Biomedical subjects

Jesse J Smith

Publications and source records attributed to Jesse J Smith.

5 recordsLinked to original sources

PubMed2004

Cold visceral perfusion improves early survival in patients with acute renal failure after thoracoabdominal aortic aneurysm repair.

INTRODUCTION: Despite advances in organ protection during thoracoabdominal aortic aneurysm (TAAA) repair, acute renal failure (ARF) remains a significant clinical problem, associated with increased morbidity and mortality. We studied outcome of ARF after TAAA repair in patients who underwent either warm or cold visceral perfusion. METHOD: Between 1991 and 2001 657 TAAA repairs were performed, of which 359 (55%) had either warm or cold visceral perfusion. Twelve patients with renal failure who had undergone preoperative dialysis were excluded from the study. Of the remaining 347 patients, ARF developed in 81 (23%) after TAAA repair. Forty-four (54%) of the 81 patients with ARF received cold visceral perfusion, and 37 (46%) patients received warm visceral perfusion. ARF was defined as either an increase of 1 mg/dL in serum creatinine (SCr) concentration per day for 2 consecutive days or dialysis requirement. Patient records were reviewed through hospital discharge. RESULTS: Twenty six (32%) of the 81 patients in whom ARF developed died, 17 of 37 (46%) patients in the warm perfusion group versus 9 of 44 (21%) patients in the cold perfusion group (P <.02). Median onset of ARF was on postoperative day 1 in both groups. Twenty-six of 81 (32%) patients recovered renal function, 10 of 37 (27%) patients in the warm perfusion group versus 16 of 44 (36%) patients in the cold perfusion group. Preoperative SCr concentration was predictive of recovery of renal function (odds ratio, 4.5 per mg/dL increase; P <.03) in patients who received either warm or cold visceral perfusion. CONCLUSIONS: ARF after TAAA repair remains a significant clinical problem. Recovery of renal function occurred in approximately one third of patients. Preoperative SCr concentration was the only significant determinant of recovered renal function. While cold visceral perfusion did not alter renal recovery, it significantly reduced hospital mortality.

Acute Kidney Injury↗

PubMed2004

Multiplex GPCR assay in reverse transfection cell microarrays.

G protein-coupled receptors (GPCRs) are a superfamily of proteins that include some of the most important drug targets in the pharmaceutical industry. Despite the success of this group of drugs, there remains a need to identify GPCR-targeted drugs with greater selectivity, to develop screening assays for validated targets, and to identify ligands for orphan receptors. To address these challenges, the authors have created a multiplexed GPCR assay that measures greater than 3000 receptor: ligand interactions in a single microplate. The multiplexed assay is generated by combining reverse transfection in a 96-well plate format with a calcium flux readout. This assay quantitatively measures receptor activation and inhibition and permits the determination of compound potency and selectivity for entire families of GPCRs in parallel. To expand the number of GPCR targets that may be screened in this system, receptors are cotransfected with plasmids encoding a promiscuous G protein, permitting the analysis of receptors that do not normally mobilize intracellular calcium upon activation. The authors demonstrate the utility of reverse transfection cell microarrays to GPCR-targeted drug discovery with examples of ligand selectivity screening against a panel of GPCRs as well as dose-dependent titrations of selected agonists and antagonists.

Dose-Response Relationship, Drug↗

PubMed2002

The effect of aortic dissection on outcome in descending thoracic and thoracoabdominal aortic aneurysm repair.

It is estimated that 20% to 40% of the patients who survive the acute phase of aortic dissection will develop significant aneurysmal dilatation of the descending thoracic or thoracoabdominal aorta. Aortic dissection has long been considered a risk factor for mortality and neurologic deficit following surgical repair of the descending thoracic and/or thoracoabdominal aorta. In this article we review the surgical approach to patients with aortic dissection and thoracoabdominal aortic aneurysms and discuss the impact of adjuncts on survival and neurologic outcome.

Aortic Dissection↗

PubMed2002

Is acute type A aortic dissection a true surgical emergency?

Untreated acute aortic dissection involving the ascending aorta (type A) is associated with a high early mortality owing to rupture. Despite advancements in surgical technique and critical care, early mortality remains high. Operative mortality may be related to the technical challenges associated with intervening on the acutely dissected aorta as well as the multiorgan insult it induces. In this article, we review our approach to acute type A aortic dissection with regard to diagnosis, initial medical management, surgical repair, and timing of repair.

Acute Disease↗

PubMed2002

Apoptotic regulation by the Crk adapter protein mediated by interactions with Wee1 and Crm1/exportin.

The adapter protein Crk contains an SH2 domain and two SH3 domains. Through binding of particular ligands to the SH2 domain and the N-terminal SH3 domain, Crk has been implicated in a number of signaling processes, including regulation of cell growth, cell motility, and apoptosis. We report here that the C-terminal SH3 domain, never shown to bind any specific signaling molecules, contains a binding site for the nuclear export factor Crm1. We find that a mutant Crk protein, deficient in Crm1 binding, promotes apoptosis. Moreover, this nuclear export sequence mutant [NES(-) Crk] interacts strongly, through its SH2 domain, with the nuclear tyrosine kinase, Wee1. Collectively, these data suggest that a nuclear population of Crk bound to Wee1 promotes apoptotic death of mammalian cells.

Active Transport, Cell Nucleus↗