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Biomedical subjects

B Callaghan

Publications and source records attributed to B Callaghan.

18 recordsLinked to original sources
PubMed2005

Nucleocapsid gene variability reveals two subgroups of Lettuce necrotic yellows virus.

The complete nucleocapsid (N) genes of eight Australian isolates of Lettuce necrotic yellows virus (LNYV) were amplified by reverse transcription PCR, cloned and sequenced. Phylogenetic analyses of these sequences revealed two distinct subgroups of LNYV isolates. Nucleotide sequences within each subgroup were more than 96% identical but heterogeneity between groups was about 20% at the nucleotide sequence level. However, less than 4% heterogeneity was noted at the amino acid level, indicating mostly third nucleotide position changes and a strong conservation for N protein function. There was no obvious geographical or temporal separation of the subgroups in Australia.

Australia↗
PubMed2004

Muscarinic M2 receptor stimulation of Cav1.2b requires phosphatidylinositol 3-kinase, protein kinase C, and c-Src.

This study investigated regulation of L-type calcium channels (Cav1.2b) by acetylcholine (ACh) in rabbit portal vein myocytes. Whole-cell currents were recorded using 5 mmol/L barium as charge carrier. ACh (10 micromol/L) increased peak currents by 40%. This effect was not reversed by the selective muscarinic M3 receptor antagonist 4-DAMP (100 nmol/L) but was blocked by the M2 receptor antagonist methoctramine (5 micromol/L). The classical and novel protein kinase C (PKC) antagonist calphostin C (50 nmol/L) abolished ACh responses, whereas the classical PKC antagonist Gö6976 (200 nmol/L) had no effect. ACh responses were also abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (20 micromol/L), by the c-Src inhibitor PP2 (10 micromol/L) (but not the inactive analogue PP3), and by dialyzing cells with an antibody to the G-protein subunit Gbetagamma. Cells dialyzed with c-Src had significantly greater currents than control cells. Current enhancement persisted in the presence of LY294002, suggesting that c-Src is downstream of PI3K. Phorbol 12,13-dibutyrate (PDBu, 0.1 micromol/L) increased currents by 74%. This effect was abolished by calphostin C and reduced by Gö6976. The PDBu response was also reduced by PP2, and the PP2-insensitive component was blocked by Gö6976. In summary, these data suggest that ACh enhances Cav1.2b currents via M2 receptors that couple sequentially to Gbetagamma, PI3K, a novel PKC, and c-Src. PDBu stimulates the novel PKC/c-Src pathway along with a second pathway that is independent of c-Src and involves a classical PKC.

Acetylcholine↗
PubMed2000

The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response.

The unfolded protein response (UPR) is a signal transduction pathway that is activated by the accumulation of unfolded proteins in the endoplasmic reticulum (ER). In Saccharomyces cerevisiae the ER transmembrane receptor, Ire1p, transmits the signal to the nucleus culminating in the transcriptional activation of genes encoding an adaptive response. Yeast Ire1p requires both protein kinase and site-specific endoribonuclease (RNase) activities to signal the UPR. In mammalian cells, two homologs, Ire1 alpha and Ire1 beta, are implicated in signaling the UPR. To elucidate the RNase requirement for mammalian Ire1 function, we have identified five amino acid residues within IRE1 alpha that are essential for RNase activity but not kinase activity. These mutants were used to demonstrate that the RNase activity is required for UPR activation by IRE1 alpha and IRE1 beta. In addition, the data support that IRE1 RNase is activated by dimerization-induced trans-autophosphorylation and requires a homodimer of catalytically functional RNase domains. Finally, the RNase activity of wild-type IRE1 alpha down-regulates hIre1 alpha mRNA expression by a novel mechanism involving cis-mediated IRE1 alpha-dependent cleavage at three specific sites within the 5' end of Ire1 alpha mRNA.

Amino Acid Sequence↗
PubMed2000

Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal.

