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Biomedical subjects

A Crowe

Publications and source records attributed to A Crowe.

At least 55 records · Page 3Linked to original sources

Alzheimer's neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2.

Ten monoclonal antibodies raised against Alzheimer's neurofibrillary tangles (ANTs) were characterized for reactivity with heat-stable microtubule fractions from bovine and human brain. Five of the antibodies showed very little reaction, but the other five reacted strongly with heat-stable microtubule associated proteins (MAPs). The proteins recognized by these antibodies have estimated molecular weights similar to those of known heat-stable MAPs, tau (52-68 kd) and MAP2 (200-250 kd). That the proteins are indeed tau and MAP2 is demonstrated by reaction of electroblotted proteins with antibodies raised in mouse and guinea pig against bovine brain tau and MAP2. One anti-ANT antibody reacts only with tau, two bind strongly to tau and weakly to MAP2, one recognizes both tau and MAP2 equally well, and one primarily stains MAP2. Extraction of ANT with 2% SDS does not remove tau or MAP2 epitopes from ANT, indicating that epitopes shared with heat-stable MAPs are integral components of ANT. The existence of tau epitopes in ANT is also demonstrated by immunoblotting of ANT-enriched fractions with anti-tau antibodies. Most of the material recognized by anti-tau antibodies in ANT-enriched fractions is present in large molecules excluded by 3% polyacrylamide gel upon electrophoresis. Anti-tau antibodies immunostain ANT in immunofluorescence and immunoperoxidase studies. The immunostaining can be blocked by absorption of anti-tau antibodies with purified tau proteins from bovine brain. Not all ANTs in any given tissue section or isolated Alzheimer perikarial preparations, however, are stained by anti-tau antibodies. These results are consistent with previous studies that have demonstrated heterogeneity of ANTs. Whether this heterogeneity is due to biochemical modification of MAPs or absence of MAPs in some ANTs is unknown. The significance of what appear to be shared epitopes recognized by monoclonal antibodies in tau and MAP2, and the implications this may have on the pathogenesis of ANT formation, requires further investigation.

Alzheimer Disease↗

Dynamic model of the equine hindlimb during the swing phase.

A dynamic model is developed to describe the swing phase of the hindlimb of a normally walking horse. The limb was represented by four rigid segments constrained to move in a sagittal plane only. The mathematical equations of motion of this four-element pendulum were formulated using Lagrange's theorem. The morphometric parameters from the hindlimb segments of 3 horses were determined using high-speed film analysis. Five muscle groups were incorporated in the model. Muscle activity was derived from earlier EMG measurements. Optimization of muscle moments resulted in a simulated swing movement that approximated that in the living animal.

Animals↗

Dendrite distribution of identified motoneurons in the lumbar spinal cord of the turtle Pseudemys scripta elegans.

Motoneurons in the turtle lumbar spinal cord were injected with HRP by electrophoresis after being electrophysiologically identified as innervating a muscle belonging to a functional group. The distribution of dendrites was studied in transverse reconstructions of 45 motoneurons, including 11 motoneurons identified as innervating knee extensor muscles, eight motoneurons innervating hip retractor and knee flexor muscles, 14 motoneurons innervating ankle and/or toe extensors and 12 motoneurons innervating ankle and/or toe flexor muscles. The dorsal dendritic tree of motoneurons innervating distally positioned musculature (ankle and/or toe extensors and flexors) was observed to contain significantly less terminal dendritic branches compared to the dorsal dendritic trees of motoneurons innervating proximally situated (hip and knee) muscles. The distribution of dendrites within the white matter was studied by measuring the total projected length of the dendritic branches within empirically defined sectors in the transverse plane. This kind of analysis also revealed differences between the dorsal dendrites of motoneurons innervating distally and proximally positioned muscles conforming to the counts of terminal dendritic branches. It is suggested that these apparent differences in the size of the dorsal dendrite may be related to the number of synapses made by primary afferents. In the white matter, the highest dendritic density for all four groups of mononeurons was found within the central part of the lateral funiculus. However, only in the ventral funiculus could slight indications be found that the dendritic density of functionally different motoneuron groups may bear some relation to the locations of the terminations of the descending pathways known to establish monosynaptic contacts with lumbar mononeurons.

Animals↗

Terminations of primary afferents on lumbar motoneurons in the turtle Pseudemys scripta elegans.

