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Accelerated aging of dermal fibroblast-like cells from senescence-accelerated mouse (SAM). 1. Acceleration of population aging in vitro.

Fibroblast-like cells were isolated from the senescence accelerated mouse (SAM) and cultured, after which evidence of accelerated senescence was sought. Fibroblast-like cell lines were established from the dorsal dermis of neonate mice of both the accelerated senescence-prone strain, SAMP11 and the accelerated senescence-resistant strain, SAMR1. All cell lines from both strains showed a crisis in growth and were immortalized. At crisis, all cultures were composed of morphologically characteristic senescent cells. However, in cell lines from SAMP11, this change was more rapid and at earlier population doublings (PDs) than seen in cell lines from SAMR1. Crises (SAMP11; SAMR1) were also operationally taken to be the point of the least change in PDs (11.2 +/- 1.1; 15.4 +/- 0.5 PDs), the least saturation density (11.3 +/- 0.8; 19.1 +/- 2.6 PDs), and the longest population doubling time (10.1 +/- 0.8; 14.2 +/- 0.6 PDs). Crisis occurred significantly earlier (P < 0.05) and the aging process was accelerated in cell lines from SAMP11, compared with lines from SAMR1. This evidence tends to support various observations made in the accelerated senescence-prone strains of SAMP, in vivo.

Aging↗

Accelerated aging of dermal fibroblast-like cells from the senescence-accelerated mouse (SAM): acceleration of changes in DNA ploidy associated with in vitro cellular aging.

Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.

Aging↗

The acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators as an electrostatic effect.

1. In order to check our hypothesis of the electrostatic nature of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, equations were solved for methane-sulfonylation with two accelerators and the reaction was studied in the presence of some single accelerators, including the sodium cation, and in the presence of two acclerators simultaneously. 2. The second-order rate constants for methanesulfonylation of the complexes between the enzyme and accelerators decamethonium, tetraethylammonium and tetramethylammonium are 90, 88 and 17 1 - mol-1 - s-1, respectively, which corresponds to a maximal acceleration of 29, 28 and 5.5 times, respectively. The dissociation constants for the binding of these accelerators to the enzyme, obtained from our acceleration experiments, are 3.7 - 10(-6), 3.2 - 10(-4) and 1.4 - 10(-3) M, respectively. These values are in good agreement with the dissociation constants of these ligands as inhibitors of acetylcholinesterase. It is interesting to note that the sodium cation also accelerates the methane-sulfonylation up to around three times, the corresponding second-order rate constant and the dissociation constant being 10 1 - mol-1 - s-1 and 1.3 M, respectively. 3. All tested cations compete in the acceleration with each other; they seem to accelerate the reaction in the same way and from the same site, the catalytic anionic site. 4. These findings confirm the hypothesis of the electrostatic nature of acceleration.

Acetylcholinesterase↗

Perception of acceleration with short presentation times: can acceleration be used in interception?

To investigate whether visual judgments of acceleration could be used for intercepting moving targets, we determined how well subjects can detect acceleration when the presentation time is short. In a differential judgment task, two dots were presented successively. One dot accelerated and the other decelerated. Subjects had to indicate which of the two accelerated. In an absolute judgment task, subjects had to adjust the motion of a dot so that it appeared to move at a constant velocity. The results for the two tasks were similar. For most subjects, we could determine a detection threshold even when the presentation time was only 300 msec. However, an analysis of these thresholds suggests that subjects did not detect the acceleration itself but that they detected that a target had accelerated on the basis of the change in velocity between the beginning and the end of the presentation. A change of about 25% was needed to detect acceleration with reasonable confidence. Perhaps the simplest use of acceleration for interception consists of distinguishing between acceleration and deceleration of the optic projection of an approaching ball to determine whether one has to run backward or forward to catch it. We examined the results of a real ball-catching task (Oudejans, Michaels, & Bakker, 1997) and found that subjects reacted before acceleration could have been detected. We conclude that acceleration is not used in this simple manner to intercept moving targets.

Humans↗

Superiority of acceleration and acceleration time over pulsatility and resistance indices as screening tests for renal artery stenosis.

