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J C Hart

Publications and source records attributed to J C Hart.

At least 19 recordsLinked to original sources
PubMed2001

Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300.

We investigated whether peroxisome proliferator-activated receptor gamma (PPARgamma) ligands (ciglitazone, troglitazone, and 15-deoxy-Delta(12,14) prostaglandin J(2)) inhibited cyclooxygenase-2 (COX-2) induction in human epithelial cells. Ligands of PPARgamma inhibited phorbol ester (phorbol 12-myristate 13-acetate, PMA)-mediated induction of COX-2 and prostaglandin E(2) synthesis. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by PPARgamma ligands. PMA-mediated induction of COX-2 promoter activity was inhibited by PPARgamma ligands; this suppressive effect was prevented by overexpressing a dominant negative form of PPARgamma or a PPAR response element decoy oligonucleotide. The stimulatory effects of PMA were mediated by a cyclic AMP response element in the COX-2 promoter. Treatment with PMA increased activator protein-1 (AP-1) activity and the binding of c-Jun, c-Fos, and ATF-2 to the cyclic AMP response element, effects that were blocked by PPARgamma ligands. These findings raised questions about the mechanism underlying the anti-AP-1 effect of PPARgamma ligands. The induction of c-Jun by PMA was blocked by PPARgamma ligands. Overexpression of either c-Jun or CREB-binding protein/p300 partially relieved the suppressive effect of PPARgamma ligands. When CREB-binding protein and c-Jun were overexpressed together, the ability of PPARgamma ligands to suppress PMA-mediated induction of COX-2 promoter activity was essentially abrogated. Bisphenol A diglycidyl ether, a compound that binds to PPARgamma but lacks the ability to activate transcription, also inhibited PMA-mediated induction of AP-1 activity and COX-2. Taken together, these findings are likely to be important for understanding the anti-inflammatory and anti-cancer properties of PPARgamma ligands.

Arthritis↗
PubMed2001

A review of 140 Octopus off-pump bypass patients over the age of seventy: procedure of choice?

BACKGROUND: Many studies have demonstrated that patients of advanced age are at increased risk for morbidity and mortality following coronary artery bypass graft (CABG) surgery. When compared to younger age groups, the risks of adverse neurological outcome or mortality have been demonstrated to be higher in septuagenarians and octogenarians. It has been suggested that off-pump coronary artery bypass (OPCAB) surgery, by avoiding the adverse effects of cardiopulmonary bypass (CPB), may improve the risks of morbidity and mortality, particularly in these higher risk elderly patients. Despite the increased rates of adverse events in patients of advanced age, various authors have described these risks to be in the acceptable range, justifying continued recommendations for operative revascularization in properly selected elderly patients. OPCAB theoretically may provide improvements in early outcomes for these patients by avoiding the unwanted sequelae of CPB. PATIENTS AND METHODS: This report is a study of the potential advantages of OPCAB techniques based on a retrospective analysis of 140 patients aged 70 or more operated on by a single surgeon at a single institution using OPCAB techniques during a 39-month period. In these operations, surgical access was almost exclusively via midline sternotomy. Exposure of target coronary arteries was by means of extended inverted-T pericardiotomy. Local occlusion of coronary arteries was achieved using proximally placed silastic tapes (Quest Medical Inc., Allen, TX). Distal occlusion was rarely needed. Stabilization was obtained exclusively with the suction-based Octopus stabilization system (Medtronic, Inc., Minneapolis, MN). A mean number of 2.36+/-0.95 distal anastomoses were constructed per patient, with a range from one to five. Multivessel OPCAB patients averaged 2.73 grafts per patient. RESULTS: Of the 142 patients who underwent OPCAB surgery, only two required elective conversion to CABG with CPB. The procedure was safe, with no need for urgent conversion to CPB. Myocardial protection was excellent, with no patient requiring inotropic support leaving the operating room, and no patient developed postoperative stroke. Several patients had evidence of temporary nocturnal confusion but recovered prior to discharge. There were no in-hospital or 30-day post-operative mortalities in this group. CONCLUSIONS: OPCAB has been demonstrated to be safe and effective, with surgeons from many centers worldwide reporting low rates of morbidity and mortality. Early patency rates appear to be equal to or perhaps even better than CABG with CPB. This report adds to a growing body of literature supporting the use of OPCAB in elderly patients requiring surgical revascularization. If further investigations continue to demonstrate improved outcomes, OPCAB may become the procedure of choice for patients of advanced age.