The existence of monosynaptic contacts between primary afferents and motoneurons in the lumbar spinal cord of the turtle Pseudemys scripta elegans was demonstrated by intracellular injections of horseradish peroxidase. Three afferent-motoneuron combinations were satisfactorily labeled and revealed 1, 4 and 6 contacts respectively. All contacts were made on the dorsal dendritic tree of the motoneurons. It is suggested that the contacting primary afferents are from muscle spindles.

Animals↗

Morphology of primary afferents to the spinal cord of the turtle Pseudemys scripta elegans.

The morphology of primary afferents to the spinal cord of the turtle Pseudemys scripta elegans was studied by means of intra-axonal injections of horseradish peroxidase. A total of 74 collaterals arising from 34 different afferents in 22 animals was investigated. Within this sample, a division into three morphologically distinct collateral types appeared possible. Collaterals of the same parent axon could always be classified to the same type. Type A collateral arborizations could be found within area I-II and III of the spinal grey matter. The number of presynaptic boutons per collateral varied considerably. However, collaterals of the same parent axon usually possessed a similar general appearance. Type B collaterals terminated within area IV and V-VI. The general shape and number of boutons could differ considerably between collaterals of different parent fibers but also between collaterals of the same axon. Type C collaterals formed terminal arborizations in the lateral parts of areas IV, V, VI and VII-VIII and demonstrated a fair constancy in general appearance and number of presynaptic boutons. Type A collaterals are thought to be derived from fibers innervating various cutaneous receptors. Terminal arborizations of type C collaterals are fully overlapping with the dorsal dendritic trees of turtle lumbar motoneurons. It is suggested that type C collaterals form contacts with these motoneurons and arise from muscle spindle innervating afferents. The origin of type B collaterals is less clear, attractive possibilities may be found in joint and/or tendon organs.

Afferent Pathways↗

Multichannel transmission of proprioceptive input to motoneurons.

A model has been developed to simulate the parallel channels of muscle spindles and their monosynaptic connections to a homonymous motoneuron in the turtle. Input to the model is muscle length and beta stimulation, output is motoneuronal membrane potential. Quality of transmission is greatly dependent upon dispersive properties of the system. The contributions of different dispersive features are compared and also cumulative effects are considered. Reference is made to conditions which are found in actual movements.

Action Potentials↗

Effect of beta-blockers on psychomotor performance in normal volunteers.

The effects of beta-adrenergic receptor antagonists on psychometric tests including vehicle handling, choice reaction time, and kinetic visual acuity (KVA), are reviewed. The beta-blockers had little effect on the performance tests, with the unexplained but reproducible effect of enhanced KVA performance with atenolol. Although the beta-blockers had little effect on performance tests they were shown to have psychotropic effects in normal volunteers. The reasons for the conflicting evidence concerning the effect of these drugs on performance tests is discussed in relation to the present experiments and to variables that may influence response. It is concluded that one should use tests that are as independent as possible from potentially confounding variables. The use of evoked potentials in the electroencephalogram is one such test. A preliminary study is described in which the effects of beta-blockers were detected using visual evoked responses on the electroencephalogram.

Adolescent↗

Studies on the excitability of the central program generator in the spinal cord of the terrapin Pseudemys scripta elegans.

We present observations on the multicyclic scratch reflex in spinal terrapins as produced by electrical stimuli applied to the shell at the specific regions at which a mechanical stimulus produces the reflex. EMGs and hip and knee movements are recorded. The responses to the electrical stimuli are similar to the responses to mechanical stimuli. There is a three phase EMG pattern (Stein and Grossman, 1980), to which the movement pattern is related (Bakker and Crowe, 1982). A response may consist of a series of up to 25 movement cycles with a total time course of up to about 30 sec. The initial cycles of a response are relatively fast (less than 1 sec), but the cycles at the expiration of the response may have a duration of 2-3 sec. A single electrical stimulus pulse is often insufficient to trigger a series response. Instead, a weak EMG burst of a few tenths of a second duration, together with a slight movement, is often seen. However, a second pulse can set the cycle series in motion even after an interval of 40 sec between the pulses. A further booster stimulus pulse given while a reflex response is taking place can increase the speed of the movement. If the booster pulse is given just after cessation of reflex activity it can restart the activity, but this second cycle series is often shorter than the first one. The results indicate that the excitability of the central program generator is not constant. Long duration changes in the excitability are produced within the spinal cord.

Animals↗

Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides.