OBJECTIVE: To compare the accuracy of four echo-Doppler-derived velocimetric indices (pulsatility and resistance indices, acceleration and acceleration time) in detecting renal artery stenosis in hypertensive patients. PATIENTS AND METHODS: In 73 hospitalized patients with moderate-to-severe hypertension, 18 of whom had normal renal arteries and 55 renal artery stenosis (50-95%) either atherosclerotic (30 cases, five bilateral) or fibromuscular dysplasia (25 cases, two bilateral), we measured the four velocimetric indices using the lateral abdominal approach and sampling Doppler waveforms distally to the stenosis. The diagnostic accuracy of each index was calculated using as cut-off limit the ideal threshold determined with the receiver-operating characteristic curves. RESULTS: On average all of the indices were altered significantly in arteries with stenosis of both aetiologies with respect to normal arteries, the alterations of pulsatility and resistance indices being, however, less pronounced than those of acceleration and acceleration time, particularly in atherosclerotic stenosis. With the cut-off limits of 0.93, 0.59 and 7.4 m/s2 and 60 ms, respectively, for pulsatility and resistance indices, acceleration and acceleration time, their diagnostic accuracies were 80, 73, 93 and 92%. In stenotic arteries, only the acceleration time was correlated with the degree of arterial narrowing, whereas, in normal arteries, only pulsatility and resistance indices were directly correlated with the age of patients. CONCLUSIONS: Acceleration and acceleration time are more accurate indices than pulsatility and resistance to screen for renal artery stenosis, probably because their alterations are less attenuated by the counterbalancing effects of age and of atherosclerosis.

Acceleration↗

Acceleration mapping by Fourier acceleration-encoding: in vitro study and initial results in the great thoracic vessels.

Acceleration mapping can be conducted by replacing the bipolar gradient pulse of a velocity mapping sequence by a tripolar pulse. However, since the acceleration encoding pulse is longer, the image quality is altered by the requirement of a long echo time. Since Fourier encoding velocity imaging has been shown to be robust, this velocity mapping method was transformed into an acceleration mapping method. Four steps of the tripolar acceleration encoding gradient pulse were applied successively; acceleration was then obtained by Fourier transform after zero-filling. The accuracy of the method was assessed with a phantom giving a pulsatile flow. Acceleration maps of the ascending aorta and pulmonary artery were obtained in 10 healthy volunteers. The acceleration values measured were in the range of known physiologic values. The feasibility of Fourier encoding acceleration imaging was also demonstrated in four patients.

Adolescent↗

Induction of cell cycle progression and acceleration of apoptosis are two separable functions of c-Myc: transrepression correlates with acceleration of apoptosis.

Analysis of amino-terminus mutants of c-Myc has allowed a systematic study of the interrelationship between Myc's ability to regulate transcription and its apoptotic, proliferative, and transforming functions. First, we have found that c-Myc-accelerated apoptosis does not directly correlate with its ability to transactivate transcription using the endogenous ornithine decarboxylase (ODC) gene as readout for transactivation. Furthermore, deletion of the conserved c-Myc box I domain implicated in transactivation does not inhibit apoptosis. Second, the ability of c-Myc to repress transcription, using the gadd45 gene as a readout, correlates with its ability to accelerate apoptosis. A conserved region of c-Myc implicated in mediating transrepression is absolutely required for c-Myc-accelerated apoptosis. Third, a lymphoma-derived Thr58Ala mutation diminishes c-Myc-accelerated apoptosis through a decreased ability to induce the release of cytochrome c from mitochondria. This mutation in a potential phosphorylation site does not affect cell cycle progression, providing genetic evidence that induction of cell cycle progression and acceleration of apoptosis are two separable functions of c-Myc. Finally, we show that the increased ability of Thr58Ala mutant to elicit cellular transformation correlates with its diminished ability to accelerate apoptosis. Bcl-2 overexpression blocked and the lymphoma-associated Thr58Ala mutation decreased c-Myc-accelerated apoptosis, and both led to a significant increase in the ability of Rat1a cells to form colonies in soft agar. This enhanced transformation was greater in soft agar containing a low concentration of serum, suggesting that protection from apoptosis is a mechanism contributing to the increased ability of these cells to proliferate in suspension. Thus, we show here for the first time that, in addition to mutations in complementary antiapoptotic genes, c-Myc itself can acquire mutations that potentiate neoplastic transformation by affecting apoptosis independently of cell cycle progression.

Animals↗

Experimental brain damage from fluid pressures due to impact acceleration. 4. comparative studies with acceleration-concussion.

In order to elucidate the cause of brain damage in head injuries experiments are often designed to cause impacts to the intact skull of animals. To study the injurious significance of the contre-coup part of the impact acceleration pressure pattern we have previously applied direct loading through a parietal opening to the rabbit skull cavity. In order to evaluate the effects of the acceleration, similar impacts were delivered with greater magnitudes of such movements of the intact reinforced rabbit skull with the same equipment attached but without trephine opening. Varied and predictable acceleration, velocity and displacement of the head, and minimized skull deformation were possible with this model. Threshold levels of such impact acceleration were studied with regard to changes in respiratory and vasomotor activities ("concussive response"). Vascular permeability changes in the brain and spinal cord were studied with Ean's blue-albumin injection before the impact. Morphological observations were also made at the end of the experiments. No significant pathophysiological or morphological effects were elicited below peak acceleration of 2000 gn (duration 0.7 ms), peak velocity of 5 m/s or total dislocation of the head of 30 mm. At higher levels of impact a "concussive response" was elicited without fractures of the skull bone or significant brain lesions. Thus, in impact tests resulting in acceleration magnitudes far below those levels the signs of brain damage induced might mainly be related to the mechanical effects added--i.e. the fluid pressure loading.

