Biomedical subjects

Paul Lee

Publications and source records attributed to Paul Lee.

43 records · Page 3Linked to original sources

PubMed2002

Glucocorticoid hormones and early brain development in schizophrenia.

While genetic factors play a role in the etiology of schizophrenia, environmental factors contribute to the etiology of the disorder as well. If a woman is exposed during the second trimester of gestation to stressors such as the death of a loved one, influenza infection, or natural and man-made disasters, her baby has an increased risk of developing schizophrenia later in life. A common mechanism may mediate the effects of these diverse risk factors: a stress response during a restricted period of gestation may affect fetal brain development and, given the appropriate genetic predisposition, result in schizophrenia in adult life. Findings in animals exposed to prenatal stress strengthen the hypothesis that exposure to high glucocorticoid levels and/or other components of the stress response increases the risk of schizophrenia. These clinical and preclinical studies could be used to develop hypotheses that could then be tested in patients with schizophrenia.

Animals↗

PubMed2002

Overexpression of yeast Hsp110 homolog Sse1p suppresses ydj1-151 thermosensitivity and restores Hsp90-dependent activity.

The Saccharomyces cerevisiae heat-shock protein (Hsp)40, Ydj1p, is involved in a variety of cellular activities that control polypeptide fate, such as folding and translocation across intracellular membranes. To elucidate the mechanism of Ydj1p action, and to identify functional partners, we screened for multicopy suppressors of the temperature-sensitive ydj1-151 mutant and identified a yeast Hsp110, SSE1. Overexpression of Sse1p also suppressed the folding defect of v-Src kinase in the ydj1-151 mutant and partially reversed the alpha-factor translocation defect. SSE1-dependent suppression of ydj1-151 thermosensitivity required the wild-type ATP-binding domain of Sse1p. However, the Sse1p mutants maintained heat-denatured firefly luciferase in a folding-competent state in vitro and restored human androgen receptor folding in sse1 mutant cells. Because the folding of both v-Src kinase and human androgen receptor in yeast requires the Hsp90 complex, these data suggest that Ydj1p and Sse1p are interacting cochaperones in the Hsp90 complex and facilitate Hsp90-dependent activity.

Adenosine Triphosphate↗

PubMed2002

Hyperhomocysteinemia and venous thrombosis.

Deep vein thrombosis (DVT) leads to venous ulcers in later life. Venous ulcers are the majority of chronic lower extremity wounds. Recent evidence suggests that hyperhomocysteinemia is an independent risk factor for venous thrombosis. Other evidence suggests that dietary supplementation with folic acids and vitamins helps to change hyperhomocysteinemia. This may be the key to wound management in future.

Journal Article↗

PubMed2002

Transforming growth factor beta mimetics: discovery of 7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid, a biaryl hydroxamate inhibitor of histone deacetylase.

Transforming growth factor beta (TGF-beta) is a multifunctional protein that has been shown to possess potent growth-inhibitory activity. To identify small molecular weight compounds with TGF-beta-like activities, high throughput screening was performed using mink lung epithelial cells stably transfected with a TGF-beta-responsive plasminogen activator inhibitor 1 promoter/luciferase construct. Biaryl hydroxamate compounds were identified that demonstrated TGF-beta-like activities. 7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid (A-161906) demonstrated complete TGF-beta-like agonist activity in the plasminogen activator inhibitor 1/luciferase construct. A-161906 inhibited the proliferation of multiple cell lines in a concentration-dependent manner. Cells were growth arrested at the G1-S checkpoint similar to TGF-beta. Consistent with the G1-S arrest, A-161906 induced the expression of the cyclin-dependent kinase inhibitor p21waf1/cip1. A-161906 produced many cellular effects similar to that of TGF-beta but did not displace labeled TGF-beta from its receptors. Cells with mutations in either of the TGF-beta receptors I or II were growth-arrested by A-161906. Therefore, the site of action of A-161906 appears to be distal to the receptors and possibly involved with the signaling events controlled by TGF-beta. The TGF-beta mimetic effect of A-161906 can be partially, if not entirely, explained by its activity as a histone deacetylase (HDAC) inhibitor. A-161906 demonstrated potent HDAC-inhibitory activity (IC50 = 9 nM). A-161906 is a novel small molecular weight compound (< 400 MW) having TGF-beta mimetic activity as a result of its potent HDAC-inhibitory activity. These results and those of others demonstrate the importance of HDACs in regulation of the TGF-beta signaling pathway(s).

Acetylation↗

PubMedDate not supplied

The challenge of staphylococcal pacemaker endocarditis in a patient with transposition of the great arteries endocarditis in congenital heart disease.

Staphylococcus aureus is a leading cause of septicaemia and infective endocarditis. The overall incidence of staphylococcal bacteraemia is increasing, contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac pacemakers has revolutionized the management of rhythm disturbances, yet this has also resulted in a group of patients at risk of pacemaker lead endocarditis and seeding in the range of 1% to 7%. We describe a 26-year-old man with transposition of the great arteries who had a pacemaker implanted and presented with S. aureus septicaemia 2 years postpacemaker implantation and went on to develop pacemaker lead endocarditis. This report illustrates the risk of endocarditis in the population with congenital heart disease and an intracardiac device.

Adult↗

PubMedDate not supplied

Visual acuity following cataract surgeries in relation to preoperative appropriateness ratings.

The authors initiated this study to consider if the formal preoperative assessment of appropriate or inappropriate utilization of cataract surgery by an expert panel could predict postoperative improvement or decline in visual acuity. They evaluated the association between ratings of appropriateness, as determined by the RAND-UCLA method, and measurements of postoperative visual acuity using Fisher's exact tests for tables greater than 2 x 2. For 768 patients, improvement of at least 2 Snellen chart lines occurred in 89% of surgeries rated as appropriate or appropriate and crucial, 68% rated as uncertain, and 36% rated as inappropriate (P < 0.0001, Fisher's exact test). These results provide evidence supporting the validity of the RAND-UCLA method to assess the appropriateness of surgery.

Aged↗

PubMedDate not supplied

Designing a simple help card for use with a syringe driver.

This paper describes how a small, simple-to-use, help card was developed for use with a Graseby MS16A syringe driver that can be used with a variety of sizes and manufacturers' syringes. Also described are ways in which it may help to reduce the chance of accidental error when setting up and monitoring the delivery of 24-hour subcutaneous infusions for pain and symptom control.

Attitude of Health Personnel↗