Measuring disorganized speech in schizophrenia: automated analysis explains variance in cognitive deficits beyond clinician-rated scales.

BACKGROUND: Conveying information cohesively is an essential element of communication that is disrupted in schizophrenia. These disruptions are typically expressed through disorganized symptoms, which have been linked to neurocognitive, social cognitive, and metacognitive deficits. Automated analysis can objectively assess disorganization within sentences, between sentences, and across paragraphs by comparing explicit communication to a large text corpus. METHOD: Little work in schizophrenia has tested: (1) links between disorganized symptoms measured via automated analysis and neurocognition, social cognition, or metacognition; and (2) if automated analysis explains incremental variance in cognitive processes beyond clinician-rated scales. Disorganization was measured in schizophrenia (n = 81) with Coh-Metrix 3.0, an automated program that calculates basic and complex language indices. Trained staff also assessed neurocognition, social cognition, metacognition, and clinician-rated disorganization. RESULTS: Findings showed that all three cognitive processes were significantly associated with at least one automated index of disorganization. When automated analysis was compared with a clinician-rated scale, it accounted for significant variance in neurocognition and metacognition beyond the clinician-rated measure. When combined, these two methods explained 28-31% of the variance in neurocognition, social cognition, and metacognition. CONCLUSIONS: This study illustrated how automated analysis can highlight the specific role of disorganization in neurocognition, social cognition, and metacognition. Generally, those with poor cognition also displayed more disorganization in their speech-making it difficult for listeners to process essential information needed to tie the speaker's ideas together. Our findings showcase how implementing a mixed-methods approach in schizophrenia can explain substantial variance in cognitive processes.

The Influence of Donor and Recipient Gender Incompatibility on Corneal Transplant Rejection and Failure.

In vascularized organ transplants, gender mismatches have higher rates of immunological rejection. We investigated the influence of gender incompatibility, including H-Y incompatibility, on corneal transplant graft rejection and failure. Patients were included who had undergone a first corneal transplant for keratoconus (KC), Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), infection and other indications. A Cox regression model was fitted for each indication to determine factors affecting graft failure and rejection at 5 years. The impact of gender, including H-Y, matching was analyzed after accounting for other factors, including known risk factors. Of 18 171 patients, 4314 had undergone a transplant for FED, 4783 for KC, 3669 for PBK, 1903 for infection and 3502 for other disorders. H-Y mismatched (male [M]→female [F]) corneas were at greater risk of graft failure or rejection. For FED, F→F were 40% less likely to fail (p < 0.0001) and 30% less likely to reject (p = 0.01); M→M were 20% less likely to fail (p = 0.04) and 30% less likely to reject (p = 0.01). For KC, M→M matched corneas were 30% less likely to fail (p = 0.05) and 20% less likely to reject (p = 0.01) compared with H-Y mismatches. H-Y antigen mismatched (M→F) patients were at greater risk of rejection or graft failure.

The impact of donor age and endothelial cell density on graft survival following penetrating keratoplasty.

PURPOSE: To determine if donor age and preoperative endothelial cell density (ECD) affect corneal endothelial failure following penetrating keratoplasty (PK). METHODS: Preoperative and postoperative data for PKs performed in the UK between April 1999 and March 2012 were analysed. Donor age was split into three groups (0-60, 61-75 and >75 years) and donor ECD was split into three groups (≤2400, 2401-2600 and >2600 cells/mm2). Cox proportional hazards regression was used to determine whether the selected subgroups of donor age and donor ECD have an impact on endothelial failure and a systematic analysis of the interaction between donor ECD and donor age was conducted. The analysis was stratified for primary corneal diagnosis (Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK) and other) and corrected for potentially confounding factors (human leukocyte antigen matching, donor trephine diameter, deep vascularisation, the occurrence of reversible rejection episodes and receipt of systemic antiviral medication, long-term steroids or other immunosuppressive agents). RESULTS: A total of 9415 patients, from the National Health Service Blood and Transplant UK Transplant Registry, who received their first PK for visual reasons were included in this study. The overall 5-year graft survival rate due to endothelial failure was 89%. Survival rates in recipients with FED, PBK and 'all other indications' were 95%, 83% and 89%, respectively. Our analysis shows that donor ECD did not affect outcome following corneal graft within the preselected categories, irrespective of diagnosis and after allowing for any potential confounding factors. Furthermore, HRs for each level of donor ECD, relative to >2600 cells/mm2, for each combination of age group and indication, were not statistically significant. CONCLUSIONS: We were unable to detect a significant effect of donor age, up to 90 years, and preoperative donor ECD, above the lower limit of 2200 cells/mm2, on endothelial failure at 5 years following PK.

