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Biomedical subjects

N Foster

Publications and source records attributed to N Foster.

At least 37 records · Page 2Linked to original sources

Immunocytochemical detection of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides in the nervous system and the excretory system of adult Nippostrongylus brasiliensis.

Vasoactive intestinal peptide-like and peptide histidine isoleucine-like immunoreactivities were detected in the excretory duct of adult male and female Nippostrongylus brasiliensis, thus indicating the source of these two physiologically active peptides previously isolated from the excretory/secretory products of adult N. brasiliensis. In the nervous system immunoreactivity to both these peptides was confined to females and was found in the neurons of the ovijector associated ganglion. This is consistent with co-synthesis of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides which has also been shown to occur in all mammalian vasoactive intestinal peptid-ergic neurons studied to date. However, in addition to this, and in common to some previous studies on helminth vasoactive intestinal peptide and peptide histidine isoleucine immunoreactivities, co-synthesis of the peptides was not indicated in a pair of branched neurons which projected posteriorly and peripherally from the ganglion associated with the ovijector of females and which terminated in two pairs of ganglia also exhibiting vasoactive intestinal peptide-like immunoreactivity only. The position of these ganglia indicated that they innervate muscles close to the body wall and may be responsible for the muscular contractions required for expulsion of eggs from female Nippostrongylus brasiliensis. This is also the first study to successfully detect these peptides in the excretory system of gastrointestinal nematodes.

Animals↗

Ulex europaeus 1 lectin targets microspheres to mouse Peyer's patch M-cells in vivo.

The interaction of latex microspheres with mouse Peyer's patch membranous M-cells was studied in a mouse gut loop model after the microspheres were coated with a variety of agents. Carboxylated microspheres (diameter 0.5 micron) were covalently coated with lectins Ulex europaeus 1, Concanavalin A, Euonymus europaeus and Bandeiraea simplicifolia 1 isolectin-B4, human immunoglobulin A or bovine serum albumin. Of the treatments examined, only Ulex europaeus (UEA1) resulted in significant selective binding of microspheres to M-cells. UEA1-coated microspheres bound to M-cells at a level 100-fold greater than BSA-coated microspheres, but binding to enterocytes was unaffected. Incubation of UEA1-coated microspheres with alpha-L-fucose reduced M-cell binding to a level comparable with BSA-coated microspheres. This indicated that targeting by UEA1 was via a carbohydrate receptor on the M-cell surface. Adherence of UEA1-coated microspheres to M-cells occurred within 10 min of inoculation into mouse gut loops and UEA1-coated microspheres were transported to 10 microns below the apical surface of M-cells within 60 min of inoculation. UEA1-coated microspheres also targeted mouse Peyer's patch M-cells after intragastric administration. These results demonstrated that altering the surface chemistry of carboxylated polystyrene microspheres increased M-cell targeting, suggesting a strategy to enhance delivery of vaccine antigens to the mucosal immune system.

Analysis of Variance↗

Transitional care: bridging the gap.

As hospitals redesign into integrated delivery systems, new services and linkages to support patients across the care continuum become necessary. The implementation and outcomes of a transitional care program are discussed and evaluated.

Continuity of Patient Care↗

A vasoactive intestinal polypeptide-like protein excreted/secreted by Nippostrongylus brasiliensis and its effect on contraction of uninfected rat intestine.

The 50-30 kDa fraction isolated from the excretory/secretory products (E/S) of the nematode Nippostrongylus brasiliensis significantly decreased the amplitude of contraction of segments of uninfected rat intestine when injected into the lumen of the segments maintained in an organ bath. Dot blot analysis of the fraction suggested that it was similar in immunoreactivity to porcine vasoactive intestinal polypeptide (VIP). When antiserum to porcine VIP was mixed with N. brasiliensis E/S and the mixtures were injected into the lumen of segments of rat intestine, the inhibitory effect of the E/S on amplitude of contraction decreased. When physiological concentrations of porcine VIP (12.9 pmol/ml) were injected into the lumen of segments of uninfected rat intestine the amplitude of contraction decreased significantly. Western blot analysis of the E/S, using antiserum to porcine VIP, recognized a 30 kDa protein in the E/S and also in whole worm homogenate suggesting that synthesis of the peptide occurs inside the nematode. Peptide histidine isoleucine (PHI)-like immunoreactivity was detected in a 68 kDa fraction of the E/S and the homogenate but this fraction did not affect the amplitude of contractions of the intestine.