Ten monoclonal antibodies to Alzheimer neurofibrillary tangles (ANTs) were produced by immunizing mice with a brain homogenate from senile dementia of the Alzheimer type (SDAT). In methanol-fixed isolated neuronal perikarya, six of these antibodies reacted with nearly every ANT, three recognized 70-88% of ANTs, and one bound to less than 30% of ANT. In paraffin sections, three of the antibodies did not bind to tangles that had been fixed in formalin, three stained weekly, and four reacted with tangles in tissues that had been in formalin for more than a decade. Immunoblotting of brain homogenates showed that all but one antibody reacted with proteins from SDAT samples insoluble in SDS and too large to enter even the 3% polyacrylamide stacking gel. Polypeptides extractable by Tris buffer of molecular weight 58, 66, and 70 kd were detected in both normal and SDAT brains by two antibodies and only in SDAT brain by two other antibodies. One antibody did not show any reaction on the immunoblot. The results demonstrate that the epitopes recognized by these antibodies are not identical and that ANTs contain unique antigenic determinants as well as determinants in common with normal brain. Whether the unique determinants are acquired during tangle development or are essential in tangle formation remains to be investigated.

Alzheimer Disease↗

Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy.

Neurofibrillary degeneration is an argyrophilic intraneuronal lesion found in several unrelated neurologic conditions. The relationship between different types of neurofibrillary tangles is investigated with two monoclonal antibodies raised against Alzheimer neurofibrillary tangles (anti-ANT). Using the peroxidase-antiperoxidase technique, the authors demonstrate that neurofibrillary tangles of progressive supranuclear palsy, containing 15-nm straight filaments, share an antigenic determinant with ANTs. Ultrastructural studies localize the antigenic determinant to filamentous elements in the parakarya. The determinant is not present in normal brain, aluminum-induced experimental tangles in the rabbit, Lewy bodies, Hirano bodies, or axonal filamentous inclusions of amyotrophic lateral sclerosis and giant axonal neuropathy. It is, however, present in ANTs regardless of the pathologic condition in which they are found, including Alzheimer's disease, Down's syndrome, and postencephalitic Parkinson's disease.

Alzheimer Disease↗

Morphology of lumbar motoneurons innervating hindlimb muscles in the turtle Pseudemys scripta elegans: an intracellular horseradish peroxidase study.

Motoneurons in the turtle lumbar spinal cord, electrophysiologically identified as innervating a muscle belonging to a functional group, were injected with horseradish peroxidase by electrophoresis. A total of 45 motoneurons were reconstructed from transverse sections. Eleven motoneurons were identified as innervating knee extensor muscles, eight as innervating hip retractor and knee flexor muscles, 14 as supplying ankle and/or toe extensors, and 12 as innervating ankle and/or toe flexor muscles. The cell bodies were elongated and spindle-shaped in the transverse plane. The mean equivalent soma diameter was calculated to be 33.4 micrometers. The mean axon conduction velocity was 15.7 m/second. Significant, though rather weak, positive correlations were found between soma diameter, axon diameter, and axon conduction velocity. The axons of the reconstructed motoneurons did not reveal a recurrent axon collateral. However, a few unidentified motoneurons did possess such collaterals. The dendritic trees were restricted to the ipsilateral side of the cord, but reached out in lateral, ventral, and ventromedial directions to the subpial surface. Easily recognizable and characteristic dendrites were found both in the dorsal dendritic tree and in the dorsomedial dendritic tree. Correlations were calculated between the soma diameter and (1) the number of first-order dendrites, (2) the mean diameter of the first-order dendrites, and (3) the combined diameter of the first-order dendrites. In each case no correlations or only weak correlations were found. Fair correlations were observed between the diameter of a first-order dendrite and the number of terminal dendritic branches (r = .61) and the combined dendritic length (r = .78). However, correlations between the combined diameter of all first-order dendrites per neuron and the total number of terminal dendritic branches and the total combined dendritic length of a neuron were extremely weak. The overall appearance of turtle spinal motoneurons is comparable to that observed in other "lower" vertebrates such as frog and lizard. However, similarities are also observed between certain morphometric parameters in turtle and cat lumbar motoneurons.

Animals↗

The organization of motoneurons in the turtle lumbar spinal cord.