Acceleration↗

The relationship between accelerated pulmonary maturity and accelerated neurological maturity in certain chronically stressed pregnancies.

Two studies were done. In the first, 51 infants from high-risk pregnancies were evaluated for accelerated clinical neurological maturation. Eight infants had accelerated neurological maturation 3 or more weeks in excess of gestational age. In the second study, a sample of 25 infants with documented acceleration of pulmonary surfactant (lecithin/sphingomyelin ratio greater than or equal to 2 at gestational age less than or equal to 32 weeks) all infants showed accelerated neurological maturation (range 3 to 8 weeks) with the conditions studied associated with accelerated pulmonary maturation (for instance, retroplacental bleeding, prolonged rupture of membranes, placental infarction, severe toxemia, hypertensive disease, circumvallation, and amnionitis). Chronic retroplacental bleeding was associated with the most dramatic pulmonary and neurological accelerations.

Birth Weight↗

[Correlation of the magnitude of fetal movement associated fetal heart rate accelerations, amplitude of "classical" accelerations and transcutaneous fetal oxygen partial pressure].

An attempt is made to provide non-empirical evidence of the "classical" amplitude of sporadic fetal heart rate accelerations of 15 bpm. Sporadic, fetal movement associated fetal heart rate accelerations are generally regarded as an indication of fetal wellbeing. A minimal amplitude of 15 bpm with unknown duration of the associated fetal body movement seems to be a prerequisite to establish an unimpaired fetal condition as reliably as possible. Including the "classical" acceleration amplitude in a ratio from the acceleration amplitude and associated fetal body movement and comparison of these calculated values with a total of 3851 actual ration from acceleration amplitudes and durations of associated body movements of 175 normotrophic and 72 hypotrophic fetuses showed that only a hypothetical acceleration amplitude of 15 bpm yields ratios which correspond to the actual values of unimpaired fetuses. There is a significant positive correlation between the actual ration and the transcutaneous basal fetal partial pressure of oxygen during birth.

Blood Gas Monitoring, Transcutaneous↗

Finite element model study of head impact based on Hybrid III head acceleration: the effects of rotational and translational acceleration.

The translational and rotational components of acceleration measured at the center of gravity of a Hybrid III dummy head were used to investigate their individual and combined effects on a two-dimensional finite element model of the human brain. Each component of acceleration generated distinct patterns of deformation. Although translational acceleration is related to pressure and rotational acceleration has a dominant effect on shear deformations, complete acceleration (combination of translation and rotation) yielded the highest values in all stresses and produced a maximum shear stress at the top of the brain.

Acceleration↗

On the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators.

1. In order to elucidate some features of the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, the methanesulfonylation of this enzyme by high concentrations of methanesulfonylfluoride, in the absence and presence of accelerators decamethonium and tetraethylammonium, was studied. 2. The results showed that the accelerator accelerates the reaction by electrostatically improving the binding between acetylcholinesterase and methanesulfonylfluoride without effecting the rate of the decomposition of the enzyme-inhibitor complex into the methanesulfonylated enzyme and product.

Acetylcholinesterase↗

Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice.

A substrain of the senescence-accelerated mouse (SAM), the SAMP1 mouse, is an animal model for accelerated senescence including the age-related acceleration of both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells. In the present study, we examine whether the accelerated presbycusis can be prevented by allogeneic BMT. Young SAMP1 (H-2(k)) mice were irradiated with 9 Gy and then reconstituted with bone marrow cells from normal BALB/c (H-2(d)) mice. Allogeneic BMT was found to prevent the development of immunological dysfunction, hearing loss, and apoptosis of spinal ganglion cells in SAMP1 mice. These findings indicate that some types of accelerated presbycusis do not result from defects in the cochlea, but do from defects in the hematopoietic stem cells (HSC) and immunocompetent cells derived from the HSC. If this is the case, either allogeneic BMT, which replaces abnormal HSC with normal HSC and reconstructs a normal immune system in the recipients, or autologous BMT using genetically modified bone marrow cells, could become a new strategy for the treatment of presbycusis.

Age Factors↗

Eye movements induced by lateral acceleration steps. Effect of visual context and acceleration levels.