Aged↗
PubMed2000

Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2 AND p38 mitogen-activated protein kinase pathways.

We investigated whether microtubule-interfering agents (MIAs: taxol, colchicine, nocodazole, vinblastine, vincristine, 17-beta-estradiol, 2-methoxyestradiol) altered cyclooxygenase-2 (COX-2) expression in human mammary epithelial cells. MIAs enhanced prostaglandin E(2) synthesis and increased levels of COX-2 protein and mRNA. Nuclear run-off assays revealed increased rates of COX-2 transcription after treatment with MIAs. Calphostin C, an inhibitor of protein kinase C, blocked the induction of COX-2 by MIAs. The stimulation of COX-2 promoter activity by MIAs was inhibited by overexpressing dominant negative forms of Rho and Raf-1. MIAs stimulated ERK, JNK, and p38 mitogen-activated protein kinases (MAPK); pharmacological inhibitors of MAPK kinase and p38 MAPK blocked the induction of COX-2 by MIAs. Overexpressing dominant negative forms of ERK1 or p38 MAPK inhibited MIA-mediated activation of the COX-2 promoter. MIAs stimulated the binding of the activator protein-1 transcription factor complex to the cyclic AMP response element in the COX-2 promoter. A dominant negative form of c-Jun inhibited the activation of the COX-2 promoter by MIAs. Additionally, cytochalasin D, an agent that inhibits actin polymerization, stimulated COX-2 transcription by the same signaling pathway as MIAs. Thus, microtubule- or actin-interfering agents stimulated MAPK signaling and activator protein-1 activity. This led, in turn, to induction of COX-2 gene expression via the cyclic AMP response element site in the COX-2 promoter.

2-Methoxyestradiol↗
PubMed2000

Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice.

Xanomeline is an M(1)/M(4) preferring muscarinic receptor agonist which decreased psychotic behaviors in patients with Alzheimer's disease, suggesting that xanomeline might be useful in the treatment of psychotic symptoms in patients with schizophrenia. The purpose of the present studies was, therefore, to compare the pharmacologic profile of xanomeline with that of known antipsychotic drugs. Electrophysiologically, xanomeline, after both acute and chronic administration in rats, inhibited A10 but not A9 dopamine cells in a manner which was blocked by the muscarinic receptor antagonist scopolamine. Behaviorally, xanomeline, like haloperidol, clozapine and olanzapine, blocked dopamine agonist-induced turning in unilateral 6-hydroxydopamine-lesioned rats, as well as apomorphine-induced climbing in mice. However, unlike the dopamine antagonist antipsychotic haloperidol, xanomeline did not produce catalepsy in rats. Moreover, xanomeline, like haloperidol, clozapine and olanzapine, inhibited conditioned avoidance responding in rats, an effect which also was blocked by scopolamine. The present results thus demonstrate that xanomeline has a pharmacologic profile which is similar to that of the atypical antipsychotics clozapine and olanzapine, thus indicating that xanomeline has the potential to be a novel approach in the treatment of psychotic symptoms in patients with schizophrenia.

Alzheimer Disease↗
PubMed2000

A review of 1,582 consecutive Octopus off-pump coronary bypass patients.

BACKGROUND: Off-pump coronary bypass may provide a safer form of surgical revascularization by avoiding the unwanted complications of cardiopulmonary bypass, particularly in the increasingly complex patients being referred for operation. This study reviews the entire experience of the Medtronic Octopus System (Medtronic, Minneapolis, MN) for beating heart bypass from 7 surgeons. Demographics, operative procedures, early outcomes, and trends in usage were examined. METHODS: Patients were selected for off-pump procedures by the individual surgeons. Data were entered prospectively into locally maintained databases and then collected for collation and analysis. RESULTS: A total of 1,582 consecutive Octopus patients were entered, representing the entire Octopus experience of each surgeon. Proportions of off-pump procedures relative to standard bypass increased over time, as did the percentage of patients receiving three or more grafts, 24.6% in 1997 and 55.9% in 1999. A total of 3,653 anastomoses were performed, 1,905 to the left anterior descending system, 837 to the circumflex distribution, and 911 to the right coronary territory. Morbidity was low. Few patients required conversion to cardiopulmonary bypass (2.6%; 0.2% urgently). Permanent stroke occurred in 0.6% and myocardial infarction in 1.2%. Operative mortality was 1%. CONCLUSIONS: Octopus off-pump bypass was demonstrated to be a safe procedure with widening applicability. With experience surgeons tend to apply the system to increasing proportions of their patients and are able to revascularize all coronary territories.

