-wise comparison of the difference in the mean number of squares exhibiting microleakage between the control and treated sites for each experimental group revealed a significant difference, based on the involvement of air abrasion. Groups involving air abrasion did not differ significantly from each other (P<0.05). In addition, no significant difference was detected between groups not involving air abrasion (P<0.05). CONCLUSION: Air abrasion, alone and in combination with tinplating/oxidation and with silanation, resulted in a significant reduction in microleakage between the metal alloy and acrylic resin.

Acrylic Resins↗
PubMed1998

Cyclic anhydride ring opening reactions: theory and application.

The development of a zero net shrinkage dental restorative material based upon a polymer-bioactive-glass composite requires a second-phase material that expands. This study details the mechanisms of organic cyclic anhydride ring expansion via hydrolysis. Six cyclic anhydrides were used to represent potential side groups, each of which could be an expanding phase or component. Maleic, 4META, tetrahydrophthalic, norbornene, itaconic, and succinic anhydrides were modeled using the Austin method (AM1), a semi-empirical molecular orbital method. The reaction pathways were determined for the anhydride ring opening reaction to form an acid for each case. The activation barriers (Ea) for the ring openings were found from the transition state geometries wherein only one imaginary eigen value in the vibration spectrum existed (a true saddle point). In each case the reaction pathway included the hydrogen bonding of a H2O molecule to the ring, weakening of the C-O bridging bonds of the ring, and, finally, the dissociation of the H2O, forming two carboxyl groups and opening the ring. The activation for the ring openings are +34.3, +36.9, +40.6, +43.1, +45.9, and +47.7 kcal/mol, respectively. The volumetric expansion of the anhydrides was estimated based upon the dilation of C-O-C atomic distances. The dimensional change was found to be 24.0%, 24.0%, 19.1%, 20.3%, 20.8%, and 17.9% for the anhydride rings, respectively. Finally, it was found that a linear correlation exists between the cyclic anhydride C-O asymmetric rocking (as-v) vibration and the activation energy (Ea) for hydrolysis to an acid. This may be used as an experimental indicator of a cyclic anhydride's activity.

Anhydrides↗
PubMed1998

Dietary fiber differentially alters cellular fatty acid-binding protein expression in exfoliated colonocytes during tumor development.

We investigated the utility of noninvasive technology utilizing feces containing exfoliated colonocytes to determine whether changes in fecal fatty acid-binding proteins have predictive value in monitoring the neoplastic process. Ninety male Sprague-Dawley rats were randomly divided into four groups in a 2 x 2 factorial design, with two dietary fiber sources (wheat bran or oat bran) and two treatment groups (injection with a carcinogen, azoxymethane, or saline). Fresh fecal samples were collected at Week 16 postinjection, and tumor frequency was determined at Week 36 of the study. Semiquantitative "mimic" reverse transcriptase polymerase chain reaction was used to quantitate the expression of liver fatty acid-binding protein (L-FABP), intestinal fatty acid-binding protein (i-FABP), and acyl CoA-binding protein (ACBP) mRNA in fecal samples to establish their prognostic value. Rats fed wheat bran diets had a lower incidence of tumors (p < 0.05). There was no effect of carcinogen injection or tumor incidence on the expression of L-FABP, i-FABP, or ACBP mRNA, L-FABP and i-FABP mRNA expression were significantly higher (p < 0.05) in feces from animals fed a wheat bran diet than in feces from animals fed an oat bran diet. In contrast, the expression of ACBP mRNA was significantly lower (p < 0.05) in animals fed a wheat bran diet than in animals fed an oat bran diet. Wheat bran also increased (p < 0.05) the total excretion of L-FABP, i-FABP, and ACBP over a 48-hour period. These data suggest that exfoliated colonocyte fatty acid-binding protein mRNA status may provide insight into the mechanisms by which diet influences colonic physiology.

Animals↗
PubMed1997

Molecular orbital models of ring expansion mechanisms in the silica-carbon monoxide system.

