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Biomedical subjects

R C Klein

Publications and source records attributed to R C Klein.

At least 37 records · Page 2Linked to original sources
PubMed1995

Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells.

The MDM2 gene is a nuclear phosphoprotein that is regulated by p53 and functions, in one capacity, to inhibit the transcriptional activity of the wild-type p53 protein. Multiple MDM2 transcripts were detected in human breast epithelial cells. In estrogen receptor-negative normal, immortal, and tumorigenic breast epithelial cells, we found a good correlation between MDM2 mRNA levels and expression of wild-type p53. When wild-type p53 was overexpressed in estrogen receptor-negative tumor cells containing a mutant or no endogenous p53, MDM2 mRNA levels increased significantly, indicating that wild-type p53 positively influences MDM2 mRNA levels in these tumor cells. Because all estrogen receptor-positive breast tumor cells had high MDM2 mRNA levels regardless of the status of their endogenous p53 protein, other factors likely influence MDM2 expression in these cells. Distinct MDM2 proteins (range, Mr 54,000-68,000 and 90,000-100,000, respectively) were differentially expressed in human breast epithelial cells. The lower molecular weight MDM2 proteins were most abundant in the normal mammary cells but present at varying levels in many of the tumor cells examined. MDM2 was a nuclear protein; however, nuclear staining intensity did not always correlate with the amount of MDM2-immunoreactive protein as determined by Western blot analysis. This discrepancy suggests that MDM2 interacts with novel cellular proteins in different kinds of breast epithelial cells.

Breast↗
PubMed1995

Posttranscriptional regulation of the c-myb proto-oncogene in estrogen receptor-positive breast cancer cells.

We have determined that expression of the c-myb proto-oncogene is associated with estrogen receptor (ER) status and not with tumor progression in human breast epithelial cells. Analysis of normal, immortalized, nontumorigenic, and tumorigenic mammary epithelial cells showed that only ER+ tumor cell lines expressed readily detectable levels of c-myb mRNA and a Mr 75,000 protein that was the same size as the c-myb transcripts and protein products present in hematopoietic cells. In this report we show that c-myb mRNA and protein levels are down-regulated during estrogen withdrawal. A 20-fold increase in c-myb mRNA and protein expression was observed upon addition of beta-estradiol to the culture medium. Nuclear run-on transcription analyses showed that c-myb was transcribed at the same rate in the presence and absence of estrogen, suggesting that c-myb mRNA accumulation was regulated at a posttranscriptional level. To provide additional evidence that c-myb mRNA was dependent on ER expression, we examined c-myb mRNA levels in MCF-7 cells selected for resistance to antineoplastic drugs. c-myb expression was decreased only in cell lines that showed concomitant loss of ER expression. Moreover, c-myb mRNA was expressed and modulated by estrogen in ER-, MDA-MB-231 cells stably transfected with a human ER gene. When considered together, these data indicate that c-myb mRNA levels are regulated by estrogens and further suggest that this proto-oncogene plays a role in the biology of ER+ breast tumor cells.

Breast↗
PubMed1993

Comparative efficacy of sotalol and class I antiarrhythmic agents in patients with ventricular tachycardia or fibrillation: results of the Electrophysiology Study Versus Electrocardiographic Monitoring (ESVEM) Trial.

The ESVEM Trial was a randomized prospective study to compare the predictive accuracy of electrophysiologic testing (EPS) to ambulatory electrocardiographic monitoring (Holter monitoring--HM) for long-term drug therapy of sustained ventricular tachyarrhythmias. 486 patients with documented ventricular tachycardia or resuscitated sudden death were randomized to EPS (n = 242) or HM (n = 244) and underwent serial drug testing with up to six antiarrhythmics; in the EPS limb a drug efficacy prediction was achieved in 108 patients (45%), compared to 188 (77%) in the HM limb (P < 0.001). Efficacy predictions were most frequent with sotalol therapy. During long-term follow-up of the 296 patients discharged on a drug predicted to be effective, there were 151 recurrences of an arrhythmic event; there were no differences in actuarial rates of arrhythmia recurrence between EPS and HM. With multivariate testing of 14 variables, only sotalol therapy and absence of prior antiarrhythmic therapy were associated with a significant reduction in risk of arrhythmia recurrence.

Actuarial Analysis↗
PubMed1992

Detecting removable surface contamination.

Although surveying for radioactive contamination by wiping surfaces is the norm, this practice can be highly variable and may be inefficient for detecting low-energy beta emitters. Relying on wipe testing may likewise be an inefficient use of personnel and may seriously underrepresent the amount of contamination present. In general practice, it is better to clean and, where applicable, renew surfaces regularly as part of standard operating protocols and work practices.

Equipment Contamination↗
PubMed1991

Salt restriction lowers resting blood pressure but not 24-h ambulatory blood pressure.

