Biomedical subjects

Jeffrey D Lee

Publications and source records attributed to Jeffrey D Lee.

5 recordsLinked to original sources

PubMed2005

Analysis of mouse embryonic patterning and morphogenesis by forward genetics.

Many aspects of the genetic control of mammalian embryogenesis cannot be extrapolated from other animals. Taking a forward genetic approach, we have induced recessive mutations by treatment of mice with ethylnitrosourea and have identified 43 mutations that affect early morphogenesis and patterning, including 38 genes that have not been studied previously. The molecular lesions responsible for 14 mutations were identified, including mutations in nine genes that had not been characterized previously. Some mutations affect vertebrate-specific components of conserved signaling pathways; for example, at least five mutations affect previously uncharacterized regulators of the Sonic hedgehog (Shh) pathway. Approximately half of all of the mutations affect the initial establishment of the body plan, and several of these produce phenotypes that have not been described previously. A large fraction of the genes identified affect cell migration, cellular organization, and cell structure. The findings indicate that phenotype-based genetic screens provide a direct and unbiased method to identify essential regulators of mammalian development.

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PubMed2005

Depression, anxiety and neuropsychological test scores of candidates for coronary artery bypass graft surgery.

The effect of depression and anxiety upon neuropsychological test scores of candidates for coronary artery bypass graft (CABG) surgery was examined. Sixty patients were administered the Beck Depression Inventory II and the State-Trait Anxiety Inventory, along with a battery of neuropsychological tests. Regression analyses were conducted in which the neuropsychological test scores were predicted using age, education, depression, anxiety, and combined depression-anxiety scores. While age and education were significant predictors of several neuropsychological test measures, no significant regression analysis results were obtained for the depression, anxiety and combined depression-anxiety scores. Similarities and discrepancies between this research and previous studies are discussed. It appears that low levels of preoperative depression and anxiety states do not affect neuropsychological functioning among CABG candidates.

Aged↗

PubMed2004

A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development.

The wave of differentiation that traverses the Drosophila eye disc requires rapid transitions in gene expression that are controlled by a number of signaling molecules also required in other developmental processes. We have used a mosaic genetic screen to systematically identify autosomal genes required for the normal pattern of photoreceptor differentiation, independent of their requirements for viability. In addition to genes known to be important for eye development and to known and novel components of the Hedgehog, Decapentaplegic, Wingless, Epidermal growth factor receptor, and Notch signaling pathways, we identified several members of the Polycomb and trithorax classes of genes encoding general transcriptional regulators. Mutations in these genes disrupt the transitions between zones along the anterior-posterior axis of the eye disc that express different combinations of transcription factors. Different trithorax group genes have very different mutant phenotypes, indicating that target genes differ in their requirements for chromatin remodeling, histone modification, and coactivation factors.

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PubMed2003

Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial.

BACKGROUND: Neurologic and clinical morbidity after coronary artery bypass grafting (CABG) can be significant. By avoiding cardiopulmonary bypass, off-pump CABG (OPCAB) may reduce morbidity. METHODS: Sixty patients (30 CABG and 30 OPCAB) were prospectively randomized. Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation. Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward. Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli. All examiners were blinded to treatment group. Clinical morbidity and costs were compared. RESULTS: Coronary artery bypass grafting was associated with more cerebral microemboli (575 +/- 278.5 CABG versus 16.0 +/- 19.5 OPCAB (median +/- semiinterquartile range) and significantly reduced cerebral perfusion after the operation to the bilateral occipital, cerebellar, precunei, thalami, and left temporal lobes (p < or = 0.01). Cerebral perfusion with OPCAB was unchanged. Compared with base line, OPCAB patients performed better on the Rey Auditory Verbal Learning Test (total and recognition scores) at both 2 weeks and at 1 year (p < or = 0.05), whereas CABG performance was statistically unchanged for all cognitive measures. Patients who underwent CABG had more chest tube drainage (1389 +/- 1256 mL CABG versus 789 +/- 586 mL OPCAB, p = 0.02) and required more blood (3.9 +/- 5.8 U CABG versus 1.2 +/- 2.2 U OPCAB, p = 0.02), fresh frozen plasma (3.0 +/- 6.0 U CABG versus 0.5 +/- 2.2 U OPCAB, p = 0.03), and hours of postoperative use of dopamine (16.3 +/- 21.2 hours CABG versus 7.3 +/- 9.7 hours OPCAB, p = 0.04). These differences culminated in higher costs for CABG ($23,053 +/- $5,320 CABG versus $17,780 +/- $4,390 OPCAB, p < 0.0001). One stroke occurred with CABG, compared with none with OPCAB (p = NS). One OPCAB patient died because of a pulmonary embolus (p = NS). CONCLUSIONS: Compared with CABG, OPCAB may reduce neurologic and clinical morbidity as well as cost.

Aged↗

PubMed2002

The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms.

Photoreceptor differentiation in the Drosophila eye disc progresses from posterior to anterior in a wave driven by the Hedgehog and Decapentaplegic signals. Cells mutant for the hyperplastic discs gene misexpress both of these signaling molecules in anterior regions of the disc, leading to premature photoreceptor differentiation and overgrowth of surrounding tissue. The two genes are independently regulated by hyperplastic discs; decapentaplegic can still be misexpressed in cells mutant for both hyperplastic discs and hedgehog, and a repressor form of the transcription factor Cubitus interruptus can block decapentaplegic misexpression but not hedgehog misexpression. Loss of hyperplastic discs causes the accumulation of full-length Cubitus interruptus protein, but not of Smoothened, in both the eye and wing discs. hyperplastic discs encodes a HECT domain E3 ubiquitin ligase that is likely to act by targeting Cubitus interruptus and an unknown activator of hedgehog expression for proteolysis.

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