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Biomedical subjects

J E Snyder

Publications and source records attributed to J E Snyder.

14 recordsLinked to original sources
PubMed2001

Repair of sulfur mustard-induced DNA damage in mammalian cells measured by a host cell reactivation assay.

DNA damage is thought to be the initial event that causes sulfur mustard (SM) toxicity, while the ability of cells to repair this damage is thought to provide a degree of natural protection. To investigate the repair process, we have damaged plasmids containing the firefly luciferase gene with either SM or its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES). Damaged plasmids were transfected into wild-type and nucleotide excision repair (NER) deficient Chinese hamster ovary cells; these cells were also transfected with a second reporter plasmid containing RENILLA: luciferase as an internal control on the efficiency of transfection. Transfected cells were incubated at 37 degrees C for 27 h and then both firefly and RENILLA: luciferase intensities were measured on the same samples with the dual luciferase reporter assay. Bioluminescence in lysates from cells transfected with damaged plasmid, expressed as a percentage of the bioluminescence from cells transfected with undamaged plasmid, is increased by host cell repair activity. The results show that NER-competent cells have a higher reactivation capacity than NER-deficient cells for plasmids damaged by either SM or CEES. Significantly, NER-competent cells are also more resistant to the toxic effects of SM and CEES, indicating that NER is not only proficient in repairing DNA damage caused by either agent but also in decreasing their toxicity. This host cell repair assay can now be used to determine what other cellular mechanisms protect cells from mustard toxicity and under what conditions these mechanisms are most effective.

Animals↗
PubMed2001

Tetracyclines inhibit activated B cell function.

Tetracyclines have recently been shown to exert a number of pleiotropic anti-inflammatory and immunomodulatory activities, independent of their antibiotic properties. These include the ability to inhibit metalloproteinases (MP), a class of enzymes involved in crucial cellular functions such as the shedding of soluble mediators and their receptors from the cell surface, as well as interaction with, and remodeling of, the extracellular matrix. Here we report that doxycycline at therapeutic concentrations (1--5 microg/ml) significantly suppresses Ig secretion and class switching by in vitro activated murine B cells. Suppression of Ig secretion correlates with a decrease in levels of mRNA for the terminal B cell differentiation-associated genes Blimp-1 and mad-4, as well as to a reduction in expression of the plasma cell markers Syndecan-1 and J chain. Inhibition of class switching occurs at the recombination stage and is also induced by other MP inhibitors, including tetracycline analogs lacking antibiotic activity and the chemically unrelated hydroxamate KB8301. These novel, direct effects of MP inhibitors on B lymphocytes suggest an intrinsic role for MP in B cell activation and likely explain some of the observed in vivo immunomodulatory properties of tetracyclines. Moreover, these findings have significant implications for tetracycline therapy in Ig-mediated autoimmune or allergic diseases and raise questions about the use of doxycycline-inducible transgenic systems for the study of B cell function.

Animals↗
PubMed2000

The efficiency of maternal transfer of lead and its influence on plasma IgE and splenic cellularity of mice.

Exposure to the well known environmental toxicant lead is typically assessed by blood and/or bone levels and has been implicated in the onset of a variety of diseases affecting multiple human systems. However, there are conflicting data regarding the efficiency of in utero versus lactational transfer of lead to offspring, and the immunomodulatory effects of lead in early life have not been well defined. Pregnant BALB/c mice were exposed to lead acetate in their drinking water beginning at approximately day 15 of gestation, and cross-fostering of exposed/nonexposed litters was performed at parturition. Significant increases of blood lead levels of all exposed offspring were found at 1 week of age with evidence for both transplacental and lactational transfer. Additionally, mice exposed to lead continuously beginning at approximately 6 days prior to birth showed significant decreases in their blood lead levels 2 weeks after weaning, despite continued exposure as adults. This result suggests maternal transfer of lead is more efficient than oral adult exposure and that substantial lead transfer occurs both transplacentally and lactationally. The incidence of childhood atopic responses including asthma has risen considerably in recent years, particularly within areas containing higher levels of environmental pollutants. Plasma IgE levels of 2-week-old neonates exposed to lead before and/or after birth were measured as an index of atopy. Neonates exposed to lead transplacentally and/or lactationally had significantly higher plasma IgE levels, a biomarker of atopy, and lower splenic white blood cell numbers than age-matched controls. These results resemble the lag in immunocompetency and increase in serum IgE noted in atopic children and suggest a role for environmental toxicants and non-allergen-specific immunology in the prevalence of atopy and asthma in children.

Aging↗
PubMed1998

Hypothermia causes a reversible, p53-mediated cell cycle arrest in cultured fibroblasts.

