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J Cheetham

Publications and source records attributed to J Cheetham.

14 recordsLinked to original sources
PubMed2005

VIP Inhibits Porphyromonas gingivalis LPS-induced immune responses in human monocytes.

Lipopolysaccharide (LPS) from the Gram-negative pathogen Porphyromonas gingivalis (Pg) stimulates cytokine secretion in immune cells, and thereby initiates the inflammation associated with periodontitis. Modulation of pro-inflammatory cytokine activity is a plausible therapeutic target in periodontal disease. Vasoactive intestinal peptide (VIP) has a role in immunoregulation, and has been identified as a molecule with therapeutically beneficial immunosuppressive effects in inflammatory and autoimmune conditions. We aimed to investigate the effect of VIP on immune responses induced by Pg LPS in vitro. VIP (10(-8) M) significantly (P < 0.05) inhibits TNF-alpha production by human monocytic THP1 cells stimulated with Pg LPS. In parallel, we showed that VIP inhibits nuclear translocation of NFkappaB and c-Jun in a time-dependent manner, but does not decrease the expression of CD14 receptors. This is the first report to show the potential of VIP as an immunomodulator of Pg-stimulated inflammatory pathways in human monocytes.

Cells, Cultured↗
PubMed2001

Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management.

OBJECTIVE: To compare the safety and efficacy of the ocular hypotensive lipid AGN 192024 (Lumigan) with those of timolol. METHODS: A 30-day, randomized, investigator-masked, clinical trial involving 100 patients with elevated intraocular pressure (IOP). Study medications were instilled topically. Doses of 0.003%, 0.01%, or 0.03% AGN 192024 were given once daily for 3 weeks then twice daily for 1 week, and vehicle control or 0.5% timolol was given twice daily for 4 weeks. Mean change in IOP from baseline was the primary efficacy variable. Safety parameters included adverse events, hyperemia grading, laser flare meter analysis, heart rate, and blood pressure. RESULTS: Timolol and all 3 concentrations of AGN 192024 lowered IOP from baseline (P < .001). A dosage of 0.03% AGN 192024 once daily lowered IOP significantly more than timolol (P < or = .02) at every study visit except day 21 (P = .053) and provided better diurnal IOP control. Twice-daily dosing of AGN 192024 provided no clinically significant benefit over once-daily dosing. All treatment regimens were safe and well tolerated, with no clinically significant effects on heart rate or blood pressure and no between-group differences in the incidence of adverse events. The only significant ocular safety finding with AGN 192024 was a dose-related mild increase in conjunctival hyperemia. CONCLUSIONS: Of the 3 concentrations tested, 0.03% AGN 192024 once daily had the best therapeutic profile. AGN 192024 was safe and well tolerated, and it provided superior ocular hypotensive efficacy and diurnal IOP control compared with timolol in patients with ocular hypertension and glaucoma.

Adult↗
PubMed2001

Asn to Lys mutations at three sites which are N-glycosylated in the mammalian protein decrease the aggregation of Escherichia coli-derived erythropoietin.

Erythropoietin (EPO) derived from Escherichia coli is unstable to elevated temperature and tends to aggregate with time, making it unsuitable for high-resolution structure analysis. The mammalian EPO contains about 40% carbohydrate, which makes this protein more stable and less prone to aggregate than non-glycosylated E.coli-derived EPO, but makes it unsuitable for high-resolution analysis owing to its size and flexibility. In an attempt to decrease the aggregation of E.coli-derived EPO, the three asparagine residues at positions 24, 38 and 83 were mutated to lysine residues. In the native protein, these residues are the sites of N-linked glycosylation, which suggests that they should be located on the surface of the protein and should not be involved in interactions in the hydrophobic protein core. Therefore, the substitution of basic amino acids for these neutral asparagine residues is not expected to affect the protein structure, but should increase the isoelectric point of the protein and its net positive charge, decreasing its tendency to aggregate at or below neutral pH due to electrostatic interactions. No apparent alterations in receptor binding, as determined by both cell-surface receptor competition assay and in vitro receptor dimerization experiments, were observed when these mutations were introduced into the EPO sequence. However, this mutant protein displayed a significant increase in stability to heat treatment and to storage, relative to the wild-type molecule. This resulted in a greater number of observable cross peaks in the mutant EPO in 2D NOESY experiments. However, the mutant was similar to the wild-type in stability when urea was used as a denaturant. This indicates that the introduced mutations resulted in a decrease in aggregation with heating or with prolonged incubation at ambient temperature, without changing the conformational stability or the receptor binding affinity of the mutant protein. This approach of placing charged residues at sites where N-glycosylation occurs in vivo could be applied to other systems as well.

Amino Acid Substitution↗
PubMed1997

Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins.

The two tandem phosphotyrosine interaction/phosphotyrosine binding (PID/PTB) domains of the Fe65 protein interact with the intracellular region of the Alzheimer's beta-amyloid precursor protein (APP). This interaction, previously demonstrated in vitro and in the yeast two hybrid system, also takes place in vivo in mammalian cells, as demonstrated here by anti-Fe65 co-immunoprecipitation experiments. This interaction differs from that occurring between other PID/PTB domain-containing proteins, such as Shc and insulin receptor substrate 1, and activated growth factor receptors as follows: (i) the Fe65-APP interaction is phosphorylation-independent; (ii) the region of the APP intracellular domain involved in the binding is larger than that of the growth factor receptor necessary for the formation of the complex with Shc; and (iii) despite a significant similarity the carboxyl-terminal regions of PID/PTB of Fe65 and of Shc are not functionally interchangeable in terms of binding cognate ligands. A role for Fe65 in the pathogenesis of familial Alzheimer's disease is suggested by the finding that mutant APP, responsible for some cases of familial Alzheimer's disease, shows an altered in vivo interaction with Fe65.

