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Biomedical subjects

A J Moss

Publications and source records attributed to A J Moss.

At least 163 records · Page 9Linked to original sources
PubMed1988

Immunochemical quantitation of DNA adducts derived from the human bladder carcinogen 4-aminobiphenyl.

To assess target-tissue exposure to the human urinary bladder carcinogen 4-aminobiphenyl (ABP), we have developed a sensitive immunochemical method for measuring the major arylamine-DNA adduct formed, N-(guan-8-yl)-ABP (Gua-C8-ABP). High-affinity polyclonal antisera from rabbits immunized with N-(guanosin-8-yl)-ABP coupled to keyhole limpet hemocyanin were characterized and shown to have high specificity for antigenic determinants on the purine and biphenyl rings of Gua-C8-ABP and minimal cross-reactivity with ABP, deoxyguanosine, or hydrolyzed DNA. Assay standards containing ABP-modified DNA were prepared by reacting [3H]N-hydroxy-ABP with calf thymus DNA. DNA samples were hydrolyzed with trifluoroacetic acid and dried under vacuum, and the residues were dissolved in dimethyl sulfoxide under argon. Using a streptavidin-biotin amplified enzyme-linked immunosorbent assay, DNA hydrolysates competed at 25 micrograms DNA/microtiter well for a limiting amount of anti-keyhole limpet hemocyanin-(Gua-C8-ABP) in the presence of excess solid-phase bovine serum albumin-(Gua-C8-ABP) coating antigen. The limit of sensitivity for this assay using 25 micrograms DNA was 2 adducts/10(8) nucleotides. Gua-C8-ABP adducts in liver and bladder epithelial DNAs were readily quantified after p.o. administration of 5 mg/kg ABP to dogs. This methodology is capable of detecting adducts at levels of biological significance and should be applicable to human target-tissue dosimetry.

Aminobiphenyl Compounds↗
PubMed1988

Occurrence, characteristics and prognostic significance of early postacute myocardial infarction angina pectoris.

To determine the incidence, clinical characteristics and prognostic significance of early spontaneous angina after acute myocardial infarction (AMI), the database involving the 867 participants of the Multicenter Post-AMI Program, who were followed for 1 to 4 years after AMI, was analyzed. Two hundred eighty-six patients (33%) had in-hospital postinfarction angina. During a mean follow-up of 31 months, patients with postinfarction angina were more frequently (p less than 0.001) hospitalized for cardiac causes and underwent coronary artery bypass graft surgery; however, their cardiac mortality rates at 1 year (8.4%) and at 4 years (14.3%) were not significantly different from those among patients without postinfarction angina (7.1 and 12.9%, respectively). The only anginal characteristic found to be associated with increased subsequent cardiac mortality (17.9% at 1 year, 39.2% at total follow-up) was high frequency angina (greater than or equal to 1 daily episodes). High frequency angina occurred in a small subset of 28 patients (3.2% of the study population, 9.8% of patients with postinfarction angina). Clinical variables representing higher grades of mechanical dysfunction and electrical instability after infarction were significantly more common among patients with high frequency angina than among those with low frequency angina. Cox survivorship analysis revealed that high frequency angina made a significant contribution to the risk of post-AMI cardiac death (hazard ratio 2.5, p = 0.01), which was independent of the effect of predischarge reduced radionuclide ejection fraction and Holter-recorded frequent or repetitive ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Estimating left ventricular ejection fraction after myocardial infarction by various clinical parameters.

The clinical predictors of left ventricular (LV) ejection fraction (EF) were determined in 760 survivors of an acute myocardial infarction (AMI). LVEF was dichotomized at less than or equal to 0.40 (n = 269) and greater than 0.04 (n = 491). Logistic regression showed that 4 of 20 preselected, clinically meaningful variables were strong and independent (p less than 0.001) predictors of LVEF less than or equal to 0.40. Independent variables together with their odds ratio (odds of having a LVEF less than or equal to 0.40 with factor present to odds with factor absent) in order of decreasing importance were: anterior AMI (4.7), congestion on chest x-ray (2.9), previous AMI (2.3) and creatine kinase greater than 1,000 U (2.1). There was a stepwise decrease in LVEF and an increase in the proportion of patients with a low LVEF for each additional clinical variable. A general estimate of LVEF was made by simply considering the total number of clinical factors present. The presence of 0 or 1 clinical variable (n = 466) predicted a high LVEF (greater than 0.40) with an accuracy of 80%. Two or more variables (n = 294) predicted a low LVEF (less than or equal to 0.40) with an accuracy of 60%. The overall predictive accuracy was 72%. Clinically significant major misclassifications were rare (less than 10%). Readily obtainable clinical variables provide the clinician with a useful bedside method of estimating LVEF after AMI.

Heart Function Tests↗
PubMed1988

Mechanism of death and prevalence of myocardial ischemic symptoms in the terminal event after acute myocardial infarction.

