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Biomedical subjects

L Harris

Publications and source records attributed to L Harris.

At least 145 records · Page 8Linked to original sources
PubMed1988

Purification and characterization of P-52 (glutathione S-transferase-P or 7-7) from normal liver and putative preneoplastic liver nodules.

A previous study from our laboratory (L.C. Eriksson et al., Biochem. Biophys. Res. Commun., 117: 740-745, 1983) revealed that a cytosolic polypeptide of approximate Mr 21,000 (designated P-21) was markedly elevated in amount in hepatocyte nodules induced by six different regimens. The molecular weight of this polypeptide, subsequently revised to approximately 26,000, was redesignated P-26 and was identified (T.H. Rushmore et al., Biochem. Biophys. Res. Commun., 143: 98-103, 1987) as a subunit of a placental form of glutathione S-transferase (K. Sato et al., Gann 75: 199-202, 1984), also named glutathione S-transferase 7-7 (H. Jensson et al., FEBS Lett., 187: 115-120, 1985). We describe here a convenient method for purifying relatively large amounts of P-26 from hepatocyte nodules involving the sequential use of affinity chromatography on S-hexyl glutathione-Sepharose 4B, CM-Sephadex, and DEAE-Sephacel. Evidence is presented that P-26 exists as a dimer of approximate Mr 52,000 (P-52). Analyses by two-dimensional electrophoresis have indicated that the subunits of Mr 26,000 may consist of five separate charged isomers. Investigations using appropriate antisera and analysis by amino acid sequencing have provided additional confirmation that P-52 is probably identical to rat placental glutathione S-transferase. Antibodies to P-52 are proving to be useful as a marker of new cell populations that appear regularly during hepatocarcinogenesis.

Amino Acid Sequence↗
PubMed1988

Endocardial mapping of ventricular tachycardia in the intact human ventricle: evidence for reentrant mechanisms.

A balloon array of 112 electrodes was used to obtain simultaneous recordings of endocardial electrograms during intraoperative mapping studies of ventricular tachycardia. Introduction of the balloon through a left atriotomy and across the mitral valve allowed endocardial activation maps to be obtained in the intact left ventricle. Of 20 patients with coronary artery disease studied in this way, suggestive evidence of endocardial reentry was found in 6. Three separate reentrant mechanisms were observed. In two patients, a single broad wave front of continuous recirculating activation reminiscent of a vortex was initiated by the formation of a functional arc of block in response to premature stimuli. In five patients, premature stimuli again produced a functional arc of block, which was circumvented by two opposing wave fronts that united on the distal side. Retrograde penetration by a narrow isthmus of slow conduction through the block initiated the tachycardia, whose activation sequence was consistent with figure eight reentry. In one patient, premature stimuli produced a region of delayed potentials. Critical timing of these resulted in microreentry in an adjacent circumscribed site, which formed the site of origin of the ensuing tachycardia. The microreentrant signals were not detected by standard unipolar recordings, but were seen on simultaneously recorded high gain electrograms. In 14 patients, although mapping identified a site of origin, the activation patterns showed either radial spread or incomplete circles. Detection of reentrant mechanisms during intraoperative mapping required high density electrode arrays and refined high gain recordings. An intact ventricle may facilitate intraoperative initiation of tachycardia.

Electrocardiography↗
PubMed1988

Electrical ablation with a balloon electrode array: chronic electrophysiologic response.

An intraoperative endocardial array of electrodes which permits simultaneous recordings from multiple sites in the intact ventricle is currently in clinical use and has provided the opportunity for exploring electrical ablation as an alternative to standard surgical ablative techniques requiring a ventriculotomy. A variation of the electrical ablative procedure adapted for this intraoperative purpose was studied in seven dogs to determine its long-term electrophysiologic and structural effects on ventricular myocardium. With the dogs on cardiopulmonary bypass, a mesh-covered latex balloon was introduced into the left ventricle via an atriotomy. Five damped sinusoidal discharges (4 of 200 J per 2 electrodes, one of 100 J to the remaining electrode) were delivered to nine silver bead electrodes sutured at 1 cm intervals onto the mesh and arranged in a 2 x 2 cm2 array. At 5-8 weeks following the ablation, no ventricular arrhythmias could be induced in any of the dogs using standard stimulation techniques. The scar produced by the ablation consisted of dense fibrous tissue, and was well demarcated from surrounding normal myocardium. Cellular electrophysiology confirmed that no action potentials could be recorded within the scarred area while at distances of 1 mm from the scar border, normal responses could be elicited from both muscle cells and Purkinje fibers. The adaptation of the described electrical ablative procedure produces an electrophysiologically inert scar.