The distribution of motoneurons in the lumbosacral spinal cord of the turtle Pseudemys scripta elegans was studied by using the technique of retrograde transport of horseradish peroxidase. A total of 19 different hindlimb muscles were injected with varying amounts of horseradish peroxidase. The resulting distribution of labeled motoneurons was studied in both longitudinal and transverse sections of spinal cord. Motoneurons innervating a particular hindlimb muscle are clustered in longitudinally arranged motorpools. Motorpools of different muscles can show considerable overlap in both the rostrocaudal and transverse planes. The distribution of the various motorpools demonstrates a somatotopic organization of motoneurons within the lumbar spinal cord. Motoneurons innervating more distally positioned muscles are generally found in the more caudal segments, while motoneurons supplying proximal muscles are distributed throughout almost the whole lumbosacral intumescence. Motoneurons innervating anterodorsally positioned muscles are found in the ventrolateral part of area IX in the ventral horn, while more dorsomedially positioned motoneurons innervate the posteroventral muscles. These features are consistent with observations in other tetrapods, although the somatotopic representation of motoneurons is more evident in higher vertebrates such as chicken and cat. The observed motorpool distribution is discussed in relation to the presumed ontogeny of the spinal cord and hindlimb muscles and also in relation to the functions of the investigated muscles.

Animals↗

Diazepam/beta-adrenoceptor antagonist interactions.

The effects of diazepam on the pharmacokinetics and pharmacodynamics of two lipophilic beta-adrenoceptor antagonists (propranolol and metoprolol) and a hydrophilic beta-adrenoceptor antagonist (atenolol) were compared in 12 subjects. Administration of propranolol and metoprolol produced small increases in the AUC0-8h for diazepam compared with placebo (P less than 0.05 for metoprolol). Atenolol had no significant effect on the AUC0-8h for diazepam. The increase in the AUC0-8h was accompanied by increases in the plasma concentrations of N-desmethyldiazepam. Diazepam had no significant effect on the pharmacokinetics of either propranolol or atenolol. The pharmacokinetic interaction could be attributed to inhibition of diazepam metabolism by the lipophilic beta-adrenoceptor antagonists. The pharmacodynamic studies showed that when compared with placebo or atenolol there was a significant impairment of kinetic visual acuity (KVA) when diazepam was co-administered with metoprolol. Although there was a significant correlation (P less than 0.02) between plasma concentrations of diazepam and impairment of KVA, the pharmacodynamic interactions may not be due solely to the small pharmacokinetic interaction observed.

Adolescent↗

The distribution of motoneurons innervating hindlimb muscles in the terrapin Pseudemys scripta elegans.

The distribution of motoneurons innervating a number of hindlimb muscles in the spinal cord of the terrapin Pseudemys scripta elegans was studied by means of intramuscularly injected horseradish peroxidase (HRP). It appeared that motoneurons innervating knee extensors were localized more rostrally in the spinal cord than those innervating knee flexors and hip retractors. Muscles on the dorsal side of the limb were positioned more ventrally in the ventral horn compared to motoneurons innervating ventral muscles. Thus, an evident somatotropic organization of motoneurons was demonstrated in the chelonian spinal cord.

Animals↗

The effects of beta motor stimulation on the interpretation of signals from muscle spindles.

A previously proposed method for the interpretation of the signals in sensory nerve fibres is extended to incorporate beta activation of muscle spindles. simulations, based on previous experimental observations, of muscles spindles subjected to ramp and hold stretches are used as input to an "interpreter", where the simulated trains of action potentials are reconverted to a length change interpretation. The interpreted signals are compared with the original length change inputs to observe the effects of beta-stimulation and stochastic variability.

Action Potentials↗

The RNA operator theory.

The aim of the RNA Operator Theory is to propose a new explanation for the mechanism of certain biological control functions, including morphogenesis and brain function. It assumes the existence of a natural computing language, the vocabulary of which, in machine language form, is constituted of bytes of nucleotide bits. These are observable empirically as, inter alia, repeated sequences in genetic nucleic acid. The assumed computing language possesses a range of operators which act directly when coded as RNS to effect the positional manipulation of matter on a molecular level.

Animals↗

A method for the interpretation of signals in afferent nerves from muscle spindles.

A method is proposed for the interpretation of the signals in sensory nerve fibres. It is applicable to systems in which the transfer function between the input to a sense organ and the action potential firing frequency is known. In the present case, the chelonian muscle spindle is considered since its output to ramp-hold-release and sinusoidal stretches can be rather accurately simulated.

Action Potentials↗