Biomedical subjects

L Ngo

Publications and source records attributed to L Ngo.

At least 19 recordsLinked to original sources

PubMed1997

Association between lifetime ambient ozone exposure and pulmonary function in college freshmen--results of a pilot study.

Human health effects due to chronic exposure to ozone (O3) have not been established due to problems with exposure assignment and the use of measures of lung function which may not reflect the site of O3 toxicity in the lung. We investigated the feasibility of retrospective assessment of O3 exposure-relevant covariates and derived lifetime "effective exposure" to ozone. Mid- and end-expiratory flows (FEF25-75%, FEF75%) were regressed against effective exposure and ecological lifetime exposure. A convenience sample of 130 UC Berkeley freshmen, ages 17-21, participated twice in the same tests (residential history, questionnaire, pulmonary function), 5-7 days apart. Students had to be lifelong residents of Northern (SF) or Southern (LA) California. Monthly ambient O3 concentrations (OZ) were assigned based on the lifetime residential history. An "effective time" (T) spent in OZ environments was derived for each residence and age stratum (0-2, 3-5, 6-11, 12+) with the use of questions about "total time spent outdoors" and time spent in "moderate" and/or "heavy" activity. Effective exposure was calculated over the lifetime (OZ x T) of each subject. Ozone metrics used were 8-hr averages (10 AM-6 PM) and "hours above 60 ppb." FEF25-75% and FEF75% decreased with both effective exposure and ecologic assignment of O3 exposure. For a 20 ppb increase (interquartile range) in 8-hr O3, FEF75% decreased 334 ml/sec (95%Cl:11-657 ml/sec), which corresponds to 14% (1.0-28.3%) of the population mean FEF75%. The corresponding effect on FEF25-75% was -420 ml/sec (95%Cl: +46 to -886, P = 0.08) or 7.2% of the mean. Use of time-activity data to define exposure had no impact on estimates. Negative confounding factors were region (SF vs LA), gender, and ethnicity. Lifetime 8-hr average O3 concentrations ranged from 16 to 74 ppb with little overlap between regions. There was no evidence for different O3 effects across regions. Effects were independent of lifetime mean PM10, NO2, temperature, or humidity. Effects on FEV1 tended to be negative whereas those for FVC, although negative in some models, where inconsistent and small. The strong relationship of lifetime ambient O3 on mid- and end-expiratory flows of college freshmen and the lack of association with FEV1 and FVC are consistent with biologic models of chronic effects of O3 in the small airways. Since the present study was designed as a pilot study, these findings have to be confirmed in a larger sample that is representative of the target population.

Adolescent↗

PubMed1996

Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.

The finding that intracellular expression of the beta-amyloid protein (Abeta) under a neuron-specific promoter led progressively to degeneration and death of neurons in the brains of transgenic mice provides a unique opportunity to utilize this animal model to both understand the mechanism that underlies neuronal cell death and define the complexity of events which may ensue. We observed a correlation between Abeta accumulation in selective neurons and activation of p53, a protein that has been implicated in the induction of apoptosis. Histological and immunohistochemical evaluations of adjacent brain sections suggest that expression of p53 is accompanied by nuclear DNA fragmentation. In certain regions with marked neuronal cell death, extracellular deposition of A(beta) became evident, together with the local activation of astrocytes. Interestingly, the neuritic structures underlying the Abeta deposits showed altered synaptophysin immunoreactivity and morphologic evidence for damage. This transgenic mouse model suggests that intracellular generation of the Abeta protein not only leads to the death of the neuron but may also functionally impair neighboring neurons as well. It further offers a mechanism whereby neuritic plaques may be derived.

Alzheimer Disease↗

PubMed1996

Second generation hybrid polar compounds are potent inducers of transformed cell differentiation.

Hybrid polar compounds, of which hexamethylenebisacetamide (HMBA) is the prototype, are potent inducers of differentiation of murine erythroleukemia (MEL) cells and a wide variety of other transformed cells. HMBA has been shown to induce differentiation of neoplastic cells in patients, but is not an adequate therapeutic agent because of dose-limiting toxicity. We report on a group of three potent second generation hybrid polar compounds, diethyl bis-(pentamethylene-N,N-dimethylcarboxamide) malonate (EMBA), suberoylanilide hydroxamic acid (SAHA), and m-carboxycinnamic acid bis-hydroxamide (CBHA) with optimal concentrations for inducing MEL cells of 0.4 mM, 2 microM, and 4 microM, respectively, compared to 5 mM for HMBA. All three agents induce accumulation of underphosphorylated pRB; increased levels of p2l protein, a prolongation of the initial G1 phase of the cell cycle; and accumulation of hemoglobin. However, based upon their effective concentrations, the cross-resistance or sensitivity of an HMBA-resistant MEL cell variant, and differences in c-myb expression during induction, these differentiation-inducing hybrid polar compounds can be grouped into two subsets, HMBA/EMBA and SAHA/CBHA. This classification may prove of value in selecting and planning prospective preclinical and clinical studies toward the treatment of cancer by differentiation therapy.

Acetamides↗

PubMed1996

Application of exponential smoothing for nosocomial infection surveillance.