Eye movement responses were obtained from six normal subjects exposed to randomly ordered rightwards/leftwards linear acceleration steps of 0.05 g, 0.1 g or 0.24 g amplitude and 650 ms duration along the interaural axis. With the instruction to gaze passively into the darkness, compensatory nystagmus was evoked with slow-phase velocity sensitivity of 49 degrees s(-1) g(-1). When subjects viewed earth-fixed targets at 30 cm, 60 cm or 280 cm, eye movements at 130 ms from motion onset were proportional to acceleration and inversely proportional to target distance, before the onset of visually guided eye movements. Our results show that a modulation with viewing distances of the earliest human otolith-ocular reflexes occurs in the presence of pure linear acceleration. However, full compensation was not attained for the nearer targets and higher accelerations.

Acceleration↗

Influence of the ambient acceleration field upon acute acceleration tolerance in chickens.

It has been demonstrated both in the Russian and in the American space programs that there is a progressive deconditioning of the circulatory system with exposure to weightlessness. Astronauts and cosmonauts returned to Earth have a significantly reduced orthostatic tolerance which will persist for a few days. We have measured the acceleration tolerance of domestic fowl, acutely exposed to a 6 g+z field, as the time over which a normal heart rate can be maintained. This period of circulatory accommodation ends abruptly with a marked bradycardia, which with continued treatment is terminal. For animals which have been previously chronically accelerated (e.g., physiologically adapted to a 2.5 g field) the acute acceleration tolerance is greatly increased. It appears that the influence of the ambient acceleration field in conditioning the responsiveness of the circulatory system is a general phenomenon.

Acceleration↗

Response of semicircular canal dependent units in vestibular nuclei to rotation of a linear acceleration vector without angular acceleration.

1. Recent experiments have shown that rotation of a linear acceleration vector round the head can generate involuntary ocular nystagmus in the absence of angular acceleration. The present experiments examine the suggestion that adequate stimulation of the semicircular canals may contribute to this response.2. Decerebrate cats were located in a stereotaxic device on a platform, slung from four parallel cables, which could be driven smoothly round a circular orbit without inducing significant angular movement of the platform. This Parallel Swing Rotation (PSR) generated a centripetal acceleration of 4.4 m/sec(2) which rotated round the head at 0.52 rev/sec.3. The discharge frequency of specifically lateral canal-dependent neural units in the vestibular nuclei of cats was recorded during PSR to right and left, and in the absence of motion. The dynamic responses to purely angular motion were also examined on a servo-driven turntable.4. Without exception all proven canal-dependent cells examined (twenty-nine cells in nine cats) were more active during PSR in the direction of endolymph circulation assessed to be excitatory to the unit, than during PSR in the opposite direction.5. The observed changes in discharge frequency are assessed to have been of a magnitude appropriate for the generation of the involuntary oculomotor response induced by the same stimulus in the intact animal.6. The findings suggest that a linear acceleration vector which rotates in the plane of the lateral semicircular canals can be an adequate stimulus to ampullary receptors, though an explanation which invokes the modulation of canal cells by a signal dependent upon the sequential activation of macular receptors cannot be positively excluded.

Acceleration↗

Symposium on low frequency harmonic acceleration, the rotatory chair. Responses to low-frequency harmonic acceleration in patients with acoustic neuromas.

There has been increased interest in harmonic acceleration (HA) for the evaluation of vestibular pathology in recent years. The purpose of this study was to determine the value of harmonic acceleration testing in 24 patients with surgically proven acoustic neuromas. All patients were tested preoperatively and postoperatively, and none were lost to follow-up. Thirteen were tested one year or more after surgery. For rotational evaluation, each patient was seated in an enclosed chair driven by a D.C. torque motor turntable system and rotated utilizing five low frequency sinusoids (.01 - .16 Hz). Slow eye movements in response to acceleration were analyzed by analog and digital computer techniques. Output measures were the phase relationships between the input stimulus velocity and the slow phase eye movement velocity and labyrinthine preponderance (LP) or asymmetry. Preoperative results showed that caloric examination identified 79% of patients with tumors and HA 67% (2 standard deviation criteria). When both tests were evaluated together they identified 91% of all patients with tumors. Of the 4 small tumors (less than 2 cm), HA identified 4 and caloric examination 2. All patients were tested approximately 7 days postoperatively and had statistically significant shifts in their phase and LP measures. The shifts in phase were stable up to 3 years after surgery; however, the LP returned toward normal values. These findings indicate that the vestibular system can compensate but not repair itself after the loss of one labyrinth. In those patients who continued to be symptomatic 1 year or more after surgery, the LP did not return to normal values. Harmonic acceleration testing complemented caloric testing in the identification of patients with tumors and objectively demonstrated patients with continued symptomatology after surgery.

Acceleration↗