Located within the tunica muscularis of the gastrointestinal (GI) tract are networks of cells known as interstitial cells of Cajal (ICC). ICC are critical for important basic functions of GI motility such as generation and propagation of slow-wave pacemaker activity and reception of regulatory inputs from the enteric nervous system. We have developed a novel procedure to identify and isolate individual ICC from freshly dispersed cell preparations of the murine small intestine and gastric fundus and to determine differential transcriptional expression We have compared the expression profiles of pacemaker ICC isolated from the murine small intestine (IC-MY) and ICC involved in neurotransmission from the gastric fundus (IC-IM). We have also compared expression profiles between ICC and smooth muscle cells (SMC) and between freshly isolated ICC and cultured ICC. Cultured ICC express smooth muscle myosin, whereas freshly dispersed ICC do not. All cell types express muscarinic receptor types M(2) and M(3), neurokinin receptors NK(1) and NK(3), and inhibitory receptor VIP-1, whereas only cultured ICC and SMC express VIP-2. Both cultured and freshly dispersed IC-IM and IC-MY express the soluble form of stem cell factor, whereas SMC from the gastric fundus express only the membrane-bound form.

Animals↗
PubMed1992

Effects of the addition of nedocromil sodium to maintenance bronchodilator therapy in the management of chronic asthma.

STUDY OBJECTIVES: To assess the efficacy and safety of nedocromil sodium metered dose aerosol as an adjunct to sustained-released theophylline therapy in adult theophylline-dependent asthma patients and to examine the ability of nedocromil sodium to substitute for theophylline. DESIGN: Randomized double-blind placebo-controlled parallel group study. Two-week baseline, eight-week treatment period. SETTING: Out-Patient Clinic. PATIENTS: Sequential sample of 35 adult chronic asthmatic patients maintained on a regimen of sustained-release theophylline (dose range, 400 to 800 mg daily) and on-demand inhaled beta 2-bronchodilators. All patients completed the study. INTERVENTIONS: 2 x 2-mg nedocromil sodium metered dose aerosol twice daily or matching placebo randomly allocated after two-week baseline. Theophylline dose reduced by half or one third after four weeks of test treatments, then stopped for final two weeks. Use of inhaled beta 2-bronchodilators permitted throughout trial period. MEASUREMENTS AND RESULTS: The following results were in favor (statistically significant findings, p less than 0.05) of nedocromil sodium compared with placebo: all diary card efficacy variables (nighttime asthma, morning tightness, daytime asthma, cough, twice daily peak expiratory flow [PEF], inhaled beta 2 use) during all periods of assessment (weeks 1 to 2, 3 to 4, 5 to 6, and 7 to 8) with the exception of cough and nighttime beta 2 use during weeks 1 to 2; patient and clinician opinion of treatment efficacy (end of weeks 4 and 8); ability to reduce the theophylline dose; clinician assessment of asthma severity at the end of the study, and clinic FEV1 at weeks 4, 5, 6, and 8. One placebo-treated patient reported transient moderately severe nausea and taste loss. No clinically significant changes were seen in the laboratory data. CONCLUSION: Nedocromil sodium, 4 mg twice daily, conferred significant benefit when added to sustained-release theophylline therapy. The results suggest that nedocromil sodium may permit a reduction in theophylline dosage and possibly substitute for theophylline in previously dependent patients.

Adolescent↗
PubMed1979

Effect of a feeding schedule on crypt cell proliferation in the small intestine of the rat.

Using a stathmokinetic technique, the mitotic rate in the small intestinal crypts of two groups of male Sprague-Dawley rats was studied. The first group was fed solids for 3 h daily only. The second group was fed solids ad libitum. In the first group it was found that the mean daily weight of food consumed rose quickly to normal 24-hour levels but the mean daily weight of the rats fell rapidly and did not approach the original level throughout the experiment. There was no significant difference in the mitotic rate of the small intestinal crypt cells between the two groups.

Animals↗