Action Potentials↗
PubMed1988

Direct endocardial recording and catheter ablation of an accessory pathway in a patient with incessant supraventricular tachycardia.

A patient presented with incessant supraventricular tachycardia due to a concealed accessory pathway. The His bundle electrocardiogram showed a large discrete accessory pathway potential following ventricular activation and resulting in retrograde atrial activation. Percutaneous catheter ablation in the region of the accessory pathway potential left nodal conduction intact but prevented retrograde activation of the atria. Symptomatic tachycardia has not recurred. Direct endocardial recording of accessory pathway potentials is rare but may offer the opportunity for catheter ablation.

Adult↗
PubMed1988

Antiarrhythmic potential of chloroquine: new use for an old drug.

Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.

Action Potentials↗
PubMed1988

A new intraoperative approach for endocardial mapping of ventricular tachycardia.

Results of operation for control of ventricular tachycardia have improved since endocardial mapping techniques have been developed that allow a directed approach to the problem. In some patients, a limitation of established techniques has been difficulty in initiating the arrhythmia after a ventriculotomy has been made to allow introduction of endocardial recording electrodes. This paper describes a transatrial approach for endocardial mapping with a balloon array of 112 electrodes, which has been used intraoperatively in 15 patients. Surgical success in this group has been compared to that obtained in a similar group of patients in whom standard techniques of intraoperative mapping were used. With our new balloon technique we have been able to easily induce and map multiple episodes of ventricular tachycardia in all cases. On the basis of detailed endocardial maps, the locations of earliest activation and possible reentry loops have been identified and ablated with either endocardial excision or application of the cryoprobe. When indicated, concomitant procedures including aneurysm resection (9/15) and bypass grafting (14/15) have been performed. Hospital mortality in this group was 20%. None of the deaths have been related to recurrent ventricular tachycardia or complications of the mapping technique. Postoperative electrophysiologic studies performed at 2 weeks have been normal in 11 of 12 or 92% of patients. To date (mean follow-up 12 +/- 6 months) there has been no clinical recurrence or evidence of ventricular tachycardia by Holter monitoring in these patients. We conclude that the transatrial balloon approach to endocardial mapping facilitates intraoperative induction of ventricular tachycardia, allows complete mapping during multiple runs of the arrhythmia without prolonging cardiopulmonary bypass time, and improves results of operation using standard ablation techniques.

Cardiac Pacing, Artificial↗
PubMed1987

Mitogenic activity in platelet-poor plasma from rats with persistent liver nodules or liver cancer.

Platelet-poor plasma (PPP) from F-344 rats with chemically-induced preneoplastic liver nodules or hepatocellular carcinoma stimulated S-phase DNA synthesis in monolayer cultures of normal rat hepatocytes. Similar mitogenic activity was detected in PPP 6 hrs to 1 week after partial hepatectomy (PH) or after necrotizing doses of CCl4 or diethylnitrosamine (DENA). Very little activity was found in PPP4 from control rats. The mitogenic activity in PPP from animals with nodules was non-dialyzable (greater than 14 kd) and bound to a heparin-sepharose affinity column. None of the mitogenic PPPs competed with [125I] epidermal growth factor (EGF) for binding sites on A431 cells or normal rat hepatocytes. These studies indicate that persistent proliferation of preneoplastic and neoplastic hepatocytes is associated with increased circulating levels of mitogenic hepatocyte growth factor.

Animals↗
PubMed1987

Patterns of ligand binding to normal, regenerating, preneoplastic, and neoplastic rat hepatocytes.

The binding of epidermal growth factor, asialoorosomucoid, and apoprotein E-rich lipoproteins to isolated hepatocytes was investigated at various time intervals during the step-by-step development of liver cancer in rats. The degree of binding of the three ligands showed a progressive reduction in early persistent and late persistent putative preneoplastic hepatocyte nodules. This was further decreased in hepatocytes isolated from unequivocal hepatocellular carcinomas. Regenerating liver hepatocytes bound lesser amounts of epidermal growth factor and asialoorosomucoid than did hepatocytes from control resting liver but increased amounts of apoprotein E-rich lipoproteins. The progressive decrease in ligand binding during the precancerous phase of hepatocarcinogenesis, the nodule-to-cancer sequence, may render nodules less responsive to the influences of their external environments.