A prospective study to determine prognostic factors for risk stratification in 867 patients surviving the coronary care unit phase of acute myocardial infarction (AMI) is reported. During a 48-month follow-up, 144 patients (17%) died. The deaths were examined for the chronology, cause, mechanism, location and presence of myocardial ischemia in the terminal event. A classification previously proposed by Hinkle and Thaler was used to define the mechanism of cardiac death and the presence of ischemia. There were 113 deaths due to coronary atherosclerotic coronary artery disease, including 5 due to complications of coronary artery bypass graft surgery. Of the remaining 108 of these deaths, 74% were classified as due to an arrhythmic mechanism and 26% as myocardial failure. Of the deaths due to an arrhythmia or to myocardial failure, 56 (52%) occurred out of hospital. The ratio of arrhythmic: myocardial failure deaths was not different for the patients who died within 3 months after the index AMI compared with later deaths. Sudden death (less than or equal to 1 hour of new symptoms) was strongly associated with arrhythmic death but 32 (54%) of patients who died greater than 1 hour after the onset of symptoms were also classified as having an arrhythmic cause of death. Previously described risk factors, including an ejection fraction less than 0.40 and greater than or equal to 10 ventricular premature complexes/hour, were independent predictors of mortality but did not differentially predict the mechanism of cardiac death. Evidence of myocardial ischemia before the terminal event was found in about 50 (60%) patients whose deaths were witnessed and who died from an arrhythmia or myocardial failure.

Coronary Disease↗
PubMed1988

Multiple coronary artery-left ventricular fistulas: a pattern of anomalous coronary microvascularization.

Fistulas between the coronary artery and the left heart chambers are exceptionally rare, especially those emptying into the left ventricle. We know of 33 cases of coronary artery-left ventricular fistulas reported in the literature, 7 of which had multiple communications. The findings in 6 additional patients with multiple coronary artery-left ventricular fistulas are reported. Three of the 6 patients from all three major coronary arteries. It is important to recognize this anomaly as it may be the source of angina in patients without angiographic evidence of major atherosclerotic coronary artery disease.

Aged↗
PubMed1988

Interactions of BCNU, low pH, glucose and hyperthermia in cultured RIF cells.

The interactions of BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) with low pH, glucose and hyperthermia were studied in cultured RIF tumor cells. The effect of a mild heat treatment of 43 degrees C, 1 h at pH 7.4 on cell killing [surviving fraction (S) = 0.27 +/- 0.05, standard error of the mean (S.E.)] was significantly enhanced by pH 6.5 (S = 0.11 +/- 0.02, S.E.) and 50 mM D-glucose (S = 0.14 +/- 0.01, S.E.). When heat (43 degrees C, 1 h) was added to BCNU, cytotoxicity was increased approximately 14-fold over BCNU alone. Moreover, pH 6.5 increased killing with BCNU and heat by an additional factor of 28. The presence of glucose at 37 degrees C at either pH 6.5 or 7.4 reduced BCNU toxicity in a dose dependent fashion. However, the presence of glucose did not reduce cell killing by BCNU at 43 degrees C. As a result BCNU cytotoxicity was enhanced by approximately 2 orders of magnitude when tumor cell acidification (glucose and low pH) was combined with BCNU and heat.

Carmustine↗
PubMed1988

Enhanced glycosylation of a 50 kD protein during development of thermotolerance in CHO cells.

During the development of thermotolerance, Chinese hamster ovary cells not only synthesized classical heat shock proteins, but also incorporated [3H]D-glucose or mannose into a glycoprotein with a Mr of approximately 50 kD. The glycosylation of the 50 kD protein correlated with the expression of thermotolerance under conditions when tolerance was induced either by acute or chronic heat conditioning. A phosphoprotein with the same molecular weight as the 50 kD glycoprotein was dephosphorylated immediately after heat conditioning. Both phosphate and glucose label in the ion front were enhanced immediately after heating, and may represent elevated levels of sugar phosphates. However, the composition of the ion front material remains to be determined. The data are consistent with a hypothesis that attributes increased heat resistance of thermotolerant cells to the glycosylation of specific heat-sensitive cellular sites.

Animals↗
PubMed1988

Tumor-targeted cell killing with 8-hydroxyquinolyl-glucuronide.

Many tumors show elevated levels of hydrolytic enzymes that may be associated with invasive processes. The RIF-1 murine tumor has levels of beta-glucuronidase that are more than four times higher than those in liver. Elevated tumor glucuronidase levels can be used as a basis for tumor-targeted therapy when systemically administered glucuronides of cytotoxic drugs are deconjugated preferentially at the tumor site. In this study we have used 8-hydroxyquinoline (8-OHQ) as a model compound for such a tumor-targeting concept. We showed that RIF tumors and spleen had the highest beta-glucuronidase activity in C3H mice; for example, RIF tumors released approximately seven times more phenolphthalein per gram of tissue from its glucuronide than liver, when compared under identical conditions. In vitro, low concentrations of 8-OHQ that might be achievable in vivo, ranging from 1 to 10 microM reduced cell survival by four orders of magnitude, while 1 mM 8-hydroxyquinolyl-glucuronide (1 h, 37 degrees C) resulted in only modest (S = 54%) cytotoxicity. Combination treatments of 8-OHQ (2.5 or 5 microM) with either hyperthermia or X radiation did not significantly change the slope of survival curves for RIF tumors in vitro, but suggest that targeted 8-OHQ toxicity combined with local hyperthermia and/or irradiation may be useful for significantly increasing therapeutic gains in vivo.

