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Biomedical subjects

P Hodge

Publications and source records attributed to P Hodge.

At least 19 recordsLinked to original sources
PubMed2000

Sulfone-linked paracyclophanes via macrocyclic aromatic thioethers: synthetic and structural investigations.

Reaction of 4,4'-sulfonylbis(benzenethiol) with 4,4'-dichlorodiphenylsulfone under pseudo-high-dilution conditions leads to macrocyclic thioethersulfones [-S-Ar-SO2-Ar-]n (Ar = 1,4-phenylene). These include a highly strained [1+1] cyclodimer (n = 2), a cyclotrimer resulting from thioetherexchange reactions, and a [2+2] cyclotetramer which can adopt two entirely different conformations in the crystalline state, one having molecular D2d ("tennis-ball-seam") symmetry. The same type of reaction is successful using 4,4'-thiobis(benzenethiol) instead of 4,4'-sulfonylbis(benzenethiol) and affords macrocycles with a higher ratio of thioether to sulfone linkages. Exhaustive oxidation of macrocyclic thioethersulfones with hydrogen peroxide affords a series of sulfone-linked paracyclophanes, [-Ar-SO2-]4, [-Ar-SO2-]6, [-Ar-SO2-]8 and [-Ar-SO2-]12. Single crystal X-ray analysis reveals [Ar-SO2-]4 to be a near-perfect square box, whilst the cyclic hexamer [-Ar-SO2-]6 adopts a much more irregular conformation. and [-Ar-SO2-]8 displays a "double-box" structure clearly related to that of [Ar-SO2-]4.

Journal Article↗
PubMed1999

Relative proportions of mononuclear cell types in periodontal lesions analyzed by immunohistochemistry.

In this study, we investigated the relative proportions of infiltrating mononuclear inflammatory cells in sections of granulation tissue from periodontitis lesions in both adult periodontitis (AP) and early onset periodontitis (EOP) patients. We utilised a set of cluster of differentiation (CD) antigen-specific monoclonal antibodies to detect different cell types within the tissues. These included anti-CD 20 (B cells), anti-CD 3 (pan T cells) and anti-CD 45RO (memory T cells), anti-CD 4 (helper T cells) anti-CD 8 (suppressor T cells) and anti-CD 68 (monocyte/macrophage). Biopsies of granulation tissue were obtained from 9 patients with adult periodontitis (AP), from 10 patients with early onset periodontitis (EOP) and for comparative purposes, biopsies of gingival tissue from 4 patients with AP. A significantly greater number of T cells (p < 0.05) were observed in EOP and gingival sections than in AP sections. In addition, a greater number of B cells were observed in the granulation tissues than in the gingiva (p < 0.05). The relative numbers of B cells (CD 20). T cells (CD 3) and macrophages (CD 68) were expressed as a percentage of their combined total for each of the patient groups and indicated that the proportion of B lymphocytes was greater in AP sections than in EOP or gingival sections (p < 0.02). The proportion of T cells was lower in the AP periodontitis sections than in the EOP periodontitis sections (p < 0.05). There were no significant differences in the proportion of macrophages between the 3 categories of tissue specimens. The relative ratios of B cells (CD 20) to T cells (CD 3) and B cells (CD 20) to memory T cells (CD 45RO) and macrophages (CD 68) to T cells (CD 3) and memory T cells (CD 45RO) were analyzed and indicated that there was a significant increase in the B to T cell ratio in AP sections compared to EOP and gingival sections (p < 0.02). There was also a significant increase in the macrophage to T cell ratio in AP sections as indicated by CD 68 to CD 3 ratios (p < 0.05). There were no differences regarding the relative proportions of memory T cells or in the ratios of CD 4+ to CD 8+ T cells in the different disease categories. In conclusion, these differences in the relative proportions of B cells, T cells and macrophages may reflect a difference in the immunopathology of AP and EOP.

Adult↗
PubMed1999

Analysis of genetic polymorphisms at the interleukin-10 and tumour necrosis factor loci in early-onset periodontitis.

