Biomedical subjects

L Ngo

Publications and source records attributed to L Ngo.

48 records · Page 3Linked to original sources

PubMed1992

Ventricular arrhythmias in patients undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group.

OBJECTIVE: To determine the incidence, clinical predictors and prognostic importance of perioperative ventricular arrhythmias. DESIGN: Prospective cohort study (Study of Perioperative Ischemia). SETTING: University-affiliated Department of Veterans Affairs Medical Center, San Francisco, Calif. SUBJECTS: A consecutive sample of 230 male patients, with known coronary artery disease (46%) or at high risk of coronary artery disease (54%), undergoing major noncardiac surgical procedures. MEASUREMENTS: We recorded cardiac rhythm throughout the preoperative (mean = 21 hours), intraoperative (mean = 6 hours), and postoperative (mean = 38 hours) periods using continuous ambulatory electrocardiographic monitoring. Adverse cardiac outcomes were noted by physicians blinded to information about arrhythmias. MAIN RESULTS: Frequent or major ventricular arrhythmias (greater than 30 ventricular ectopic beats per hour, ventricular tachycardia) occurred in 44% of our patients: 21% preoperatively, 16% intraoperatively, and 36% postoperatively. Compared with the preoperative baseline, the severity of arrhythmia increased in only 2% of patients intraoperatively but in 10% postoperatively. Preoperative ventricular arrhythmias were more common in smokers (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.2 to 15.0), those with a history of congestive heart failure (OR, 4.1; 95% CI, 1.9 to 9.0), and those with electrocardiographic evidence of myocardial ischemia (OR, 2.2; 95% CI, 1.1 to 4.7). Preoperative arrhythmias were associated with the occurrence of intraoperative and postoperative arrhythmias (OR, 7.3; 95% CI, 3.3 to 16.0, and OR, 6.4; 95% CI, 2.7 to 15.0, respectively). Nonfatal myocardial infarction or cardiac death occurred in nine men; these outcomes were not significantly more frequent in those with prior perioperative arrhythmias, albeit with wide CIs (OR, 1.6; 95% CI, 0.4 to 6.2). CONCLUSION: Almost half of all high-risk patients undergoing noncardiac surgery have frequent ventricular ectopic beats or nonsustained ventricular tachycardia. Our results suggest that these arrhythmias, when they occur without other signs or symptoms of myocardial infarction, may not require aggressive monitoring or treatment during the perioperative period.

Aged↗

PubMed1992

Cloning of a D-type cyclin from murine erythroleukemia cells.

We report the complete coding sequence of a cDNA, designated CYL2, derived from a murine erythroleukemia cell library. CYL2 is considered to encode a D-type cyclin because (i) there is cross hybridization with CYL1 (a murine homolog of human cyclin D1) and the encoded protein has 64% amino acid sequence identity with CYL1 and (ii) murine erythroleukemia cell-derived CYL2 contains an amino acid sequence identical to that previously reported for the C-terminal portion of a partially sequenced CYL2. Transcripts of murine erythroleukemia cell CYL2 undergo alternative polyadenylylation like that of human cyclin D1. A major 6.5-kilobase CYL2 transcript changes its expression during the cell cycle with a broad peak through G1 and S phases and a decrease in G2/M phases. The present findings suggest that CYL2 plays a role in the G1 to S phase progression.

Amino Acid Sequence↗

PubMed1992

Changes in p34cdc2 kinase activity and cyclin A during induced differentiation of murine erythroleukemia cells.