Tissue and corneal donation and transplantation in the UK.

NHS Blood and Transplant (NHSBT) was established in 2005 as a Special Health Authority when the National Blood Authority and UK Transplant merged. This helped to bring tissue banking and organ transplantation services under one umbrella organization. This merger means that ~!95% of all deceased donors (whether tissue, organ or both) are now facilitated by one organization. NHSBT Tissue Services is the largest tissue establishment in the UK, and is a multi-tissue bank that specializes in the consent, retrieval, processing, storage, and dispatch of donated tissue coordinated from a purpose built, state-of-the-art tissue bank in Liverpool. Tissue donations can come from either tissue-only donors or solid organ donors who also donate tissue. Annually there are ~450 multi-tissue donors and 2500 eye donors in the UK, resulting in many thousands of transplants, including 3564 cornea transplants in 2010-2011. The separation of tissue- and organ-specific donors is largely artificial, and while organ transplantation can be life-saving, tissue transplantation can also have a dramatic effect on a patient's quality of life. It is hoped that all donors, both organ and tissue, will be recognized for the gift they make to society after their death.

Antiviral treatment following penetrating keratoplasty for herpetic keratitis.

PURPOSE: To assess the effect of antiviral treatment on corneal graft survival following penetrating keratoplasty for herpetic keratitis. METHODS: Retrospective cohort study of 454 patients receiving primary penetrating keratoplasties (PKs) for viral infection reported to NHS Blood and Transplant (NHSBT) between April 1999 and June 2005. Follow-up data were available on 403 PKs. Kaplan-Meier survival estimates were used to determine graft survival for the three treatment groups: no medication, topical antiviral, and oral antiviral medication. A Cox regression model was used to investigate the combined effects of all additional factors on graft failure. The model was fitted using all pre-operative factors first and then post-operative factors including type of antiviral medication were included. RESULTS: Patients who received oral antiviral medication post-operatively had consistently better graft survival than those receiving no medication or only topical medication. Patients receiving oral antivirals were less than a third as likely to have a failed graft at 5 years compared with those on no antiviral medication (relative risk (RR) 0.3, CI: 0.2-0.7, P=0.002). Other factors that were found to influence the risk of graft failure were the presence of deep corneal vascularisation (P=0.009), PK performed for therapeutic reasons (P=0.03), large diameter grafts (P=0.04), and experiencing a rejection episode (P=0.003). CONCLUSION: Oral antiviral treatment reduces the risk of graft failure in patients undergoing primary PK for herpetic keratitis and should be routinely used in this group of patients post-operatively unless contra-indicated.

Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial.

One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death (DCD). Such kidneys have a high rate of delayed graft function (DGF) following transplantation. We conducted a multicenter, randomized controlled trial to determine whether kidney preservation using cold, pulsatile machine perfusion (MP) was superior to simple cold storage (CS) for DCD kidneys. One kidney from each DCD donor was randomly allocated to CS, the other to MP. A sequential trial design was used with the primary endpoint being DGF, defined as the necessity for dialysis within the first 7 days following transplant. The trial was stopped when data were available for 45 pairs of kidneys. There was no difference in the incidence of DGF between kidneys assigned to MP or CS (58% vs. 56%, respectively), in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys. Renal function at 3 and 12 months was similar between groups, as was graft and patient survival. For kidneys from controlled DCD donors (with mean cold ischemic times around 14 h), MP offers no advantage over CS, which is cheaper and more straightforward.

The visual and refractive outcomes of combined and sequential penetrating keratoplasty, cataract extraction, and intraocular lens insertion.