The development of a zero net shrinkage dental restorative material based upon a polymer-bioactive glass composite requires a second-phase material that expands. This study details the mechanisms of silica ring expansion by reaction with carbon monoxide. Carbon monoxide was used as a model adduct to represent potentially active sites on the polymer phase of the dental restorative. Silica rings were used to model the bioactive-glass phase of the composite. The 3-, 4-, 5-, and 6-"member" silica rings have been modeled using the Austin Method (AM1) semi-empirical molecular orbital calculations. The reaction pathways were determined for carbon monoxide (CO) reaction addition to each of the rings. The activation barriers (Ea) for the ring expansions were determined from the transition state geometries wherein only one imaginary eigenvalue in the vibration spectrum existed (a true saddle point). In each case the reaction pathway included the hydrogen bonding of CO with a silicon, exothermic pentacoordinate bonding to silicon by the CO and weakening of the Si-O bridging bonds of the ring, and, finally, the incorporation of CO into the ring, forming a silica-carbonate ring. The activation for the ring expansions are +4.3, +6.1, +7.0, and -2.9 Kcal/mol for 3-, 4-, 5-, and 6-"member" silica rings, respectively. The volumetric expansion of the silica was estimated based upon the dilation of adjacent silicon-silicon atomic distances. The dimensional change was calculated to be 3.9%, 21.3%, 19.4%, and 24.2% for 3-, 4-, 5-, and 6-membered silica-carbonate rings, respectively.

Biocompatible Materials↗
PubMed1997

Effect of insulin on GLUT4 cell surface content and turnover rate in human skeletal muscle as measured by the exofacial bis-mannose photolabeling technique.

Insulin-stimulated glucose transport across the skeletal muscle cell membrane is a major regulatory step in postprandial glucose disposal. To estimate the total molar concentration of GLUT4 as well as the turnover rate of GLUT4 in human vastus lateralis muscles at the cell surface in the basal state and after insulin exposure, we have applied the sensitive exofacial bis-mannose photolabeling technique on in vitro incubated human skeletal muscle strips from healthy subjects. In addition, we have measured 3-O-methylglucose transport in other muscle strips prepared from the same surgically removed human skeletal muscle biopsies to compare glucose transport with cell surface level of GLUT4. Maximal in vitro insulin stimulation (2,400 pmol/l) resulted in a twofold increase compared with basal in both surface GLUT4 content (0.38 +/- 0.05 vs. 0.19 +/- 0.03 pmol/g wet muscle wt, P < 0.005) and 3-O-methylglucose transport (1.24 +/- 0.13 vs. 0.63 +/- 0.08 pmol x ml(-1) x h(-1), P < 0.005). The insulin-induced increment in 3-O-methylglucose transport was strongly correlated with the insulin-induced increase in cell surface GLUT4 content (r2 = 0.91; P < 0.005). The calculated turnover rate of human skeletal muscle GLUT4 amounted to approximately 8 x 10(4) min(-1) at 35 degrees C and was unaffected by insulin. In conclusion, maximal in vitro insulin stimulation of vastus lateralis muscle strips from healthy subjects resulted in a twofold rise in glucose transport as well as in cell surface content, whereas the turnover rate of GLUT4 was unaffected by insulin under the chosen experimental conditions.

3-O-Methylglucose↗
PubMed1997

Clinical use of a bioactive glass particulate in the treatment of human osseous defects.

The dental practitioner has a wide choice of materials available for use in bone grafting procedures. A bioactive glass particulate possesses many favorable qualities not often found in other materials, including the ability to remain where placed even with adjacent suctioning; hemostasis; and incorporation into the host bone without the fibrous encapsulation encountered with most other synthetic materials. It is also quick and easy to prepare. This article reviews clinical experiences with PerioGlas in the setting of private practice periodontics, in which this material was used as the grafting material for periodontal defects, apicoectomies, cysts, and ridge augmentation and maintenance procedures, as well as for implant repairs. Several cases detail the advantages of this grafting material.

Adult↗
PubMed1996

Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein.