Normal human fibroblasts grown in cell culture undergo a reversible growth arrest when incubated at 28 degrees C. During incubation at 28 degrees C, levels of p53 and p21 rise in these cells and cell cycle analysis shows that they have undergone a cell cycle arrest. To examine the importance of p53 in mediating this arrest, mouse embryo fibroblasts that are either wild-type or that are defective in p53 were also subjected to hypothermia. Only those cells with wild-type p53 undergo a cell cycle arrest, indicating that p53 has a role in mediating this response. Because many tumor cells have defective p53, this suggests that hypothermia may increase the selective toxicity of chemotherapeutic agents for tumor cells.

Animals↗
PubMed1996

A critical appraisal of quantitative spectro-temporal analysis of the signal-averaged ECG: predicting arrhythmic events after myocardial infarction.

The objective of this study was to determine if spectro-temporal analysis of the signal-averaged ECG (SAECG) predicts spontaneous sustained ventricular tachyarrhythmias and sudden death in patients prospectively followed after myocardial infarction (MI). A SAECG was recorded in 177 patients 9 +/- 5 days after MI. Spectro-temporal analysis of the SAECG involved incrementing a Hanning window every 3 ms beginning 20 mg before the end of the QRS complex and extending into the ST segment. Quantitative analysis was performed using a cross-correlation function to create a normality factor. A normality factor < 0.3 was deemed abnormal. The SAECG was abnormal in 41% of patients using time-domain analysis and 44% of patients using spectro-temporal analysis. There was no correlation between an abnormal SAECG in the time domain and the frequency domain. Patients with inferior wall MI were more likely to have an abnormal spectro-temporal map (odds ratio 2.26, P < 0.05). Time-domain analysis of the SAECG (relative risk (RR) 2.6) was a statistically significant univariate predictor of arrhythmic events. Spectro-temporal analysis of the SAECG was only weakly (RR 1.8) and not significantly (P = 0.15) associated with the spontaneous occurrence of these arrhythmias. When both time-domain analysis and spectro-temporal analysis of the SAECG were abnormal, the relative risk for an arrhythmic event was increased by 3.3-fold. Quantitative spectro-temporal analysis of high frequency signals within the SAECG cannot by itself predict the occurrence of spontaneous ventricular arrhythmias in patients after MI.

Aged↗
PubMed1995

Vestibulo-ocular reflex gain as a measure of vestibular function in guinea pigs while in a recompression chamber: apparatus design and effects of nitrogen narcosis.

There are several mechanisms whereby alteration of barometric pressure can produce vertigo in divers or aviators. Development of a reliable measure of vestibular function in an animal model is the first requirement for further study of these mechanisms. This report presents the development of a rotatory table device capable of evoking the vestibulo-ocular reflex (VOR) of a guinea pig while in a hyperbaric chamber. To assess the reproducibility of this response, eight animals were monitored by electronystagmography during rotations at three table velocities (62.4, 83.3, and 100 degrees/s). Two test sessions were performed on each animal with a 6-hour interval between sessions. The VOR gain was calculated by dividing the average peak velocity of the slow phase component of the nystagmus by the peak stimulus velocity. At least eight observations per test speed were averaged; calibration of eye movement was performed prior to each session by forced ocular abduction. Multifactorial analysis of variance revealed no significant differences (p > .05) between the differing rotation speeds nor between test sessions for individual animals. However, there was a significant difference in VOR gain between animals (p < .002). The VOR gain was then measured, using the same techniques, in another group of seven animals before, during, and after an air dive to the equivalent of 200 feet of seawater (7.06 atmospheres absolute) to assess the effects of nitrogen narcosis. Pre- and post-dive VOR gains were significantly greater than those measured at depth (p < .05). These results are consistent with the slow processing model of nitrogen narcosis and the controversial theory that central nervous system depressants decrease the VOR gain. The results also demonstrate the ability of this inexpensive apparatus to provide a sensitive measure of pressure-induced changes of vestibular function in guinea pigs.

Analysis of Variance↗
PubMed1990

Effects of position changes on transcutaneous carbon dioxide tension in neonates with respiratory distress.

Routine neonatal care includes frequent position changes. Recent research has concluded that positions other than supine may result in beneficial physiologic responses. Specifically, several studies suggest that neonates may ventilate more effectively in a prone rather than in a supine position. This study tested the hypothesis that transcutaneous carbon dioxide tension (TcPCO2) would be lower in the prone than in the supine position in neonates with respiratory distress. Fourteen ventilated infants were studied. TcPCO2 was measured and recorded in prone, supine, and right-side-lying positions for each subject. There were no statistically significant differences in mean TcPCO2 values between the three positions (F = .45; df 2,39; P = .64). The relationship between TcPCO2 and PaCO2 values was stable (r = .88) during the studies. The results indicate that changing a neonate's position does not significantly alter transcutaneous carbon dioxide tension.

