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Biomedical subjects

M Begg

Publications and source records attributed to M Begg.

7 recordsLinked to original sources
PubMed2002

Modulation of the release of endogenous adenosine by cannabinoids in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum.

1. Interactions between the cannabinoid system and the adenosine system were investigated in the myenteric plexus-longitudinal muscle (MPLM) of the guinea-pig ileum. 2. Electrically-evoked contractions of the MPLM were inhibited in a concentration dependent manner by exogenous adenosine and the adenosine receptor agonist 2-chloroadenosine. These inhibitory effects were reversed by the selective A(1) receptor antagonist DPCPX (20 nM). 3. Preincubation of the MPLM with the cannabinoid receptor agonist CP55,940 (1 nM) or the endogenous cannabinoid ligand anandamide caused a significant leftward shift in the concentration-effect curves to adenosine and 2-chloroadenosine. 4. Electrically-evoked contractions of the MPLM were inhibited in a concentration dependent manner by the adenosine uptake inhibitor dipyridamole. This inhibition was reversed by DPCPX (20 nM). 5. Pretreatment with CP55,940 (1 nM) or anandamide (10 microM) significantly reduced the inhibition produced by dipyridamole, an effect which was completely reversed by the selective CB(1) receptor ligand SR141716 (100 nM). 6. Electrically evoked adenosine release, measured in real time by means of adenosine-specific biosensors, was inhibited by CP55,940 (10 nM). This inhibition was blocked when CP55,940 was applied in the presence of SR141716 (100 nM). 7. These results confirm the presence of presynaptic CB(1) and A(1) receptors in the guinea-pig MPLM, and suggest that CB(1) receptor stimulation reduces electrically-evoked adenosine release. Overall the data raise the possibility that the cannabinoid system plays a role in the modulation of adenosine transmission in the MPLM.

Adenosine↗
PubMed2001

Signal transduction of cannabinoid CB1 receptors in a smooth muscle cell line.

1. The effects of cannabinoid (CB) receptor stimulation on membrane currents in single cells from the Syrian hamster vas deferens cell line DDT1MF-2 were investigated using the whole cell patch clamp technique. 2. The CB receptor agonist CP55,940 evoked a concentration-dependent transient outward current. The selective CB1 receptor ligand SR141716 (1 microM), but not the selective CB2 receptor ligand SR144528 (1 microM), inhibited the outward current. Pertussis toxin (100 ng ml-1 for 20 h) completely abolished the outward current. 3. Western blotting with an antibody against the rat (r)CB1 receptor showed a band characteristic for the CB1 receptor around 63 kDa in DDT1MF-2 cells. 4. The reversal potential for the outward current measured using a voltage ramp protocol was -84 +/- 5 mV. The current was inhibited by the Ca2+-dependent K+ channel blockers iberiotoxin (10 nM) and charybdotoxin (10 nM). 5. Removal of Ca2+ from the bathing solution, or the addition of 0.1 mM Cd2+ completely abolished the outward current evoked by 10 microM CP55,940. 6. The sarcoplasmic Ca2+ pump inhibitor thapsigargin reduced the outward current evoked by 10 microM CP55,940 in a concentration-dependent manner. 7. The mitogen-activating protein kinase (MAP kinase) inhibitor PD98059, but not the phospholipase C inhibitor U73122, inhibited the outward current evoked by 10 microM CP55,940. 8. The adenylyl cyclase inhibitor SQ22,536 (100 microM) and 8-Br-cyclic AMP (10 microM) significantly reduced the outward current evoked by 10 microM CP55,940. 9. Our data suggest that CB1 receptor stimulation in DDT1MF-2 cells leads to activation of a large conductance Ca2+-dependent K+ channel through a Gi/Go protein-mediated rise in [Ca2+]i, for which both inhibition of adenylyl cyclase and activation of MAP kinase are required. In addition, the cannabinoid-induced increase in [Ca2+]i is likely to arise from capacitive Ca2+ entry.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Observations on patellar height following opening wedge proximal tibial osteotomy.

