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Biomedical subjects

A T Jones

Publications and source records attributed to A T Jones.

At least 37 records · Page 2Linked to original sources
PubMed1996

The effects of Helicobacter pylori colonization on gastric function and the incidence of portal hypertensive gastropathy in patients with cirrhosis of the liver.

OBJECTIVES: To investigate the prevalence of Helicobacter pylori infection in 50 cirrhotic patients with biopsy-proven cirrhosis with and without portal hypertensive gastropathy and to study whether or not the effects of H. pylori colonization of the stomach on gastric acid and pepsin secretion, serum gastrin and pepsinogen I levels, gastric mucus, and gastric emptying contributed to the development of portal hypertensive gastropathy in cirrhotics. METHODS: All patients underwent an upper GI endoscopy followed by determination of basal and pentagastrin and insulin-stimulated gastric acid and pepsin secretion and serum gastrin and pepsinogen I levels. The gastric biopsies were stained to detect H. pylori infection, portal hypertensive gastropathy, and gastritis. The amount of gastric mucus was estimated by a microanalytical technique. The rate of gastric emptying was assessed by the radionuclide method using a semi-solid meal. RESULTS: Thirty-three (66%) patients had endoscopic evidence of portal hypertensive gastropathy, 10 with the severe (20%) and 23 with mild form (46%). Twenty (40%) patients had histological evidence of H. pylori infection. Eleven out of 33 (33%) patients with endoscopic portal hypertensive gastropathy had microscopic evidence of H. pylori infection. Eighteen out of 20 (90%) patients with chronic active gastritis had concomitant H. pylori colonization. In contrast, the gastric mucosa was histologically normal in 21 of the 30 patients (70%) not infected with H. pylori. Marked hypochlorhydria and reduced pepsin secretion associated with a tendency to hypergastrinemia were observed in cirrhotic patients colonized with H. pylori compared with those without. However, there was no significant difference in serum pepsinogen I concentrations, the ratio of polymeric to degraded gastric mucus, or the rate of gastric emptying between cirrhotics with and without H. pylori colonization of the stomach. Furthermore, these parameters were not significantly different in patients with portal hypertensive gastropathy with and without H. pylori infection. CONCLUSION: These observations suggest that H. pylori infection is unlikely to be involved in the pathogenesis of portal hypertensive gastropathy.

Adolescent↗
PubMed1995

Phosphatidylinositol 3-kinase activity is required for early endosome fusion.

The homotypic fusion between early endosomes from baby-hamster kidney cells is blocked by addition of the fungal metabolite wortmannin with an IC50 of approx. 15 nM. Over this concentration range, wortmannin has been regarded as a specific inhibitor of phosphatidylinositol (PI) 3-kinase. Further confirmation of the participation of a PI 3-kinase in the fusion reaction has been obtained by demonstrating a sensitivity to an additional, structurally unrelated, PI 3-kinase inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]. Assays constructed such that only the membranous component has been incubated with wortmannin show in vitro fusion to be sensitive to treatment with the drug. Assays in which only the cytosolic component has been treated with wortmannin also showed inhibition of in vitro fusion, but to a lesser extent. PI 3-kinase action almost certainly involves direct regulation of membrane fusion, as no vesicular intermediate has been identified, despite previous extensive morphological examination of in vitro endosome fusions.

Androstadienes↗
PubMed1995

Phosphatidylinositol 3-kinase regulation of fluid phase endocytosis.

Endocytosis of the fluid phase marker, horse radish peroxidase, into baby hamster kidney cells is inhibited by treatment of cells with the fungal metabolite wortmannin. The IC50 of approximately 5 nM is consistent with the well-described action of wortmannin upon phosphatidylinositol (PI) 3-kinase. Analysis of the kinetics of uptake indicates a > 50% decrease in the initial rate of marker internalisation, a concomitant decrease in the volume of the early endosome and an increased efficiency of recycling of that marker which is internalised. As PI 3-kinase binds to activated growth factor receptors our data suggest that receptor activation can be coupled to receptor internalisation (down regulation) by localising PI 3-kinase stimulation of endocytosis.

Androstadienes↗
PubMed1995

Species identification of Cecidophyopsis mites (Acari: Eriophyidae) from different Ribes species and countries using molecular genetics.

Cecidophyopsis mites were studied by PCR amplification of parts of their ribosomal DNA, followed by restriction enzyme analysis. Mite specimens on Ribes nigrum (black currant) from six countries gave the same digestion pattern, which was distinct from the pattern for mites found on R. rubrum from Poland and Finland and for R. grossularia from the USA. This suggests that each Ribes species is host to a different mite species: C. ribis, C. selachodon and C. grossulariae, respectively. Two other mite samples from R. alpinum and R. aureum were identical but were distinct from each of the other species.

Animals↗
PubMed1994

Characterization of the activation-associated isoform of CD43 on murine T lymphocytes.

