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Joseph S McLaughlin

Publications and source records attributed to Joseph S McLaughlin.

5 recordsLinked to original sources

Dynorphin A inhibits NMDA receptors through a pH-dependent mechanism.

Dynorphin A (DynA), an endogenous agonist of kappa-opioid receptors, has also been reported to directly interact with the NMDA receptor. DynA inhibition of NMDA receptor function has been suggested to be involved in its neuroprotective action during ischemic and acidic conditions. However, the effect of external pH on DynA inhibition of the NMDA receptor has not been reported. Here, we show that DynA inhibition of the NMDA receptor is dependent on extracellular pH over the range of pH 6.7-8.3, and the inhibition by 10 microM DynA increases at low pH by three- to four-fold in hippocampal neurons and in Xenopus oocytes expressing NR1-1a/2B subunits. Molecular studies showed that the interacting site for DynA on the NMDA receptor is distinct from that of proton or redox sites. Peptide mapping demonstrated important contributions of positively charged residues and specific structural organization of the peptide to the potency of DynA inhibition. Thus, DynA inhibits NMDA receptors through an allosteric mechanism, which is pH dependent and involves the specific structural features of the peptide.

Allosteric Regulation↗

The renegade fact.

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Aorta, Thoracic↗

Beating-heart mitral valve surgery: preliminary model and methodology.

OBJECTIVE: It is our hypothesis that image-guided mitral valve repair can be performed on the beating heart without cardiopulmonary bypass. As a first phase, we tested the feasibility of suturing the anterior and posterior mitral valve leaflets under image guidance. METHODS: In a water bath model, imaging approaches and suturing techniques were developed. Then, in 6 pigs, the left atrium was cannulated with a custom-made 15-mm valved port through a left thoracotomy. Atrial pressure was elevated by shunting of arterial blood to minimize air induction. A multiplane transesophageal echocardiographic probe was evaluated in the intraesophageal and epicardial positions. With a commercial endoscopic suturing device, sutures were placed through the anterior and posterior mitral leaflets under echocardiographic guidance. The animals were killed, and suture accuracy was evaluated by measuring the distance from the intended target areas on the anterior and posterior mitral leaflets. Air induction was monitored by echocardiography and graded as minimal to severe. RESULTS: There were no cases of hemodynamic instability or significant arrhythmia. The most effective imaging plane was a short-axis view that used the transesophageal echocardiographic probe epicardially at the heart base. Air induction was minimal in 2 animals, mild in 3, and moderate in 1. Sutures were successfully placed 9 of 12 times (mean error 0.8 +/- 0.5 cm). CONCLUSIONS: With these methods, off-pump, image-guided suturing of the beating-heart mitral valve was possible. This model may be a useful starting point for developing off-pump mitral valve repair procedures.

Animals↗

Management of traumatic aortic rupture: a 30-year experience.

OBJECTIVE: To present the authors' 30-year experience with traumatic aortic rupture (TAR). SUMMARY BACKGROUND DATA: TAR is a highly lethal injury. Most institutions manage a small number of cases, and most surgeons receive only modest exposure during training. METHODS: Between 1971 and 2001, the authors operated on 219 patients with a diagnosis of TAR. Diagnosis of TAR since 1994 has been based exclusively on the use of contrast-enhanced spiral computed tomography, with angiography reserved for equivocal cases (periaortic mediastinal hematoma without aortic wall abnormalities). Patients were divided according to surgical technique. Eighty-two patients (group A) were operated on with a clamp-and-sew technique. Sixty-four patients (group B) underwent surgery with the use of a passive shunt, and 73 patients (group C) were treated using heparin-less partial cardiopulmonary bypass. RESULTS: Mortality was 18 patients for group A (21.9%), 23 patients for group B (35.9%), and 13 patients for group C (17.8%) (P =.03). Paraplegia occurred in 15 of 64 survivors in group A (23.4%), 7 of 41 survivors in group B (17%), and 0 of 60 survivors in group C ( P=.0005). Aortic occlusion without lower body perfusion for longer than 30 minutes (P =.004) and surgical technique without lower body bypass support (P =.0005) were associated with paraplegia. CONCLUSIONS: Surgery for TAR based on spiral computed tomography screening and diagnosis is reliable. The use of heparin-less distal cardiopulmonary bypass in the authors' hands is safe and is associated with a reduced incidence of paraplegia.

Adolescent↗