Interprofessional attitudes and perceptions: Results from a longitudinal controlled trial of pre-registration health and social care students in Scotland.

This study made use of a controlled longitudinal design to assess the impact on pre-registration health and social care students of an interprofessional intervention on the attitudes to and perceptions of interprofessional ideals. Evaluation, over four years, of Nursing, Occupational Therapy, Podiatry, Prosthetics and Orthotics, Physiotherapy and Radiography students was performed using the adapted versions of the Readiness for Interprofessional Learning Scale (RIPLS) and the Interdisciplinary Education Perception Scale (IEPS). Baseline samples of the control and experimental groups were 260 and 313 respectively. Support for Interprofessional Education (IPE) appears high but possibly idealistically so initially. Restricted Maximum Likelihood (REML) models were used to assess intervention effects as well as any possible profession or time effects. The intervention was found to have had a significant effect on five of the measured sub-scales and the professions were found to react in a significantly different way on four of the sub-scales. The inclusion of a control group has confirmed previous findings from other studies but also highlights the possible effects of the general learning and teaching methodologies employed within various professions as well as the need for research into the influence of the timing, duration, style and content of clinical placement periods.

Requirement of borate cross-linking of cell wall rhamnogalacturonan II for Arabidopsis growth.

Turgor-driven plant cell growth depends on wall structure. Two allelic l-fucose-deficient Arabidopsis thaliana mutants (mur1-1 and 1-2) are dwarfed and their rosette leaves do not grow normally. mur1 leaf cell walls contain normal amounts of the cell wall pectic polysaccharide rhamnogalacturonan II (RG-II), but only half exists as a borate cross-linked dimer. The altered structure of mur1 RG-II reduces the rate of formation and stability of this cross-link. Exogenous aqueous borate rescues the defect. The reduced cross-linking of RG-II in dwarf mur1 plants indicates that plant growth depends on wall pectic polysaccharide organization.

A calorimetric study of dimyristoylphosphatidylcholine phase transitions and steroid-liposome interactions for liposomes prepared by thin film and proliposome methods.

Using high sensitivity differential scanning calorimetry (HSDSC), the phase transitions of dimyristoylphosphatidylcholine (DMPC) liposomal bilayers and their interaction with the model steroid beclomethasone dipropionate (BDP) were found to be dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no phospholipid pretransition, a main transition of high enthalpy and a low onset temperature, and a very low incorporation of the steroid (maximum 1 mol%). This was attributed to an alcohol-induced interdigitation of the bilayers, which was not apparently reversed by flushing the liposome dispersion with nitrogen in an attempt to remove ethanol. For liposomes manufactured by thin film or particulate-based proliposome methods, 1-2.5 mol% steroid was optimal for incorporation within bilayers, although the nature of the steroid interaction with the bilayers differed between the two methods. For liposomes manufactured by the thin film method, a higher steroid concentration resulted in a broadened main transition and a reduced melting cooperativity. This suggests that BDP formed separate domains within the bilayers which caused non-ideal mixing and phase separation at 5 mol% steroid. This observation was absent for liposomes generated from particulate-based proliposomes, indicating separate steroid domains were not formed and subsequent non-ideal mixing and phase separation did not occur. In addition, liposomes generated from particulate-based proliposomes showed reduced pretransition and main transition enthalpies. These differences were attributed to the employment of sucrose to manufacture the particulate-based proliposomes. This study has shown that the thermal behaviour of liposomes and their interaction with beclomethasone dipropionate were dependent on the method of liposome manufacture. Moreover, particulate-based proliposomes may provide a reasonable alternative to the conventional thin film method in producing liposomes incorporating this steroid.

Recent developments for the analysis of data obtained from isothermal calorimetry.

Isothermal calorimetry is rapidly becoming an indispensable tool for the quantitative determination of a variety of kinetic and thermodynamic parameters for a wide range of systems. In particular calorimetry is finding increased application to the investigation of stability and incompatibility of pharmaceutical materials. In order to draw meaningful conclusions and to predict behaviour in related systems it is necessary to have the means to calculate accurately parameters such as the rate constant and enthalpy. To this end several groups have been developing equations which describe calorimetric output in these terms. This paper will briefly outline some of these equations and discuss some of the limitations that currently exist in their application. A particular emphasis is placed on the recent developments relating to the application of these equations to flow calorimetric data. The main application of these equations is usually found in the pharmaceutical industry. Pharmaceutical formulations are usually extremely complex mixtures consisting of many different excipients as well as the active drug. Because of these large numbers of ingredients it is often observed that multiple chemical and physical process occur over the lifetime of the study. This complexity is then reflected in the calorimetric data rendering the application of the simple equations useless. Dealing with this complexity is a major issue amongst the calorimetric community and some of the recent advances in this field are also discussed.