PURPOSE: The aim of this study was to investigate the visual and refractive outcome of combined penetrating keratoplasty, cataract extraction, and intraocular lens insertion (triple procedure) compared with cataract surgery following penetrating keratoplasty (sequential surgery). METHODS: Retrospective cohort study of 1256 first penetrating keratoplasty for Fuchs' dystrophy performed between April 1999 and December 2005. In all, 1202 triple and 54 sequential procedures were reviewed. At 1 year, refractive outcomes were available for 499 triple procedure and 26 sequential surgery eyes. At 2 years, data were available for 264 triple procedure and 10 sequential surgery eyes. At 1 and 2 years postoperatively, graft survival, best-corrected visual acuity (BCVA), spherical equivalent, and cylindrical error were recorded. chi(2)-Tests were used to compare visual outcomes between the two groups. RESULTS: At 1 year after triple procedure surgery, 61% of eyes attained BCVA of >or=6/12, with 47% of eyes within+/-2 D of emmetropia. After sequential surgery, 59% achieved BCVA of >or=6/12 with 67% of eyes within+/-2 D of emmetropia (=0.05). Mean spherical equivalent (MSE) at 1 and 2 years after triple procedure was +1.20 D (SD 5.45) and +0.15 D (SD 3.58), respectively. MSE following sequential surgery at 1 and 2 years was +0.08 D (SD 3.06) and -1.50 D (SD 3.14), respectively. Mean refractive cylinder after combined surgery was +4.16 D (SD 5.11) and +3.91 D (SD 2.79) at 1 and 2 years, respectively, compared with +3.65 D (SD 2.24) and +3.70 D (SD 2.06) after sequential surgery. In all, 29% of triple procedure and 27% sequential surgery eyes had an astigmatic error >or=5.0 D after 1 year (P=0.64), which increased to 34 and 30%, respectively, by the second year. The 5-year graft survival was 85% in both groups. There were no differences in graft survival, visual or refractive outcomes between triple procedure, and sequential surgery techniques. CONCLUSIONS: This analysis provided no evidence of improved visual or refractive outcome after sequential surgery compared with triple procedure.

Efficiency is a legitimate consideration in equitable distribution of cadaveric transplants: development of an efficiency-equality model of equity.

It is proposed that equity is a trade-off, or compromise, between equality and efficiency. The kidney transplant allocation algorithm currently used in the United Kingdom (NAT) was tested in the efficiency-equity model. In an exercise of 2000 past UK donors and a dynamic waiting list of 5000 potential recipients, 4000 transplants were allocated according either by NAT, by equal allocation (EQ) (a lottery), or by efficiency (EF). Diabetic recipients received 7.4% of transplants in NAT, 8.6% in EQ, and 0% in EF; paediatric recipients received 6.8% in NAT, 0.6% in EQ, and 0.7% in EF model. For HLA matching, there were 77.9% favourable or 000 matches in NAT, 3.0% in EQ, and 53.1% in EF. Predicted survival showed better outcomes in EF versus NAT (P < .0001) and in NAT versus EQ (P = .05). The NAT allocation system favours paediatric recipients and does not deny diabetics the chance of a transplant, broadly in line with published public and professional opinions. The NAT scheme achieves better HLA matching than the EF model, and this suggests that the rationale for allocation based primarily on HLA matching could be reexamined.

Calcium mobilisation and CCK secretion induced by modified fatty acids and latex microspheres reveal dual receptor mechanisms for lipid stimulation of STC-1 cells.