Detection of outbreaks of infection or increases in bacterial resistance to antimicrobial agents is an essential component of hospital infection control surveillance. The authors applied the method of exponential smoothing to microbiology data from 1987-1992 to investigate a suspected outbreak of gentamicin resistance among Pseudomonas aeruginosa bacteria at the Department of Veterans Affairs Medical Center, San Francisco, California, in 1991-1992. The years 1987-1990 were used to develop the baseline for the forecast model. Application of the model indicated that two observed prominent peaks in the annual cumulative incidence of gentamicin-resistant P. aeruginosa were within the upper bounds of their respective 95% confidence intervals as estimated by the forecast model--i.e., that no epidemic was in progress. This prediction was supported by investigations by the hospital's infection control team which indicated that the apparent increases were due to readmission of patients previously known to harbor these organisms. In contrast, application of a typically employed method that ignores the time series data structure indicated that there were 6 months in which incidence rates exceeded the upper bounds of their respective 95% confidence intervals, thereby erroneously suggesting that an epidemic was in progress. Recursive algorithms and some simplifying assumptions that do not affect the validity of inferences make the application of this method practical for nosocomial infection control programs.

Anti-Bacterial Agents↗

PubMed1996

A knowledge-based model construction approach to medical decision making.

We present a framework for representing the probabilistic effects of actions and contingent treatment plans. Our language has a well-defined declarative semantics and we have developed an implemented algorithm (named BNG) that generates Bayesian networks (BN) to compute the posterior probabilities of queries. In this paper we address the problem of projecting a contingent treatment plan by automatically constructing a structure of interrelated BNs, which we call a BN-graph, and applying the available propagation procedures on it. To address the optimal plan generation, we base our approach on the observation that normally the target plan space has a well-defined structure. We provide a language to describe plan spaces which resembles a programming language with loops and conditionals. We briefly present the procedures for finding the optimal plan(s) from such specified plan spaces.

Acute Disease↗

PubMed1995

Effect of older age on survival in human immunodeficiency virus (HIV) disease.

To evaluate the impact of older age (> 50 years old) on survival in late-stage human immunodeficiency virus (HIV) disease, the authors analyzed 846 HIV-infected patients at the San Francisco Veterans Affairs Medical Center from 1987 to 1992. The median age was 42 years with 171 (20.2%) subjects aged 50 or more years. Survival was measured from the date of initial lymphocyte testing (median CD4 count, 223 cells/mm3) until death or censoring. Compared with those aged less than 40 years, and after multivariate proportional hazards adjustment for other significant determinants of survival (CD4 percentage, CD8 count, hematocrit, and prior acquired immunodeficiency syndrome diagnosis), there was no difference in survival for those aged 40-49 years, but there was a trend toward decreased survival in those aged 50-59 years (relative hazard = 1.32, 95% confidence interval 0.90-1.94) and in those aged 60 or more years (relative hazard = 1.56, 95% confidence interval 0.99-2.46). The impact of older age on mortality in HIV disease is, however, less than the impact of age on overall mortality in the United States. Accordingly, while older HIV-infected patients do have a somewhat poorer survival, this risk need not be too highly emphasized in individual patients; older patients deserve aggressive management.

Adult↗

PubMed1995

Gain of function mutations for paralogous Hox genes: implications for the evolution of Hox gene function.

To investigate the functions of paralogous Hox genes, we compared the phenotypic consequences of altering the embryonic patterns of expression of Hoxb-8 and Hoxc-8 in transgenic mice. A comparison of the phenotypic consequences of altered expression of the two paralogs in the axial skeletons of newborns revealed an array of common transformations as well as morphological changes unique to each gene. Divergence of function of the two paralogs was clearly evident in costal derivatives, where increased expression of the two genes affected opposite ends of the ribs. Many of the morphological consequences of expanding the mesodermal domain and magnitude of expression of either gene were atavistic, inducing the transformation of axial skeletal structures from a modern to an earlier evolutionary form. We propose that regional specialization of the vertebral column has been driven by regionalization of Hox gene function and that a major aspect of this evolutionary progression may have been restriction of Hox gene expression.

Animals↗

PubMed1995

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Age Factors↗

PubMed1995

Functional inactivation but not structural mutation of p53 causes liver cancer.

Structural mutations in the p53 gene are seen in virtually every form of human cancer. To determine whether such mutations are important for initiating tumorigenesis, we have been studying hepatocellular carcinoma, in which most cases are associated with chronic hepatitis B virus infections. Using a transgenic mouse model where expression of a single HBV gene product, the HBx protein, induces progressive changes in the liver, we show that tumour development correlates precisely with p53 binding to HBx in the cytoplasm and complete blockage of p53 entry into the nucleus. Analysis of tumour cell DNA shows no evidence for p53 mutation, except in advanced tumours where a small proportion of cells may have acquired specific base substitutions. Our results suggest that genetic changes in p53 are late events which may contribute to tumour progression.

Animals↗

PubMed1995

Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life.