Pectins: structure, biosynthesis, and oligogalacturonide-related signaling.

Pectin is a family of complex polysaccharides present in all plant primary cell walls. The complicated structure of the pectic polysaccharides, and the retention by plants of the large number of genes required to synthesize pectin, suggests that pectins have multiple functions in plant growth and development. In this review we summarize the current level of understanding of pectin primary and tertiary structure, and describe new methods that may be useful to study localized pectin structure in the plant cell wall. We also discuss progress in our understanding of how pectin is biosynthesized and review the biological activities and possible modes of action of pectic oligosaccharides referred to as oligogalacturonides. We present our view of critical questions regarding pectin structure, biosynthesis, and function that need to be addressed in the coming decade. As the plant community works towards understanding the functions of the tens of thousands of genes expressed by plants, a large number of those genes are likely to be involved in the synthesis, turnover, biological activity, and restructuring of pectin. A combination of genetic, molecular, biochemical and chemical approaches will be necessary to fully understand the function and biosynthesis of pectin.

Isolation and structural characterization of beta-D-glucosyluronic acid and 4-O-methyl beta-D-glucosyluronic acid-containing oligosaccharides from the cell-wall pectic polysaccharide, rhamnogalacturonan I.

Rhamnogalacturonan I (RG-I), a pectic polysaccharide isolated from the walls of suspension-cultured sycamore cells, was shown by glycosyl-residue composition analysis to contain D-glucosyluronic acid (GlcpA) residues (1 mol%) and 4-O-methyl-D-glucosyluronic acid (4-O-Me-GlcpA) residues (0.5 mol%). These monosaccharides were shown, by glycosyl-linkage analysis, to be present in RG-I as terminal nonreducing residues. The glycosyl sequences containing GlcpA and 4-O-Me-GlcpA were determined by structurally characterizing the acidic oligosaccharides released by partial acid hydrolysis of RG-I. Six acidic oligosaccharides were purified by semipreparative high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) and characterized by glycosyl-residue and glycosyl-linkage composition analyses, GLC-CIMS, GLC-EIMS, electrospray MS (ESMS), and 1H NMR spectroscopy. We propose that three of the acidic oligosaccharides characterized, 4-O-Me-beta-D-GlcpA-(1-->6)-D-Gal, beta-D-GlcpA-(1-->6)-D-Gal, and beta-D-GlcpA-(1-->4)-D-Gal, originate from the galactosyl-containing side chains of RG-I. The three other acidic oligosaccharides characterized, alpha-D-GalpA-(1-->2)-L-Rha, alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalpA+ ++-(1-->2)-alpha-L-Rha, and alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-->4)-alpha-D-GalpA+ ++-(1-->2)-alpha-L- Rhap-(1-->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rha, were generated by partial hydrolysis of the RG-I backbone. No evidence was obtained for the presence of galactosyluronic acid in the side chains of RG-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural characterization of endo-glycanase-generated oligoglycosyl side chains of rhamnogalacturonan I.

Rhamnogalacturonan I (RG-I) has been isolated from the walls of suspension-cultured sycamore cells (Acer pseudoplatanus), and additional structural features of the polysaccharide were elucidated. Treatment of RG-I with a purified endo-(1-->5)-alpha-L-arabinanase released a series of arabinose-containing oligosaccharides with degrees of polymerization (dp's) between 2 and 20. These oligosaccharides were shown, by glycosyl-linkage composition analysis, to contain terminal, 5-, and (3-->5)-linked Araf residues. These results provide evidence that a branched arabinan is attached to the backbone of RG-I. RG-I was freed of 95% of its arabinosyl residues by treating the polysaccharide with a combination of endo-(1-->5)-alpha-L-arabinanase and alpha-L-arabinosidase. No galacturonic acid was released by these enzymes, which is evidence that the arabinosyl-containing portions of the side chains do not contain galactosyluronic acid residues. The galactose-containing portions of the side chains of RG-I were not fragmented by an endo-(1-->4)-beta-D-galactanase. However, approximately 85% of the galactose and small amounts of galacturonic acid were released by digestion of arabinose-depleted RG-I with a combination of endo- and exo-beta-D-galactanases. The galacturonic acid may have been released by small amounts of an exo-alpha-galactosyluronidase contaminating the galactanases. Treatment of RG-I with this mixture of endo- and exo-glycanases resulted in a relatively size-homogeneous, almost side chain-free backbone composed of the O-acetylated diglycosyl repeating unit -->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap. A combination of 1H NMR spectroscopy and periodate oxidation established that the backbone repeating unit contained a single O-acetyl substituent on C-2 or C-3 of each galactosyluronic acid residue.