Dietary salt restriction is the most common therapeutic recommendation given to hypertensives, but past studies have assessed the effect of salt restriction using resting blood pressure (BP) measurements not with the newer technique of 24-h ambulatory BP monitoring. We compared the effect of high (250 mEq Na/day) and low (10 mEq Na/day) salt diets on resting versus ambulatory BP in 12 normal and 15 hypertensive subjects. Each diet was given for 7 days. Ambulatory BP was monitored from day 6 to day 7 of each diet; resting supine BP was measured on the morning of day 8. In normal subjects, neither resting nor ambulatory BP changed with sodium restriction. In hypertensives, resting BP fell 14 +/- 3/6 +/- 2 mm Hg (systolic/diastolic; P less than .01 for both) with sodium restriction while ambulatory BP fell only 4 +/- 2/2 +/- 2 (P = NS). The resting BP fall was significantly greater than the ambulatory BP fall (P less than .05) for both systolic and diastolic pressure. Ambulatory heart rates were also significantly greater during sodium restriction, suggesting that the low salt diet activated the sympathetic nervous system. This may, in turn, have partially offset the hypotensive effect of sodium restriction. We conclude that using resting BP to assess the effect of sodium restriction may overestimate the efficacy of this therapy. Ambulatory BP monitoring should be employed in future studies of sodium restriction.

Ambulatory Care↗
PubMed1991

Management of mixed wastes from biomedical research.

Mixed radioactive and chemical wastes generated by biomedical research were characterized, and various treatment methods for reducing their volume were evaluated. These wastes consist primarily of organic solvents used in the extraction and purification of radiolabeled biomolecules that are contaminated with low levels of the long-lived radionuclides, 3H and 14C. The Rockefeller University's mixed wastes fall into three broad chemical categories: phenol/chloroform, acetonitrile/water, and mixtures of miscellaneous solvents such as carbon tetrachloride, benzene, and other hazardous chemicals. Currently, with the exception of liquid scintillation cocktails (deregulated in 1981), there are no commercial disposal outlets for mixed wastes nor may they be stored legally for more than 90-180 d. Most of these mixed wastes can be effectively rendered into nonradioactive chemical and aqueous radioactive waste, both of which can be disposed of in accordance with existing regulations. However, to do so requires a Resource Conservation and Recovery Act (RCRA) Part B permit for licensure as a treatment, storage, and disposal facility. For many university research facilities, this may require financial and personnel resources disproportionate to the small amounts of waste produced. Also, such treatment, if not done properly, presents potential occupational hazards from the direct handling of waste materials. Deregulation of certain mixed wastes would be the safest, most cost-effective, and practical method for dealing with many mixed wastes of biomedical origin. In any event, a national regulatory solution must be found.

Hazardous Substances↗
PubMed1990

Virus penetration of examination gloves.

Examination gloves worn for protection from biohazards were sampled and evaluated for their ability to exclude virus particles. We found that thin gloves manufactured from polyethylene or polyvinyl chloride are ineffective barriers while gloves of thin latex are superior but not without failure. Polyethylene and polyvinyl chloride gloves had failure rates of 40% and 22%, respectively. Following exposure to the common disinfectant, 70% ethanol, these failure rates increased to 94% and 56% for polyethylene and polyvinyl chloride gloves, respectively. Latex, although permeable to ethanol, was penetrated by virus less than 1% of the time regardless of whether the latex had been pre-exposed to disinfectant or not. This study highlights the need for caution on the part of those who rely upon examination gloves for protection from infectious agents as well as the need for establishing more adequate standards and testing procedures for their manufacture.

Ethanol↗
PubMed1989

Use of electrophysiologic testing in patients with nonsustained ventricular tachycardia: prognostic and therapeutic implications.

Forty patients with coronary artery disease and nonsustained ventricular tachycardia on ambulatory electrocardiographic monitoring underwent programmed electrical stimulation. In 22 patients, monomorphic ventricular tachycardia was induced at baseline drug-free electrophysiologic testing; 9 of these patients subsequently developed a clinical sustained ventricular tachyarrhythmia. In 18 patients, no tachycardia could be induced, and none of these 18 had subsequent tachycardia. In 25 of the 40 patients, arrhythmia management was guided by the results of electrophysiologic testing; this group included 11 patients who received antiarrhythmic therapy for induced ventricular tachycardia and 14 patients without inducible ventricular tachycardia who did not receive antiarrhythmic therapy. In the remaining 15 patients, arrhythmia management was not based on the results of electrophysiologic testing. Only two episodes of clinical sustained tachyarrhythmia occurred in the group receiving electrophysiologically guided therapy compared with seven episodes in the group treated without electrophysiologic guidance (p less than 0.01). Thus, in patients with coronary artery disease with nonsustained ventricular tachycardia on ambulatory electrocardiography, electrophysiologic testing can identify those at high and low risk for subsequent clinical tachycardia events. Furthermore, results of such testing can be used to optimize arrhythmia management in these patients.

Adult↗
PubMed1989

Comparison of antihypertensive therapies by noninvasive techniques.