Animals↗

Vasoactive intestinal polypeptide-like and peptide histidine isoleucine-like proteins excreted/secreted by Nippostrongylus brasiliensis, Nematodirus battus and Ascaridia galli.

Vasoactive intestinal polypeptide (VIP)-like protein was detected by dot blot analysis in the excretions/secretions (E/S) of Nematodirus battus and Ascaridia galli and was confirmed in the E/S of Nippostrongylus brasiliensis. ELISA analysis showed that N. brasiliensis E/S contained the highest proportion of VIP-like protein (28.04 pmoles/mg of total E/S protein) and A. galli E/S contained the lowest (10.89 pmoles/mg of total E/S protein). Peptide histidine isoleucine (PHI)-like protein was detected by dot blot analysis in the E/S products of N. brasiliensis, N. battus and A. galli. ELISA analysis suggested that A. galli E/S contained the highest proportion of PHI (20.77 nmoles/mg of total E/S protein) and N. battus E/S contained the lowest (0.67 nmoles/mg of total E/S protein). The possible significance of VIP-like and PHI-like substances in the E/S of gastrointestinal nematodes is discussed.

Animals↗

Targeting to intestinal M cells.

The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of murine intestine have also been demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specificity for rabbit or rat Peyer's patch M cells. Knowledge of human M cells is limited and no lectin has yet been identified with specificity for these cells. However, at least one lectin exhibits binding specificity for FAE in the human ileum. In the future, knowledge of the regional patterns of M cell carbohydrate expression within a species may allow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.

Administration, Oral↗

Isolation, characterization and protection studies in mice of a streptomycin-dependent mutant of Streptococcus suis type 1/2.

An avirulent, streptomycin-dependent (Str-D) mutant of Streptococcus suis type 1/2 was produced and characterized by its antimicrobial susceptibility, growth kinetics, biochemical reactions and reversion rate. Homologous and heterologous vaccine trials in mice resulted in complete protection against challenge with S. suis types 1 and 1/2 and partial protection against challenge with S. suis type 2.

Animals↗

The effect of homogenates and excretory/secretory products of Nippostrongylus brasiliensis and of acetylcholinesterase on the amplitude and frequency of contraction of uninfected rat intestine in vitro.

Whole worm homogenates and excretory/secretory (E/S) products of adult Nippostrongylus brasiliensis significantly decreased the amplitude of contractions of segments of uninfected rat intestine maintained in an organ bath, with significantly larger volumes of E/S products being required to bring about a similar decrease to that caused by the whole worm homogenate. Boiled samples of homogenate and E/S products significantly decreased the amplitude of contractions of uninfected rat intestine, but larger volumes were needed than with unboiled samples. Frequency of contraction was unaltered by homogenates or E/S products. When electric eel AChE was injected into the lumen of segments of uninfected rat intestine maintained in an organ bath there was no significant decrease in the amplitude of contractions. These results suggest that substances present in the E/S products of N. brasiliensis significantly reduce the amplitude of contractions of uninfected rat intestine in vitro and that the biochemical holdfast responsible for this phenomenon may not be AChE.

Acetylcholinesterase↗

Development of the National Marine Mammal Tissue Bank.

The National Marine Mammal Tissue Bank (NMMTB) has been established as part of a comprehensive effort to obtain reliable information on contaminant levels in marine mammal tissues. A four component program consisting of the NMMTB, stranding networks, monitoring and quality assurance has been developed. The development and current status of the NMMTB and its relationship to the other three components will be described.

Animals↗

Longitudinal sensitivity of the Fuld cholinergic profile to Alzheimer's disease.

The diagnostic sensitivity of a profile (Fuld, 1984) thought to mark cholinergic changes in Alzheimer's Disease (AD) was examined in a sample of 53 patients meeting criteria for AD on two occasions and in 19 patients for three occasions. The low obtained sensitivities of the Fuld profile (17%-26%) across testings is consistent with previous studies that used a single time point. The findings also revealed unstable positive and negative profiles over time. There were no performance differences on intellectual or memory measures when comparing subjects identified as positive or negative by the Fuld index. The results demonstrate that the index is insensitive to the dementing process and is a poor diagnostic marker for AD.

