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Biomedical subjects

P Cummins

Publications and source records attributed to P Cummins.

At least 19 recordsLinked to original sources
PubMed2006

Functional interplay between platelet activation and endothelial dysfunction in patients with coronary heart disease.

Platelet-monocyte binding and surface P-selectin expression are sensitive markers of platelet activation. Endothelium-derived factors are known to inhibit platelet activation and may confer important anti-atherothrombotic effects. We assessed the relationship between platelet activation and endothelium-dependent vasomotion in patients with coronary heart disease (CHD). Twenty male patients with stable CHD were compared with 20 healthy men. Platelet-monocyte binding and platelet surface expression of P-selectin were assessed using two-colour flow cytometry on whole blood. Forearm blood flow was assessed in patients using venous occlusion plethysmography during intra-arterial infusions of substance P, acetylcholine and sodium nitroprusside. Platelet activation was higher in patients than healthy men (platelet-monocyte binding, 27 +/- 3 vs. 20 +/- 1%; P < 0.05). In patients with CHD, there was an inverse correlation between maximal substance P induced vasodilatation and both platelet-monocyte binding (P = 0.003) and P-selectin expression (P = 0.02). A similar correlation was observed between platelet-monocyte binding and the vasomotor response to acetylcholine (P = 0.08) but not with sodium nitroprusside. In patients with stable coronary heart disease, there is a strong inverse relationship between markers of platelet activation and endothelium-dependent vasomotor function. This may explain the pathophysiological mechanism linking endothelial vasomotor dysfunction and the risk of acute atherothrombotic events.

Analysis of Variance↗
PubMed2001

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Acetaminophen↗
PubMed2001

Altered expression of C/EBP family members results in decreased adipogenesis with aging.

Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-alpha, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBP alpha in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBP alpha-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP beta, which modulates C/EBP alpha-expression, did not change with age, but the truncated, dominant-negative C/EBP beta-liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP beta-LIP in preadipocytes from young rats impaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.

Adipocytes↗
PubMed2000

Preference for nonsteroidal antiinflammatory drugs versus acetaminophen and concomitant use of both types of drugs in patients with osteoarthritis.

OBJECTIVE: To analyze results of treatment of osteoarthritis (OA) with acetaminophen and the nonsteroidal antiinflammatory drugs (NSAID) through a patient survey. METHODS: A 15 minute telephone survey was conducted with 300 patients, including 172 with confirmed OA. RESULTS: Twenty-four percent of patients who took acetaminophen rated it as "very helpful," compared to 31% for ibuprofen, 30% for naproxen, and 56% for diclofenac. Drug continuation beyond 24 months was reported by 33% of patients for acetaminophen, 21% for ibuprofen, 17% for naproxen, and 19% for diclofenac. Acetaminophen was significantly less likely to be discontinued because of toxicity than NSAID. Patients who indicated that they would not take a drug again, and therefore be unlikely to participate in a clinical trial involving this drug, were 26% for acetaminophen, 40% for ibuprofen, 38% for naproxen, and 28% for diclofenac. About 30% of patients who took acetaminophen reported concurrent use of ibuprofen, naproxen, or diclofenac. Among the 67% of patients who identified a drug as "most helpful," 80% named an NSAID, compared to 20% who named acetaminophen or another analgesic as the "most helpful" drug. CONCLUSION: Patients take many different drugs for OA, most of which are not continued beyond 2 years. Many patients take both acetaminophen and an NSAID. Most patients who identified a drug as "most helpful" named an NSAID rather than acetaminophen or an analgesic drug. These findings may be of value in further development of management strategies and guidelines for OA.

Acetaminophen↗
PubMed1998

Phosphorylation-specific antibodies for human cardiac troponin-I.