Hexamethylene bisacetamide (HMBA)-induced murine erythroleukemia (MELC) differentiation is characterized by a prolongation of the initial G1 which follows passage through S phase in the presence of inducer. Commitment to terminal cell division is first detected in a portion of the cell population during this prolonged G1. HMBA-induced commitment is stochastic. This study has examined changes in two known cell cycle regulators, p34cdc2 and cyclin A, in cycle-synchronized MELC in the absence and presence of HMBA. Histone H1 kinase activity of p34cdc2, and the levels of CDC2Mm mRNA, 1.8-kilobase mRNA of cyclin A, and cyclin A protein changed during cell cycle progression in MELC, and all of them were suppressed during G1. The suppression of the H1 kinase activity and cyclin A expression continued through the prolonged G1 in MELC cultured with HMBA, whereas p34cdc2 protein level did not vary through the cell cycle in MELC cultured without or with inducer. Phosphorylation of p34cdc2 in uninduced MELC gradually increased as cells progressed from G1 to S. In induced MELC, an increase in phosphorylation of p34cdc2 occurred during the prolonged G1, and prior to the exit of the bulk of the cells from G1 to S. These results suggest that in HMBA-induced MELC, p34cdc2 phosphorylation per se is not a limiting factor in determining G1 to S progression. The persistent suppression of cyclin A expression and histone H1 kinase activity may play a role in HMBA-induced commitment to terminal differentiation.

Acetamides↗

PubMed1991

Liver cancer in transgenic mice carrying the human immunodeficiency virus tat gene.

Patients with the acquired immunodeficiency syndrome are at risk to develop a variety of different cancers. Based on epidemiological data, Kaposi's sarcoma and non-Hodgkin's lymphoma have been clearly associated with infection by the human immunodeficiency virus (HIV). Additional cancers such as basal cell and squamous cell carcinomas, melanoma, and hepatocellular carcinoma have also been reported to be associated with a diagnosis of acquired immunodeficiency syndrome. A direct causal role of HIV has yet to be established for any of these cancers. We now report that transgenic mice carrying the HIV tat gene develop a high incidence of hepatocellular carcinoma after a long latency and that these changes in the liver are likely to be initiated by extrahepatic growth signals from the tat expressing cells in these mice. We predict that as acquired immunodeficiency syndrome patients begin to respond to therapy and show prolonged survival, such "secondary" malignancies induced by HIV will become increasingly prevalent.

Animals↗

PubMed1991

Potent cytodifferentiating agents related to hexamethylenebisacetamide.

Bishydroxamic acids are effective inducers of differentiation in murine erythroleukemia cells. Flexible analogs of suberic acid bisdimethylamide are approximately 100 times as active as the parent compound or hexamethylenebisacetamide. They also induce differentiation of human promyelocytic leukemia cells (HL-60) and a subclone of human colon carcinoma cells (HT-29-U4). Some rigid bishydroxamic acids with benzene rings in the spacers are even more active toward murine erythroleukemia cells but show curious biological differences. In contrast to the flexible molecules, those with benzene spacers show poor activity toward HL-60 cells; they also have different geometric requirements, and they are not additive with hexamethylenebisacetamide in their effect. It is likely that rigid bishydroxamic acids, with a benzene ring spacer, induce differentiation by a different mechanism in spite of their chemical resemblance to the flexible bisamide and bishydroxamic acid inducers.

Acetamides↗

PubMed1991

Characteristics of erythroleukemia cells selected for vincristine resistance that have accelerated inducer-mediated differentiation.

The induction of murine erythroleukemia cells (MELC; DS19/Sc9) to terminal differentiation by hexamethylenebisacetamide (HMBA) is characterized by a latent period of 10-12 hr before onset of commitment to terminal-cell division and increased transcription of globin genes. MELC variants, derived from this parental cell line, selected for resistance to vincristine (VC), can be induced to differentiate with little or no latent period. This study shows that accelerated HMBA-induced commitment is characteristic of MELC with a low level (2- to 5-fold) of VC resistance in four independently derived cell lines. Both resistance to VC and accelerated differentiation are stable phenotypes for at least 50 passages (approximately 5 months) in the absence of VC. Low-level VC-resistant MELC do not display increased levels of P-glycoprotein or mdr1, mdr2, and mdr3 mRNAs, nor do they exhibit cross-resistance to colchicine or doxorubicin. These cells do show (i) increased level of protein kinase C activity, (ii) reduced accumulation of [3H]VC, and (iii) restoration of VC sensitivity in the presence of verapamil. MELC selected for higher levels of VC resistance (approximately 500-fold) do express high levels of P-glycoprotein and the mdr3 gene. During HMBA-induced differentiation, DS19/Sc9 decrease [3H]VC accumulation, but P-glycoprotein content does not change. A VC-transport-associated protein, also critical for the process of induced differentiation, may be constitutively present in VC-resistant MELC, accounting for their enhanced sensitivity to inducer. This protein accumulates by exposure of VC-sensitive cells to HMBA, contributing to their differentiation and decreased level of VC accumulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction.