Patellar height and patellar ligament length were assessed pre- and postoperatively in 28 patients who underwent a medial opening wedge proximal tibial osteotomy for varus gonarthrosis. This procedure produced no significant change in patellar ligament length. Pre- and postoperative Insall-Salvati ratios were 0.96+/-0.12 and 0.97+/-0.15, respectively (P=.30). The Insall-Salvati ratio decreased in 29% of patients, and no patient experienced a decline >0.07. The distance between the patella and tibiofemoral joint line ("patellar height") decreased in 100% of patients. The mean Blackburne-Peel ratio declined from 0.75+/-0.13 to 0.53+/-0.15 (P<.001). Sixty-four percent of the postoperative Blackburne-Peel values satisfied the radiographic criterion for patella infera (Blackburne-Peel ratio <0.54). Whereas the loss of patellar height, historically associated with lateral closing wedge proximal tibial osteotomy, is a function of patellar ligament contracture, the decreased distance between the patella and the tibiofemoral joint line following medial opening wedge proximal tibial osteotomy is a function of joint line elevation. The high incidence of patella infera following medial opening wedge proximal tibial osteotomy may have deleterious effects on patellofemoral biomechanics or may complicate subsequent total knee arthroplasty.

Adult↗
PubMed1996

Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis.

BACKGROUND & AIMS: Cyclin D1 gene amplification and/or overexpression occurs in several human cancers. The level of expression of cyclin D1 protein during the multistage process of human colon carcinogenesis was determined. METHODS: Cyclin D1 protein abundance was determined by immunostaining samples of normal colonic mucosa(n=23), transitional normal mucosa adjacent to adenomas or adenocarcinomas (n=41), hyperplastic polyps (n=8), adenomatous polyps (=35), and adenocarcinomas (n=27), using a polyclonal anti-human cyclin D1 antibody. RESULTS: Cyclin D1 nuclear staining occurred in 30% of adenocarcinomas and 34% of adenomatous polyps but not in hyperplastic polyps or normal or transitional mucosa. Nuclear staining did not correlate with sex, age, size, or dysplasia of the adenomatous polyps or with differentiation and Dukes' staging of the adenocarcinomas. Left-sided colon neoplasms showed nuclear staining more frequently than those right-sided lesions. Diffuse or supranuclear cytoplasmic staining occurred in about one third of hyperplastic polyps, adenomas, and adenocarcinomas and in transitional mucosa adjacent to adenocarcinoma. CONCLUSIONS: Increased nuclear expression of cyclin D1 occurs in around one third of colonic tumors as an early event during multistage process of colon carcinogenesis. Increased expression of cyclin D1 may perturb cell-cycle control in benign adenomas and thereby enhance tumor progression.

Adenocarcinoma↗
PubMed1993

Maternal exercise during pregnancy, physical fitness, and fetal growth.

The value of exercise during pregnancy is controversial; both benefits and risks have been hypothesized. As empiric evidence is scant, the issue was investigated in a prospective study that assessed the impact on fetal growth of maternal exercise in each trimester of pregnancy. A cohort of over 800 prenatal patients was recruited from obstetric practices in Pennsylvania and New York between January 1987 and June 1989. Subjects were interviewed at entry into care and recontacted at 28 and 36 weeks of gestation. In women with prior adverse outcomes or a lack of conditioning, the associations between maternal exercise and fetal growth were equivocal. In fit, low-risk, prenatal patients, exercise was positively associated with fetal growth. With low-moderate exercise levels, the adjusted mean birth weights were about 100 g higher than in nonexercisers (117 g; 95% confidence interval 17 to 217 g). With heavier exercise, larger birth weight increments were seen, close to 300 g in those who exercised throughout pregnancy at levels of about 2,000 kcal/week in energy expenditure (276 g; 95% confidence interval 54 to 497 g). These results suggest that the guidelines issued by the American College of Obstetricians and Gynecologists may be too stringent for well-conditioned, low-risk, prenatal patients. Additional research to define safe limits more precisely seems warranted.

Adult↗