A rat mAb termed 1B11 recognizes a 130-kDa cell surface glycoprotein expressed on T lymphocytes. Transfection studies using the Cd43 gene transfected into murine L cells, and immunoblots using anti-peptide Abs specific for the CD43 polypeptide identified the 1B11 Ag as the 130-kDa isoform of murine CD43. mAb 1B11 fails to recognize the other major CD43 isoform, 115-kDa CD43, either by Western blotting or by FACS analysis, thus differing from the previously characterized anti-CD43 mAb S7 that recognizes only the CD43 115-kDa isoform and not the CD43 130-kDa isoform. CD43 130-kDa recognized by mAb 1B11 is differentially expressed on T lymphocytes. Whereas most CD4-8-, CD4+8+, and CD4-8+ thymocytes express 130-kDa CD43 constitutively, the Ag is expressed by less than 20% of CD4+ T cells in immature and mature populations. On activation, expression of 130-kDa CD43 is up-regulated dramatically on CD4+ T lymphocytes, and to a lesser extent on CD8+ T lymphocytes. In contrast, T cell activation resulted in only minor up-regulation of 115-kDa CD43. CD43 130-kDa contains sialylated O-linked carbohydrate; however, recognition by mAb 1B11 is not dependent on the presence of sialic acid. Interestingly, removal of sialic acid by neuraminidase treatment of 1B11-negative CD4+ T lymphocytes or 1B11-negative EL4 cells confers 1B11 reactivity, suggesting that the 1B11 epitope is masked by sialic acid residues on the CD43 115-kDa isoform. The isoelectric point (pl) of 130-kDa CD43 was determined to be 6.0, which is higher than the pl reported for 115-kDa CD43. Different molecular properties of 115-kDa and 130-kDa CD43 and their differential expression in T cell subsets may indicate specific roles for these CD43 isoforms in T cell ontogeny and/or T cell function.

Animals↗
PubMed1994

Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease.

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.

Acute Disease↗
PubMed1994

Ribosomal spacer length variability in the large raspberry aphid, Amphorophora idaei (Aphidinae: macrosiphini).

The large raspberry aphid, Amphorophora idaei, has several biotypes described by their abilities to overcome plant resistance genes. Bioassays of field populations showed a strong shift towards A1 resistance-breaking biotypes since the 1960s. RFLP analysis of the rDNA cistron was used to study variation found within and between standard clones of three A. idaei biotypes and twenty-nine field populations collected over 3 years. Probing genomic DNA with the ribosomal DNA probe pBG 35 produced consistent differences in RFLPs between standard clones of biotypes. However, analysis of field populations gave more complex RFLP patterns that were not biotype-specific, unlike characteristic intergenic spacer (IGS) patterns reported for Schizaphis graminum biotypes. All but one sample collected from separate fields showed considerable genetic diversity within populations, attributed to alate migrations of parthenogenetic females in summer and males in autumn.

Animals↗
PubMed1994

Carbohydrate does not modulate the in vivo effects of injected interleukin-3.

Murine interleukin-3 (IL-3) has extensive N-linked glycosylation. Experiments were performed to determine whether the T cell-derived glycosylated IL-3 differs in its biological activity in vivo when compared with a chemically synthesized form of nonglycosylated IL-3. Groups of mice were treated by intravenous injection with identical units of IL-3 bioactivity as determined in vitro in a cell-proliferation assay. Mice that were treated with seven 5000-unit doses of either form of IL-3, given in 12-hour intervals, showed a small but significant increase in the frequency of mast cell precursor cells in the spleen and of IL-3-responsive colony-forming unit cells (CFU-C). There was no difference in potency of glycosylated and nonglycosylated IL-3. Induction, by IL-3, of histidine decarboxylase in bone marrow and spleen cells was used as a second measure for IL-3 bioactivity. Both IL-3 preparations showed good in vivo histidine decarboxylase inducing activity; however, T cell-derived glycosylated IL-3 was significantly more effective than synthetic IL-3 in inducing the enzyme histidine decarboxylase in bone marrow and in spleen cells. Pharmacokinetic studies showed that chemically synthesized IL-3 was cleared about twice as fast as the T cell-derived IL-3 and that there may be some tissue trapping of glycosylated IL-3. The shorter in vivo half-life of nonglycosylated IL-3 appears to have significant pharmacological consequences on the short-term effect of inducing histidine decarboxylase activity, but not on the effect of the long-term treatment of IL-3 on stimulating the increase of hematopoietic progenitor cells.

Animals↗
PubMed1993

Human pepsin 3b peptide map sequence analysis, genotype and hydrophobic nature.