How fatty acids stimulate enteroendocrine cells to release cholecystokinin (CCK) is largely unknown. Recently, we proposed that the murine enteroendocrine cell line, STC-1, responds to insoluble fatty acid aggregates rather than fatty acid monomers in solution. This hypothesis led to two testable predictions. First, other insoluble particles of similar size but unrelated to fatty acid may be able to stimulate STC-1 cells in a similar fashion to dodecanoic acid and second, fatty acid sensing in STC-1 cells should be fairly insensitive to chemical modifications of the fatty acid as long as these modifications do not greatly alter the ability of the molecule to form insoluble aggregates. We used several analogues of dodecanoic acid and several varieties of latex microsphere (varying in size and surface charge) to see whether the predictions of our model hold. We found that while there was at least one latex microsphere that could induce CCK secretion and calcium mobilisation in STC-1 cells, there was a very poor correlation between the presence of insoluble aggregates and a cellular response. Instead the most important property, determining the potency of fatty acid analogues as stimulants of CCK secretion, was their amphipathicity. Removal of either the polar head or lipophilic tail completely abolished the ability of a given fatty acid analogue to stimulate STC-1 cells. These data suggested that while fatty acids can stimulate cells as aggregates, they may also be acting in monomeric form with the oil:water partitioning coefficient playing a crucial role. We finally resolved this issue with the observation that the sulfate ion greatly altered the response of STC-1 cells to monomeric dodecanoic acid. In the presence of sulfate, STC-1 cells will only respond to dodecanoic acid aggregates whereas when sulfate is replaced with chloride the cells clearly respond to dodecanoic acid monomers which are completely in solution. In summary, we propose that dodecanoic acid can stimulate STC-1 cells via two separate pathways one involving fatty acid monomers in solution and one involving fatty acid aggregates. Which pathway dominates depends on the presence of sulfate in the extracellular medium.

Fatty acid signalling in a mouse enteroendocrine cell line involves fatty acid aggregates rather than free fatty acids.

Fatty acids induce cholecystokinin (CCK) secretion both in humans and from murine enteroendocrine cell lines. In both cases, only fatty acids above a critical acyl chain length (C(10)) are capable of inducing a response. Using the enteroendocrine cell line STC-1, the aim of this study was to determine whether this acyl chain length dependency is related to the fact that longer chain fatty acids are relatively insoluble in aqueous solutions and, if so, whether it is insoluble aggregates of fatty acids rather than free fatty acids which evoke CCK secretion. Solutions of fatty acids (chain length C(8)-C(14)), which were judged by filtration and Zeta sizer measurement to contain no fatty acid aggregates, never evoked CCK secretion from STC-1 cells. Filtering fatty acid solutions (of chain length C(10), C(12) and C(14)) through polytetrafluoroethylene (PTFE) filters (0.45 microm pore size) revealed a narrow concentration range for each acid over which the amount of fatty acid removed from the solution increased sharply due to the formation of fatty acid aggregates. Filtration experiments, in which suspensions of C(10), C(12) and C(14) fatty acids were passed through pore sizes of 0.2, 0.45 or 1.2 microm, suggested that STC-1 cells did not respond to fatty acid aggregates of greater than 1.2 microm, while at least 50 % of the CCK response was mediated by aggregates which were smaller than 0.45 microm. Fatty acids induce CCK secretion from STC-1 cells by elevating intracellular Ca(2+) concentration ([Ca(2+)](i)). We therefore measured the effects on [Ca(2+)](i) of filtered C(10), C(12) and C(14) fatty acids. In all cases, [Ca(2+)](i) responses were closely correlated with CCK secretion. Interestingly, while filtrates of fatty acid solutions evoked CCK secretion and elevated [Ca(2+)](i), freshly prepared solutions of fatty acids at the same concentration as the filtrates did not. This suggested that fatty acid aggregates were not in equilibrium with the solvent after filtration. The observation that the ability of C(10), C(12) and C(14) filtrates to elevate [Ca(2+)](i) decayed with time was consistent with this hypothesis. Furthermore, sonication of the filtrates abolished their ability to elevate [Ca(2+)](i). These data further suggest that it is a physical property of the fatty acid solution (the presence of insoluble fatty aggregates) which is responsible for the observed cellular responses. We conclude that Ca(2+) mobilisation and CCK secretion in STC-1 cells is driven by a signal transduction mechanism that senses insoluble fatty acid aggregates, rather than free fatty acids in solution.

The molecular properties of humic substances isolated from a UK upland peat system: a temporal investigation.