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

Continuous-wave Doppler for the noninvasive evaluation of aortic blood velocity and rate of change of velocity: evaluation in dogs.

A new continuous-wave Doppler device is described, which has the capability of measuring peak aortic blood velocity and acceleration noninvasively in the ascending aorta of patients. To test the accuracy of the device, blood velocity and acceleration in the ascending aorta were compared with measurements obtained using an electromagnetic flowmeter in 16 open-chest anesthetized dogs. The Doppler probe was hand held directly on the aorta. Aortic flow was measured with a cuff electromagnetic flow transducer placed at the root of the aorta. Isoproterenol and propranolol, sometimes in combination with lidocaine, were administered intravenously to augment or reduce left ventricular contractile performance. Values of peak velocity, measured with the Doppler, corresponded closely to values measured with the electromagnetic flowmeter (r = 0.95). Values of peak acceleration also corresponded closely with the electromagnetic flow measurements (r = 0.96). The results indicate that valid measurements of blood acceleration in the ascending aorta, as well as blood velocity, can be obtained with continuous-wave Doppler.

Animals↗
PubMed1986

Real-time orthogonal mode scanning of the heart. I. System design.

A necessary percursor to real-time three-dimensional echocardiographic imaging is the ability to obtain multiple planes of acoustic data simultaneously. A new ultrasound imaging technique facilitates the display of two real-time orthogonal B-mode images (O-mode). The O-mode technique uses a novel two-dimensional transducer and system processor to interrogate the two perpendicular planes simultaneously, yielding sector arcs that share one origin. It permits simultaneous display of two sector arcs on a single monitor either side by side or in a two-dimensional projection designed to convey the three-dimensional nature of the acoustic data. Clinical results from the first 50 patients undergoing O-mode evaluation indicate that image quality in the two simultaneously obtained planes is equal to that of a single plane when the system is operating in its conventional format. These data confirm the feasibility of real-time multiplane imaging. The system design offers the potential for the future addition of more simultaneous planes and, thus, the possibility of real-time three-dimensional ultrasound imaging.

Adult↗
PubMed1986

Noninvasive evaluation of left ventricular performance based on peak aortic blood acceleration measured with a continuous-wave Doppler velocity meter.

Peak aortic blood acceleration is recognized to be a sensitive index of global left ventricular performance. In the present study peak acceleration was assessed noninvasively in patients with a continuous-wave Doppler velocity meter. Peak aortic blood velocity and peak blood acceleration were measured by placing the ultrasonic transducer at the suprasternal notch. Measurements were obtained in 36 patients undergoing diagnostic cardiac catheterization. Peak velocity and acceleration were measured at rest just before left ventriculography. In patients with ejection fractions greater than 60%, peak acceleration was 19 +/- 5 m/sec/sec. In patients with ejection fractions of 41% to 60%, peak acceleration was lower, at 12 +/- 2 m/sec/sec (p less than .001). In patients with ejection fractions of 40% or less, peak acceleration (8 +/- 2 m/sec/sec) was markedly lower than in patients with ejection fractions greater than 60% (p less than .001). Peak acceleration showed a good linear correlation with ejection fraction (r = .90), and a better power fit (r = .93). These results indicate that peak acceleration, measured noninvasively with a continuous-wave Doppler velocity meter, is a useful indicator of global left ventricular performance.

Aorta↗
PubMed1982

Visual evoked potential and pupillary signs. A comparison in optic nerve disease.

We measured the pupil cycle time, the relative afferent pupillary defect, and the pattern-reversal visual evoked potential (VEP) in 41 patients with unilateral anterior ischemic optic neuropathy (AION) and 24 patients with unilateral optic neuritis. We speculated that the relative afferent pupillary defect would match the VEP amplitude and that the pupil cycle time would correspond to the VEP latency. We found a correlation between the relative afferent pupillary defect and VEP amplitude in patients with AION, but not in patients with optic neuritis. We also found that the pupil cycle time and VEP latency were weakly correlated, but only in patients with optic neuritis. In these two groups of patients with unilateral optic neuropathy, the most sensitive objective indicator of disease was the relative afferent pupillary defect. The least sensitive indicator was the pupil cycle time.

Aged↗
PubMed1979

[Electroophthalmological characteristics in ischemic retinopathy (author's transl)].

In the ERG the b-wave and the oscillatory potentials are reduced or nonrecordable in ischemic retinopathy. The photopic b-wave appeared to be more sensitive than the scotopic b-wave. In the EOG the slow oscillation is reduced. These clinical observations are in accordance with the results of experimental studies in rhesus monkeys.

Animals↗
PubMed1970

Infection control.

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Cross Infection↗