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Biomedical subjects

N Greenberg

Publications and source records attributed to N Greenberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

The impact of bcl-2 expression and bax deficiency on prostate homeostasis in vivo.

Prostatic glandular epithelial cells undergo apoptosis in response to androgen-deprivation. The molecular determinants of androgen-responsiveness in these cells are incompletely understood. Recent evidence suggests that bcl-2 gene family members may be important in this context. We used the probasin promoter to target a human bcl-2 transgene specifically to the prostate in order to assess its impact on conferring resistance to androgen withdrawal in, otherwise sensitive, prostatic glandular epithelial cells in vivo. We examined the contribution of bax to mediating androgen-responsiveness in prostatic glandular epithelial cells using bax knockout mice. The histologic appearance of the prostates from probasin-bcl-2 transgenic mice or bax-/- mice did not differ from those of control littermates. There was no evidence of hyperplastic or neoplastic growth. There was no difference between probasin bcl-2 transgenic mice, bax-/- mice, and control littermates in steady-state levels of apoptosis. Following castration our findings suggest that both bax and bcl-2 may each contribute to the androgen-responsiveness of prostatic glandular epithelial cells. It is apparent from these results, however, that bax is not required to mediate cell death in prostatic glandular epithelial cells following castration. A comparison between the apoptotic indices in the ventral prostate from the probasin-bcl-2 and bax-/- mice following castration suggests that the presence of bcl-2 may be a more important indicator of androgen-sensitivity than a deficiency of bax.

Androgen-Binding Protein↗
PubMed1999

Effect of color coding and subtraction on the accuracy of contrast echocardiography.

BACKGROUND: Contrast echocardiography may be used to assess myocardial perfusion. However, gray scale assessment of myocardial contrast echocardiography (MCE) is difficult because of variations in regional backscatter intensity, difficulties in distinguishing varying shades of gray, and artifacts or attenuation. We sought to determine whether the assessment of rest myocardial perfusion by MCE could be improved with subtraction and color coding. METHODS AND RESULTS: MCE was performed in 31 patients with previous myocardial infarction with a 2nd generation agent (NC100100, Nycomed AS), using harmonic triggered or continuous imaging and gain settings were kept constant throughout the study. Digitized images were post processed by subtraction of baseline from contrast data and colorized to reflect the intensity of myocardial contrast. Gray scale MCE alone, MCE images combined with baseline and subtracted colorized images were scored independently using a 16 segment model. The presence and severity of myocardial contrast abnormalities were compared with perfusion defined by rest MIBI-SPECT. Segments that were not visualized by continuous (17%) or triggered imaging (14%) after color processing were excluded from further analysis. The specificity of gray scale MCE alone (56%) or MCE combined with baseline 2D (47%) was significantly enhanced by subtraction and color coding (76%, p<0.001) of triggered images. The accuracy of the gray scale approaches (respectively 52% and 47%) was increased to 70% (p<0.001). Similarly, for continuous images, the specificity of gray scale MCE with and without baseline comparison was 23% and 42% respectively, compared with 60% after post processing (p<0.001). The accuracy of colorized images (59%) was also significantly greater than gray scale MCE (43% and 29%, p<0.001). The sensitivity of MCE for both acquisitions was not altered by subtraction. CONCLUSION: Post-processing with subtraction and color coding significantly improves the accuracy and specificity of MCE for detection of perfusion defects.

Contrast Media↗
PubMed1999

Development and use of analytical quality specifications in the in vitro diagnostics medical device industry.

Manufacturers of in vitro diagnostic (IVD) medical devices have become integral partners with their customers in determining the quality of laboratory results. Design controls imposed by ISO 9001 quality system standards and various regulations require manufacturers to implement a formal design process, which begins and ends with customer requirements. For IVD systems, this means that manufacturers must establish analytical quality specifications as part of their design input. This provides greater assurance that commercial products will satisfy customer requirements. In the case of quantitative IVD measurement systems, analytical quality specifications include total allowable uncertainty (bias, imprecision, non-specificity). The primary source of customer requirements is the laboratory-customer, who should have established analytical quality specifications based on the needs of its physician-clients. The total allowable uncertainty budget is allocated in the design process to the individual components of the system, such as reagents, instrumentation, calibrators and accessories, and to other factors such as operator, specimen and environmental interactions. Their performance must collectively meet the total allowable uncertainty specification when they are finally integrated into a measurement system. The design control model requires objective evidence that design specifications have been met (verification) and, finally, that the system will satisfy the needs of its intended users (validation). Compliance with the quality system standards is monitored through independent audits, government inspections and post-market surveillance.