The present investigation evaluated the effects of maternal smoking during pregnancy on the growth of lung function during the first 18 mo of life in 159 infants who were part of a longitudinal study of the effects of maternal smoking on respiratory health. Infant pulmonary function was assessed at 2 to 6 wk of age and at 4 to 6, 9 to 12, and 15 to 18 mo of age by partial expiratory flow-volume curves and helium dilution FRC. Maternal smoking was assessed by standard questionnaire and urine cotinine measurements. Maternal smoking during pregnancy was associated with a reduction of 9.4 +/- 4.3 ml (p = 0.029) for FRC and 33 +/- 12.3 ml/s (p = 0.008) reduction for flow at FRC (VFRC) after controlling for the effects of growth (length). The effect of maternal smoking was greater for female infants than for male infants. At 1 yr female infants exposed in utero were predicted to have a 16% reduction in VFRC compared with 5% for male infants. No sex difference was seen for FRC or VFRC/FRC. Exposure to environmental tobacco smoke in the postnatal period was not significantly related to reduced FRC or VFRC. These data provide further evidence that maternal smoking during pregnancy may play a greater role than postnatal and childhood exposure on the observed effects on lung function in children.

Female↗

PubMed1995

Clinical simulation using context-sensitive temporal probability models.

We present a language for representing context-sensitive temporal probabilistic knowledge. Context constraints allow inference to be focused on only the relevant portions of the probabilistic knowledge. We provide a declarative semantics for our language and an implemented algorithm (BNG) that generates Bayesian networks to compute the posterior probabilities of queries. We illustrate the use of the BNG system by applying it to the problem of modeling the effects of medications and other interventions on the condition of a patient in cardiac arrest.

Artificial Intelligence↗

PubMed1994

Factors associated with survival in human immunodeficiency virus-infected patients with very low CD4 counts.

The authors examined the survival experience of 289 human immunodeficiency virus (HIV)-infected men to identify factors independently associated with survival in patients with very low CD4 counts (< or = 100/mm3). All subjects were HIV-infected men cared for at the San Francisco Veterans' Affairs Medical Center between January 1988 and November 1991. Survival was measured from the date on which a patient was first known to have a CD4 count < or = 100/mm3 until death or censoring. Factors potentially associated with survival were examined initially using the product limit (Kaplan-Meier) method; a multivariate model of survival was constructed using a proportional hazards (Cox) regression. Four variables were identified as independently associated with survival (p < 0.05) in the Cox proportional hazards model: CD4 count, hematocrit, azidothymidine use, and clinical stage (prior history of acquired immunodeficiency syndrome vs. no prior history). All 16 possible combinations of these four (dichotomized) variables were examined; eight different patterns of survival were detected. Identification of survival patterns that can be described by data obtained as part of routine clinical care has implications for patient care, the design of clinical trials, the study of mechanisms of progression of HIV-related immunosuppression, and planning of health care resource needs for populations of patients with very low CD4 counts.

Adult↗

PubMed1994

V-sis induces Egr-1 expression by a pathway mediated by c-Ha-Ras.

The early growth response gene, Egr-1, is up-regulated transiently by mitogens and many other stimuli in all cells tested. Using NIH3T3 cells conditionally expressing v-sis from a metallothionein promoter, we show that the addition of Zn2+ stimulates the production of PDGF-B (v-sis) and elicits the expression of Egr-1 in a dose-dependent and time-regulated manner. The signal is likely independent of protein kinase C, but depends on tyrosine kinase and other kinase activities and is mediated by c-Ha-Ras since the presence of dominant-negative mutants of Ras and Raf abrogates the induction of Egr-1 expression by Zn2+. Transiently activated Ras expression in NIH3T3 cells also stimulates the transient expression of Egr-1, but cells that constitutively express Ras do not have elevated levels of Egr-1. Transient assays also demonstrated that Zn2+ or activated Ras expression stimulate the activity of a 950 bp Egr-1 promoter-reporter gene construct and this is abrogated in the presence of mutant Ras and Raf. The accumulated data show that Egr-1 gene expression is regulated by multiple mechanisms, as would be needed for putative roles in cell proliferation, in suppression of transformation and in differentiation.

3T3 Cells↗

PubMed1993

Effects of nitric acid gas alone or in combination with ozone on healthy volunteers.

Nitric acid (HNO3) is the most prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. To study this potential, we measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 micrograms/m3 of HNO3 gas or filtered air for 4 h during moderate exercise (ventilatory rate, 40 L/min) and underwent bronchoscopy 18 h later. Under an identical protocol, 10 healthy subjects were exposed to 500 micrograms/m3 of HNO3 gas plus 0.20 ppm ozone (O3) or 0.20 ppm O3 alone to determine if HNO3 might enhance the toxicity of O3. In addition to bronchoalveolar lavage (BAL), we employed the techniques of isolated left mainstem bronchial lavage and bronchial biopsy to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by BAL. We found no significant differences in pulmonary function tests or in the cellular or biochemical constituents in either the BAL or the left mainstem lavage fluids between the HNO3 and the air exposures. Similarly, there were no differences in these end points between the HNO3/O3 and the O3 exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the HNO3 and air exposures or between the HNO3/O3 and O3 exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