The study concerns the possible changes in the molecular characteristics of humic materials isolated from the same source as a function of time. A great deal of data has been reported concerning the contrast in molecular characteristics of humic substances isolated from different environments. This has primarily been an attempt to identify source-specific molecular characteristics. However, data presented in this paper suggests that humic substances isolated from a single catchment have significant changes in molecular characteristics over time. Two naturally occurring peat pools (X and Y) situated upon a small organic catchment on Great Dun Fell, Cumbria, UK were sampled monthly between November 1994 and November 1996. Dissolved organic matter (DOM) from the pool water samples was fractionated using macroporous nonionic resins (XAD8 and 4), and the humic, fulvic and hydrophilic acids were collected. These fractions were analysed for elemental composition (C, H and N), weight average molecular weight, functional group content and adsorption (340 nm) of a 1 g l(-1) solution measured in a 1-cm spectrophotometer cell. The molecular characteristics were compared to those of natural DOM described by Scott et al. (1998). Scott et al. reported that drought conditions and seasonal climatic changes could have appreciable effects upon molecular characteristics of natural DOM. Results showed that the atomic H/C ratio of the humic substances increased immediately after strong drought conditions experienced in the summer of 1995. This change was temporary with atomic H/C ratio decreasing gradually over the following months. A similar decrease was observed in the carboxyl group content of the isolated compounds. The data set suggested that atomic H/C ratio in the fulvic and hydrophilic fractions exhibited seasonal characteristics of higher ratios during the late summer/early autumn months. This was not observed in the humic fraction. Humic acids exhibited a seasonal pattern of higher weight average molecular weight during the summer months. These trends were explained in terms of summer production of DOM in the catchment soils, their sequestering in the soil due to limited soil water movement during the summer months and their relative ease of dissolution when rainfall and soil water movement increased during the late summer/early autumn period. The results were found to support seasonal and long-term patterns observed in natural DOM as reported by Scott et al. (1998).

The biodegradation of surfactants in the environment.

The possible contamination of the environment by surfactants arising from the widespread use of detergent formulations has been reviewed. Two of the major surfactants in current use are the linear alkylbenzene sulphonates (LAS) and the alkyl phenol ethoxylates (APE). These pass into the sewage treatment plants where they are partially aerobically degraded and partially adsorbed to sewage sludge that is applied to land. The biodegradation of these and a range of other surfactants both in wastewater treatment plants and after discharge into natural waters and application to land resulting in sewage sludge amended soils has been considered. Although the application of sewage sludge to soil can result in surfactant levels generally in a range 0 to 3 mg kg(-1), in the aerobic soil environment a surfactant can undergo further degradation so that the risk to the biota in soil is very small, with margins of safety that are often at least 100. In the case of APE, while the surfactants themselves show little toxicity their breakdown products, principally nonyl and octyl phenols adsorb readily to suspended solids and are known to exhibit oestrogen-like properties, possibly linked to a decreasing male sperm count and carcinogenic effects. While there is little serious risk to the environment from commonly used anionic surfactants, cationic surfactants are known to be much more toxic and at present there is a lack of data on the degradation of cationics and their fate in the environment.

Effect of grafted polyethylene glycol (PEG) on the size, encapsulation efficiency and permeability of vesicles.

Liposomes have been prepared by the vesicle extrusion method (VETs) from mixtures of dipalmitoylphosphatidylcholine (DPPC), phosphatidylinositol (PI) and dipalmitoylphosphatidylethanolamine with covalently linked poly(ethylene glycol) molecular mass 5000 and 2000 (DPPE-PEG 5000 and DPPE-PEG 2000) covering a range of 0-7.5 mole%. The encapsulation of D-glucose has been studied and found to be markedly dependent on the mole% DPPE-PEG. The permeability of the liposomes to D-glucose has been measured both as a function of temperature and liposome composition. The permeability coefficients for D-glucose increase with mole% DPPE-PEG 5000 and with temperature over the range 25-50 degrees C. The activation energies for glucose permeability range from 90 to 23 kJ mol(-1). The decrease in activation energy with increasing temperature is attributed to an increasing number of bilayer defects as the liposome content of PEG-grafted lipid is increased. The dependence of D-glucose encapsulation as a function of PEG-grafted lipid content is discussed in terms of the conformation of the PEG molecules on the inner surface of the bilayer. For liposomes containing DPPE-PEG 5000 the relative percentage encapsulation of glucose, assuming that the PEG surface layer excludes glucose, is comparable to that predicted from the mushroom and brush conformational models.

