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Biomedical subjects

R J Lee

Publications and source records attributed to R J Lee.

At least 91 records · Page 5Linked to original sources
PubMed1997

Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death.

BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.

3-Iodobenzylguanidine↗
PubMed1997

Cooperation between the Fc epsilonR1 and formyl peptide receptor signaling pathways in RBL(FPR) cells: the contribution of receptor-specific Ca2+ mobilization responses.

RBL(FPR) mast cells express the tyrosine kinase-coupled IgE receptor, Fc epsilonR1, and the G-protein-coupled formyl peptide receptor, FPR. Fc epsilonR1 crosslinking causes Ca2+ stores release, Ca2+ influx, Ins(1,4,5)P3 production and secretion. FPR ligation also mobilizes Ca2+, but without measurable Ins(1,4,5)P3 production or secretion. Co-stimulating the FPR and Fc epsilonR1 induces more Ins(1,4,5)P3 production and secretion than Fc epsilonR1 cross-linking alone. Costimulation also produces more rapid and sustained Ca2+ responses than are generated by Fc epsilonR1 activation alone. We identified multiple differences between the FPR- and Fc epsilonR1-coupled Ca2+ responses, including a more rapid Ca2+ spike response to FPR ligation; intracellular Ca2+ stores that are empty following Fc epsilonR1 crosslinking but partially full following FPR activation; a more sustained Ca2+ influx response to Fc epsilonR1 crosslinking; and the immediate inhibition of stimulated Ca2+ influx by FPR antagonists but not by monovalent ligand that terminates Fc epsilonR1 crosslinking. We hypothesize that the interaction of receptor-specific Ca2+ mobilization pathways contributes to the FPR-mediated potentiation of Fc epsilonR1-coupled secretion.

Animals↗
PubMed1997

Risk of thromboembolism in chronic atrial flutter.

Anticoagulant therapy is not conventionally used in the treatment of patients with atrial flutter. This recommendation has been based on sparse clinical experience, and recent preliminary reports suggest a significant risk of thromboembolism for these patients. A retrospective study was undertaken to assess the frequency of thromboembolic events as well as potential risk factors for these events in a cohort of patients with atrial flutter referred for radiofrequency ablation treatment. Eighty-six consecutive patients with a primary diagnosis of atrial flutter were evaluated. A history of embolic events was noted in 12 of 86 patients (14%) with atrial flutter, with an annual risk of approximately 3%. There were no differences in the prevalence of coronary artery disease, cardiomyopathy, valvular disease, or atrial fibrillation between the 2 groups of patients having an embolic event and those of patients without embolic events. Left ventricular function and left atrial size were also similar between the 2 groups. The only significant risk factor was hypertension (p < 0.05). However, in a regression model with other clinical variables (i.e., age, gender, left atrial size, presence or absence of any cardiac disease, length of time in flutter, left ventricular function, type of flutter, flutter cycle length, type of secondary arrhythmias) no significant predictors were found. Patients with transient ischemic attacks or pulmonary emboli were then excluded from the analysis in order to compare the thromboembolic risk in the present study to that reported in major atrial fibrillation trials. The overall risk becomes 7% (6 of 86), which over a mean follow-up period of 4.5 years yields an annual risk of approximately 1.6%. Although this risk is only 1/3 of that for patients with atrial fibrillation, this risk is higher than previously recognized for patients with chronic atrial flutter. Anticoagulant therapy should be seriously considered for these patients.

Adult↗
PubMed1997

Complications of absorbable pelvic mesh slings following surgery for rectal carcinoma.