Animals↗
PubMed1987

Caffeine as a possible cause of ventricular arrhythmias during the healing phase of acute myocardial infarction.

Caffeine (300 mg) was administered to each of 70 patients a mean (+/- standard error of the mean) of 7 +/- 1 days after the onset of acute myocardial infarction to determine its effects on ventricular arrhythmias. The study was designed as a randomized, double-blind, within-patient comparison between caffeine and placebo. Continuous Holter electrocardiographic recording for 4 hours showed no significant differences in the proportion of patients who had ventricular ectopic activity or the total number and complexity of ventricular premature complexes after caffeine vs placebo. Caffeine increased mean blood pressure from 116 +/- 2/70 +/- 1 mm Hg to a maximum of 125 +/- 3/78 +/- 2 mm Hg (p less than 0.001) at 4 hours. Plasma epinephrine increased (p less than 0.01) from 58 +/- 4 pg/ml to a maximum 88 +/- 6 pg/ml 3 hours after caffeine ingestion, whereas the plasma norepinephrine level did not change. Although caffeine caused significant hemodynamic and humoral responses in this population of relatively caffeine-naive postinfarction patients, it did not increase the occurrence or severity of ventricular arrhythmias.

Arrhythmias, Cardiac↗
PubMed1987

Identification of a characteristic cytosolic polypeptide of rat preneoplastic hepatocyte nodules as placental glutathione S-transferase.

Evidence is presented that a distinctive type of glutathione-S-transferase (GSHTase-P), and a cytosolic polypeptide of Mr 52,000 (P-52), each appearing in greatly increased amounts in hepatocyte nodules during liver carcinogenesis in the rat, are so far indistinguishable. The probable identity of the two polypeptides was established with the use of SDS polyacrylamide gel electrophoresis and Western blot techniques with purified GSHTase-P and P-52 and their respective antibodies and by comparison of the sequence of the first 26 N-terminal amino acids. Since the enzyme and the polypeptide are each considered to be the best available early markers for hepatocyte nodules, as putative precancerous lesions, their probable identity makes them attractive cellular components for in depth studies on their transcriptional and translational regulation and their use in new approaches to the sequential analysis of liver carcinogenesis.

Amino Acid Sequence↗
PubMed1987

Activation sequence of ventricular tachycardia: endocardial and epicardial mapping studies in the human ventricle.

Thirty-five patients with ischemic heart disease and ventricular arrhythmias underwent intraoperative activation mapping at the time of coronary artery bypass surgery. During ventricular tachycardia, the sequence of activation in the intact ventricle was recorded simultaneously from 110 endocardial or 110 epicardial sites, or both. A balloon array of electrodes, inserted across the mitral valve, was used to obtain endocardial recordings in the left ventricle, and this appeared to facilitate the induction of ventricular tachycardia. Of 61 episodes of tachycardia, 16 (15 patients) were recorded with the epicardial sock and 45 (20 patients) with the additional use of the endocardial balloon. The sequence of activation during tachycardia was observed to conform to one of four configurations: monoregional spread was the most common activation sequence recorded on both the endocardium and epicardium, while biregional activation and figure eight sequences were recorded exclusively on the epicardium and endocardium, respectively. The fourth sequence was a circular spread of activation observed on both surfaces. Continuous activation throughout the tachycardia cycle length was an infrequent finding. Simultaneous recordings of endocardial and epicardial activation were obtained in 45% of episodes. The sequence of activation recorded on one surface was matched by a similar sequence on the remaining surface in less than half of these. The onset of endocardial activation preceded that of the epicardium in greater than 90% of tachycardia episodes, and the duration of left ventricular endocardial excitation often exceeded that recorded epicardially over both ventricles. The epicardium, however, did appear to be an important determinant of surface electrocardiographic configuration.

Cardiac Catheterization↗
PubMed1987

Intraoperative electrical ablation of ventricular arrhythmias: a "closed heart" procedure.