The use of immunoliposomes for specific delivery of antimicrobial agents to oral bacteria immobilized on polystyrene.

Antibacterial immunoliposomes have been prepared using covalently bound antibody, raised to the cell surface of the bacterium Streptococcus oralis (S. oralis), and incorporating the bactericides chlorhexidine and Triclosan. A regrowth assay, in which the ability of a bacterial biofilm immobilised on polystyrene to grow after exposure to a test solution, was undertaken to study the action of the antibacterial immunoliposomes. The antibacterial anti-oralis immunoliposomes show enhanced growth inhibition of S. oralis, compared to free bactericide, using low bactericide concentrations. For short exposure times to the biofilms, antibacterial anti-oralis immunoliposomes can show several times enhanced growth inhibition of S. oralis compared to free bactericide. Antibacterial anti-oralis immunoliposomes inhibit the growth of S. oralis more than that of other oral bacteria. The extent of growth inhibition by antibacterial anti-oralis immunoliposomes is linearly related to the number of immunoliposomes targeted to the biofilm surface.

Hydrogen peroxide production from reactive liposomes encapsulating enzymes.

Reactive cationic and anionic liposomes have been prepared from mixtures of dimyristoylphosphatidylcholine (DMPC) and cholesterol incorporating dimethyldioctadecylammonium bromide and DMPC incorporating phosphatidylinositol, respectively. The liposomes were prepared by the vesicle extrusion technique and had the enzymes glucose oxidase (GO) encapsulated in combination with horseradish peroxidase (HRP) or lactoperoxidase (LPO). The generation of hydrogen peroxide from the liposomes in response to externally added D-glucose substrate was monitored using a Rank electrode system polarised to +650 mV, relative to a standard silver-silver chloride electrode. The effects of encapsulated enzyme concentration, enzyme combinations (GO+HRP, GO+LPO), substrate concentration, electron donor and temperature on the production of hydrogen peroxide have been investigated. The electrode signal (peroxide production) was found to increase linearly with GO incorporation, was reduced on addition of HRP and an electron donor (o-dianisidine) and showed a maximum at the lipid chain-melting temperature from the anionic liposomes containing no cholesterol. To aid interpretation of the results, the permeability of the non-reactive substrate (methyl glucoside) across the bilayer membranes was measured. It was found that the encapsulation of the enzymes effected the permeability coefficients of methyl glucoside, increasing them in the case of anionic liposomes and decreasing them in the case of cationic liposomes. These observations are discussed in terms of enzyme bilayer interactions.

Surfactants in membrane solubilisation.

An understanding of the action of many drugs requires a knowledge of how the drug reaches the site of action in a cell. A detailed knowledge of the structure and function of cell membranes is often required to understand the transport of drugs across the plasma membrane. To obtain this information proteins must be isolated. The isolation and characterisation of cell membrane proteins usually requires the solubilisation of the membrane and a method of separation of the various membrane proteins and glycoproteins. The starting point for such an investigation is the choice of a suitable surfactant (detergent) to solubilise the membrane. This review considers the range of surfactants that are available for membrane solubilisation, how surfactants interact with membranes, the part they play in the separation of integral membrane proteins and in the reconstitution of membrane proteins for functional studies. The solubilisation of specific membrane proteins and glycoproteins including the human erythrocyte anion transporter, mitochondrial porin, sarcoplasmic reticulum Ca(2+)-ATPase, the ATPase-active multidrug transporter P-glycoprotein, bacteriorhodopsin and rhodopsin are also discussed.

Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility.