Aged↗

Determination of the relative amounts of free and complexed manganese ions in aqueous solution by nuclear magnetic resonance.

The ratio of the transverse relaxation rate to the longitudinal relaxation rate of water protons (T1/T2) at 90 MHz can be used to determine the relative amounts of free Mn2+ ions (the hexaquo ion) and chelated manganese ions when both species are present in the same aqueous solution. This technique is demonstrated for simple aqueous solutions containing known concentrations of both the free Mn2+ ion and a manganese(III) porphyrin. The accuracy of the method is found to be +/- 7.3% for the solutions considered in this report. The determinations of the relative amounts of the free Mn2+ ion and the manganese(III) porphyrin by this T1/T2 method are shown to agree well with those determined by nuclear magnetic resonance dispersion profiles. The theoretical basis of this ratio method as well as the scope and limitations in its application to aqueous solutions containing both free Mn2+ ions and chelated manganese species other than manganese(III) porphyrins are also discussed. This work demonstrates a unique use of NMR as a means for the quantitative analysis of manganese in which the effects of the metal ion on the solvent, and not the metal itself, are observed.

Magnetic Resonance Spectroscopy↗

Dilemmas surrounding the identification of essential rural hospitals.

Criteria are needed for use in designating some rural hospitals as essential so that they may receive state or federal assistance. Three types of criteria are considered in this analysis: hospital volume measures, hospital competitiveness measures, and community need measures. The criteria sets reflect different assumptions about the relationship between need and demand for health services. Analysis of available data reveals that neither hospital volume nor competitiveness is correlated with community need, meaning that different hospitals would be designated as essential under each system. Implications are discussed.

Bed Occupancy↗

Studies of interactions of porphyrins with transfer RNA by high-resolution NMR.

The interactions of tetra-4N-methylpyridyl porphyrin and its zinc(II), copper(II) and manganese(III) complexes with brewer's yeast type V phenylalanine specific tRNA have been evaluated by high-resolution NMR. Differences in chemical shifts have been noted for three proton resonances in response to the presence of small quantities of the free base and the zinc and copper complexes. The protons giving rise to these signals are located on bases T54 and psi 55, both of which are involved in the primary intraloop and interloop hydrogen bonds that hold the D and T psi C loops together in the tertiary structure. In addition, broadening of specific resonances due to hydrogen bonding protons in the D stem at low ratios of porphyrin to tRNA indicates that the association of porphyrins increases the rate of imino proton exchange. The titration of the tRNA with the manganese(III) complex did not reveal shifts or specific broadening comparable to the other porphyrins at low ratios. The changes induced in the NMR spectrum of tRNA by porphyrins define their site of interaction with the polynucleotide. This site, at the outside of the elbow-bend in the tRNA 'L', is different from the locus of binding in tRNA for other classical DNA intercalators. Furthermore, a new mode of binding may be involved that is neither intercalative nor simply electrostatic.

Binding Sites↗

Analysis of the structure of synthetic and natural melanins by solid-phase NMR.

The structures of one synthetic and two natural melanins are examined by solid-state NMR using cross polarization, magic angle sample spinning, and high-power proton decoupling. The structural features of synthetic dopa melanin are compared to those of melanin from malignant melanoma cells grown in culture and sepia melanin from squid ink. Natural abundance 13C and 15N spectra show resonances consistent with known pyrrolic and indolic structures within the heterogeneous biopolymer; 13C spectra indicate the presence of aliphatic residues in all three materials. These solid-phase experiments illustrate the promise of solid-phase NMR for elucidating structural information from insoluble biomaterials.

Animals↗

Interactions of porphyrins and transfer RNA.