Alzheimer Disease↗
PubMed1992

Molecular analysis of patients with Wiedemann-Beckwith syndrome. I. Gene dosage on the short arm of chromosome 11.

Wiedemann-Beckwith syndrome (WBS) is characterised by a specific group of congenital malformations associated with an increased concurrent risk for development of a defined group of childhood neoplasms. The mode of inheritance is complex, but recently compiled family data suggest that it is an autosomal dominant trait of varying expression. It has previously been suggested that major rearrangements on the short arm of chromosome 11 may be involved in the aetiology of the disease, particularly in the region of the insulin like growth factor II (IGF-II) gene (11p15.5). This gene is thought to be parentally imprinted in the mouse and it has been suggested that in the human, duplication of the non-imprinted locus in WBS patient might lead to diploid expression of the gene and consequent general hyperplasia. This model predicts that there should be both frequent and parental origin specific duplication of the IGF-II gene in the patients. It was the aim of this study to examine the IGF-II locus and its surrounding chromosomal environment for such lesions in a large number of WBS patients. Using restriction fragment length polymorphism analysis for four linked markers on 11p and genomic clones internal to the IGF-II locus we could find no evidence of alteration or amplification of this area in any of the 11 patients investigated. In one patient who developed a Wilms tumour we could find no evidence for loss of any material on the short arm of chromosome 11 as reported previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Beckwith-Wiedemann Syndrome↗
PubMed1989

Adenylate kinase activity in ejaculated bovine sperm flagella.

Adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) activity was detected in the flagella of ejaculated bovine spermatozoa. This activity provided sufficient ATP to produce normal motility in cells permeabilized with digitonin and treated with 0.5 mM MgADP. In the presence of ADP, adenylate kinase activity was inhibited by P1,P5-di(adenosine 5')-pentaphosphate (Ap5A), an adenylate kinase-specific inhibitor, and motility was stopped. ATP-supported motility was not affected by Ap5A. Mitochondrial adenylate kinase activity allowed AMP to stimulate respiration in permeabilized sperm. Adenylate kinase activity in tail fragments was most active in a pH range from 7.6 to 8.4, and a similar pH sensitivity was observed for this enzyme activity in a hypotonic extract of whole sperm. The apparent km of adenylate kinase activity in permeabilized tail fragments was about 1.0 mM ADP in the direction of ATP synthesis. The fluctuation of nucleotide concentrations in normal and metabolically stimulated sperm suggested that adenylate kinase was most active when the cell was highly motile, although adenylate kinase activity did not appear to be coupled strictly with motility.

Adenosine Diphosphate↗
PubMed1986

The ocular hypertensive effect of 0.25% fluorometholone in corticosteroid responders.

Fourteen subjects known to be corticosteroid responders participated in a double-masked, randomized study comparing the ocular hypertensive effect of 0.25% fluorometholone suspension with that of 0.1% dexamethasone sodium phosphate. Subjects instilled one drop of fluorometholone in one eye and one drop of dexamethasone in the fellow eye four times daily for up to six weeks. Although both medications increased intraocular pressure, endpoint substitution analysis demonstrated that mean intraocular pressure increases from baseline in the eyes treated with fluorometholone were significantly lower than those in the eyes treated with dexamethasone at weeks 2, 4, and 6 (P less than or equal to .05). Also, mean maximum intraocular pressure was significantly lower in the eyes treated with fluorometholone than in the eyes treated with dexamethasone (P = .001). These results indicated that 0.25% fluorometholone is less likely to increase intraocular pressure in corticosteroid responders than 0.1% dexamethasone.

Adrenal Cortex Hormones↗
PubMed1985

Teratocarcinoma cells cultured on embryonic substrates show accelerated migrating behavior in vitro and increased metastatic activity in vivo.

Teratocarcinoma cells (402AX) were grown on feeder layers of whole mouse embryos (Day 4) or mouse embryonic fibroblasts and then were either examined in vitro or transplanted in vivo. After twenty-four hours of coculture, teratocarcinoma cells demonstrate accelerated cell migration in vitro. Furthermore, transplantation of teratocarcinoma cells with embryonic substrates into syngeneic hosts produces grossly detectable lymph node metastases. These effects appear to be due to soluble factor(s) produced by embryonic substrates which enhance tumor cell proliferative/migratory activity. This suggests that tumor cell invasion and metastasis may be stimulated by soluble factors produced by host tissues.

Animals↗
PubMedDate not supplied

Ultrasonography of the equine larynx.

Nasopharyngeal and laryngeal evaluation is important when examining horses with upper airway signs for poor performance. Currently endoscopy is the most common method to evaluate the equine upper airway. Ultrasonography of the equine larynx has not previously been described. Using six cadaveric specimens and four standing horses, the ultrasonographic appearance of the equine larynx was established. A scanning technique, including useful acoustic windows and the normal ultrasonographic appearance at each site, is described. Ultrasound allowed visualization of portions of the hyoid apparatus, laryngeal cartilages, associated soft tissues, and intrinsic and extrinsic laryngeal musculature, that are not seen using endoscopy. Additionally, real-time ultrasound allowed observation of the movement of the vocal folds and the arytenoid cartilages during respiration. In three horses with arytenoid chondritis, ultrasonography aided in the diagnosis and localization of arytenoid abcessation and perilaryngeal inflammation. The establishment of this technique will serve as the basis for future investigations in the evaluation of clinical patients with upper airway abnormalities.

Animals↗