Early onset periodontitis (EOP) is considered to have a substantial genetic basis, although the gene or genes involved have not been elucidated. The aim of the present study was to investigate possible links between generalized EOP (GEOP) and genes regulating expression of the cytokines tumour necrosis factor (TNF) and interleukin-10 (IL-10). Microsatellite marker DNA sequences corresponding to phenotypic variations in cytokine response were analysed. Genotypic variations in cytokine response have been shown in vitro for TNF and IL-10, and specific alleles are implicated in diseases such as systemic lupus erythmatosus (SLE) and rheumatoid arthritis (RA). Two microsatellites at the IL-10 locus, IL10.R and IL10.G, and 1 microsatellite at the TNF locus, TNFa, were typed for 77 GEOP patients in the West of Scotland. Due to the highly polymorphic nature of the microsatellite loci, a statistical comparison with ethnically matched healthy controls (TNFa, n = 91, IL10.R, n = 94, IL10.G, n = 102) was conducted using a Monte Carlo simulation for each marker. No significant differences were observed for any of the 3 markers, although there were possible indications of trends similar to those observed in SLE for the IL10.G marker. In conclusion, no links were found between GEOP and microsatellites at TNFa, IL10.R or IL10.G loci.

Adult↗
PubMed1995

Mitogenic effects and nuclear localisation of procorticotrophin-releasing hormone expressed within stably transfected fibroblast cells (CHO-K1).

To investigate the intracellular localisation and biological activity of procorticotrophin-releasing hormone (proCRH), we have established stably transfected CHO-K1 cells expressing the rat pre-proCRH cDNA. Using immunoblot analysis of cell lysates of transfected CHO-K1 cells, we detected a major CRH immunoreactive band with an apparent molecular weight of approximately 19 kDa. This 19 kDa band could account for full length proCRH molecule which has not undergone post-translational modifications. Metabolic labelling followed by immunoprecipitation, SDS-PAGE and autoradiography indicated that no endoproteolytic processing of proCRH takes place within the transfected CHO-K1 cells. Immunofluorescence staining localises the CRH precursor to both the cytoplasm and to the nucleus in transfected CHO-K1 cells. This result was confirmed using subcellular fractionation techniques on radiolabelled CHO-K1 cells expressing immunoreactive CRH. A major CRH-immunoreactive band of 19 kDa was detected both in the microsomal and secreted fractions, indicating the presence of proCRH within the secretory pathway of these cells. This was also evident in the nuclear fraction, therefore confirming the nuclear localisation of proCRH. Analysis of DNA concentration, cell number and DNA synthesis showed that stably transfected CHO-K1 cells expressing proCRH have a higher proliferation and DNA synthesis rate than wildtype CHO-K1 cells or CHO-K1 cells transfected with pEE14 alone. Our results therefore suggest a mitogenic role for the intact proCRH molecule within CHO-K1 cells. Furthermore, treatment of mouse corticotrophic tumour cells (AtT20/D16-16) with conditioned medium from transfected CHO-K1 cells expressing proCRH, stimulated both DNA synthesis and cell proliferation above basal levels. Our results constitute the first reported direct evidence of a mitogenic role for proCRH acting on a corticotrophic cell population.

Animals↗
PubMed1994

Adsorption of a novel fluorescent derivative of a poly(ethylene oxide)/poly(butylene oxide) block copolymer on octadecyl glass studied by total internal reflection fluorescence and interferometry.

We have used total internal reflection fluorescence (TIRF) to measure the adsorption kinetics of a newly synthesized fluorescent derivative of a triblock copolymer comprising two poly(ethylene oxide) arms connected by a poly(butylene oxide) segment. The composition is (EO)400 (BO)55 (EO)400, in which EO represents ethylene oxide, BO represents butylene oxide, and one or both of the terminal OH groups of the two (EO)400 arms are labeled with tetramethylrhodamine. The poly(butylene oxide) segment binds to hydrophobic octadecyl glass, used as a substratum. The TIRF signal is shown to be derived almost entirely from surface-adsorbed polymer. This facilitates calculation of adsorption isotherms from 0.1-0.005% bulk polymer solution by means of diffusion kinetics. Information about the effective thickness of the adsorbed polymer, determined by optical interference microscopy, corresponds with what is known about the conformation of similar molecules at interfaces and indicates monolayer adsorption on the glass.