Aged↗
PubMed1999

A two-year, three institution experience with the Medtronic Octopus: systematic off-pump surgery.

BACKGROUND: The popularity of beating heart coronary artery bypass (CAB) has grown with the development of mechanical stabilizers. Multicenter study offers an opportunity to examine methods and risk relating to this practice. METHODS: The experience since March 1997, utilizing both the original Medtronic Octopus system and the second-generation, retractor-mounted, Octopus II for beating heart CAB (Medtronic, Inc, Minneapolis, MN), was retrospectively reviewed at three institutions. RESULTS: Four hundred fifty-six patients completed Octopus CAB (Medtronic, Inc), performed through left thoracotomy (54), partial (33), or full (374) sternotomy, and epigastric (3) incisions with an average of 1.9 grafts/patient. Morbidities were reviewed: transfusion (20.6%), reoperation for bleeding (1.0%), atrial fibrillation (13.3%), completed stroke (0.2%), perioperative myocardial infarction (0.8%), and new intraaortic balloon pump (IABP) (0.4%), without episodes of deep sternal infection or renal failure. The mortality rate (0.32%), when compared to the Society of Thoracic Surgeons' (STS)-predicted mortality (1.37% and 2.36%) at two institutions, was significantly less (p < 0.05). Twelve nonurgent and one urgent conversion to cardiopulmonary bypass occurred. Six patients have required reintervention on bypassed vessels. CONCLUSIONS: To facilitate lateral and inferior wall grafting, a variety of techniques were utilized, including positioning, sternal and pericardial mobilization, and a new pericardial-based sling retractor, all designed to improve exposure while maintaining hemodynamic stability. The Octopus devices were safely applied with low morbidity and mortality utilizing varied operative approaches at three institutions.

Cardiopulmonary Bypass↗
PubMed1999

Cardiopulmonary bypass on a patient with malaria.

There are special considerations when performing cardiopulmonary bypass (CPB) on a patient with malaria. A 70-year-old female with a recent history of severe aortic stenosis was scheduled to undergo elective aortic valve replacement. One week prior to surgery, the patient developed shaking chills and fever, with a positive malaria smear. An extensive literature search was undertaken to determine the effect of CPB on a patient with active malaria, but no prior reference was found. One major concern was the lysis of red blood cells while on bypass. The surgery was performed uneventfully, following 2 weeks of treatment with primaquine phosphate.

Aged↗
PubMed1999

Standardized visual evoked potentials for telematic electrodiagnosis from five laboratories in three European countries.

The pattern-reversal visual evoked potential (PR VEP) is an electrodiagnostic test which uses an alternating checkerboard pattern as the visual stimulus. To validate the performance of an automated testing system, the equipment was installed in five locations in three countries (the UK, Greece and Cyprus). PR VEPs require accurate control of stimulus size, luminance, contrast, timing, multichannel recordings and various modes of signal processing. Recordings were obtained from 70 subjects, 18-34 years old (seven male and seven female in each laboratory). The data were transmitted by telephone line to the central station in Bristol. Only in Bristol were the operators experienced. There were no significant differences between laboratories in latency or amplitude of the N70 and P100 components. There were no significant differences between eyes. There were significant differences between the sexes but this was related to head size. Decreased square size used in stimulation produced an increased latency in both components. The amplitude of the N70 component increased while that of the P100 decreased with reduced square size. The results confirmed the ability of the automated system to produce standardized PR VEP recordings comparable to those obtainable in advanced laboratories. The system performed well in different locations using inexperienced operators. The system is suitable for multicentre research studies and telemedicine.

Adolescent↗
PubMed1999

Radiographic trends of dental offices and dental schools.

BACKGROUND: A survey of private practice facilities in the United States that perform dental radiography was conducted in 1993 and repeated in dental schools in 1995-1996. METHODS: Both surveys were conducted as part of the Nationwide Evaluation of X-ray Trends, or NEXT, survey program. A representative sample of dental facilities from each participating state were surveyed, and data on patient radiation exposure, radiographic technique, film-image quality, film-processing quality and darkroom fog were collected. RESULTS: The authors found that dental schools use E-speed film more frequently than do private practice facilities. The use of E-speed film and better film processing by dental schools resulted in lower patient radiation exposures without sacrificing image quality. The authors also found that dental school darkrooms had lower ambient fog levels than did those of private practice facilities. CONCLUSIONS: The distribution for the 1993 NEXT survey facilities was greater than that observed for dental schools for radiation exposure, film-processing quality and darkroom fog. Dental schools, in general, had better film quality and lower radiation exposures than did private practice facilities. PRACTICE IMPLICATIONS: Facilities need to emphasize better quality processing and the use of E-speed film to reduce patient exposure and improve image quality.