The vesicle-associated membrane proteins [VAMPs; vesicle SNAP receptors (v-SNAREs)] present on GLUT4-enriched vesicles prepared from rat adipose cells [Cain, Trimble and Lienhard (1992) J. Biol. Chem. 267, 11681-11684] have been identified as synaptobrevin 2 (VAMP 2) and cellubrevin (VAMP 3) by using isoform-specific antisera. Additional antisera identify syntaxins 2 and 4 as the predominant target membrane SNAP receptors (t-SNAREs) in the plasma membranes (PM), with syntaxin 3 at one-twentieth the level. Syntaxins 2 and 4 are enriched 5-10-fold in PM compared with low-density microsomes (LDM). Insulin treatment results in an 11-fold increase in immunodetectable GLUT4 in PM and smaller (approx. 2-fold) increases in VAMP 2 and VAMP 3, whereas the subcellular distributions of the syntaxins are not altered by insulin treatment. To determine which of the SNAP receptors (SNAREs) in PM might participate in SNARE complexes with proteins from GLUT4 vesicles, complexes were immunoprecipitated with anti-myc antibody from solubilized membranes after the addition of myc-epitope-tagged N-ethylmaleimide-sensitive fusion protein (NSF) and recombinant alpha-soluble NSF attachment protein (alpha-SNAP). These complexes contain VAMPs 2 and 3 and syntaxin 4, but not syntaxins 2 or 3. Complex formation requires ATP and is disrupted by ATP hydrolysis. When all membrane fractions are prepared from basal cells, few or no VAMPs and no syntaxin 4 are immunoprecipitated in SNARE complexes obtained from LDM alone (or from immunoisolated GLUT4 vesicles). The content of syntaxin 4 depends on the presence of PM, and participation of VAMPs 2 and 3 is enhanced 4-6-fold by the addition of solubilized GLUT4 vesicles to PM. The latter increase is greater than can be explained by the 2-fold higher levels of VAMPs added to the reaction mixture. When all membrane fractions are prepared from insulin-stimulated cells, SNARE complexes formed from PM alone contain similar levels of syntaxin 4 but 5-6-fold higher levels of VAMPs 2 and 3 compared with PM alone from basal cells. Addition of GLUT4 vesicle proteins to PM from insulin-treated cells results in a further 2-fold increase in VAMP 2 recovered in SNARE complexes. Therefore the VAMPs in PM of insulin-treated but not basal cells, and in GLUT4-vesicles from cells in either condition, are in a form that readily forms a SNARE complex with PM t-SNAREs and NSF. Insulin seems to activate PM and/or GLUT4 vesicles so as to increase the efficiency of SNARE complex formation.

Adipose Tissue↗
PubMed1996

A study of enzymes involved in catecholamine metabolism in parents of patients with schizophrenia.

The concentrations of serum homovanillic acid (HVA), norepinephrine (NE), tyrosine (Tyr), phenylalanine (Phe) and tryptophan (Trp), and the activities of serum dopamine-beta-hydroxylase (DBH), platelet monoamine oxidase (MAO), and erythrocyte catechol-O-methyl transferase (COMT) were measured in 68 healthy parents who had schizophrenic offspring. The results show a significant correlation between the parents of schizophrenic patients in serum HVA (r=0.38, n=34, p<0.05), NE (r=0.40, n=33, p<0.02), Phe (r=0.44, n=34, p<0.0l), Tyr (r=0.43, n = 34, p <0.02) and DBH activity (r=0.51, n = 30, p <0.005), but do not show a significant correlation in erythrocyte COMT (r=0.01, n=27), platelet MAO (r=0.04, n=23) or serum Trp (r=0.10, n=34). There were no significant correlations in these measurements between randomly matched parents. The present study suggests that both parental sides of schizophrenic patients are likely to have similar alleles associated with the catecholamine pathway, and their ill offspring may possess a double dose of the schizophrenogenic alleles.

Adult↗
PubMed1996

Decreased tyrosine transport in fibroblasts from schizophrenics: implications for membrane pathology.

Two independent studies reported recently have shown a significant decrease in Vmax of tyrosine transport in fibroblasts grown from schizophrenics' skin compared with controls. It has also been shown that tyrosine transport into the brain is decreased in schizophrenics compared with controls. In view of the importance of these findings in elucidating the biochemical mechanism(s) associated with schizophrenia, we have studied the kinetics of tyrosine transport and the levels of monoamine oxidase (MAO) activity in fibroblasts grown from the skins of schizophrenics and unrelated control subjects. Using the Lineweaver-Burk plot, the Eadie Hostee plot and the Hanes plot we have calculated the Km and Vmax for tyrosine transport. We have found a significant decrease in the Km and Vmax values for tyrosine transport in schizophrenics compared with control fibroblast samples. No changes were observed in the levels of MAO. Using Lineweaver-Burk plot (1/S Versus 1/V) it has been shown that the tyrosine transport inhibition is uncompetitive. This finding proposes that the inhibition is in the substrate transport protein complex, which may be taking place during the transit of the substrate through the cell membrane. From the observed findings and from the literature evidence we suggest that the altered metabolism of phospholipids in schizophrenics, such as deficiency of arachidonic acid and docosahexaenoic acid, may be contributing to this observed phenomena.

Adolescent↗