Adsorption↗
PubMed1994

Use of recombinant vectors derived from herpes simplex virus 1 mutant tsK for short-term expression of transgenes encoding cytoplasmic and membrane anchored proteins in postmitotic polarized cortical neurons and glial cells in vitro.

We constructed three recombinant vectors derived from the herpes simplex virus type 1 mutant tsK, each of which contained a different transgene under the control of the herpes simplex virus type 1 immediate early 3 promoter inserted into the thymidine kinase locus: the prokaryotic enzymes beta-galactosidase and chloramphenicol acetyl transferase, and a fusion gene consisting of human tissue inhibitor of metalloproteinases linked to the last exon of Thy-1, which encodes for a glycosyl-phosphatidyl-inositol membrane anchor. Infection of postmitotic neocortical and hippocampal neurons in low-density primary cultures with these vectors, achieved reliable expression of all three foreign gene products in various neocortical cell types, e.g. pyramidal neurons, non-pyramidal neurons, and glial cells. The percentage of neurons expressing transgenes ranged from 1 to 46% depending on the multiplicity of infection (highest assayed = 5); the percentage of glial cells expressing transgenes ranged from 0.5 to 98% (highest multiplicity assayed = 3.4). Expression of transgenes could be detected for up to three days in approximately 20% of neurons infected at a multiplicity of infection of 1. Infection of neurons with tk K-derived recombinant vectors inhibited their protein synthesis by 40-50% at a multiplicity of infection of 10, but no effect was observed at a multiplicity of infection of 1. Infection of glial cells with the same vectors at a multiplicity of infection of 1 inhibited protein synthesis by more than 90%. Analysis of neuronal viability at different times post-infection indicated that more than 98% of neurons expressing transgenes 48 h post-infection were viable. Thus, low-density neuronal cultures can be used to assess the efficiency of herpes simplex virus type 1-derived gene transfer vectors and transgene expression in developing cortical postmitotic cells, before and after they establish polarity. In addition, we show that two cytoplasmic enzymes, beta-galactosidase and chloramphenicol acetyl transferase, are able to diffuse freely in the cytoplasm reaching even growth cones in young neurons, while the chimeric protein tissue inhibitor of metalloproteinases/Thy-1 is correctly targeted to the plasma membrane via a glycosyl-phosphatidylinositol anchor. This model system should be useful for investigation of cellular and molecular aspects of the development and establishment of neuronal polarity, as well as for analysis of signals involved in protein targeting in postmitotic neurons.

Amino Acid Sequence↗
PubMed1994

Neuropeptide gene transfer into neuronal and glial cell lines.

Procorticotrophin-releasing hormone (ProCRH) is the precursor to the hypothalamic neuropeptide CRH(1-41) which mediates the neuroendocrine response to stress. In neuroendocrine cells and neurones, peptide hormones and neuropeptides are targeted to the dense-core vesicles of the regulated secretory pathway. These vesicles are transported to the ends of the cellular processes where they are stored until they are released upon an external stimulus. In order to study the post-translational processing and intracellular trafficking of neuropeptides in neuronal cells we have established stably transfected Neuro2A cells and NG115-401L cells expressing proCRH. The expression vector used contains glutamine synthetase (GS) coding sequences which are used as a dominant selectable marker in cells already containing GS genes. The various clonal cell lines isolated express different levels of CRH as assessed using a specific radioimmunoassay (RIA) thus indicating that the level of expression of the exogenous gene must depend upon the site of chromosome integration. Using immunofluorescence labelling, we have demonstrated that in Neuro2A and NG115-401L cells proCRH is packaged in vesicles which accumulate at the tips of cellular processes.

Animals↗
PubMed1975

Raman studies of some diunsaturated olefinic and acetylenic fatty acids and their derivatives.

The Raman spectra of CCl4 solutions of the 6,12; 7,12; 8,12; 9,12; and 10,12 isomers of octadecadiynoic acid and of the octadecadienoic acid methyl esters of both the cis,cis and trans,trans series are reported. Provided that there are two or more methylene groups between the unsaturated groups, the double and triple bond vibrational wavenumber values are close to those found in monounsaturated derivatives. An attempt has been made to obtain a correlation between the relative intensities of the nu(CequalsC) and delta(CH2) bands and the ratio of the number of double bonds to methylene groups in the molecule.

Fatty Acids, Unsaturated↗