The interactions of the free base porphyrin, tetra-(4N-methylpyridyl)porphyrin and its copper(II), manganese(III) and zinc(II) complexes with brewer's yeast type V phenylalaninyl tRNA were evaluated by UV-visible spectroscopy, circular dichroism and melting temperature studies over a range of magnesium ion concentrations and ionic strengths. Scatchard analysis of absorption spectra of the porphyrins in the presence of tRNA showed the free base, copper and zinc porphyrins to have binding constants of 7.3 X 10(7), 1.7 X 10(6) and 2.3 X 10(8), respectively; the manganese(III) complex did not demonstrate changes in its electronic spectra that enable the calculation of a binding constant. The results of the spectroscopic studies indicate a mode of binding for the free base, copper(II) and zinc(II) complexes that is neither intercalative nor simply outside electrostatic. The magnitude of the binding constants and the UV-visible results support intercalation, but the analyses of the thermal denaturation studies and the circular dichroism evaluations suggest that the porphyrins are associating at a single site in a fold of the tertiary structure of the tRNA close to several crucial hydrogen bonds, perhaps in the vicinity of the P10 loop. That the manganese(III) complex does not bind in this site points to constraints on the axial thickness of a molecule that may be accommodated in this locus.

Cations, Divalent↗

Relation of EEG alpha background to parietal lobe function in Alzheimer's disease as measured by positron emission tomography and psychometry.

Fourteen patients with Alzheimer's disease were evaluated by psychometric testing, fluorodeoxyglucose positron emission tomography (PET), and EEG. They were divided into two groups according to the EEG findings. Group A (seven patients) had normal alpha backgrounds and group B (seven patients) had decreased alpha backgrounds. Group A had significantly higher WAIS Performance IQ scores (p = 0.005) than group B. Group A also had higher Weschler Memory Scale scores (p = 0.047) and parietal glucose metabolic rates (p = 0.038) than group B, but these differences are not statistically significant given the multiple comparisons made between the two groups. Relative intactness of parietal lobe function, as measured by psychometric testing and PET, appears to correlate with preservation of EEG alpha background. The EEG may be useful in assessing regional cortical involvement or the clinical stage in Alzheimer's disease.

Aged↗

Separation of metalloporphyrins from metallation reactions by liquid chromatography and electrophoresis.

The analytical separation of the indium and manganese complexes of three synthetic, meso-substituted, water-soluble porphyrins from their respective free bases in metallation reaction mixtures is described. The ligands tetra-3N-methylpyridyl porphyrin, tetra-4N-methylpyridyl porphyrin and tetra-N,N,N-trimethylanilinium porphyrin are complexed with In (III) and Mn (III) and are separated from residual free base by high-performance liquid chromatography (HPLC) in acidic conditions with gradient elution on ODS bonded stationary phase. Electrophoretic separation is achieved on both cellulose polyacetate strips and polyacrylamide tube gels under basic conditions. Although analytical separations can be achieved by both HPLC and electrophoresis, only HPLC is suitable for the development of preparative scale separations. Column chromatography, ion-pairing and ion-suppression HPLC techniques fail to separate such highly charged and closely related aromatic compounds.

Chemical Phenomena↗

Superinduction of T lymphocyte-endothelial cell (EC) binding by treatment of EC with interleukin 1 and protein synthesis inhibitors.

We have previously reported that marked enhancement of the in vitro binding of lymphocytes to endothelial cell (EC) monolayers is observed after stimulation of the EC with interleukin 1 (IL 1). To determine whether new protein synthesis was required for this effect of IL 1, EC were incubated with IL 1 in the presence of cycloheximide or puromycin. Three different effects of these protein synthesis inhibitors on T-EC binding were observed. First, preincubation of the EC with both IL 1 and an inhibitor blocked the increase in binding if the inhibitor was present during both the preincubation and the 1 hr duration of the T-EC binding assay, suggesting that new protein synthesis is required for the enhancement of T-EC adhesion by IL 1. Second, preincubation of the EC with low doses of the inhibitors (0.1 to 1 microgram/ml) in the absence of IL 1 consistently increased T-EC binding, even if the inhibitors were present during the T-EC adhesion assay; in addition, the inhibitors additionally increased the stimulatory effect of IL 1 if the EC were washed free of the inhibitor before the assay step. The binding-enhancing effect of low concentrations of cycloheximide could be inhibited by an antibody to the CDw18 complex on the T cell, suggesting an up-regulation of the ligand on the EC involved in CDw18-dependent T cell adhesion. Third, higher concentrations of the inhibitors (3 to 10 micrograms/ml) were toxic for the EC in the presence of IL 1, possibly due to the combined blocking effect of IL 1 and inhibitors on EC protein synthesis.

Antigens, Surface↗