Clinical Laboratory Techniques↗
PubMed1998

Regional and temporal separation of serotonergic activity mediating social stress.

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.

Aggression↗
PubMed1997

Quantifying the performance limitations of older and younger adults in a target acquisition task.

In a stationary target acquisition task, both 65-year-old and 20-year-old adults exhibited a negatively accelerated curvilinear relationship between the spatial variability of submovement endpoints and average submovement velocity. For high velocities, the variability was greater for the older adults. This elevated motor noise is considered a primary cause of their slower performance. Both age groups also exhibited a linear relationship between submovement duration and the logarithm of submovement relative accuracy. A stochastic model indicates that the two age groups were similar in the strategies they used to compose single movements from a variety of submovements. However, when performing sequences of movements containing varied target distances, older adults exhibited a repetition effect whereas younger adults exhibited a contrast effect. Older adults may plan movements individually, whereas younger adults plan sequences.

Acoustic Stimulation↗
PubMed1997

Tempo, Rhythm, and Aging in Golf.

Older (n = 12) and younger (n = 12) golfers attempted to hit a golf ball into a target net a short distance away. An accelerometer attached to the back of the clubhead measured the applied force. In contrast to the more typical finding of slower perceptual-motor performance by older adults, older golfers reached their peak downswing force earlier in the shot and also exhibited a trend toward a faster overall speed or tempo of the shot. Additionally, older golfers exhibited greater changes in applied force and greater variability. A pattern of divergence among the force-time histories from multiple shots suggested that the overall person-plus-golf-club dynamics were unstable during a part of the shot. Older adults may be slower in controlling this instability. Half of the participants heard a tone whose pitch was proportional to their force. These participants had a slower follow-through; however, they did not make significantly more or fewer shots than participants who had not been presented with the tone. Analyses of the temporal covariation among the backswing, downswing, and follow-through favored a chain-like temporal structure over a hierarchical, proportional structure. The pattern of covariation suggests that the tempo and rhythm of the shot are not independent and that changing one's tempo may disrupt rhythm.

aging↗
PubMed1997

Physical and physiological determinants of pulmonary venous flow: numerical analysis.

To study the physical and physiological determinants of transmitral and pulmonary venous flow, a lumped-parameter model of the cardiovascular system has been created, modeling the instantaneous pressure, volume, and influx/efflux of the pulmonary veins, left atrium and ventricle, systemic arteries and veins. right atrium and ventricle, and pulmonary arteries. Initial validation has been obtained by direct comparison with transesophageal echocardiographic recordings of mitral and pulmonary venous velocity for the following clinical situations: normal diastolic function, delayed ventricular relaxation, restrictive filling due to severe systolic dysfunction, severe mitral regurgitation before and after valve repair surgery, and premature atrial contraction occurring during ventricular systole. Sensitivity analysis has been performed with a Jacobian matrix, representing the proportional change in a group of output indexes (yi) in response to isolated changes in input parameters (xj), [(delta yi/yi)/ ([delta xj/xj)], demonstrating the complementary nature of mitral and pulmonary venous A-wave velocity for predicting ventricular stiffness and atrial systolic function. This unified numerical-experimental programming environment should facilitate model refinement and physiological data exploration, in particular guiding more accurate interpretations of Doppler echocardiographic data.

Animals↗
PubMed1995

Activation of central biogenic amines following aggressive interaction in male lizards, Anolis carolinensis.