A panel of seven monoclonal antibodies (mAbs) raised against cardiac troponin-I (CdTnI) isolated from canine and human hearts, which have been shown to be cardiac-specific but cross-species reactive [Cummins, B., Aukland, M. L. & Cummins, P. (1987) Amer. Heart J. 113, 1333-1344], were used in this study. These mAbs were tested against recombinant wild-type and mutant human CdTnI proteins to assess their value as probes for the phosphorylation status of CdTnI. Four mAbs were found to react positively with the recombinant wild-type protein and their epitopes were contained in residues 31-210 of the human cardiac protein. Two of these mAbs appeared to be directed against the same epitope site within this region. The remaining three mAbs only reacted against the recombinant wild-type protein when it was phosphorylated, showing that these three antibodies were directed against the phosphate group(s) on Ser23 and/or Ser24. In order to investigate this further, a series of single and double mutants of CdTnI were used in which either Ala (to direct the enzymatic phosphorylation) or Asp (to mimic the phosphate group) replaced the Ser23 and/or Ser24. It was found the all three mAbs were able to react with the mono-phosphorylated form of the [Ala23]CdTnI single mutant but not the mono-phosphorylated form of the [Ala24]CdTnI single mutant, showing that they specifically required phosphorylation at Ser24. Experiments with a synthetic peptide composed of residues 1-29 of human CdTnI confirmed these data. Two of the three phosphorylation-specific mAbs were able to react with mutants containing either two Asp residues replacing Ser23 and Ser24 or one Asp residue instead of Ser24, indicating that a negative charge at position Ser24 is sufficient to invoke a reaction. The other mAb was more specific in that it would only react with CdTnI species with a phosphate group on Ser24.

Amino Acid Sequence↗
PubMed1998

Differential changes in transforming growth factor-beta isoform expression during postnatal cardiac growth.

Transforming growth factor-beta (TGF-beta) is synthesised as an inactive precursor protein; this is cleaved to produce the mature peptide and a latency associated protein (LAP), which remains associated with the mature peptide until activation by LAP degradation. Isoform specific antibodies raised against the LAPs for TGF-beta 2 and -beta 3 were used to determine the myocardial levels of LAP (activatable TGF-beta) and full length precursor (inactive TGF-beta) forms during post-natal development in the rat. TGF-beta 2 was present predominantly as the precursor in 2 day old myocardium. There was an age-dependent shift from precursor protein to LAP between 2 and 28 days. A corresponding increase in the level of mature (activatable) TGF-beta 2 was found. TGF-beta 3 was detected in significant quantities only as LAP. However, a four-fold increase in the expression of TGF-beta 3 LAP was observed between 2 and 28 days. The substantial increases in activatable forms of TGF-beta 2 and -beta 3 that occur in myocardium during the first 28 days of life in the rat support a role for these proteins in post-natal cardiac development.

Amino Acid Sequence↗
PubMed1997

The Structure of Nonionic Micelles in Less Polar Solvents

Small angle neutron scattering, SANS, has been used to investigate the structure and geometry of nonionic micelles of monododecyl octaethylene glycol C12EO8, monododecyl hexaethylene glycol C12EO6, and monohexadecyl octaethylene glycol C16EO8 in less polar solvents: mixed solvents of water and glycerol, sorbitol, and ethylene glycol. For C12EO8 in glycerol/water solvent mixtures the addition of glycerol results in an increase in the micelle aggregation number and a decrease in the ethylene oxide (EO) headgroup hydration. The increase in micelle size is associated with the dehydration of the ethylene oxide headgroup and the consequent closer proximity of the lower consolute boundary. This follows from the observation that the same trends are seen at fixed glycerol content and increasing temperature where the intermicellar interactions become attractive. For C12EO6 micelles in water/ethylene glycol mixtures similar trends are observed, and the same conclusions may be drawn despite an increase in the clouding temperature. This can be explained by a greater dehydration of the solvent ethylene glycols such that the rate of change of solvent quality for the micelles with temperature is suppressed. A combination of SANS and Couette shear flow alignment has been used to investigate the structure of C16EO8 micelles in water/sorbitol and water/glycerol mixtures. The addition of sorbitol or glycerol results in less anisotropically shaped micelles. The resulting micelles are more labile, and show evidence of flexibility and shear induced transformations or extreme polydispersity. The temperature dependence of the micelle rod length of C16EO8/water/glycerol is similar to that previously observed for C16EO6 and C16EO8 micelles in water and for the mixed micelles of C16EO6/C16TAB.