PURPOSE: To evaluate the intraoperative, postoperative, and long-term complications of an absorbable pelvic mesh sling after surgery for rectal carcinoma. METHODS: A retrospective review of medical records from April 8, 1991, through April 8, 1996. RESULTS: Twenty patients with a mean age of 57 (range, 37-79) years underwent pelvic mesh sling placement. The tumor stages were as follows: Stage I, 5; Stage II, 2; Stage III, 11; and Stage IV, 1. A recurrent perianal basal cell carcinoma was not included in the staging group. Surgery consisted of 18 abdominoperineal resections, 1 total proctocolectomy, and one Hartmann's procedure. Mean follow-up was 18 (range, 2-49) months. There were no intraoperative complications related to mesh placement. Twenty-nine complications occurred in 14 patients during the immediate postoperative period. Five were possibly mesh-related and included a pelvic abscess, perineal seroma, toxic perineal wound, pulmonary embolus, and lower extremity deep venous thrombosis, respectively. A mild postoperative ileus developed in 17 patients (85 percent), and a diet was initiated at a mean of seven (range, 4-24) days. Fourteen patients received postoperative radiotherapy with a mean dose of 5,339 (range, 2,500-7,020) cGy delivered in 180-cGy fractions. There were 14 immediate complications caused by radiotherapy in 11 patients, but only two patients required delays in treatment. Two patients had diarrhea alone, six developed perineal dermatitis alone, and three patients had both diarrhea and perineal dermatitis. All patients with diarrhea had received chemoradiation. One patient developed a partial small-bowel obstruction following radiation. CONCLUSIONS: Absorbable pelvic mesh sling placement can be performed with minimum morbidity and is recommended following surgery for rectal cancer when radiation is anticipated as part of multimodality therapy.

Adenocarcinoma↗
PubMed1997

The effect of tumor necrosis factor-alpha and cAMP on induction of AP-1 activity in MA-10 tumor Leydig cells.

The immunostimulant tumor necrosis factor-alpha (TNF alpha), produced by monocytes/macrophages in response to inflammatory disorders, regulates gene expression in part through induction of mitogen-activated protein kinases (MAPKs), including the stress-activated protein kinase (SAPK) (c-Jun N-terminal kinase [JNK]) and the extracellular signal-regulated kinases (ERKs). In testicular Leydig cells, the induction of steroidogenesis by cAMP is inhibited by TNF alpha. To examine the potential mechanisms governing the mutual inhibition between cAMP and TNF alpha in Leydig cells, the intracellular signaling pathways that contribute to AP-1-dependent gene expression were examined in the mouse MA-10 Leydig cell line. TNF alpha induced SAPK activity sixfold at 15 min, and the PKC inhibitor calphostin C reduced the induction of SAPK by 30%. cAMP induced SAPK activity twofold but reduced TNF alpha-induced SAPK activity. ERK activity was inhibited by both cAMP and TNFa. TNFa increased c-Jun protein, but only weakly induced FOS proteins (c-Fos, FosB, Fra-1, and Fra-2) whereas cAMP increased the abundance of several FOS proteins (c-Fos, FosB, Fra-1, and Fra-2), with little effect on c-Jun levels. AP-1 binding activity, assessed using electrophoretic mobility shift assays, was increased twofold by TNF alpha and fivefold by cAMP. Cyclic AMP alone induced AP-1-responsive reporter (p3TPLUX) activity threefold after 2 h with peak effect of 4-fold at 4 hr. AP-1 reporter was not induced by TNF alpha alone but in the presence of cAMP, TNF alpha induced AP-1 reporter activity 12-fold. In conclusion, TNF alpha and cAMP induce distinct components that separately contribute to the modulation of AP-1 activity in MA-10 cells.

Animals↗
PubMed1997

Biophysical characteristics of radiofrequency lesion formation in vivo: dynamics of catheter tip-tissue contact evaluated by intracardiac echocardiography.