We compared the antihypertensive effects of the beta-blocker atenolol and the converting enzyme inhibitor lisinopril during 12 weeks of treatment in patients with mild to moderate essential hypertension. Atenolol (n = 10) significantly decreased conventionally measured blood pressure from 144/103 to 135/93 mm Hg and lisinopril (n = 9) from 150/104 to 130/92 mm Hg. Based on data derived from automated 24-h ambulatory blood pressure monitoring, atenolol decreased the average whole-day systolic pressure by 18 +/- 6 mm Hg (p less than 0.02) and the diastolic pressure by 11 +/- 2 mm Hg (p less than 0.01). Lisinopril produced decreases of 27 +/- 5 mm Hg (p less than 0.01) and 13 +/- 2 mm Hg (p less than 0.001). Examination of the 24-h blood pressure patterns showed that the efficacies of the two drugs were similar. Each appeared to be effective throughout the whole-day monitoring period, although only lisinopril significantly decreased blood pressure during the final four-h period (4 AM to 8 AM) preceding the next day's dose. Neither drug produced significant echocardiographic changes in left ventricular wall thickness or muscle mass during the short-term treatment. Lisinopril and atenolol effectively decrease blood pressure during a 24-h period. Moreover, we found that automated whole-day blood pressure monitoring is a useful tool for comparing the efficacy and duration of action of differing antihypertensive agents.

Adult↗
PubMed1988

Efficacy of intravenous amiodarone as short-term treatment for refractory ventricular tachycardia.

The antiarrhythmic efficacy and safety of intravenous amiodarone were evaluated in 13 patients with recurrent sustained ventricular tachycardia. All patients had been refractory to at least three prior antiarrhythmic agents (mean, 3.3 per patient), and 11 had multiple direct current cardioversions. Intravenous amiodarone suppressed sustained tachycardia in seven patients; the concurrent use of procainamide resulted in suppression in two additional patients. Ventricular tachycardia recurred in three patients, two within 2 hours of initiation of amiodarone. Adverse effects necessitated the discontinuation of amiodarone in one patient because of significant hemodynamic deterioration. The use of intravenous amiodarone was associated with a significant fall in heart rate and cardiac output. Plasma amiodarone levels were high after initial bolus loading but declined to low or less than therapeutic levels within 60 minutes. Thus although we found intravenous amiodarone to be effective in the short-term treatment of refractory ventricular tachycardia, administration of amiodarone can be associated with significant hemodynamic deterioration. The dosing protocol used should be modified to a lower initial bolus and a higher early maintenance infusion rate.

Adult↗
PubMed1988

Diastolic blood pressure and left ventricular filling.

Many factors appear to influence diastolic left ventricular (LV) filling, including age, hypertension, and myocardial and coronary disease. Doppler-echocardiography was used to asses the influences of blood pressure (BP) on LV filling in 43 normotensive volunteers aged 12 +/- 0.98 years with heart rates less than or equal to 90 beats/min. Doppler peak diastolic transmitral flow velocities, diastolic flow integrals, and early diastolic deceleration were measured. An interesting difference was noted between the influence of systolic and diastolic BP. Systolic BP was related to LV mass (r = 0.43; P less than 0.005), but was unrelated to any of the Doppler filling indices. Diastolic BP was unrelated to LV mass, but was inversely related to peak early diastolic flow velocity (r = -0.37; P less than 0.05), early diastolic flow velocity integral (r = -0.34; P less than 0.05). The ratio of late-to-early filling (A/E) was directly related to diastolic BP (r = 0.42; P less than 0.005). The relationship between A/E and diastolic BP was strong in subjects (n = 21) with bimodal P waves in electrocardiogram (ECG) lead V1 (r = 0.61; P less than 0.005), but absent in those (n = 15) with unimodal P waves (r = 0.18; P = NS). Thus, the pattern of LV filling is related to the level of diastolic BP in normal adolescents, especially in those with bimodal P waves on ECG. These diastolic BP related changes are independent of heart rate and LV hypertrophy and may represent very early pre-hypertensive alterations in LV diastolic function.

Adolescent↗
PubMed1987

Effect of antihypertensive therapy on the circadian blood pressure pattern.

This study employed 24-hour automated ambulatory blood pressure monitoring to evaluate whole-day patterns of blood pressure in age-matched groups of normotensive volunteers, untreated hypertensive patients, and hypertensive patients treated with prazosin. As would be expected, overall systolic and diastolic blood pressures were found to be lowest in the normotensive subjects and highest in the untreated hypertensive patients. The systolic and diastolic blood pressure values for patients receiving prazosin twice daily were significantly lower than in the untreated patients; they were slightly, but not significantly, higher than the values recorded for the normotensive volunteers. The data from 24-hour monitoring revealed no between-group differences in the actual circadian rhythm of the blood pressure. This finding established that the blood pressure pattern for hypertensive patients treated with prazosin was parallel to that for normal individuals. Thus, prazosin administered twice daily reduces blood pressure throughout a full 24-hour period in a fashion that maintains the normal circadian pattern of the blood pressure.

Blood Pressure↗