Evidence that the acidic polysaccharide secreted by Agrobacterium radiobacter (ATCC 53271) has a seventeen glycosyl-residue repeating unit.

The extracellular anionic polysaccharide produced by the bacterium Agrobacterium radiobacter (ATCC 53271) contains D-galactose, D-glucose, and pyruvic acid in the molar ratio 2:15:2. Analysis of the methylated polysaccharide indicated the presence of terminal, non-reducing glucosyl, 3-, 4-, 6-, 2,4-, and 4,6-linked glucosyl residues, 3-linked 4,6-O-[(S)-1-carboxyethylidene]glucosyl residues, and 3-linked galactosyl residues. Partial acid hydrolysis of the methylated polysaccharide, followed by reduction with NaB2H4 and then O-ethylation, gave a mixture of alkylated oligoglycosyl alditols that were separated by reversed-phase h.p.l.c. and analyzed by 1H-n.m.r. spectroscopy, g.l.c.-m.s., and glycosyl-linkage composition analysis. Smith degradation of the polysaccharide gave three diglycosyl alditols that were separated by semi-preparative, high-pH anion-exchange chromatography, and were analyzed by 1H-n.m.r. spectroscopy, g.l.c.-m.s., and glycosyl-linkage composition analysis. The polymer obtained by NaBH4 reduction of the periodate-oxidized polysaccharide was methylated, and the noncyclic acetals were hydrolyzed with aq. 90% formic acid to generate a mixture of partially O-methylated mono- and di-glycosyl alditols. The partially O-methylated oligoglycosyl alditols were O-ethylated. The resulting alkylated oligoglycosyl alditols were separated by reverse-phase h.p.l.c. and then characterized by 1H-n.m.r. spectroscopy, g.l.c.-m.s., and glycosyl-linkage composition analysis. The results from the studies described here provide strong evidence that the acidic polysaccharide secreted by A. radiobacter (ATCC 53271) has a heptadecasaccharide repeating unit.

Structure of the extracellular gelling polysaccharide produced by Enterobacter (NCIB 11870) species.

The gelling polysaccharide produced by a species of Enterobacter (NCIB 11870) contains L-fucose, D-glucose, and D-glucuronic acid in the ratios 1:2:1. Analysis of the methylated and methylated, carboxyl-reduced polysaccharide revealed terminal non-reducing glucose, (1----3)-linked fucose, (1----3,1----4)-linked glucose, and (1----4)-linked glucuronic acid in the ratios 1:1:1.2:0.8. From the results of Smith degradation of the polysaccharide and spectroscopic studies of the acidic tetra- and octa-saccharides produced by bacteriophage-induced enzymic depolymerization of the polysaccharide, the following tetrasaccharide repeating-unit is proposed. (Formula: see text). This repeating-unit is identical to that of the capsular polysaccharide produced by Klebsiella aerogenes serotype K54 except for the absence of O-acetyl groups. The effects of the O-acetyl groups on the secondary structure and rheological properties of these polysaccharides are discussed.

Isolation and structural characterization of endo-rhamnogalacturonase-generated fragments of the backbone of rhamnogalacturonan I.