BACKGROUND & AIMS: Fatty acids induce cholecystokinin (CCK) secretion and modify gastric motility, but the chain length requirements for these effects are not known. Nor is it clear whether the effects of fatty acids on gastric motility in humans are CCK mediated or directly exerted. The aim of this study was to determine the role of fatty acyl chain length in CCK secretion and in influencing gastric motility. METHODS: Fatty acids were infused into the upper gut in healthy volunteers; plasma CCK was determined by radioimmunoassay. Effects of fatty acids on antral contractility were determined by percutaneous ultrasonography; effects on proximal gastric tone were studied during fundal distention. RESULTS: Plasma CCK concentration was consistently and similarly elevated by fatty acids with a chain of 12 carbon atoms or longer, whereas those of 11 or fewer carbon atoms failed to increase plasma CCK. A 12-carbon but not a 10-carbon-long chain fatty acid reduced antral contractile amplitude, an effect that was abolished by loxiglumide (a specific CCK-A receptor antagonist). The 12-carbon fatty acid also reduced proximal gastric tone more than the 10-carbon fatty acid. CONCLUSIONS: A highly specific, chain length-sensitive fatty acid recognition system exists in the proximal gut mediating CCK secretion and gastric motility. An additional, probably CCK-independent, effect of fatty acid also regulates proximal gastric tone.

Phospholipid free thin liquid films with grafted poly(ethylene glycol)-2000: formation, interaction forces and phase states.

Free thin liquid films (foam films) formed from aqueous dispersions of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylethanolamine with covalently bound poly-(ethylene glycol) of molecular weight 2000 (DPPE-PEG-2000) were studied by the thin liquid film microinterferometric technique of Scheludko and Exerowa in the temperature range 14-36 degrees C. The surface tension kinetics of the dispersions were studied in order to ensure equilibration of the foam films. These measurements showed that the rate of surface coverage depends slightly on the temperature and does not reach equilibrium values within reasonable time intervals for the dispersions containing only one amphiphile (DPPE-PEG-2000). The destruction of the vesicles at the air/(aqueous dispersion) interface was much faster for the dispersions containing DMPC/DPPE-PEG-2000 mixtures above 23 degrees C, the temperature of the chain-melting phase transition of the main lipid component (DMPC). The dependence of the equilibrium thickness of the foam films on the electrolyte concentration was measured for 1 and 9 mol% DPPE-PEG-2000 at 28 degrees C in the range 10-3 to 0.5 M NaCl. These results indicate that at the low electrolyte concentrations the electrostatic and van der Waals interactions are dominant similar to the foam films stabilized with DMPC alone. At the high electrolyte concentrations the steric repulsion of the PEG layers becomes dominant. The temperature-composition dependence of the bilayer thickness was measured for the foam bilayers at 0.14 M NaCl. The data for the foam bilayer thickness and the comparison with the phase diagrams of PC/PE-PEG dispersions, show that the DMPC/DPPE-PEG-2000 foam bilayers are able to exist in two phase states characterised by different conformations (mushroom and brush) of the grafted polymer.

The specificity and affinity of immunoliposome targeting to oral bacteria.

Immunoliposomes have been prepared using antibodies raised to an antigenic determinant on the cell surface of the oral bacterium Streptococcus oralis (S. oralis) in an investigation of their potential to reduce dental plaque. The N-succinimidyl-S-acetylthioacetate (SATA) derivative of the antibodies were conjugated through the reactive m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) derivative of dipalmitoyl-phosphatidylethanolamine (DPPE) incorporated into liposomes. The degree of antibody conjugation to the liposomes was controlled by the percentage of DPPEMBS incorporated into the liposomes. The chemical modification of the antibodies did not affect the ability of the antibodies to bind to a S. oralis biofilm. However, the affinity of the immunoliposomes for S. oralis was much lower than that of the free antibody. The anti-oralis antibodies were highly specific for S. oralis. The anti-oralis immunoliposomes showed the greatest affinity for S. oralis, when targeted to a range of different oral bacterial biofilms. The immunoliposome targeting affinity for S. oralis was largely unaffected by the number of antibodies conjugated to the liposomal surface or by the net charge of the liposomal lipid bilayer. The immunoliposomes showed a greater affinity for S. oralis than 'naked' (bearing no antibody) liposomes. However, positively charged liposomes, incorporating stearylamine, adsorbed to S. oralis with greater affinities than the immunoliposomes. The immunoliposomes appeared to be physically stable over a period of 18 months, as judged by particle-size measurements.