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At least 451 records · Page 25Linked to original sources
PubMed2006

Lysozyme amyloidogenesis is accelerated by specific nicking and fragmentation but decelerated by intact protein binding and conversion.

We have revisited the well-studied heat and acidic amyloid fibril formation pathway (pH 1.6, 65 degrees C) of hen egg-white lysozyme (HEWL) to map the barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic mechanism is presented where all steps involving protein hydrolysis, fragmentation, assembly and conversion into amyloid fibrils are accounted for. Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL unfolds within minutes, followed by irreversible steps of partial acid hydrolysis affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment is a requirement for efficient amyloid fibril formation, indicating that it forms the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently into amyloid fibrils in the fibril growth phase or using mature fibrils as seeds, which abolished the lag phase completely. Mature amyloid fibrils of HEWL are composed mainly of nicked HEWL in the early equilibrium phase but go through a "fibril shaving" process, affording fibrils composed of the 49-101 fragment and 53-101 fragment during more extensive maturation (incubation for longer than ten days). Seeding of the amyloid fibril formation process using sonicated mature amyloid fibrils accelerates the fibril formation process efficiently; however, addition of intact full-length lysozyme at the end of the lag phase slows the rate of amyloidogenesis. The intact full-length protein, in contrast to nicked lysozyme, slows fibril formation due to its slow conversion into the amyloid fold, probably due to inclusion of the non-amyloidogenic 1-48/102-129 portion of HEWL in the fibrils, which can function as a "molecular bumper" stalling further growth.

Amino Acid Sequence↗
PubMed2004

Decreased final height of children with growth deceleration secondary to poor weight gain during late childhood.

Eighteen healthy, short children with normal growth during most of their childhood were evaluated after a sustained fall in weight and reduced linear growth. Growth was followed after nutritional counseling until final height. This report demonstrates the need for an appropriate-for-age weight gain in growing children as a relatively minor but prolonged caloric restriction, leading to a sustained fall in weight centiles, will affect growth velocities long term and may lead to reduced final heights.

Body Height↗
PubMed1995

Intermittent v continuous ischemia decelerates adenylate breakdown and prevents norepinephrine release in reperfused rabbit heart.

Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous ischemia of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12 x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stopped continuously for 24 or 36 min followed by a flat 36-min reperfusion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles, ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occurred regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in proglycogen levels occurred. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilization; such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Another beneficial effect of intermittent ischemia was the near-complete absence of free interstitial norepinephrine, which exacerbates myocardial ischemic insults. In addition, the exponential correlations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.

Adenine Nucleotides↗
PubMed2002

Fetal heart rate parameters predictive of neonatal outcome in the presence of a prolonged deceleration.

OBJECTIVE: To correlate the presence of baseline variability and the duration of a prolonged deceleration/bradycardia in intrapartum fetal heart rate (FHR) tracings with the development of neonatal acidemia. METHODS: We identified 186 patients with term gestations who had continuous electronic fetal monitoring for at least 2 hours before delivery, with an identified bradycardia during that period. Each patient had umbilical artery cord analysis done and delivery within 30 minutes of that bradycardia. One investigator blinded to the cord gas outcome reviewed the last 2 hours of the tracing using the National Institute of Child Health and Human Development guidelines for FHR monitoring. We assessed the presence or absence of variability before the bradycardia and recovery or no recovery of the bradycardia and placed the patients into four groups. Group 1 (128 patients) with normal variability and recovery, group 2 (40 patients) with normal variability and no recovery, group 3 (nine patients) with decreased variability and recovery, and group 4 (nine patients) with decreased variability and no recovery. We compared the incidence of neonatal acidosis defined as a pH of less than 7.0 at birth among the four groups. The relationship between the various groups was assessed using analysis of variance and the chi(2) test. In addition, a multiple logistic regression model was developed with the parameters of amplitude and recovery used to predict pH at birth. RESULTS: The presence of decreased variability and no recovery of the FHR of a bradycardia was associated with the lowest pH 6.83 +/- 0.16 and a 78% incidence of significant acidosis. Decreased variability before FHR bradycardia was the FHR parameter significantly correlated with low pH. CONCLUSION: The most significant factor predicting the development of pathologic neonatal acidemia and indicating the need for urgent delivery in the presence of a bradycardia is decreased variability before the bradycardia.

Acidosis↗
PubMed1991

Vertical deceleration trauma. Principles of management.

A highly complex interaction of several physical and biomechanical factors determines the patterns of injury and probability of survival in free falls. Falls from extreme heights result in massive visceral and vascular injuries, which are usually lethal. Urban falls tend to result in severe lower extremity, spinal, and pelvic fractures. Retroperitoneal hemorrhage is a significant cause of death and is best managed by emergency angiography and embolization. Early fixation of fractures reduces morbidity.

Accidental Falls↗
PubMed2001

The role of target position in smooth pursuit deceleration and termination.

Subjects smoothly pursued a target moving horizontally at 15 deg/s. After pursuit for 1 s, the target jumped 3 deg ahead of the fovea. At the moment of the jump, target velocity became 0 and 'effective visual feedback' assumed a value of either 0 (target retinally stabilized), -0.2, -0.4, or -1.0 (target fixed in space). With 0 visual feedback the eye continued to move smoothly at a moderate velocity, an apparent response to target position relative to the fovea. When negative visual feedback was present eye velocity decreased. With -0.2 and -0.4 feedback, this decrease was not a simple exponential, but often consisted of an initial fast decrease followed by slower decrease. With -1.0 feedback, eye velocity quickly decreased in an approximately exponential manner, and stopped. We were able to simulate these pursuit responses using a simple model of the pursuit system. Key features of the model are: (a) a target-velocity channel whose output decreases with target offset from the fovea, and whose gain switches from high to low as pursuit velocity approaches zero; (b) a target-position channel with a saturation non-linearity at 1-3 deg; and (c) a positive feedback loop with gain of less than 1.0. All of these features are essential to simulate the pursuit responses, especially with visual feedback values of -0.2 and -0.4. Our results and model suggest that target position serves as an important stimulus in guiding smooth pursuit as pursuit velocity decreases, and especially during pursuit termination.

Feedback↗
PubMed1984

Deceleration of self-injurious and stereotypic responding by exercise.

A jogging exercise program was implemented for two severely retarded adults who exhibited high rates of self-injurious behavior and stereotyped mannerisms. Exercise was increased from one mile per day to three miles per day over a six-week period. Baseline measures were taken on the self-injurious behavior, stereotyped body rocking and pacing, sitting, and social interactions. Aberrant responding gradually decreased over the six weeks. Daily response rates were lower after the exercise as contrasted with before. When the program was terminated aberrant responding again increased.

Adult↗