A combination of commercially available preparations of Aspergillus niger beta-D-galactosidase, endo-alpha-L-arabinanase, alpha-L-arabinosidase, and endo-beta-D-galactanase has been used to generate oligoglycosyl fragments of the backbone of rhamnogalacturonan I (RG-I) that had been isolated from the walls of suspension-cultured sycamore cells. The backbone-cleaving enzyme, which is present in the beta-D-galactosidase preparation, only fragments the RG-I backbone when many of the neutral oligoglycosyl side chains have been removed by the other exo- and endo- glycanases. The oligosaccharides released from the backbone were separated from the partially fragmented RG-I and then purified, as their oligoglycosyl aldonic acids, by HPAEC-PAD. Those backbone fragments with degrees of polymerization (dp's) between 2 and 11 were characterized using one- and two-dimensional 1H NMR spectroscopy, electrospray mass spectrometry, and glycosyl-residue and glycosyl-linkage composition analyses. Two series of oligoglycosyl fragments were identified. The quantitatively predominant series has the structure alpha-D-GalpA-(1 --> 2)- alpha-L-Rhap-[ --> 4)-alpha-D-GalpA-(1 --> 2)-alpha-L-Rhap-(1 --> ]n-4-D-GalpA, and the quantitatively minor series has the structure alpha-L-Rhap-[ --> 4)-alpha-D-GalpA-(1 --> 2)-alpha-L-Rhap-(1 --> ]n-4-D- GalpA (n = 1-5). Thus, the enzyme preparations contain an alpha-L-rhamnosidase in addition to the endo- rhamnogalacturonase. The products of the endo-rhamnogalacturonase provide additional evidence that the backbone of RG-I is composed of the diglycosyl repeating unit: --> 4)-alpha-D-GalpA-(1 --> 2)-alpha-L-Rhap- (1 -->. The endo-rhamnogalacturonase from the A. niger beta-D-galactosidase preparation and the endo- rhamnogalacturonase secreted by Aspergillus aculeatus [H.A. Schols et al. Carbohydr. Res., 206 (1990) 117-129] have the same substrate specificities and generate similar oligoglycosyl fragments.

Structural characterization of the pectic polysaccharide, rhamnogalacturonan-II.

An octasaccharide was released from sycamore cell wall rhamnogalacturonan-II (RG-II) by selective acid hydrolysis of the glycosidic linkages of apiosyl residues and purified to homogeneity by gel-permeation and high-performance anion-exchange chromatographies. The octasaccharide 1 contains a terminal nonreducing beta-L-arabinofuranosyl residue linked to position 2 of the alpha-L-rhamnopyranosyl residue of the aceric acid-containing heptasaccharide 2 that had been previously isolated from RG-II [M.W. Spellman et al. Carbohydr. Res., 122 (1983) 131-153]. Heptasaccharide 2 and octasaccharide 1 were found to be mono- or di-O-acetylated. The O-acetyl groups were located, by ESMSMS, on the terminal nonreducing 2-O-methyl-alpha-L-fucosyl residue and/or on the 2-linked beta-L-aceryl acid residue. Octasaccharide 1 and heptasaccharide 2 have the following structures: [structure: see text]

Structural characterization of red wine rhamnogalacturonan II.

The pectic polysaccharide rhamnogalacturonan II (RG-II), which accounts for approximately 20% of the ethanol-precipitable polysaccharides in red wine, has been isolated from wine polysaccharides by anion-exchange chromatography. Four fractions enriched with RG-II were obtained and the RG-II then purified to homogeneity by Concanavalin A affinity and size-exclusion chromatographies. The glycosyl-residue compositions of the four RG-IIs are similar; all the RG-IIs contain the monosaccharides (apiose, 2-O-methyl-L-fucose, 2-O-methyl-D-xylose, Kdo, Dha, and aceric acid) that are diagnostic of RG-II. The glycosyl-linkages of the neutral and acidic sugars, including aceric acid, were determined simultaneously by GC-EIMS analysis of the methylated alditol acetates generated from per-O-methylated and carboxyl-reduced RG-II. Two of the RG-IIs contain boron, most likely as a borate di-ester that cross-links two molecules of RG-II together to form a dimer. The dimer contains 3'- and 2,3,3'-linked apiosyl residues whereas the monomer contains only 3'-linked apiosyl residues which suggests that the borate di-ester is located on at least one of the apiosyl residues of RG-II. Although the wine RG-IIs all have similar structures they are not identical since they differ in the length and degree of methyl-esterification of the RG-II backbone and in the presence or absence of borate di-esters. Nevertheless, these studies show that the major structural features of wine and primary cell wall RG-II are conserved.

Structural analysis of an acidic polysaccharide secreted by Xanthobacter sp. (ATCC 53272).