Both intraoperative endocardial mapping and surgical ablation for ventricular arrhythmias have until now required a ventriculotomy. Such an incision may be associated with an increase in morbidity and mortality, especially when performed through friable myocardium. A "closed heart" technique of intraoperative endocardial mapping and ablation of ventricular arrhythmias was developed in which a balloon array of 112 electrodes was introduced into the left ventricular cavity by a transmitral approach. The array permitted safe delivery of repeated electrical discharges of up to 150 J at each electrode. In four patients with coronary artery disease and no ventricular aneurysm, this "closed heart" technique was used to map and treat seven distinct ventricular tachycardias. The time taken to map each tachycardia varied from 3 to 13 minutes. Between 100 and 150 J was then delivered at each of 10 to 42 electrode sites, and the ablation procedure took 7 to 16 minutes per patient to complete. One patient died 24 hours postoperatively from preexisting thrombocytopenic purpura. There was no significant deterioration in left ventricular function in the three survivors and all have remained arrhythmia free, without antiarrhythmic agents, for 4 to 11 months. This technique offers a new method of surgical treatment of ventricular tachycardia without ventriculotomy, and is particularly suited to patients without a discernible left ventricular aneurysm.

Arrhythmias, Cardiac↗
PubMed1987

Nasofrontal duct: CT in frontal sinus trauma.

Radiologic evaluation of frontal sinus fractures is instrumental in determining the need for surgery. Computed tomography (CT) is an excellent modality for evaluation of frontal sinus trauma, particularly for anterior and posterior wall fractures. However, fractures of the nasofrontal duct are more difficult to delineate, and judgments about operating for this problem are often made on less than concrete evidence of duct trauma. To evaluate the usefulness of CT in identifying nasofrontal duct trauma, a two-part study was done. First, CT was performed on cadavers to study the anatomic relationship of the nasofrontal duct to midface anatomy. Then, a retrospective study was performed in 19 patients with suspected frontal sinus fractures who underwent frontal sinus surgery. Findings at surgery were compared with preoperative evaluation with CT. Correlations were identified and criteria developed that can be used to identify patients needing surgical intervention in frontal sinus trauma. These criteria include findings of either a fracture involving the base of the frontal sinus or a fracture of the anterior ethmoid complex, or both.

Adolescent↗
PubMed1986

BSF1 induces membrane protein phosphorylation but not phosphoinositide metabolism, Ca2+ mobilization, protein kinase C translocation, or membrane depolarization in resting murine B lymphocytes.

The findings presented in this study provide evidence that BSF1 receptors and mIg transmit signals via dissimilar transduction mechanisms that result in a common biologic response, hyper-Ia expression. Specifically, BSF1-containing supernatant does not induce PtdInsP2 hydrolysis as determined by measurement of PtdOH and InsP3. Additionally, BSF1 does not stimulate Ca2+ mobilization, PKC translocation from cytosol to membrane, or membrane depolarization. All of these metabolic events appear to play a central role in hyper-Ia expression mediated by mIg and are initiated after treatment of resting B cells with anti-Ig antibodies. In vitro phosphorylation studies with partially purified plasma membranes from resting B cells revealed that BSF1 interaction with membrane receptors stimulates a membrane-associated protein kinase that phosphorylates an endogenous protein of 44 KDa. Anti-Ig does not stimulate phosphorylation of the 44 KDa protein, suggesting that it does not activate the membrane-associated protein kinase. This observation provides the first evidence of a signal transduction mechanism associated with BSF1-receptor ligation. It indicates that although BSF1 does not modulate events associated with PKC activation, it may function via activation of a membrane-associated protein kinase. This provides a focal point for further studies directed at elucidating signal transduction resulting from BSF1-receptor interaction.

Animals↗
PubMed1986

Morbidity patterns in a general paediatric unit in rural Western Australia.

Admissions to the Medical Paediatric Unit at Derby Regional Hospital in 1984 were reviewed. There were 536 admissions (289 males and 247 females). The average number of inpatients per day was 11.7, average duration of stay was 8.0 days, and there was one hospital death. Aboriginal children represented 90% of admissions and 59% of these were under two years of age. Several major problems were often encountered in individual children; these included respiratory, gastrointestinal and renal disease, failure to thrive and anaemia. Plasma electrolyte levels were measured in 82 children with gastroenteritis. Of these children 45 (55%) had a serum potassium level of less than 3.0 mmol/L and eight (10%) had a serum potassium level of less than 2 mmol/L. One hundred and four children were diagnosed as having pneumonia; 74 (71%) of them responded to penicillin. In 19 (21%) of 92 children who failed to thrive, no definite medical cause was found. The remainder had a combination of diarrhoeal disease, and chest and urinary tract infections. Anaemia, renal calculi and rheumatic fever are also common medical problems in the Kimberley region.

Australia↗