During clinical radiofrequency catheter ablation a wide range of delivered power may be necessary to achieve success despite an apparently stable catheter position on fluoroscopy. The purpose of this study was to use intracardiac echocardiography to characterize the relation between catheter tip-tissue contact and the efficiency of heating during applications of radiofrequency energy in vivo and to determine whether intracardiac echocardiography could be used prospectively to improve tissue contact. A closed-loop temperature feedback control system was used during radio-frequency applications at five anatomic regions in the right atrium of 15 anesthetized dogs to ensure achievement of a predetermined temperature (70 degrees C) at the catheter tip thermistor by automatic adjustment of delivered power (maximum 100 W). The efficiency-of-heating index was defined as the ratio of steady-state temperature (degrees Celsius) to power (watts). Two-dimensional intracardiac echocardiography was used to evaluate movement of the catheter tip relative to the endocardium. Perpendicular contact was scored as good, average, or poor and lateral catheter sliding as < 2, 2 to 5, or > 5 mm. Two groups of animals were included: group 1, in which tissue contact was guided by fluoroscopic and electrographic criteria for stability of contact, with intracardiac echocardiography used simply to observe the application; and group 2, in which tissue contact was guided by intracardiac echocardiography. Of 66 applications, 18 (27.3%) had poor perpendicular contact on echocardiography, and 12 (18.2%) demonstrated lateral sliding of > 5 mm even though they had been considered to have good tissue contact by fluoroscopic and electrographic criteria. Perpendicular catheter contact and anatomic location were shown to be independently related to the efficiency-of-heating index. Applications with good perpendicular contact had a significantly higher efficiency-of-heating index and a significantly greater lesion size than those with average or poor contact. The percentage of applications having good perpendicular tissue contact and the lesion size were significantly greater when tissue contact was guided by intracardiac echocardiography compared with fluoroscopic and electrographic guidance. This study demonstrates that variations in catheter tip-tissue contact account for differences in the efficiency of tissue heating, independently of the anatomic site of the application. Poor tissue contact was observed by intracardiac echocardiography and confirmed by indexes of tissue heating in approximately one third of radiofrequency applications despite a fluoroscopic appearance and electrographic morphologic appearance suggestive of good tissue contact. There was a significant correlation between echocardiographic evaluation of tissue contact, parameters of tissue heating (efficiency-of-heating index), and lesion size. In addition, intracardiac echocardiography could be used prospectively to improve the percentage of good contact applications and increase the lesion size.

Analysis of Variance↗
PubMed1997

Serological survey of chlamydial antibody in post-natal sera.

Questionnaires (3426; 72.8%) and blood samples (3890; 82.6%) were analysed from 4704 women post-natally. The answers to the questionnaire confirmed that those patients living in areas with the highest percentage employed in agriculture were most likely to be in direct or indirect contact with sheep or sheep products. When the 788 (20.3%) of the sera with group specific antibody were examined for type-specific antibody, 291 (7.5%) reacted with Chlamydia trachomatis, 153 (3.9%) with Chlamydia pneumoniae, but only one (0.03%) with Chlamydia psittaci. Thus, it would appear that C. psittaci was not an important pathogen in this survey, despite the largest proportion of blood samples being submitted from those most likely to be employed in agriculture. However, in the course of this survey the three patients who had previously suffered chlamydia-associated abortion had successful pregnancies and submitted blood specimens. Serological studies on the serial bloods from these patients showed that, despite developing antibody to the C. psittaci pool and the ovine abortion strain of C. psittaci following abortion, this antibody waned. At the time of the subsequent successful pregnancy, serological results would not have detected a previous C. psittaci infection, but one due to C. pneumoniae. Thus, the results of a survey such as this must be interpreted with caution.

Adolescent↗
PubMed1997

Inappropriate sinus tachycardia. Diagnosis and treatment.

Inappropriate sinus tachycardia is characterized by consistently elevated heart rates and exaggerated responses to minimal physiologic activity. The syndrome of inappropriate sinus tachycardia is defined by the clinical presentation of palpitations and presyncope that commonly appear to be out of proportion to the severity of the tachycardia. The development of a potentially curative procedure for patients suffering from inappropriate sinus tachycardia has renewed interest in the treatment of such patients. Continued research directed at the pathophysiology of inappropriate sinus tachycardia and what the optimal end point for achieving adequate rate control by radiofrequency catheter ablation without the need for the implantation of a permanent pacemaker is required. The optimal treatment may be the use of drugs that specifically inhibit sinus node pacemaker current.

Catheter Ablation↗
PubMed1997

Mechanism of initiation of atrial flutter in humans: site of unidirectional block and direction of rotation.