Animals↗
PubMed1987

Apoptosis induced by cold shock in vitro is dependent on cell growth phase.

Chinese hamster V79 fibroblast cells were exposed to brief periods of cold but non-freezing temperatures at different points on the population growth curve. Upon rewarming, cells at the transition from logarithmic to stationary growth exhibited apoptosis (programmed cell death). Cells in other stages of growth, or after reentry into logarithmic growth by refeeding, did not exhibit apoptosis. Apoptosis was expressed by marked cytoplasmic blebbing, by a characteristic non-random fragmentation of DNA into nucleosomal-sized pieces, and by loss of colony-forming ability. The data suggest that cold shock served as a stimulus for susceptible cells to undergo apoptosis. Thus, the experiments describe a new in vitro system for studying the mechanisms of apoptosis.

Animals↗
PubMed1987

Decreased heart rate variability and its association with increased mortality after acute myocardial infarction.

A high degree of heart rate (HR) variability is found in compensated hearts with good function, whereas HR variability can be decreased with severe coronary artery disease, congestive heart failure, aging and diabetic neuropathy. To test the hypothesis that HR variability is a predictor of long-term survival after acute myocardial infarction (AMI), the Holter tapes of 808 patients who survived AMI were analyzed. Heart rate variability was defined as the standard deviation of all normal RR intervals in a 24-hour continuous electrocardiogram recording made 11 +/- 3 days after AMI. In all patients demographic, clinical and laboratory variables were measured at baseline. Mean follow-up time was 31 months. Of all Holter variables measured, HR variability had the strongest univariate correlation with mortality. The relative risk of mortality was 5.3 times higher in the group with HR variability of less than 50 ms than the group with HR variability of more than 100 ms. HR variability remained a significant predictor of mortality after adjusting for clinical, demographic, other Holter features and ejection fraction. A hypothesis to explain this finding is that decreased HR variability correlates with increased sympathetic or decreased vagal tone, which may predispose to ventricular fibrillation.

Arrhythmias, Cardiac↗
PubMed1987

The mortality risk associated with digitalis treatment after myocardial infarction.

We examined the effects of digitalis therapy on postinfarction mortality throughout a 24-month to 48-month follow-up in 867 patients who survived an acute myocardial infarction. During follow-up, 145 patients died (16.7% mortality). At the time of hospital discharge, 31% of the patients were taking digitalis. The digitalis-treated patients were older, had more medical-cardiac risk factors, and had a higher mortality rate throughout the follow-up than the nondigitalis-treated patients. Statistical techniques were used to adjust for clinical imbalances between the digitalis-treated patients and nondigitalis-treated patients. The survival analysis (n = 728 patients) utilized the Cox regression model, and the digitalis-associated mortality risk was identified only after all significant covariates were allowed, so that mortality could be predicted as accurately as possible. Digitalis therapy was associated with a significantly increased postinfarction mortality risk after adjustment for the predictor covariates (relative risk 2.3, 95% confidence interval 1.4-3.7, p less than 0.001). The findings from this large multicenter study suggest that it would be prudent to exercise caution in the use of digitalis in postinfarction patients.

Aged↗
PubMed1987

Secondary prevention with calcium channel-blocking drugs in patients after myocardial infarction: a critical review.

The rationale for evaluating the efficacy and safety of calcium entry-blocking drugs to prevent secondary complications in patients after myocardial infarction is presented. The data currently available from postinfarction trials involving verapamil, nifedipine, and diltiazem are critically reviewed, and a comparison of the findings from three major trials of calcium entry-blocking drugs is provided.

Calcium Channel Blockers↗
PubMed1986

Left coronary arterial blood flow: noninvasive detection by Doppler US.

Continuous wave (CW) and pulsed Doppler ultrasound studies with spectral analysis were used to detect the left coronary arterial blood flow in patients who were undergoing routine echocardiography. The pulmonary artery is a stable ultrasonic landmark from which detection of the blood flow can be effected. The left coronary artery can be distinguished by its blood flow toward the cardiac apex and by specific, functional flow features. Flow patterns vary among the left main, circumflex, and anterior descending arteries; patterns also vary with respiration cycles. In the present study, coronary arterial blood flow was detected in 58 of 70 patients (83%). Findings were validated by selectively injecting an agitated saline contrast medium into the left coronary artery and, in another study, by comparing human Doppler phasic flow waveforms with electromagnetic flowmeter recordings obtained in dogs.

Animals↗