Absorptiometry, Photon↗
PubMed1999

Muscarinic receptor agonists, like dopamine receptor antagonist antipsychotics, inhibit conditioned avoidance response in rats.

The purpose of our studies was to determine the effects of muscarinic receptor agonists on conditioned avoidance responding in the rat. Rats were trained to avoid or escape an electric shock delivered to the feet in a discrete trial procedure. The muscarinic receptor agonists pilocarpine and [2-ethyl-8-methyl-2,8-diazaspiro(4. 5)decane-1,3-dione] hydrochloride (RS86) and the cholinesterase inhibitor physostigmine all decreased the percentage of avoidance responses at doses that produced less than approximately 30% response failures. Similar results were obtained with the antipsychotic drugs haloperidol, trifluoperazine, chlorpromazine, and clozapine. However, the benzodiazepine anxiolytic diazepam did not decrease avoidance responding up to doses that produced ataxia. On the other hand, oxotremorine and arecoline decreased avoidance responding only by producing response failures, whereas aceclidine produced intermediate changes. The muscarinic receptor antagonists scopolamine, trihexyphenidyl, and benztropine were without effect when administered alone but antagonized the decreases in avoidance responding produced by pilocarpine and RS86. Scopolamine had little effect on the decreases in avoidance responding produced by haloperidol. The newer muscarinic receptor partial agonists or agonist/antagonists [R-(Z)-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2. 2]octane-3-acetonitrile] hydrochloride, talsaclidine, milameline, and xanomeline also produced dose-related decreases in avoidance responding. Our results demonstrate that muscarinic receptor agonists can decrease avoidance responding in a manner similar to dopamine-receptor antipsychotic drugs, suggesting that muscarinic receptor agonists may provide an alternative approach to the treatment of psychosis.

Animals↗
PubMed1999

Off-pump multivessel coronary artery bypass utilizing the Octopus tissue stabilization system: initial experience in 374 patients from three separate centers.

BACKGROUND: Renewed interest in coronary artery bypass without heart-lung support has lead to the development of specialized instrumentation to permit surgical exposure and grafting in all territories of the beating heart. This report summarizes the results of a multicenter, prospective trial using a single system of mechanical stabilization for multivessel revascularization without cardiopulmonary bypass. METHODS: Three principal investigators at different institutions performed off-pump coronary grafting utilizing the Medtronic Octopus suction stabilization system which provides a motionless region encompassing the target coronary artery. Positioning and stabilization strategies evolved during the trial but eventually lead to a consistent approach for accessing all regions of the heart. Clinical data sets were collected prospectively and pooled for evaluation of early and short-term endpoints of success. RESULTS: A total of 374 patients underwent beating heart coronary bypass procedures with only a single death for an in-hospital 30-day mortality rate of 0.26%. There were 140 single-vessel revascularizations (37.4% of patients), 119 double coronary grafts (31.8%), 90 triple-vessel grafts (24.1%), and 25 four-vessel grafts (6.7%), for a mean of 1.96 grafts per patient. If the single vessel cases are removed from analysis, the mean number of grafts performed in the multivessel cohort was 2.6 grafts per patient. All anatomic regions of the heart were successfully grafted including traditionally difficult locations such as the obtuse marginal branches of the circumflex and posterior descending branches of the right coronary artery. Only one patient suffered a new neurologic deficit which occurred 15 days postoperatively, for an overall incidence of only 0.26%. No patient required a new intra-aortic balloon pump or dialysis for renal insufficiency. The incidence of atrial fibrillation (12.8%) was age related and essentially unchanged from the overall incidence observed in patients operated at the same institutions using conventional techniques. CONCLUSIONS: Multivessel grafting on the beating heart using the Octopus stabilization system results in remarkably low perioperative mortality and morbidity, with very low incidences of cerebrovascular, renal, and respiratory complications. However, the incidence of postoperative atrial fibrillation is not reduced. Expanded clinical use of beating heart surgery with suction-based stabilization appears to be a promising technique for achieving global revascularization without the need for cardiopulmonary bypass.