Many stimuli, including social aggression, activate endocrine stress mechanisms, presumably mediated or modulated by central neurotransmitters. To determine the effects of aggression on central neurochemistry, reproductively active male Anolis carolinensis were paired and allowed to establish social dominance relationships. While combatants cohabited, the fight losers invariably became socially subordinate and displayed darker color, selection of lower perch sites, and lower body posture than the winners. After one hour, one day, one week, or one month of cohabitation animals were sacrificed. Each member of a pair was killed at approximately the same time, along with animals kept isolated as controls. Diencephalon, non-optic lobe midbrain and hindbrain were analyzed for indoleamines, catecholamines and metabolites by coulochem electrode array HPLC. Early activation (by one hour) of the serotonergic system in subordinate male lizards was indicated by decreased serotonin (5-HT), increased 5-hydroxy-indoleacetic acid (5-HIAA) levels and 5-HIAA/5-HT ratio. Substrate 5-hydroxy-tryptophan (5-HTP) also increased in losing males, suggesting enhanced production as well as turnover. Significant 5-HTP and 5-HIAA/5-HT increases for subordinate males, compared with levels in control and dominant males, were greatest at one hour and diminished thereafter. This pattern of indoleamine system activation is consistent with stress-induced stimulation of the serotonergic system and prolonged activation of the stress response in subordinate animals, as well as serotonergic inhibition of aggression. In contrast with serotonin, subordinate males did not have increased catecholamine system activation following one hour of interaction. The ratio of DOPAC/dopamine was lower following one hour of interaction in subordinate males. Adrenergic system activation, indicated by metanephrine/epinephrine ratio, increased with time in losing males, except that after one month of cohabitation, turnover returned to levels that equaled those of control animals. Noradrenergic metabolite MHPG, as well as MHPG/NE ratio, were significantly reduced in dominant males at one hour and one week. Changes in adrenergic system activation, not seen in or registered by noradrenergic systems, indicate a possible role for central epinephrine in social stress accommodation.

Aggression↗
PubMed1994

Somatic correlates of adrenergic activity during aggression in the lizard, Anolis carolinensis.

Aggressive interactions in Anolis carolinensis result in increased circulating levels of epinephrine (Epi) and norepinephrine (NE) and conspicuous color changes. This activation of the adrenergic component of an acute stress response is externally represented by the darkening of the postorbital eyespot of A. carolinensis. In adult males, this site darkens in response to stressful physical stimulation (trauma, passive restraint) or psychological stimuli, most notably the sight of an aggressively intruding conspecific. Aggressive male A. carolinensis exhibit postorbital eyespot darkening; animals that have a longer latency to expression of this eyespot and those that never show this response were defeated in agonistic interactions. Also, during agonistic interactions, subjects that subsequently win are the first to display eyespot darkening. Plasma catecholamine levels are significantly elevated within 30 sec in both combatants. At 30 sec following the determination of the outcome, winning male lizards have plasma NE levels which are higher than those of losers. Castration, however, significantly increases the latency to eyespot darkening and extends its duration. Testosterone levels may therefore enhance the onset of Epi-mediated eyespot darkening as well as other aspects of the endocrine stress response. Elevated androgen levels and more rapid activation of acute catecholamine response increases the likelihood of becoming socially dominant.

Adrenergic Fibers↗
PubMed1994

A comparison of conventional and matched filtering techniques for rapid eye movement detection of the newborn.

This paper compares an extended conventional filter technique for automated detection and analysis of rapid eye movements (REM) in neonates, using amplitude, synchrony, velocity, and coherence threshold criteria, with a matched filtering technique using the morphology of the REM waveform. Analyses of both simulated and real data were carried out. Automated REM tabulations are compared with visual scoring by a trained observer. Both preterm and fullterm neonates were used to test these methods. Both the advantages and disadvantages of these two techniques are discussed as compared with conventional methods which use only amplitude and synchrony threshold criteria. The major advantage of the extended conventional over the conventional method, as well as the matched filtering over the extended conventional technique, is the increased REM detection rate for ten minute intervals of artifact-free sleep. More accurate methods of automated REM detection that can be applied over extended monitoring periods are still needed.

Computer Simulation↗
PubMed1994

Preferential overexpression of a 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development.