This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.

Adult↗

PubMed1990

Plasma prohormone atrial natriuretic peptides 1-98 and 31-67 increase with supraventricular and ventricular arrhythmias.

Recently two peptides consisting of amino acids (AA) 1-30 and 31-67 of the N-terminus of the 126 AA prohormone of atrial natriuretic factor (pro ANF) as well as atrial natriuretic factor (ANF, AA 99-126; C-terminus) were found to have vasodilatory and natriuretic properties. These peptides as well as ANF circulate in man as part of the N-terminus of the prohormone. To determine if the polyuria, associated with both ventricular and supraventricular arrhythmias, is associated with increased circulating concentrations of the N-terminus and C-terminus of the ANF prohormone, 20 individuals with spontaneous arrhythmias, including ten persons with atrial fibrillation, six with paroxysmal supraventricular tachycardia, and four with ventricular tachycardia, were evaluated before and after conversion to sinus rhythm. In all 20 patients, the circulating concentrations of the whole N-terminus (ie, AA 1-98), the midportion of the N-terminus (pro ANF 31-67) that circulates as a distinct 3900 molecular weight peptide after being proteolytically cleaved from the N-terminus, and the C-terminus were significantly higher (p less than 0.001) than their concentration in 54 persons with sinus rhythm. With conversion to sinus rhythm, the plasma C-terminus concentration of these 20 arrhythmia patients decreased to the level of persons with sinus rhythm within 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Acute and sustained release of atrial natriuretic factor with acute myocardial infarction.

The present investigation was designed to determine if acute ischemic cardiac injury causes the release of atrial natriuretic factor (ANF). Seventeen patients with acute myocardial infarction but without clinical evidence of congestive heart failure had their circulating concentration of ANF and creatine phosphokinase monitored daily for 14 days. All 17 patients had an elevated plasma ANF concentration at time of presentation. Maximal increase in ANF was on day 2 and 3 post-infarction. This maximal increase correlated with the size of infarction estimated by the maximal creatine phosphokinase concentration (r = 0.475; p less than 0.05), but did not correlate with the amount of left ventricular dysfunction. ANF began to decrease by day 4 post-infarction and was normal at 10 days post-infarction in 14 of the 17 (82%) patients. At 12 days post-infarction, all 17 patients had normal ANF levels. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured ANF levels in these patients were within our normal range and were significantly lower (p less than 0.001) than those seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina likewise had normal circulating ANF concentrations during prolonged episodes of chest pain. These levels were also significantly lower (p less than 0.001) than the 17 patients with acute infarcts not given tPA. The distinct pattern of release of ANF may be useful as an adjunct to serum cardiac enzymes in determining if a myocardial infarction has occurred.

Adult↗

PubMed1989

Prohormone atrial natriuretic peptides 1-30, 31-67, and 99-126 increase in proportion to right ventricular pacing rate.