Peptides from a Staphylococcus aureus (V8) proteinase digest of human pepsin 3b have been identified by amino acid sequence analysis. Only 137 out of 326 expected residues were detected from the C and N terminal regions of the molecule. Comparison with amino acid sequences derived from nucleotide analysis of three different pepsinogen A genes, identified 2 out of 4 possible substitutions. The presence of valine at position 30 and leucine at 291 indicates that the major pepsin component of gastric juice, pepsin 3b, corresponds to pepsinogen genotype PGA-3. Reversed-phase chromatography of native human pepsin 3b on C4 (300 A), C18 (300 A) or polymer (1000 A) columns was optimal on the C4 column and gradient elution with 2-propanol rather than acetonitrile. Denaturation of the protein in guanidinium hydrochloride, urea or high pH resulted in irreversible column retention. The marked hydrophobicity of denatured pepsin 3b may thus explain why the central segment of the protein was not revealed by peptide map analysis.

Amino Acid Sequence↗
PubMed1993

Enhancement of the biologic effects of interleukin-3 in vivo by anti-interleukin-3 antibodies.

Interleukin-3 (IL-3) has been shown to be a promising agent in the stimulation of bone marrow regeneration following myeloablative therapy. The biologic half-life of this agent is very short (5 to 15 minutes), which limits the effectiveness of low-dose therapy. Here we show that the biologic effects of low-dose IL-3 in mice may be enhanced by concurrent use of polyclonal anti-IL-3 antibodies. The biologic effects of IL-3 in vivo were enhanced dramatically by the combination of the cytokine and polyclonal rabbit anti-IL-3 antibodies, which recognized a peptide comprising the first 29 amino acids of the IL-3 molecule. Enhancing effects were not apparent in vitro, where weak neutralizing properties were observed for these antibodies. The mechanism of this enhancement by the antibody appears to be via a ninefold reduction in the total-body clearance of the cytokine in vivo. The apparent volumes of distribution for IL-3 and for the IL-3/antibody complex were surprisingly similar and exceeded the expected intravascular volume. The prolonged biologic half-life of IL-3 was reproducibly associated with a threefold to fivefold increase in splenic mast-cell precursors over levels observed in mice treated with IL-3 alone; increases in the numbers of mature mucosal-type mast cells in the spleen, but not in the jejunum or lung; increases in IL-3-dependent colony-forming unit-cell in the spleen; and an apparent redistribution of mast cells away from the bone marrow. These experiments demonstrate that antibodies to a cytokine can enhance the biologic activity of that cytokine in vivo.

Animals↗
PubMed1993

Assay of gastricsin and individual pepsins in human gastric juice.

AIMS: To develop and validate an analytical procedure for the quantitation of pepsins and gastricsin in human gastric juice and to assess its potential in a controlled gastric secretory study. METHODS: High performance ion-exchange chromatography was used to separate human pepsin 1, 3a, 3b, 3c and gastricsin from gastric juice. Computed chromatographic areas for each enzyme were quantified by relation to a known amount of a secondary standard porcine pepsin. The assay procedure was validated by recovery and analytical precision studies. Gastric secretions after pentagastrin and insulin stimulation from 10 patients with portal hypertension were used to assess the potential of the analytical procedure. RESULTS: The assay precision varied from 1.5 to 9.0% within batch and 7.5 to 18.1% between batch, with about 100% recoveries of porcine pepsin A from human gastric juice over the assay range 0.025-0.5 mg/ml. A fourfold increase in combined pepsin and gastricsin concentration was observed following pentagastrin and insulin stimulation. The mean percentage content of pepsins 3a, 3b, 3c, and 1 in non-stimulated gastric juice were 4%, 72%, 12% and 1.4%, respectively, and did not change significantly after gastric stimulation. An approximate doubling of the percentage of gastricsin (10% to 20%) relative to the pepsins was observed, however, after both insulin and pentagastrin stimulation. CONCLUSIONS: This procedure for quantifying individual human pepsins and gastricsin in gastric juice is simple and reliable. It may be of considerable importance in determining the mechanisms involved in the control and secretion of these digestive enzymes in man, including the effect of anti-ulcer drugs and our understanding of the pathophysiology of peptic ulcer disease.

Chromatography, Ion Exchange↗
PubMed1992

Peptide maps of five human pepsin isoenzymes and other aspartic proteinases.

Peptide maps of five individual human pepsins were developed using reversed-phase high-performance liquid chromatography after protein digestion with either Staphylococcus aureus proteinase (V8) or alpha-chymotrypsin. Human pepsins 3a, 3b and 3c produced almost identical peptide maps suggestive of proteins with very similar amino acid sequences. The map for human pepsin 1 was similar to pepsin 3b (the most predominant human pepsin) but less than half the expected amount of each equivalent peptide fragment was generated, indicating that the actual mass of digested protein used was less than the dry weight measurement would suggest, probably as a result of carbohydrate attached to pepsin 1. Comparison of human pepsin 3b maps with other aspartic proteinases confirmed a significant homology with swine pepsin A but not with endothiapepsin. The alpha-chymotrypsin digests compared with V8 gave more complex peptide maps as a result of its broader bond cleavage specificities.

Animals↗