OBJECTIVES: Using a standardized induction protocol, we investigated the mechanism of initiation of atrial flutter, before ablation, to determine the site of initiating unidirectional block and to test the hypothesis that the direction of rotation of atrial flutter depends on the pacing site from which it initiates. BACKGROUND: The high recurrence rate of atrial flutter after presumed successful ablation may be due to difficulty in reinduction after termination. In addition, induction of clockwise flutter is currently of unknown clinical importance. METHODS: Ten patients with documented typical flutter were studied before ablation. A standard protocol consisting of single and double extrastimuli followed by burst pacing was performed from four sites in the right atrium (high and low trabeculated and smooth right atrium) to assess efficacy at inducing atrial flutter. A 20-pole halo catheter placed around the tricuspid annulus and a decapole catheter placed in the coronary sinus were used for mapping during initiation to determine type of flutter induced and the site of unidirectional block during initiation. RESULTS: Atrial flutter was induced in 52 (6.2%) of 838 attempted inductions. Of these, 33 were counterclockwise and 20 were clockwise. Of the 20 inductions resulting in clockwise flutter, 18 were from the trabeculated right atrium, whereas all the counterclockwise inductions were from the smooth right atrium. In all but the two inductions, the site of unidirectional block was identified between the os of the coronary sinus and the low lateral right atrium for both counterclockwise and clockwise flutter, in the same isthmus at which ablation is targeted. CONCLUSIONS: Even in patients with clinical counterclockwise flutter, clockwise flutter is frequently induced before ablation and is dependent on the site of induction: Pacing from the smooth right atrium induces counterclockwise flutter, whereas pacing from the trabeculated right atrium induces clockwise flutter. The site of the unidirectional block during the initiation of either form of flutter is in the low right atrium isthmus.

Aged↗
PubMed1997

Slow AV nodal pathway ablation utilizing a unique temperature controlled radiofrequency energy system.

Thirty-nine consecutive patients with symptomatic AV nodal reentrant tachycardia (AVNRT) underwent temperature guided slow AV nodal pathway ablation (group 1). Forty-three consecutive patients undergoing nontemperature guided slow AV nodal pathway ablation late in our experience compose the control population (group 2). Slow pathway ablation was achieved in all patients of both groups. The mean fluoroscopy and ablation times for group 1 were significantly shorter than for group 2 (26.1 +/- 14.9 vs 33.9 +/- 18.9 min, P < 0.05; 19.9 +/- 12.1 vs 30.9 +/- 23.3 min, P < or = 0.02). There were no episodes of coagulum formation in group 1, while there were 15 episodes (7.1% of energy applications) in group 2 (P = 0.0006) despite a significantly higher applied power in group 1 (53.4 +/- 25.1 vs 35.6 +/- 9.5W, P = 0.0001). Successful energy applications were associated with significantly higher temperatures than unsuccessful applications in group 1 (55.6 degrees +/- 5.8 degrees C vs. 52.9 degrees +/- 6.8 degrees C, P < or = 0.03). The minimum temperature required for successful ablation was 48 degrees C for two patients (5%) and was > or = 50 degrees C for the remainder of patients (37/39 [95%]). The catheter ablation system used in this study was safe, effective, and prevented coagulum formation while delivering relatively high power. In addition, shorter ablation times and radiation exposure were seen with this system. Although successful energy applications and the production of junctional rhythm were associated with higher achieved temperatures, temperature alone did not predict either endpoint. Future prospective, randomized trials are needed to confirm these findings and further evaluate the value of temperature monitoring.

Atrioventricular Node↗
PubMed1997

Electrocardiographic and electrophysiologic characterization of atypical atrial flutter in man: use of activation and entrainment mapping and implications for catheter ablation.

INTRODUCTION: Although the circuit in typical counterclockwise atrial flutter has been clearly delineated, the mechanisms of "atypical atrial flutters" have been less well characterized. The purpose of this study was to investigate the ECG and electrophysiologic (EP) characteristics of atypical atrial flutter. METHODS AND RESULTS: Thirty-three patients with at least one form of atypical atrial flutter underwent EP evaluation with multipolar atrial activation and entrainment mapping. Nineteen patients with clockwise flutter had: (1) stereotypic ECG morphology; (2) same cycle length as counterclockwise flutter; (3) clockwise activation around the tricuspid annulus; (4) recording of discrete split potentials along the length of the crista terminalis, suggesting the presence of conduction block; (5) concealed entrainment from the low right atrial isthmus; (6) successful ablation in this isthmus. Twenty patients with atypical flutter not consistent with a clockwise mechanism ("true atypical flutter") showed: (1) heterogeneous ECG morphology; (2) cycle length shorter than that of clockwise flutter; (3) frequent transitions from and to atrial fibrillation; (4) could be entrained in only six patients and, when accomplished, demonstrated surface fusion when entraining from the low right atrial isthmus. CONCLUSIONS: Atypical flutter falls into two broad categories. Clockwise flutter uses the same circuit with the same endocardial barriers as its counterclockwise counterpart and is best considered a form of typical flutter. True atypical flutter induced in the EP laboratory is a heterogeneous group of arrhythmias that are transitional to atrial fibrillation. Although it may superficially resemble clockwise or counterclockwise flutter based on the 12-lead ECG alone, the distinction can be readily made from a combined evaluation including activation and entrainment mapping.