Regulatory sequences derived from the rat whey acidic protein gene have been used to preferentially overexpress a murine 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice. Several different lines of mice expressing the 172Arg-->Leu mutant p53 displayed an impaired ability to lactate, and the mice expressing the highest levels of mutant p53 were unable to nurse their young. This failure was related to the inhibition of normal lobuloalveolar development that occurred during late pregnancy and a marked decrease in milk protein gene expression at early lactation. Interestingly, immunohistochemical analysis revealed that the mutant p53 was localized predominantly in the cytoplasm of alveolar cells. Ductal development was not overtly impaired in these mice. Expression of the 172Arg-->Leu mutant p53 resulted in radiation-induced apoptosis, and transactivation or repression of the expression of a number of genes, including mdm-2 and proliferating cell nuclear antigen, known properties of wild-type p53. The availability of lines of mice preferentially expressing specific p53 mutants in the mammary gland should facilitate evaluation of the roles of other factors, such as hormones, oncogenes and chemical carcinogens, in the etiology of breast cancer.

Animals↗
PubMed1993

Effects of intravenous magnesium sulfate on arrhythmias in patients with congestive heart failure.

Intravenous magnesium is an effective treatment for ventricular tachycardia of some etiologies, and in patients with congestive heart failure low serum magnesium concentrations are associated with frequent arrhythmias and high mortality. This suggests that magnesium administration may decrease the frequency of ventricular arrhythmias in patients with heart failure. We therefore assessed the impact of an intravenous magnesium infusion upon the frequency of ventricular premature depolarizations in 40 patients with New York Heart Association (NYHA) class II to IV heart failure and serum magnesium < or = 2.0 mg/dl. Within 1 week of a baseline 6-hour ambulatory electrocardiographic recording, an infusion of 0.2 mEq/kg of MgSO4 was given over 1 hour and a repeat 6-hour recording was obtained. There was an inverse relationship between the change in magnesium concentration and the change in frequency of premature ventricular depolarizations; premature ventricular depolarizations declined by 134 +/- 207 hr-1 in patients in whom serum magnesium concentration increased > or = 0.75 mg/dl, but increased by 72 +/- 393 hr-1 in patients with a change < 0.75 mg/dl (p < 0.05). For all patients, the frequency of premature ventricular depolarizations was 283 +/- 340 hr-1 pretreatment and 220 +/- 269 hr-1 following magnesium infusion (p = 0.21). Patients with > or = 300 premature ventricular depolarizations hr-1 demonstrated a decrease from 794 +/- 309 to 369 +/- 223 hr-1 (p < 0.001). Intravenous magnesium administration decreased the frequency of couplets from 233 +/- 505 to 84 +/- 140 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Manual performance of a repeated pattern by older and younger adults with supplementary auditory cues.

Ss performed the same M-shaped manual movement pattern on repeated trials using a visual display of instantaneous error. With practice, Ss' effective time delays were diminished by increased anticipation as evidenced by an increased correlation of their movement patterns with the input velocity. However, younger adults had lower error scores, performed larger movements, and had shorter effective time delays than did older adults. Supplementary auditory displays additionally contributed to greater anticipation. However, men exhibited this effect most with an auditory display of input velocity and women with an auditory display of input position. This benefit of the auditory displays did not carry over after these displays were withdrawn. When the visual display was additionally withdrawn, benefits of the auditory training were manifest among the older adults as relatively greater temporal modulation of movement.

Acoustic Stimulation↗
PubMed1993

Central and endocrine aspects of tongue-flicking and exploratory behavior in Anolis carolinensis.

Tongue-flicking in reptiles is frequently seen to increase in novel habitats and is presumed to involve the acquisition of chemical information. Like most behavioral patterns, however, tongue-flicking has both multiple causes and multiple functions, only some of which involve chemosensation. This paper describes units of exploratory behavior, including use of the tongue, in a microsmatic lizard, the green anole, Anolis carolinensis. This species employs its tongue in a manner suggestive of chemosensory exploration, but it possesses modest peripheral chemosensory organs and reduced central representation of chemosensory target cell groups. Further, specific elements of exploratory behavior are affected differently by treatments that involve altering levels of stress-sensitive hormones, androgen, and central catecholamines. Such differential responses suggest that exploratory behavior is an ensemble of individual units, some of which are selectively sensitive to specific physiological elements of the stress response and of elevated arousal.

Androgens↗