The structure of an acidic polysaccharide secreted by a Xanthobacter sp. has been investigated by glycosyl-residue and glycosyl-linkage composition analyses, and the characterization of oligoglycosyl fragments of the polysaccharide has been carried out by chemical analyses, 1H-n.m.r. spectroscopy, fast-atom bombardment mass spectrometry, and electron-impact mass spectrometry. The polysaccharide, which contains O-acetyl groups (approximately 5%) that have not been located, has the tetraglycosyl repeating unit 1 and belongs to a group of structurally related polysaccharides synthesized by both Alcaligenes and Pseudomonas species.

Structural characterization of the pectic polysaccharide rhamnogalacturonan II: evidence for the backbone location of the aceric acid-containing oligoglycosyl side chain.

Monomeric rhamnogalacturonan II (mRG-II) was isolated from red wine and the reducing-end galacturonic acid of the backbone converted to L-galactonic acid by treatment with NaBH4. The resulting product (mRG-II'ol) was treated with a cell-free extract from Penicillium daleae, a fungus that has been shown to produce RG-II-fragmenting glycanases. The enzymatically generated products were fractionated by size-exclusion and anion-exchange chromatographies and the quantitatively major oligosaccharide fraction isolated. This fraction contained structurally related oligosaccharides that differed only in the presence or absence of a single Kdo residue. The Kdo residue was removed by acid hydrolysis and the resulting oligosaccharide then characterized by 1- and 2D 1H NMR spectroscopy, ESMS, and by glycosyl-residue and glycosyl-linkage composition analyses. The results of these analyses provide evidence for the presence of at least two structurally related oligosaccharides in the ratio approximately 6:1. The backbone of these oligosaccharides is composed of five (1-->4)-linked alpha-D-GalpA residues and a (1-->3)-linked L-galactonate. The (1-->4)-linked GalpA residue adjacent to the terminal non-reducing GalpA residue of the backbone is substituted at O-2 with an apiosyl-containing side chain. Beta3-L-Araf-(1-->5)-beta-D-DhapA is likely to be linked to O-3 of the GalpA residue at the non-reducing end of the backbone in the quantitatively major oligosaccharide and to O-3 of a (1-->4)-linked GalpA residue in the backbone of the minor oligosaccharide. Furthermore, the results of our studies have shown that the enzymically generated aceryl acid-containing oligosaccharide contains an alpha-linked aceryl acid residue and a beta-linked galactosyl residue. Thus, the anomeric linkages of these residues in RG-II should be revised.

Ultrastructural aspects of the microvasculature of the cochlea: the internal spiral network.

We performed a study of the microvasculature of the cochlea with scanning electron microscopy on corrosion casts in the guinea pig. This study was performed in 140 cochleas from healthy adult guinea pigs. Different microvascular techniques were used, including injection-microdissection in 53 cases, injection-diaphanization in 27 cases, a histologic technique in 34 cases, injection-microdissection-diaphanization in 32 cases, and scanning electron microscopy on corrosion casts in 14 cases. The internal radiating arterioles branch off as collateral branches of the spiral modiolar artery, as first-order collateral branches. We detail the morphology, caliber, trajectory, and collateral branches. Among their collateral branches, are third-order arterioles, the arterioles to the spiral ganglia, and the arterioles of the tympanic lip. The arterioles of the tympanic lip form, through their anastomosis, a rich capillary network at the edge of the spiral lamina, called the internal spiral network. We emphasize the glomeruli of Schwalbe, which arise near the scala tympani as third-order arterioles with a medium caliber of 14 microm. The upper glomeruli, situated in the bony wall, and the lower glomeruli, situated in the width of the osseous spiral lamina, form vascular loops made of anastomosed capillaries with a caliber of less than 10 microm. These loops play an important role as efficient devices, or "relay stations," for regulation of cochlear blood flow. The comparison of results obtained with each technique gave the perspective of the cochlear microvasculature with great accuracy.

Health as an irreversible part of the welfare state: Canadian government policy under the Tories.

This article provides an assessment of the health policy of the Canadian Conservative government under Brian Mulroney, 1984-1993. Underlying this assessment is the need to test the theory of the irreversibility of the welfare state in the light of its health component. The author argues that despite a political rhetoric that might have presaged a sharp rollback of Canada's Medicare, either through residualization or progressive commodification, Canada emerged from this period of New Right federal government with its state-funded health care system still in place. This argument is substantiated through a consideration of the social policy model inherited by the Mulroney government and how it was affected by the government's fiscal policies between 1984 and 1993.

Does usnic acid affect microtubules in human cancer cells?

Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 microM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.