Adult↗
PubMed1997

Intracellular Ca2+ handling and vulnerability to ventricular fibrillation in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) with ventricular hypertrophy show an increased vulnerability for the development of potentially lethal ventricular arrhythmias such as ventricular fibrillation (VF). The mechanisms of this increased vulnerability are not fully understood but may be related to abnormal intracellular Ca2+ ([Ca2+]i) handling under stress conditions. We therefore investigated whether [Ca2+]i handling is abnormal in hypertrophied hearts of SHR without heart failure during stimulation stress, and if so whether abnormal [Ca2+]i handling is a determinant of the increased vulnerability to VF in SHR. [Ca2+]i was measured by indo-1 surface fluorescence in perfused hearts of 8- to 10-month-old control Wistar-Kyoto rats (WKY) and age-matched SHR. The state of [Ca2+]i handling was analyzed during three different forms of stimulation stress: rapid pacing, the long rest period after cessation of rapid pacing, and preprogrammed ventricular stimulation that was simultaneously used for the determination of VF threshold. The pulse number VF threshold was used as an index to determine vulnerability to VF and to analyze the relationship of [Ca2+]i handling to vulnerability. Although VF thresholds were lower in SHR than in WKY, we found that both demonstrated similar [Ca2+]i handling during stimulation stress. The extent and rate of [Ca2+]i accumulation during rapid pacing and those of the [Ca2+]i decline after cessation of pacing were similar in SHR and WKY. In addition, the relationship between [Ca2+]i and VF threshold was unaltered in SHR. Thus, we conclude that [Ca2+]i handling is normal in hypertrophied hearts of SHR without heart failure during stimulation stress and that it is not a determinant of the increased vulnerability to VF in SHR.

Animals↗
PubMed1997

Lipidic vector systems for gene transfer.

Clinical application of gene therapy depends on the development of suitable gene transfer vehicles (vectors). Although generally not as efficient as viral vectors, nonviral systems such as lipidic vectors have the potential advantages of being less toxic, nonrestrictive in cargo DNA size, potentially targetable, and easy to produce in relatively large amounts. More important, lipidic vectors generally lack immunogenicity, allowing repeated in vivo transfection using the same vector. In this paper, we will attempt to summarize some of the recent advances in lipidic gene delivery vectors. Three types of lipidic gene transfer vectors are described: 1) DNA/cationic liposome complexes, 2) DNA encapsulated in neutral or anionic liposomes, and 3) liposome-entrapped, polycation-condensed DNA (LPDI and LPDII). We review the various factors affecting vector structure and gene delivery efficiency, and we discuss the possible mechanisms of gene transfer and their implications in vector design.

Animals↗
PubMed1996

Induction of cyclin D1 by simian virus 40 small tumor antigen.

Cell-cycle progression is mediated by a co-ordinated interaction between cyclin-dependent kinases and their target proteins including the pRB and E2F/DP-1 complexes. Immunoneutralization and antisense experiments have established that the abundance of cyclin D1, a regulatory subunit of the cyclin-dependent kinases, may be rate-limiting for G1 phase progression of the cell cycle. Simian virus 40 (SV40) small tumor (t) antigen is capable of promoting G1 phase progression and augments substantially the efficiency of SV40 transformation through several distinct domains. In these studies, small t antigen stimulated cyclin D1 promoter activity 7-fold, primarily through an AP-1 binding site at -954 with additional contributions from a CRE site at -57. The cyclin D1 AP-1 and CRE sites were sufficient for activation by small t antigen when linked to an heterologous promoter. Point mutations of small t antigen between residues 97-103 that reduced PP2A binding were partially defective in the induction of the cyclin D1 promoter. These mutations also reduced activation of MEK1 and two distinct members of the mitogen-activated protein kinase family, the ERKs (extracellular signal regulated kinases) and the SAPKs (stress-activated protein kinases), in transfected cells. Dominant negative mutants of either MEK1, ERK or SEK1, reduced small t-dependent induction of the cyclin D1 promoter. SV40 small t induction of the cyclin D1 promoter involves both the ERK and SAPK pathways that together may contribute to the proliferative and transformation enhancing activity of small t antigen.