Coronary Artery Bypass↗
PubMed1998

Prediction of the mechanisms of enzyme-catalysed reactions using hybrid quantum mechanical/molecular mechanical methods.

The use of hybrid methods, involving both quantum mechanics and molecular mechanics, to model the mechanism of enzyme-catalysed reactions, is discussed. Two alternative approaches to treating the electrostatic interactions between the quantum mechanical and molecular mechanical regions are studied, involving either the inclusion of this term in the electronic Hamiltonian (QM/MM), or evaluating it purely classically (MO + MM). In the latter scheme, possible problems of using force fields that are standard for macromolecular modelling are identified. The use of QM/MM schemes to investigate the mechanism of the enzymes thymidine phosphorylase (ThdPase) and protein tyrosine phosphatase (PTP) is described. For both systems, transition states have been identified using a PM3 Hamiltonian. For ThdPase, concerted motion of the enzyme during the course of the reaction is suggested and, for PTP, a two-step dephosphorylation reaction is indicated, both with quite low barriers.

Catalysis↗
PubMed1996

The scotopic electroretinogram to blue flashes and pattern reversal visual evoked potentials in insulin dependent diabetes.

Pattern reversal visual evoked responses (PR-VEPs), the electroretinogram (ERG) to blue flashes of light in dark adaptation, the steady state ERG to 40 Hz flicker, and alterations in pupil diameter following dark adaptation were studied in 56 juvenile onset diabetics, 34 of whom had no ophthalmoscopic or photographic evidence of diabetic retinopathy (DR-group). The remaining 22 had mild background retinopathy (DR+group). Normal data was obtained from 24 subjects matched for age and sex with diabetics. Skin electrodes were used for all recordings. The scotopic 'b' wave of the ERG was significantly lower in amplitude in the DR- diabetics and it was even more reduced in the DR+group. The PR-VEP was significantly delayed in diabetics but there was no difference between the two groups. The steady state ERG was not significantly different between normals and diabetics. These findings indicate that retinal and more central abnormalities develop early in diabetics. Detection of objective electrophysiological abnormalities may be used to identify persons at risk of developing retinopathy and to monitor the effects of treatment.

Adolescent↗
PubMed1994

Electrodiagnostic evaluation of the visual system: the role of the clinician.

Visual electrodiagnosis is a new discipline with a long history. The foundations include the disciplines of psychophysics, neurophysiology, electronics, computer science, statistics and medicine. However, with such a complex heritage, visual electrodiagnosis has taken a considerable time to evolve to its present form. Today visual electrodiagnostic assessment is relevant, not only for conditions primarily affecting the visual system, but also in more generalised pathological states in which eye changes may be a manifestation. Pressures for more refined and accurate diagnoses stem both from a continuing improvement in knowledge of disease processes by the medical profession and greater expectations on the part of patients seeking advice. Specialised investigative services such as electrodiagnosis, if these are appropriately funded and maintained, provide data to clinicians which is repeatable and objective, without resorting to invasive technology.

Adult↗
PubMed1990

Assessment of working memory in rats using spatial alternation behavior with variable retention intervals: effects of fixed-ratio size and scopolamine.

The effects of fixed-ratio (FR) size, scopolamine, and the interactions between FR size and scopolamine were investigated in male F344 rats on working memory as assessed by spatial alternation behavior maintained under FR schedules of food presentation where the interval between trials was varied among values of 2, 4, 8, 16, and 32 s within each session. The magnitude of the FR size on the correct and incorrect levers was varied systematically from 1 response to 2, 4, 8, or 16 responses in order to determine whether the FR size influenced either the percentage of correct responding, rates of responding, or both. Under the primary baseline condition, that is when the FR size on both the correct and incorrect levers was one response (designated FR1 FR1), the percentage of correct responses decreased with increasing retention interval duration. Increasing the FR size on the correct lever produced FR-dependent increases in the percentage of correct responding as well as in rates of responding. Increasing the FR size on the incorrect lever produced FR-dependent decreases in correct responding, but had little effect on rates of responding. Dose-effect curves for scopolamine were determined on performance maintained under FR values on the correct and incorrect levers, respectively, of FR1 FR1, FR1 FR10, FR10 FR1, and FR10 FR10. In general, scopolamine produced dose-related decreases in the percentage of correct responding, although the magnitude of the effects of scopolamine varied not only with dose, but also with the length of the retention interval and with changes in FR size.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