To determine whether heart rate contributes to release of three new peptide hormones synthesized in the heart, right ventricular pacing at rates of 100, 125, 150, and 180 bpm was performed in six dogs with measurement of the plasma concentration of these peptides at each pacing rate while right atrial and systemic blood pressures were simultaneously monitored. These three peptides of the 126-amino-acid prohormone of atrial natriuretic factor (ANF), consisting of amino acids 1-30 (pro ANF 1-30), 31-67 (pro ANF 31-67), and 99-126 (ANF), increased incrementally at paced heart rates of 125, 150, and 180 bpm (r = 0.8, p less than 0.001). Right atrial pressure decreased with increasing heart rate but systemic blood pressure did not decrease until the heart rate was 180 bpm, at which time these peptides had obtained their maximal circulating concentrations. After pacing, mean right atrial pressure and levels of ANF returned to prepacing values within 30 minutes. Mean arterial blood pressure, on the other hand, increased throughout the 120-minute period after pacing. At 2 hours after pacing, levels of pro ANFs 1-30 and 31-67 were elevated compared with prepacing values. These data demonstrate that, at heart rates of 125 bpm and above, pro ANF 1-30, pro ANF 31-67, and ANF (99-126) are simultaneously and incrementally released in direct proportion to heart rate. The sustained elevation in pro ANFs 1-30 and 31-67 seen 2 hours after pacing suggests that they may contribute to the prolonged diuresis seen after cardiac pacing or tachycardia.

Animals↗

PubMed1989

Polar/apolar chemical inducers of differentiation of transformed cells: strategies to improve therapeutic potential.

N,N'-Hexamethylenebisacetamide (HMBA) induces transformed cells to differentiate, accompanied by suppression of oncogenicity. Clinical trials have shown that HMBA can cause positive therapeutic responses in some cancer patients, but clinical efficacy may be limited, in part, by dose-related toxicity. Potential improvements in efficacy may be accomplished by changes in the chemical structure of inducing agents and by increasing the sensitivity of tumor cells to inducers of differentiation. We have previously described an approach to improving tumor cell responsiveness to inducing agents. Transformed cell lines that have acquired low levels of resistance to vincristine display a markedly increased sensitivity to HMBA. We now report on a series of hybrid polar/apolar compounds--some of which are as active as HMBA and several of which are significantly more active than HMBA in vitro--whose chemical structures make it likely that they have different pharmacokinetics. Vincristine-resistant murine erythroleukemia cells also are shown to have marked increased sensitivity to these hybrid polar/apolar compounds. Thus these findings suggest potentially useful strategies for the application of polar/apolar inducers of differentiation to the treatment of cancers. These studies also provide approaches to further understanding of the biological process of terminal differentiation.

Acetamides↗

PubMedDate not supplied

Reliability of lifetime residential history and activity measures as elements of cumulative ambient ozone exposure assessment.

UNLABELLED: Assessment of long-term effects of lifetime ambient oxidant pollution relies on ecological exposure assignment. Given the characteristics of ozone exposure profiles, with daily and seasonal peaks and clearly lower indoor concentrations, exposure misclassification is of considerable concern. This study considered residential location, time spent outdoors, and outdoors activity as major determinants of "effective" lifetime ozone exposure. Given the lack of a valid "gold standard" for these measures, we evaluated the repeatability of the retrospective assessment of these factors. METHODS: A convenience sample of 175 college students raised in California participated in the study, designed as test-retest 5-7 days apart. Lifetime residential history and outdoors activity ("moderate" and "heavy") for each residence were extensively evaluated on both visits. RESULTS: Although reliability of residential location decreased considerably with increasing number of lifetime residences, assigned lifetime ambient ozone concentrations from the nearest monitor yielded highly reliable cumulative values (intraclass correlation = 0.99). "Doers" of both "moderate" and "heavy" activity could be identified reliably (kappa = 0.83 and 0.93, respectively). Derived "hours per month" were reasonably correlated across visits (r = 0.73 for "moderate," 0.64 for "heavy") with 27% and 36% of the variance between visits, respectively. Reporting errors increased with increasing levels of activity. CONCLUSIONS: Among students 17-21 years old, lifetime residential location could be repeatedly assessed. The overall performance of the set of activity questions was reasonably reliable and compares well with other measures used in epidemiology, such as blood pressure or dietary intake. Such questionnaires may be useful tools in reducing misclassification of lifetime exposure to ambient oxidants.

Adolescent↗