Journal Article↗
PubMed1995

The relationship between the pressor response to involuntary isometric exercise and the contractile protein profile of the active muscle in man.

The present investigation examined the relationship between the pressor response during electrically evoked isometric ankle plantar flexion and the contractile protein profile of the active muscle in seven young men [mean (SD) age, 26 (6) years] and five older men [70 (4) years]. Muscle biopsy samples were taken from lateral gastrocnemius (LG) and soleus (SOL) of each subject. These were analysed for isomyosin composition using non-denaturing pyrophosphate polyacrylamide gel electrophoresis. The degree of association was examined between the cardiovascular changes and the fast isomyosin content of LG and SOL individually and in combination (SOL/LG). In the total subject group there was no association between the heart rate response or the change in systolic blood pressure (BP) and the fast isomyosin composition. However, the change in diastolic BP was significantly associated with the fast isomyosin composition of SOL/LG (delta diastolicBP = 0.31 + 0.045% FM SOL/LG, r = 0.65, P = 0.029). These findings suggest that the magnitude of the peripheral reflex mediated pressor response to isometric exercise and the fast isomyosin content of the active muscle are related.

Adult↗
PubMed1995

Electrically evoked torque-velocity characteristics and isomyosin composition of the triceps surae in young and elderly men.

The electrically evoked isokinetic torque-velocity relationship of the triceps surae of eight elderly and four non-trained young men was examined in relation to the isomyosin composition of the soleus and the gastrocnemius muscles, determined under non-denaturing conditions using pyrophosphate gel electrophoresis. The angle specific torque-velocity properties of the triceps surae were measured using maximal percutaneous electrical stimulation at 50 Hz and a release technique. The elderly subjects generated significantly (P < 0.05) less absolute torque at all angular velocities when compared with the young subjects. When the isokinetic data were normalized to the isometric torque, the lower normalized torques generated by the elderly subjects were not statistically different from the young. The total fast isomyosin (FM) content of the soleus and gastrocnemius in the elderly subjects was 22 +/- 13 and 35+/- 18%, respectively. This compared with 29 +/- 8 (n.s) and 44 +/- 8% (n.s.) in the young subjects. When the gastrocnemius and soleus muscles were given an equal weighting and considered together to represent the whole triceps surae, the normalized torque at the fixed angular velocity of 5 rads s-1 was significantly associated with %FM (r = 0.90, P < 0.01), and the isomyosin bands %FM1 (r = 0.90, P < 0.01) and %FM2 (r = 0.93, P < 0.001) when only the elderly subjects were considered. No relationships were observed between contractile characteristics and contractile protein profile when only the young subjects were considered. This was despite the inclusion of a further two sprint and three endurance trained athletes to increase the range of contractile characteristics and differences in muscle composition.

Adult↗
PubMed1991

Release of creatine kinase-MB and cardiac specific troponin-I following percutaneous transluminal coronary angioplasty.

Up to 20% of patients undergoing successful coronary angioplasty have been shown to have a mild elevation of creatine kinase-MB (CK-MB). The purpose of this study was to investigate the relationship between clinical and angioplasty procedural variables and circulating markers for cardiac injury. We measured both CK-MB and totally cardiac-specific troponin inhibitory protein (Tn-I) in 22 patients immediately before and at an average time of 10 h 36 min following successful angioplasty. Of these patients 16 had stable angina, six had unstable angina and none had recent myocardial infarction. Four patients had minor complications associated with the procedure (prolonged chest pain, limited coronary artery dissection) but none of these patients had increases in either CK-MB or Tn-I. In two patients there was a mild increase in enzyme-activity assayed CK-MB but none of the 22 patients had significant elevation of mass-assayed CK-MB or cardiac-specific Tn-I. This study supports the view that no significant myocardial damage occurs as a result of successful coronary angioplasty irrespective of the stability of the coronary artery disease. This study confirms the known discrepancies between results obtained by immunoassay and immunoinhibition enzyme assay, due to the false-positive results which can be yielded by the latter technique.

Angina Pectoris↗