Animals↗
PubMed1996

Angiotensin II activation of cyclin D1-dependent kinase activity.

Angiotensin II (AII) binds to specific G protein-coupled receptors and is mitogenic in adrenal, liver epithelial, and vascular smooth muscle cells. Since the cyclin D1 gene encodes the regulatory subunit of the cyclin D1-dependent kinase (CD1K) required for phosphorylation of the retinoblastoma protein (pRB), an essential and rate-limiting step in G1 phase progression of the cell cycle, we examined the effect of AII on cyclin D1 expression and CD1K activity in the human adrenal cell line H295R. AII (10(-6) M) stimulated G1 phase progression within 12 h, with a maximal effect after 72 h. This action was antedated by the induction of cyclin D1 mRNA (3-fold), cyclin D1 nuclear protein abundance (4-fold), and CD1K activity (4-fold). AII induced cyclin D1 promoter activity 4-fold, via the AT1 receptor through an enhancer sequence at -954 base pairs. c-Fos and c-Jun bound the cyclin D1 -954 enhancer sequence, and the abundance of c-Fos within this complex was increased by AII treatment. AII induced extracellular signal-regulated kinase (ERK) activity 7-fold, and dominant-negative mutants of either p21(ras) or ERK reduced AII-stimulated cyclin D1 promoter activity. These findings suggest that AII may stimulate mitogenesis by increasing CD1K activity through a p21(ras)/ERK/activator protein 1 pathway.

Angiotensin II↗
PubMed1996

Activation and entrainment mapping defines the tricuspid annulus as the anterior barrier in typical atrial flutter.

BACKGROUND: The importance of anatomic barriers in the atrial flutter reentry circuit has been well demonstrated in canine models. It has been shown previously that the crista terminalis and its continuation as the eustachian ridge form a posterior barrier. In this study we tested the hypothesis that the tricuspid annulus forms the continuous anterior barrier to the flutter circuit. METHODS AND RESULTS: Thirteen patients with typical atrial flutter were studied. A 20-pole halo catheter was situated around the tricuspid annulus. A mapping catheter was used for activation and entrainment mapping from seven sequential sites around the tricuspid annulus and from three additional sites including the tip of the right atrial appendage, at the fossa ovalis, and in the distal coronary sinus. Sites were considered to be within the circuit when the postpacing interval minus the flutter cycle length and the stimulus time minus the activation time were < or = 10 ms; sites were considered to be outside the circuit when these intervals were > 10 ms. All seven annular sites were within the circuit; activation occurred sequentially around the annulus and accounted for 100% of the flutter cycle length. The fossa ovalis, the distal coronary sinus, and the right atrial appendage were outside the circuit. CONCLUSIONS: Closely spaced sites around the tricuspid annulus are activated sequentially, and are all within the flutter circuit according to entrainment criteria. This demonstrates that the tricuspid annulus constitutes a continuous anterior barrier constraining the reentrant wave front of human counterclockwise atrial flutter.

Aged↗
PubMed1996

Measurement of endosome pH following folate receptor-mediated endocytosis.

Free folic acid is believed to enter some cells by folate receptor-mediated endocytosis at membrane invaginations termed caveolae. Folate conjugated macromolecules also enter cells by folate receptor-mediated endocytosis, but their site of entry has never been conclusively identified. In this paper, we show that internalization of folate-macromolecule conjugates by receptor-bearing KB cells can be blocked by agents that specifically inhibit caveolae assembly or internalization such as nystatin and phorbol-12-myristate acetate (PMA). To characterize the intracellular conditions to which the macromolecule-folate conjugates are subsequently exposed, we have measured the pH of the major compartments of the folate endocytosis pathway. pH values of individual endosomal compartments in KB cells were determined by dual-excitation laser-scanning confocal microscopy, where the fluorescence ratio of folate-DM-NERF-dextran (pH-sensitive) and Texas Red-dextran (pH-insensitive) was used to calculate pH. These studies revealed that the pH of folate conjugate-containing endosomes commonly varies between 4.7 and 5.8, with the pH in some endosomes as low as 4.3. The most frequent pH value in these compartments was approximately 5.0.

Biological Transport↗